@Article{info:doi/10.2196/66556,
author="Miller, Catriona
and Portlock, Theo
and Nyaga, M. Denis
and Gamble, D. Greg
and O'Sullivan, M. Justin",
title="Code Error in ``Diagnostic Classification and Prognostic Prediction Using Common Genetic Variants in Autism Spectrum Disorder: Genotype-Based Deep Learning''",
journal="JMIR Med Inform",
year="2025",
month="May",
day="6",
volume="13",
pages="e66556",
keywords="autism prediction",
keywords="machine learning",
keywords="data leakage",
doi="10.2196/66556",
url="https://medinform.jmir.org/2025/1/e66556"
}


@Article{info:doi/10.2196/71016,
author="Tuan Huynh, An
and Vu, Anh Hoang
and Chuong, Quoc Ho
and Anh, Hoang Tien
and Viet Tran, An",
title="The rs243865 Polymorphism in Matrix Metalloproteinase-2 and its Association With Target Organ Damage in Patients With Resistant Hypertension: Cross-Sectional Study",
journal="JMIR Cardio",
year="2025",
month="May",
day="1",
volume="9",
pages="e71016",
keywords="resistant hypertension",
keywords="matrix metalloproteinase-2",
keywords="gene polymorphism",
keywords="target organ damage",
keywords="arterial stiffness",
abstract="Background: Resistant hypertension (RH) presents significant clinical challenges, often precipitating a spectrum of cardiovascular complications. Particular attention recently has focused on the role of matrix metalloproteinase-2 (MMP-2) gene polymorphisms, implicated in hypertensive target organ damage (TOD). Despite growing interest, the specific contribution of MMP-2 polymorphisms to such damage in RH remains inadequately defined. Objective: This study is the first to examine the rs243865 (?1306C>T) polymorphism in the MMP-2 gene in the Vietnamese population and patients with RH, underscoring its critical role as a genetic determinant of TOD. Methods: A cross-sectional study with both descriptive and analytical components was conducted with 78 patients with RH at the Can Tho Central General Hospital and Can Tho University of Medicine and Pharmacy Hospital from July 2023 to February 2024. Results: More than three-quarters of patients with RH had carotid-femoral pulse wave velocity (PWV) >10 m/s and microalbuminuria at a prevalence of 79\% (62/78) and 76\% (59/78), respectively, and more than half of patients with RH had left ventricular mass index, relative wall thickness, and carotid artery stenosis with a prevalence of 56\% (45/78), 55\% (43/78), and 53\% (41/78), respectively. Of the 78 studied patients with RH, the presence of genotype CC was 77\% (60/78), genotype CT accounted for 21\% (16/78), and genotype TT for 3\% (2/78). The presence of single nucleotide polymorphism rs243865 (?1306C>T) with allele T was 23\% (18/78). The MMP-2 gene polymorphism 1306C/T (rs243865) was significantly associated with ejection fraction and carotid artery stenosis with odds ratios (ORs) 8.1 (95\% CI 1.3?51.4; P=.03) and 4.5 (95\% CI 1.1?20.1; P=.048), respectively. The allele T was found to be significantly associated with arterial stiffness including brachial-ankle PWV and carotid-femoral PWV with the correlation coefficient of OR 2.2 (95\% CI 0.6?3.8) and OR 1.8 (95\% CI 0.5?3.2), respectively. Conclusions: The MMP-2 gene polymorphism rs243865 (?1306C>T) may have an association with measurable TOD in RH. ",
doi="10.2196/71016",
url="https://cardio.jmir.org/2025/1/e71016"
}


@Article{info:doi/10.2196/63028,
author="Biswas, Sawona
and So, Joyce
and Wallerstein, Robert
and Gonzales, Ralph
and Tout, Delphine
and DeAngelis, Lisa
and Rajkovic, Aleksandar",
title="Assessing the Utilization of Electronic Consultations in Genetics: Seven-Year Retrospective Study",
journal="JMIR Form Res",
year="2025",
month="Apr",
day="30",
volume="9",
pages="e63028",
keywords="genomic",
keywords="e-Consult",
keywords="genetic",
keywords="utility",
keywords="retrospective",
keywords="assessment",
keywords="effectiveness",
keywords="electronic consultation",
keywords="healthcare providers",
keywords="genetic experts",
keywords="university",
keywords="consultations",
keywords="e-Consult frameworks",
keywords="accessibility",
keywords="genetic testing",
keywords="patient care",
abstract="Background: Patient and health care provider access to genetic subspecialists is challenging owing to limited number of genetics experts across the United States. The University of California San Francisco (UCSF) Genetics electronic consultation (e-Consult) service was implemented along with the usual referral pathway to improve access to timely genetic expertise through robust asynchronous provider-to-provider communication. Objectives: This study examined the impact of the UCSF Genetics e-Consult service on patient access to genetics expertise. Methods: A retrospective chart review of 622 e-Consult requests was conducted. Data pertinent to e-Consult completion rates, provider response times, consultation content, and adherence to geneticist recommendations were abstracted. Results: From October 2016 to March 2024, the UCSF Genetics e-Consult service received a total of 622 consultation orders, with yearly volumes increasing from 34 in 2017 to 144 in 2023. A total of 360/622 (57.8\%) consultations were completed, of which 197/360 (54.6\%) were resolved without requiring a specialty care visit. Of the 262/622 (42.1\%) e-Consult orders declined by the geneticist reviewer, 184/262 (70.2\%) were scheduled for a synchronous genetics visit due to case complexity precluding an appropriate e-Consult response and 29.8\% (78/262) were recommended to be referred to a different and more appropriate specialty. Geneticists responded to 83.9\% (522/622) of e-Consults within 3 days, with most spending between 5 and 20 minutes on their e-Consult response. Nearly half of the genetics e-Consult requests (69/144; 47.9\%) came from primary care providers and pediatricians. Among the 144 e-Consult requests in 2023, 50.6\% (73/144) were about diagnostic queries, 17\% (25/144) were on symptom management, and 11\% (16/144) were about test interpretation. Provider adherence to geneticists' recommendations was observed in 84\% (116/144) of cases. Conclusions: The UCSF Genetics e-Consult service has demonstrated efficiency in providing timely genetic consultations, with a high rate of provider adherence to recommendations. These findings support the potential of e-Consult frameworks as a viable strategy for enhancing access to genetic health care services. ",
doi="10.2196/63028",
url="https://formative.jmir.org/2025/1/e63028"
}


@Article{info:doi/10.2196/60681,
author="Li, Huanhuan
and Zhao, Yanjie
and Li, Wei
and Wang, Wenxia
and Zhi, Shengze
and Wu, Yifan
and Zhong, Qiqing
and Wang, Rui
and Sun, Jiao",
title="A WeChat-Based Decision Aid Intervention to Promote Informed Decision-Making for Family Members Regarding the Genetic Testing of Patients With Colorectal Cancer: Randomized Controlled Trial",
journal="J Med Internet Res",
year="2025",
month="Apr",
day="21",
volume="27",
pages="e60681",
keywords="decision aid",
keywords="genetic testing",
keywords="hereditary colorectal cancer",
keywords="informed decision-making",
keywords="RCT",
keywords="WeChat based",
abstract="Background: Identifying patients with inherited colorectal cancer (CRC) syndromes offers many potential benefits. However, individuals often experience decisional conflict regarding genetic testing for CRC, and the uptake rate remains low. Given the growing popularity of genetic testing and the increasing demands on genetic service providers, strategies are needed to promote informed decision-making, increase genetic testing uptake among at-risk individuals, and ensure the rational use of genetic service resources. Objective: This study aims to determine whether a decision aid (DA) tool could promote informed decision-making among family members regarding the genetic testing of a patient with CRC. Methods: A single-center, parallel-group, randomized controlled trial was conducted. We randomized 82 family members of patients with CRC, who were involved in major medical decision-making for the patient, to either a DA intervention or usual care. The primary outcome was informed decision-making, assessed through measures of knowledge, decisional conflict, decision self-efficacy, and preparation for decision-making. Secondary outcomes included patients' uptake of genetic counseling and testing, participants' CRC screening behavior, healthy lifestyle scores, anxiety and depression levels, quality of life, and satisfaction with the intervention. Data were collected at baseline (T0), after the intervention (T1), and 3 months after the baseline survey (T2). The DA intervention and outcome assessments at T1 and T2 were delivered via WeChat. The effects of the intervention were analyzed using generalized estimating equation models. Results: Statistically significant improvements were observed in knowledge (T1: $\beta$=2.049, P<.001; T2: $\beta$=3.317, P<.001), decisional conflict (T1: $\beta$=--11.660, P<.001; T2: $\beta$=--17.587, P<.001), and decision self-efficacy (T1: $\beta$=15.353, P<.001; T2: $\beta$=22.337, P<.001) in the DA group compared with the usual care group at both T1 and T2. Additionally, the DA group showed significantly greater improvement in processed and red meat intake ($\beta$=--1.494, P<.001) at T1 and in healthy lifestyle scores ($\beta$=1.073, P=.03) at T2. No differences were found between the groups for other outcomes. Conclusions: A DA tool may be a safe, effective, and resource-efficient approach to facilitate informed decision-making about genetic testing. However, the current DA tool requires optimization and further evaluation---for example, by leveraging more advanced technology than WeChat to develop a simpler and more intelligent DA system. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100048051; https://www.chictr.org.cn/showproj.html?proj=129054 ",
doi="10.2196/60681",
url="https://www.jmir.org/2025/1/e60681"
}


@Article{info:doi/10.2196/66003,
author="Nian, Hui
and Bai, Yu
and Yu, Hua",
title="Assessing the Causal Association Between COVID-19 and Graves Disease: Mendelian Randomization Study",
journal="JMIR Form Res",
year="2025",
month="Apr",
day="8",
volume="9",
pages="e66003",
keywords="Graves disease",
keywords="COVID-19",
keywords="Mendelian randomization",
keywords="causal relationship",
keywords="autoimmune disease",
abstract="Background: Graves disease (GD) is an autoimmune thyroid disorder characterized by hyperthyroidism and autoantibodies. The COVID-19 pandemic has raised questions about its potential relationship with autoimmune diseases like GD. Objective: This study aims to investigate the causal association between COVID-19 and GD through Mendelian randomization (MR) analysis and assess the impact of COVID-19 on GD. Methods: We conducted an MR study using extensive genome-wide association study data for GD and COVID-19 susceptibility and its severity. We used stringent single nucleotide polymorphism selection criteria and various MR methodologies, including inverse-variance weighting, MR-Egger, and weighted median analyses, to assess causal relationships. We also conducted tests for directional pleiotropy and heterogeneity, as well as sensitivity analyses. Results: The MR analysis, based on the largest available dataset to date, did not provide evidence supporting a causal relationship between COVID-19 susceptibility (odds ratio [OR] 0.989, 95\% CI 0.405?2.851; P=.93), COVID-19 hospitalization (OR 0.974, 95\% CI 0.852?1.113; P=.70), COVID-19 severity (OR 0.979, 95\% CI 0.890?1.077; P=.66), and GD. Tests for directional pleiotropy and heterogeneity, as well as sensitivity analyses, supported these findings. Conclusions: This comprehensive MR study does not provide sufficient evidence to support a causal relationship between COVID-19 and the onset or exacerbation of GD. These results contribute to a better understanding of the potential association between COVID-19 and autoimmune diseases, alleviating concerns about a surge in autoimmune thyroid diseases due to the pandemic. Further research is warranted to explore this complex relationship thoroughly. ",
doi="10.2196/66003",
url="https://formative.jmir.org/2025/1/e66003"
}


@Article{info:doi/10.2196/65645,
author="Goes Job, Eduarda Maria
and Fukumasu, Heidge
and Malta, Maistro Tathiane
and Porfirio Xavier, Luiz Pedro",
title="Investigating Associations Between Prognostic Factors in Gliomas: Unsupervised Multiple Correspondence Analysis",
journal="JMIR Bioinform Biotech",
year="2025",
month="Mar",
day="12",
volume="6",
pages="e65645",
keywords="brain tumors",
keywords="bioinformatics",
keywords="stemness",
keywords="multiple correspondence analysis",
abstract="Background: Multiple correspondence analysis (MCA) is an unsupervised data science methodology that aims to identify and represent associations between categorical variables. Gliomas are an aggressive type of cancer characterized by diverse molecular and clinical features that serve as key prognostic factors. Thus, advanced computational approaches are essential to enhance the analysis and interpretation of the associations between clinical and molecular features in gliomas. Objective: This study aims to apply MCA to identify associations between glioma prognostic factors and also explore their associations with stemness phenotype. Methods: Clinical and molecular data from 448 patients with brain tumors were obtained from the Cancer Genome Atlas. The DNA methylation stemness index, derived from DNA methylation patterns, was built using a one-class logistic regression. Associations between variables were evaluated using the $\chi${\texttwosuperior} test with k degrees of freedom, followed by analysis of the adjusted standardized residuals (ASRs >1.96 indicate a significant association between variables). MCA was used to uncover associations between glioma prognostic factors and stemness. Results: Our analysis revealed significant associations among molecular and clinical characteristics in gliomas. Additionally, we demonstrated the capability of MCA to identify associations between stemness and these prognostic factors. Our results exhibited a strong association between higher DNA methylation stemness index and features related to poorer prognosis such as glioblastoma cancer type (ASR: 8.507), grade 4 (ASR: 8.507), isocitrate dehydrogenase wild type (ASR:15.904), unmethylated MGMT (methylguanine methyltransferase) Promoter (ASR: 9.983), and telomerase reverse transcriptase expression (ASR: 3.351), demonstrating the utility of MCA as an analytical tool for elucidating potential prognostic factors. Conclusions: MCA is a valuable tool for understanding the complex interdependence of prognostic markers in gliomas. MCA facilitates the exploration of large-scale datasets and enhances the identification of significant associations. ",
doi="10.2196/65645",
url="https://bioinform.jmir.org/2025/1/e65645"
}


@Article{info:doi/10.2196/65366,
author="Lee, Yugyung
and Shelke, Sushil
and Lee, Chi",
title="Cardiac Repair and Regeneration via Advanced Technology: Narrative Literature Review",
journal="JMIR Biomed Eng",
year="2025",
month="Mar",
day="8",
volume="10",
pages="e65366",
keywords="advanced technologies",
keywords="genetics",
keywords="biomaterials",
keywords="bioengineering",
keywords="medical devices",
keywords="implantable devices",
keywords="wearables",
keywords="cardiovascular repair and regeneration",
keywords="cardiac care",
keywords="cardiovascular disease",
abstract="Background: Cardiovascular diseases (CVDs) are the leading cause of death globally, and almost one-half of all adults in the United States have at least one form of heart disease. This review focused on advanced technologies, genetic variables in CVD, and biomaterials used for organ-independent cardiovascular repair systems. Objective: A variety of implantable and wearable devices, including biosensor-equipped cardiovascular stents and biocompatible cardiac patches, have been developed and evaluated. The incorporation of those strategies will hold a bright future in the management of CVD in advanced clinical practice. Methods: This study employed widely used academic search systems, such as Google Scholar, PubMed, and Web of Science. Recent progress in diagnostic and treatment methods against CVD, as described in the content, are extensively examined. The innovative bioengineering, gene delivery, cell biology, and artificial intelligence--based technologies that will continuously revolutionize biomedical devices for cardiovascular repair and regeneration are also discussed. The novel, balanced, contemporary, query-based method adapted in this manuscript defined the extent to which an updated literature review could efficiently provide research on the evidence-based, comprehensive applicability of cardiovascular devices for clinical treatment against CVD. Results: Advanced technologies along with artificial intelligence--based telehealth will be essential to create efficient implantable biomedical devices, including cardiovascular stents. The proper statistical approaches along with results from clinical studies including model-based risk probability prediction from genetic and physiological variables are integral for monitoring and treatment of CVD risk. Conclusions: To overcome the current obstacles in cardiac repair and regeneration and achieve successful therapeutic applications, future interdisciplinary collaborative work is essential. Novel cardiovascular devices and their targeted treatments will accomplish enhanced health care delivery and improved therapeutic efficacy against CVD. As the review articles contain comprehensive sources for state-of-the-art evidence for clinicians, these high-quality reviews will serve as a first outline of the updated progress on cardiovascular devices before undertaking clinical studies. ",
doi="10.2196/65366",
url="https://biomedeng.jmir.org/2025/1/e65366"
}


@Article{info:doi/10.2196/67794,
author="Wellman, L. Mariah
and Owens, M. Camilla
and Holton, E. Avery
and Kaphingst, A. Kimberly",
title="Examining BRCA Previvors' Social Media Content Creation as a Form of Self and Community Care: Qualitative Interview Study",
journal="J Med Internet Res",
year="2025",
month="Mar",
day="3",
volume="27",
pages="e67794",
keywords="BRCA",
keywords="breast cancer",
keywords="genetic testing",
keywords="social media",
keywords="breast cancer gene",
keywords="content creation",
keywords="self care",
keywords="community care",
keywords="qualitative interview",
keywords="qualitative",
keywords="interview",
keywords="previvors",
keywords="cancer previvors",
keywords="genetic mutations",
keywords="online",
keywords="content",
keywords="interviews",
keywords="thematic analysis",
abstract="Background: Genetic testing has become a common way of identifying a woman's risk of developing hereditary breast and ovarian cancer; however, not all medical providers have the necessary information to support patients interested in genetic testing, nor do they always have the proper information for patients once they have been diagnosed. Therefore, many ``previvors''---the name given to those who have tested positive for the BRCA genetic mutation---have taken to social media to inform others about the importance of genetic testing and explain to them how to understand their test results. Historically, those desiring to speak about their medical issues online have sought out structured support groups or chat rooms; however, many previvors today are instead posting on their own personal social media accounts and creating more niche communities. Objective: This study aimed to examine why BRCA previvors are sharing content on their personal social media accounts and how posting online in this way serves a purpose for their larger community. Methods: A total of 16 semistructured interviews were conducted with individuals who posted about their experience being diagnosed with the BRCA genetic mutation and their subsequent treatment on their personal social media accounts, specifically for followers interested in their medical journey. The interviews were recorded, transcribed, and coded by an experienced qualitative researcher and a graduate student using inductive techniques, and a reflexive thematic analysis was applied to the transcripts. Results: The results suggest BRCA previvors want to control the narrative around their personalized medical experiences rather than participating in existing groups or chat rooms. Controlling their own story, rather than adding to existing narratives, gives previvors a sense of control. It also allows them to set boundaries around the types of experiences they have online when sharing their medical journey. Finally, previvors said they feel they are serving the larger BRCA community by each sharing their individual journeys, to hopefully avoid stereotyping and homogenizing the experience of patients with BRCA genetic mutations. Conclusions: Research with the objective of understanding the experiences of BRCA previvors should include exploring how and why they talk about their journeys, especially due to the lack of knowledge BRCA previvors say many of their medical providers have. We suggest further research should examine how other patients with the BRCA genetic mutation, especially racial and ethnic minority patients, are navigating their own content creation, especially considering content moderation policies that social media platforms are continuing to implement that directly impact users' ability to share about their medical experiences. ",
doi="10.2196/67794",
url="https://www.jmir.org/2025/1/e67794",
url="http://www.ncbi.nlm.nih.gov/pubmed/40053732"
}


@Article{info:doi/10.2196/70075,
author="Raharja, Risky Putu Angga
and Birowo, Ponco
and Rachmadi, Lisnawati
and Wibowo, Heri
and Kekalih, Aria
and Duarsa, Kusuma Gede Wirya
and Abbas, Tariq
and Wahyudi, Irfan",
title="Histopathological Comparison and Expression Analysis of COL1A1, COL3A1, and ELN in the Proximal and Distal Ventral Dartos of Patients With Hypospadias: Protocol for Prospective Case-Control Study",
journal="JMIR Res Protoc",
year="2025",
month="Feb",
day="18",
volume="14",
pages="e70075",
keywords="chordee",
keywords="superficial chordee",
keywords="COL1A1",
keywords="COL3A1",
keywords="dartos tissue",
keywords="dartos fascia",
keywords="ELN",
keywords="elastin",
keywords="histopathological",
abstract="Background: The exact cause of penile curvature in hypospadias remains unknown. Resection of the dartos fascia has been observed to straighten the penis, indicating the involvement of the dartos fascia in the superficial chordee. However, the characteristics of dartos tissue in the distal territory of the ventral penile shaft may differ from those in the proximal aspect of the penile shaft. Objective: This study aims to investigate the distinct histopathological profiles and expression of COL1A1 (collagen type 1), COL3A1 (collagen type 3), and ELN (elastin) in proximal and distal ventral dartos of patients with hypospadias compared to those without hypospadias. Methods: This prospective case-control study compares the ventral dartos tissue of patients with hypospadias at different locations with that of patients without hypospadias. Dartos samples will be taken during surgery, with age matching. Histopathology examination uses hematoxylin and eosin and Masson's trichrome stain. The mRNA expression of COL1A1, COL3A1, and ELN will be quantified using a 2-step reverse transcription--polymerase chain reaction analysis. Results: Previous studies have documented different characteristics of dartos tissue between patients with hypospadias and those without hypospadias. Some studies even suggest resection of the dartos tissue during hypospadias repair. However, this is the first study to compare the characteristics of ventral dartos tissue in patients with hypospadias based on its location along the penile shaft, suggesting potential differences between the distal and proximal locations. We have obtained ethical approval to conduct a prospective case-control study aimed at elucidating these differences in dartos tissue characteristics. The findings of the study are anticipated to be available by 2025. Conclusions: Differences in the characteristics of dartos fascia based on its location may require tailored surgical strategies. If the properties of distal dartos tissue closely mirror those of typical dartos tissue, the possibility of avoiding its excision during hypospadias surgery could be considered. International Registered Report Identifier (IRRID): DERR1-10.2196/70075 ",
doi="10.2196/70075",
url="https://www.researchprotocols.org/2025/1/e70075",
url="http://www.ncbi.nlm.nih.gov/pubmed/39964742"
}


@Article{info:doi/10.2196/62836,
author="Li, Hui
and Zou, Ruyi
and Xin, Hongxia
and He, Ping
and Xi, Bin
and Tian, Yaqiong
and Zhao, Qi
and Yan, Xin
and Qiu, Xiaohua
and Gao, Yujuan
and Liu, Yin
and Cao, Min
and Chen, Bi
and Han, Qian
and Chen, Juan
and Wang, Guochun
and Cai, Hourong",
title="Mortality Risk Prediction in Patients With Antimelanoma Differentiation--Associated, Gene 5 Antibody--Positive, Dermatomyositis--Associated Interstitial Lung Disease: Algorithm Development and Validation",
journal="J Med Internet Res",
year="2025",
month="Feb",
day="5",
volume="27",
pages="e62836",
keywords="antimelanoma differentiation--associated gene 5 antibody",
keywords="dermatomyositis",
keywords="interstitial lung disease",
keywords="3-month mortality",
keywords="machine learning",
keywords="ML",
keywords="tool",
keywords="web based",
keywords="mortality",
keywords="idiopathic inflammatory myopathy",
keywords="myopathy",
keywords="lung disease",
keywords="melanoma",
keywords="imaging",
keywords="clinical outcome",
abstract="Background: Patients with antimelanoma differentiation--associated gene 5 antibody--positive dermatomyositis--associated interstitial lung disease (anti-MDA5+DM-ILD) are susceptible to rapidly progressive interstitial lung disease (RP-ILD) and have a high risk of mortality. There is an urgent need for a reliable prediction model, accessible via an easy-to-use web-based tool, to evaluate the risk of death. Objective: This study aimed to develop and validate a risk prediction model of 3-month mortality using machine learning (ML) in a large multicenter cohort of patients with anti-MDA5+DM-ILD in China. Methods: In total, 609 consecutive patients with anti-MDA5+DM-ILD were retrospectively enrolled from 6 hospitals across China. Patient demographics and laboratory and clinical parameters were collected on admission. The primary endpoint was 3-month mortality due to all causes. Six ML algorithms (Extreme Gradient Boosting [XGBoost], logistic regression (LR), Light Gradient Boosting Machine [LightGBM], random forest [RF], support vector machine [SVM], and k-nearest neighbor [KNN]) were applied to construct and evaluate the model. Results: After applying inclusion and exclusion criteria, 509 (83.6\%) of the 609 patients were included in our study, divided into a training cohort (n=203, 39.9\%), an internal validation cohort (n=51, 10\%), and 2 external validation cohorts (n=92, 18.1\%, and n=163, 32\%). ML identified 8 important variables as critical for model construction: RP-ILD, erythrocyte sedimentation rate (ESR), serum albumin (ALB) level, age, C-reactive protein (CRP) level, aspartate aminotransferase (AST) level, lactate dehydrogenase (LDH) level, and the neutrophil-to-lymphocyte ratio (NLR). LR was chosen as the best algorithm for model construction, and the model demonstrated excellent performance, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.866, a sensitivity of 84.8\%, and a specificity of 84.4\% on the validation data set and an AUC of 0.90, a sensitivity of 85.0\%, and a specificity of 83.9\% on the training data set. Calibration curves and decision curve analysis (DCA) confirmed the model's accuracy and clinical applicability. Moreover, the model showed strong predictive performance in the external validation cohorts (cohort 1: AUC=0.836, 95\% CI 0.754-0.916; cohort 2: AUC=0.915, 95\% CI 0.871-0.959), indicating good generalizability. This model was integrated into a web-based tool to predict the 3-month mortality for patients with anti-MDA5+DM-ILD. Conclusions: We successfully developed a robust clinical prediction model and an accompanying web tool to estimate the 3-month mortality risk for patients with anti-MDA5+DM-ILD. ",
doi="10.2196/62836",
url="https://www.jmir.org/2025/1/e62836"
}


@Article{info:doi/10.2196/59464,
author="Rivera Rivera, N. Jessica
and Snir, Moran
and Simmons, Emilie
and Schmidlen, Tara
and Sholeh, Misha
and Maconi, Leigh Melinda
and Geiss, Carley
and Fulton, Hayden
and Barton, Laura
and Gonzalez, D. Brian
and Permuth, Jennifer
and Vadaparampil, Susan",
title="Developing and Assessing a Scalable Digital Health Tool for Pretest Genetic Education in Patients With Early-Onset Colorectal Cancer: Mixed Methods Design",
journal="JMIR Cancer",
year="2025",
month="Jan",
day="17",
volume="11",
pages="e59464",
keywords="genetic education",
keywords="genetic testing",
keywords="genetic counseling",
keywords="digital health",
keywords="early-onset colorectal cancer",
abstract="Background: National guidelines recommend germline genetic testing (GT) for all patients with early-onset colorectal cancer. With recent advances in targeted therapies and GT, these guidelines are expected to expand to include broader groups of patients with colorectal cancer. However, there is a shortage of genetic professionals to provide the necessary education and support for informed consent. As such, there is a pressing need to identify alternative approaches to facilitate and expedite access to GT. Objective: This study describes the development of a pretest education intervention, Nest-CRC, to facilitate the uptake of germline GT among patients with early-onset colorectal cancer. Patients with early-onset colorectal cancer and health care providers reviewed Nest-CRC, and their reactions and recommendations were captured using a nested mixed methods approach. Methods: Using the learner verification approach, we conducted 2 sequential phases of surveys and interviews with English- and Spanish-speaking patients with early-onset colorectal cancer and health care providers. The surveys assessed participants' experiences with genetic services and provided immediate feedback on the Nest-CRC genetic education modules. Semistructured interviews evaluated participants' perceptions of self-efficacy, attraction, comprehension, cultural acceptability, and usability of Nest-CRC. Survey data were analyzed using descriptive statistics (mean, median, and proportions), while interview data were analyzed through line-by-line coding of the transcribed interviews. After each phase, Nest-CRC was refined based on participants' recommendations. Results: A total of 52 participants, including 39 patients with early-onset colorectal cancer and 13 providers, participated in the study. Of these, 19 patients and 6 providers participated in phase 1 (N=25), and 20 patients and 7 providers participated in phase 2 (N=27). Most participants (phase 1: 23/25, 92\%, to 25/25, 100\%; phase 2: 24/27, 89\%, to 27/27, 100\%) agreed that each of the 5 education modules was easy to understand and helpful; 13 patients reported no history of GT, with 11 (85\%) expressing interest in GT and 2 (15\%) remaining unsure after completing Nest-CRC. Participants reported that Nest-CRC provided sufficient information to help them decide about GT. The tool was deemed acceptable by individuals from diverse backgrounds, and participants found it visually attractive, easy to comprehend, and user-friendly. Conclusions: The findings revealed that Nest-CRC is a promising strategy for facilitating pretest education and promoting GT. Nest-CRC has been refined based on participant recommendations and will be re-evaluated. ",
doi="10.2196/59464",
url="https://cancer.jmir.org/2025/1/e59464"
}


@Article{info:doi/10.2196/65047,
author="Fukushima, Takuya
and Manabe, Masae
and Yada, Shuntaro
and Wakamiya, Shoko
and Yoshida, Akiko
and Urakawa, Yusaku
and Maeda, Akiko
and Kan, Shigeyuki
and Takahashi, Masayo
and Aramaki, Eiji",
title="Evaluating and Enhancing Japanese Large Language Models for Genetic Counseling Support: Comparative Study of Domain Adaptation and the Development of an Expert-Evaluated Dataset",
journal="JMIR Med Inform",
year="2025",
month="Jan",
day="16",
volume="13",
pages="e65047",
keywords="large language models",
keywords="genetic counseling",
keywords="medical",
keywords="health",
keywords="artificial intelligence",
keywords="machine learning",
keywords="domain adaptation",
keywords="retrieval-augmented generation",
keywords="instruction tuning",
keywords="prompt engineering",
keywords="question-answer",
keywords="dialogue",
keywords="ethics",
keywords="safety",
keywords="low-rank adaptation",
keywords="Japanese",
keywords="expert evaluation",
abstract="Background: Advances in genetics have underscored a strong association between genetic factors and health outcomes, leading to an increased demand for genetic counseling services. However, a shortage of qualified genetic counselors poses a significant challenge. Large language models (LLMs) have emerged as a potential solution for augmenting support in genetic counseling tasks. Despite the potential, Japanese genetic counseling LLMs (JGCLLMs) are underexplored. To advance a JGCLLM-based dialogue system for genetic counseling, effective domain adaptation methods require investigation. Objective: This study aims to evaluate the current capabilities and identify challenges in developing a JGCLLM-based dialogue system for genetic counseling. The primary focus is to assess the effectiveness of prompt engineering, retrieval-augmented generation (RAG), and instruction tuning within the context of genetic counseling. Furthermore, we will establish an experts-evaluated dataset of responses generated by LLMs adapted to Japanese genetic counseling for the future development of JGCLLMs. Methods: Two primary datasets were used in this study: (1) a question-answer (QA) dataset for LLM adaptation and (2) a genetic counseling question dataset for evaluation. The QA dataset included 899 QA pairs covering medical and genetic counseling topics, while the evaluation dataset contained 120 curated questions across 6 genetic counseling categories. Three enhancement techniques of LLMs---instruction tuning, RAG, and prompt engineering---were applied to a lightweight Japanese LLM to enhance its ability for genetic counseling. The performance of the adapted LLM was evaluated on the 120-question dataset by 2 certified genetic counselors and 1 ophthalmologist (SK, YU, and AY). Evaluation focused on four metrics: (1) inappropriateness of information, (2) sufficiency of information, (3) severity of harm, and (4) alignment with medical consensus. Results: The evaluation by certified genetic counselors and an ophthalmologist revealed varied outcomes across different methods. RAG showed potential, particularly in enhancing critical aspects of genetic counseling. In contrast, instruction tuning and prompt engineering produced less favorable outcomes. This evaluation process facilitated the creation an expert-evaluated dataset of responses generated by LLMs adapted with different combinations of these methods. Error analysis identified key ethical concerns, including inappropriate promotion of prenatal testing, criticism of relatives, and inaccurate probability statements. Conclusions: RAG demonstrated notable improvements across all evaluation metrics, suggesting potential for further enhancement through the expansion of RAG data. The expert-evaluated dataset developed in this study provides valuable insights for future optimization efforts. However, the ethical issues observed in JGCLLM responses underscore the critical need for ongoing refinement and thorough ethical evaluation before these systems can be implemented in health care settings. ",
doi="10.2196/65047",
url="https://medinform.jmir.org/2025/1/e65047"
}


@Article{info:doi/10.2196/60838,
author="Ahmad Zamri, Liyana
and Abu Seman, Norhashimah
and Zainal Abidin, Azlin Nur
and Hamzah, Sarah Siti",
title="Exploring Molecular Genetics Research on Obesity in Malaysia: Protocol for a Scoping Review",
journal="JMIR Res Protoc",
year="2024",
month="Dec",
day="30",
volume="13",
pages="e60838",
keywords="genetics",
keywords="biomarkers",
keywords="molecular",
keywords="obesity",
keywords="Malaysia",
keywords="scoping review",
keywords="protocol",
abstract="Background: Obesity presents a growing challenge to public health, and its intricate association with genetics continues to be a compelling field of study. In countries such as Malaysia, where diverse genetic backgrounds converge, exploring the molecular genetics of obesity is even more imperative. Objective: This scoping review aimed to explore the literature on molecular genetics of obesity in Malaysia. Specifically, we sought to characterize existing studies, identify the genetic determinants of obesity, and assess their association with obesity predisposition in the population. Methods: This scoping review followed the methodology of the Joanna Briggs Institute and used the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist as its guiding framework. Searches were conducted using electronic databases such as PubMed, ScienceDirect, and Scopus, filtering for human studies published until March 2024. Eligible studies included peer-reviewed articles on the Malaysian population irrespective of age or sex. This review excluded review articles, book chapters, non--peer-reviewed conference proceedings, gray literature, and preclinical studies, and the reference lists of the retrieved studies were manually examined to ensure thorough inclusion. The articles were subjected to a 2-stage screening process (title/abstract and full text) conducted by 2 reviewers to assess eligibility. Eligible articles were then extracted following a data extraction framework and organized into a charting table. Only studies investigating the genetics of obesity in Malaysian populations were included. Results: As of March 2024, our extensive search strategy has yielded 572 records. After removing 153 duplicates, 419 records were screened by title and abstract, resulting in 47 selected for full-text review. Of these, 34 were chosen for data extraction and detailed analysis. These studies predominantly involved participants from major ethnic groups (Malay, Chinese, and Indian) recruited from local health centers and university communities. The articles primarily explored the relationship between specific gene variants and obesity or obesity-related health parameters. This ongoing research is expected to be completed with a comprehensive scoping review by April 2025. Conclusions: This review provides valuable insights into the genetic determinants of obesity in Malaysia, despite limitations such as no quality appraisal being conducted for the included studies and the search strategy being restricted to selected databases, potentially omitting relevant studies. However, this review ensured reliability and reproducibility by adhering to the Joanna Briggs Institute and PRISMA-ScR guidelines. Ultimately, this study advances the understanding of local research and sets the foundation for future molecular genetic studies to improve obesity risk prediction and management in Malaysia's multiethnic population. International Registered Report Identifier (IRRID): DERR1-10.2196/60838 ",
doi="10.2196/60838",
url="https://www.researchprotocols.org/2024/1/e60838"
}


@Article{info:doi/10.2196/56649,
author="Diaz-Ordo{\~n}ez, Lorena
and Duque-Cordoba, Andrea Paola
and Nieva-Posso, Andr{\'e}s Daniel
and Saldarriaga, Wilmar
and Gutierrez-Medina, David Juan
and Pachajoa, Harry",
title="Phenotype-Genotype Correlation in Morquio A Syndrome: Protocol for a Meta-Analysis",
journal="JMIR Res Protoc",
year="2024",
month="Nov",
day="14",
volume="13",
pages="e56649",
keywords="Morquio A syndrome",
keywords="genotype-phenotype associations",
keywords="rare diseases",
keywords="scoping review",
keywords="Mucopolysaccharidosis type IV",
keywords="meta-analysis",
keywords="genotype",
keywords="GALNS gene",
keywords="N-acetylgalactosamine-6-sulfatase",
keywords="pathophysiology",
keywords="laboratories",
keywords="mutations",
abstract="Background: Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome, is a rare lysosomal storage disease characterized by autosomal recessive inheritance of mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. This leads to a deficiency of the GALNS enzyme, causing the accumulation of glycosaminoglycans in tissues. Morquio A syndrome primarily affects the skeletal system and joints but can also impact various organs, resulting in symptoms such as hearing and vision loss, respiratory issues, spinal cord compression, heart diseases, and hepatomegaly. The genotype-phenotype relationship is diverse, with studies highlighting variants associated with classic, nonclassic, or intermediate phenotypes. Understanding these genetic factors is crucial for predicting disease prognosis and tailoring effective treatment strategies for individuals with Morquio A syndrome. Objective: The aim of this meta-analysis is to comprehend the relationship between the severity of the phenotype and the genotype of patients with MPS IVA, considering factors such as the type of variant and its location in the different domains of the protein. Methods: This meta-analysis will include articles featuring participants of all genders and age groups who have a molecular diagnosis of MPS IVA and a description of the phenotype. Literature published in English, Spanish, and Portuguese will be considered. Exclusion criteria will encompass studies lacking full-text availability and those involving patients with an MPS IVA diagnosis but without phenotype information. The databases to be searched include PubMed, MEDLINE, ScienceDirect, and Scopus. The screening of literature, paper selection, and data extraction will involve 2 independent reviewers, who will conduct the process blindly. In the event of disagreements between the 2 reviewers at any stage, resolution will be sought through discussion or with the involvement of an additional reviewer. The final selection of manuscripts will be based on consensus. The results of the review will be presented using descriptive statistics, and the information will be organized in either diagrammatic or tabular formats, following the guidelines provided by the Joanna Briggs Institute. Genotype-phenotype relationships will be analyzed using IBM SPSS Statistics, using chi-square tests, Fisher exact tests, and regression analysis to interpret the data. Results: A literature search conducted in January 2024 produced 760 results. The review is expected to be completed by the end of 2024. Conclusions: This meta-analysis will gather and analyze information on the phenotype-genotype relationship in patients diagnosed with MPS IVA. The data collection and resulting analyses will make a substantial contribution to understanding the underlying mechanism of the disease, enabling the prediction of the syndrome's progression and severity. International Registered Report Identifier (IRRID): DERR1-10.2196/56649 ",
doi="10.2196/56649",
url="https://www.researchprotocols.org/2024/1/e56649"
}


@Article{info:doi/10.2196/52282,
author="Pitoyo, Joko
and Alvarino
and Darwin, Eryati
and Yanwirasti",
title="Differences in Messenger RNA Expression of Fibulin-1, Elastin, Matrix Metalloproteinase-1, Basic Fibroblast Growth Factor, and $\alpha$-Smooth Muscle Actin Between the Ventral and Dorsal Tunica Dartos in Patients With Hypospadias and Chordee: Protocol for a Prospective Cohort Study",
journal="JMIR Res Protoc",
year="2024",
month="Oct",
day="30",
volume="13",
pages="e52282",
keywords="chordee",
keywords="gene expression",
keywords="hypospadias",
keywords="polymerase chain reaction",
keywords="mRNA",
abstract="Background: Hypospadias is a common congenital anomaly characterized by the displacement of the urethral opening to the ventral side of the penis. Surgical correction is often necessary for functional and psychological reasons. The etiology involves genetic and environmental factors, and chordee, a downward curvature of the penis, is a common complication. Proteins such as fibulin-1, elastin, matrix metalloproteinase-1, basic fibroblast growth factor, and $\alpha$-smooth muscle actin play roles in hypospadias development. Objective: The study's aim is to investigate the differences in messenger RNA (mRNA) expression of fibulin-1, elastin, matrix metalloproteinase-1, basic fibroblast growth factor, and $\alpha$-smooth muscle actin between the ventral and dorsal tunica dartos in patients with hypospadias and chordee. Methods: This prospective cohort study aims to investigate differences in mRNA expression of the abovementioned proteins between the ventral and dorsal tunica dartos in patients with hypospadias and chordee. Ethics approval has been obtained, and consent from parents will be obtained before data collection. Eligible participants are aged 6-18 months, diagnosed with hypospadias and chordee, and planned for urethroplasty. Tissue samples will be collected from both aspects of the tunica dartos and analyzed using real-time quantitative reverse transcription--polymerase chain reaction. Data analysis will involve statistical tests and normalization of housekeeping genes. Results: This study is at the protocol development stage. A pilot study regarding its feasibility has been ongoing as of August 2023. The study results are expected to be available by the end of 2024. Conclusions: The study of mRNA expressions of various proteins in the tunica dartos of patients with hypospadias and chordee is expected to improve the understanding and expand the knowledge of the pathophysiology of hypospadias and chordee. International Registered Report Identifier (IRRID): DERR1-10.2196/52282 ",
doi="10.2196/52282",
url="https://www.researchprotocols.org/2024/1/e52282"
}


@Article{info:doi/10.2196/58439,
author="Oyovwi, Sr Mega Obukohwo
and Ohwin, Peggy Ejiro
and Rotu, Arientare Rume
and Olowe, Gideon Temitope",
title="Internet-Based Abnormal Chromosomal Diagnosis During Pregnancy Using a Noninvasive Innovative Approach to Detecting Chromosomal Abnormalities in the Fetus: Scoping Review",
journal="JMIR Bioinform Biotech",
year="2024",
month="Oct",
day="16",
volume="5",
pages="e58439",
keywords="internet-based",
keywords="abnormal chromosomal diagnosis",
keywords="pregnancy",
keywords="noninvasive",
keywords="innovative approach",
keywords="detecting",
keywords="preventing",
keywords="chromosomal abnormalities",
keywords="fetus",
abstract="Background: Chromosomal abnormalities are genetic disorders caused by chromosome errors, leading to developmental delays, birth defects, and miscarriages. Currently, invasive procedures such as amniocentesis or chorionic villus sampling are mostly used, which carry a risk of miscarriage. This has led to the need for a noninvasive and innovative approach to detect and prevent chromosomal abnormalities during pregnancy. Objective: This review aims to describe and appraise the potential of internet-based abnormal chromosomal preventive measures as a noninvasive approach to detecting and preventing chromosomal abnormalities during pregnancy. Methods: A thorough review of existing literature and research on chromosomal abnormalities and noninvasive approaches to prenatal diagnosis and therapy was conducted. Electronic databases such as PubMed, Google Scholar, ScienceDirect, CENTRAL, CINAHL, Embase, OVID MEDLINE, OVID PsycINFO, Scopus, ACM, and IEEE Xplore were searched for relevant studies and articles published in the last 5 years. The keywords used included chromosomal abnormalities, prenatal diagnosis, noninvasive, and internet-based, and diagnosis. Results: The review of literature revealed that internet-based abnormal chromosomal diagnosis is a potential noninvasive approach to detecting and preventing chromosomal abnormalities during pregnancy. This innovative approach involves the use of advanced technology, including high-resolution ultrasound, cell-free DNA testing, and bioinformatics, to analyze fetal DNA from maternal blood samples. It allows early detection of chromosomal abnormalities, enabling timely interventions and treatment to prevent adverse outcomes. Furthermore, with the advancement of technology, internet-based abnormal chromosomal diagnosis has emerged as a safe alternative with benefits including its cost-effectiveness, increased accessibility and convenience, potential for earlier detection and intervention, and ethical considerations. Conclusions: Internet-based abnormal chromosomal diagnosis has the potential to revolutionize prenatal care by offering a safe and noninvasive alternative to invasive procedures. It has the potential to improve the detection of chromosomal abnormalities, leading to better pregnancy outcomes and reduced risk of miscarriage. Further research and development in this field is needed to make this approach more accessible and affordable for pregnant women. ",
doi="10.2196/58439",
url="https://bioinform.jmir.org/2024/1/e58439",
url="http://www.ncbi.nlm.nih.gov/pubmed/39412876"
}


@Article{info:doi/10.2196/63551,
author="Li, Guorong
and Tholance, Yannick
and Mallouk, Nora
and Waeckel, Louis
and Flandrin, Pascale
and Bali, Bruno
and Badet, Lionel
and Cornillon, Pierre",
title="Quantification of Urinary Exosomal Prostate-Specific Antigen for the Diagnosis of Prostate Cancer Using Clinical Laboratory--Based Techniques: Protocol for a Case-Control Study",
journal="JMIR Res Protoc",
year="2024",
month="Sep",
day="11",
volume="13",
pages="e63551",
keywords="liquid biopsy",
keywords="urinary exosome",
keywords="diagnosis",
keywords="PSA",
keywords="prostate-specific antigen",
keywords="prostate cancer",
abstract="Background: Prostate cancer is the most common cancer in men and represents a major public health problem. The current method for the diagnosis or screening of prostate cancer is invasive and costly. There have been renewed and innovative studies searching for urinary biomarkers to aid in the diagnosis of prostate cancer, especially with technologies based on urinary exosomes. However, technologies based on urine exosomes usually need expensive machines such as an ultracentrifuge and they are difficult to standardize, which hinder their application in clinical laboratories. We have optimized and standardized the isolation of urinary exosomes with the precipitation method. We have found that urinary exosomal prostate-specific antigen (PSA) can be quantified by automatic Elecsys total PSA technique. Objective: In this study, our objective is to utilize urinary exosomes from prostate cancer for the development of a test to aid in its diagnosis. Methods: Exosomes from the prostate cancer cell line LNCaP was used to set up the technique. To analyze urine samples from patients, the methods include the collection of first-void urine using the Colli-Pee device, the isolation of urine exosomes using the optimized precipitation method, and the quantification of exosomal PSA by Elecsys total PSA. Results: This will be a 2-year study. We will start including patients and controls in the last quarter of 2024. We expect the results to be published in the second quarter of 2027. Conclusions: This is the first study to quantify urinary exosomal PSA using the Elecsys total PSA technique for the diagnosis of prostate cancer. This study emphasizes techniques that are suitable for implementation in clinical laboratories, which will facilitate the application of urinary exosomes to simplify and improve the diagnosis and screening of prostate cancer. International Registered Report Identifier (IRRID): PRR1-10.2196/63551 ",
doi="10.2196/63551",
url="https://www.researchprotocols.org/2024/1/e63551",
url="http://www.ncbi.nlm.nih.gov/pubmed/39024018"
}


@Article{info:doi/10.2196/49230,
author="Sharma, Videha
and McDermott, John
and Keen, Jessica
and Foster, Simon
and Whelan, Pauline
and Newman, William",
title="Pharmacogenetics Clinical Decision Support Systems for Primary Care in England: Co-Design Study",
journal="J Med Internet Res",
year="2024",
month="Jul",
day="23",
volume="26",
pages="e49230",
keywords="personalized medicine",
keywords="genomic medicine",
keywords="pharmacogenetics",
keywords="user-centred design",
keywords="medical informatics",
keywords="clinical decision support systems",
keywords="side effect",
keywords="information technology",
keywords="data",
keywords="primary care",
keywords="health informatic",
abstract="Background: Pharmacogenetics can impact patient care and outcomes through personalizing the selection of medicines, resulting in improved efficacy and a reduction in harmful side effects. Despite the existence of compelling clinical evidence and international guidelines highlighting the benefits of pharmacogenetics in clinical practice, implementation within the National Health Service in the United Kingdom is limited. An important barrier to overcome is the development of IT solutions that support the integration of pharmacogenetic data into health care systems. This necessitates a better understanding of the role of electronic health records (EHRs) and the design of clinical decision support systems that are acceptable to clinicians, particularly those in primary care. Objective: Explore the needs and requirements of a pharmacogenetic service from the perspective of primary care clinicians with a view to co-design a prototype solution. Methods: We used ethnographic and think-aloud observations, user research workshops, and prototyping. The participants for this study included general practitioners and pharmacists. In total, we undertook 5 sessions of ethnographic observation to understand current practices and workflows. This was followed by 3 user research workshops, each with its own topic guide starting with personas and early ideation, through to exploring the potential of clinical decision support systems and prototype design. We subsequently analyzed workshop data using affinity diagramming and refined the key requirements for the solution collaboratively as a multidisciplinary project team. Results: User research results identified that pharmacogenetic data must be incorporated within existing EHRs rather than through a stand-alone portal. The information presented through clinical decision support systems must be clear, accessible, and user-friendly as the service will be used by a range of end users. Critically, the information should be displayed within the prescribing workflow, rather than discrete results stored statically in the EHR. Finally, the prescribing recommendations should be authoritative to provide confidence in the validity of the results. Based on these findings we co-designed an interactive prototype, demonstrating pharmacogenetic clinical decision support integrated within the prescribing workflow of an EHR. Conclusions: This study marks a significant step forward in the design of systems that support pharmacogenetic-guided prescribing in primary care settings. Clinical decision support systems have the potential to enhance the personalization of medicines, provided they are effectively implemented within EHRs and present pharmacogenetic data in a user-friendly, actionable, and standardized format. Achieving this requires the development of a decoupled, standards-based architecture that allows for the separation of data from application, facilitating integration across various EHRs through the use of application programming interfaces (APIs). More globally, this study demonstrates the role of health informatics and user-centered design in realizing the potential of personalized medicine at scale and ensuring that the benefits of genomic innovation reach patients and populations effectively. ",
doi="10.2196/49230",
url="https://www.jmir.org/2024/1/e49230"
}


@Article{info:doi/10.2196/47389,
author="Onstwedder, Maria Suzanne
and Jansen, Elizabeth Marleen
and Cornel, Cornelia Martina
and Rigter, Tessel",
title="Policy Guidance for Direct-to-Consumer Genetic Testing Services: Framework Development Study",
journal="J Med Internet Res",
year="2024",
month="Jul",
day="17",
volume="26",
pages="e47389",
keywords="genetic testing",
keywords="direct-to-consumer testing",
keywords="health policy",
keywords="genetic privacy",
keywords="online market",
keywords="informed consent",
keywords="public health genomics",
keywords="policy decision",
keywords="mHealth",
keywords="mobile health",
keywords="privacy",
abstract="Background: The online offer of commercial genetic tests, also called direct-to-consumer genetic tests (DTC-GTs), enables citizens to gain insight into their health and disease risk based on their genetic profiles. DTC-GT offers often consist of a combination of services or aspects, including advertisements, information, DNA analysis, and medical or lifestyle advice. The risks and benefits of DTC-GT services have been debated and studied extensively, but instruments that assess DTC-GT services and aid policy are lacking. This leads to uncertainty among policy makers, law enforcers, and regulators on how to ensure and balance both public safety and autonomy and about the responsibilities these 3 parties have toward the public. Objective: This study aimed to develop a framework that outlines aspects of DTC-GTs that lead to policy issues and to help provide policy guidance regarding DTC-GT services. Methods: We performed 3 steps: (1) an integrative literature review to identify risks and benefits of DTC-GT services for consumers and society in Embase and Medline (January 2014-June 2022), (2) structuring benefits and risks in different steps of the consumer journey, and (3) development of a checklist for policy guidance. Results: Potential risks and benefits of DTC-GT services were mapped from 134 papers and structured into 6 phases. In summary, these phases were called the consumer journey: (1) exposure, (2) pretest information, (3) DNA analysis, (4) data management, (5) posttest information, and (6) individual and societal impact. The checklist for evaluation of DTC-GT services consisted of 8 themes, covering 38 items that may raise policy issues in DTC-GT services. The themes included the following aspects: general service content, validity and quality assurance, potential data and privacy risks, scientific evidence and robustness, and quality of the provided information. Conclusions: Both the consumer journey and the checklist break the DTC-GT offer down into key aspects that may impact and compromise individual and public health, safety, and autonomy. This framework helps policy makers, regulators, and law enforcers develop methods to interpret, assess, and act in the DTC-GT service market. ",
doi="10.2196/47389",
url="https://www.jmir.org/2024/1/e47389"
}


@Article{info:doi/10.2196/51347,
author="Wang, Meng
and Peng, Yun
and Wang, Ya
and Luo, Dehong",
title="Research Trends and Evolution in Radiogenomics (2005-2023): Bibliometric Analysis",
journal="Interact J Med Res",
year="2024",
month="Jul",
day="9",
volume="13",
pages="e51347",
keywords="bibliometric",
keywords="radiogenomics",
keywords="multiomics",
keywords="genomics",
keywords="radiomics",
abstract="Background: Radiogenomics is an emerging technology that integrates genomics and medical image--based radiomics, which is considered a promising approach toward achieving precision medicine. Objective: The aim of this study was to quantitatively analyze the research status, dynamic trends, and evolutionary trajectory in the radiogenomics field using bibliometric methods. Methods: The relevant literature published up to 2023 was retrieved from the Web of Science Core Collection. Excel was used to analyze the annual publication trend. VOSviewer was used for constructing the keywords co-occurrence network and the collaboration networks among countries and institutions. CiteSpace was used for citation keywords burst analysis and visualizing the references timeline. Results: A total of 3237 papers were included and exported in plain-text format. The annual number of publications showed an increasing annual trend. China and the United States have published the most papers in this field, with the highest number of citations in the United States and the highest average number per item in the Netherlands. Keywords burst analysis revealed that several keywords, including ``big data,'' ``magnetic resonance spectroscopy,'' ``renal cell carcinoma,'' ``stage,'' and ``temozolomide,'' experienced a citation burst in recent years. The timeline views demonstrated that the references can be categorized into 8 clusters: lower-grade glioma, lung cancer histology, lung adenocarcinoma, breast cancer, radiation-induced lung injury, epidermal growth factor receptor mutation, late radiotherapy toxicity, and artificial intelligence. Conclusions: The field of radiogenomics is attracting increasing attention from researchers worldwide, with the United States and the Netherlands being the most influential countries. Exploration of artificial intelligence methods based on big data to predict the response of tumors to various treatment methods represents a hot spot research topic in this field at present. ",
doi="10.2196/51347",
url="https://www.i-jmr.org/2024/1/e51347",
url="http://www.ncbi.nlm.nih.gov/pubmed/38980713"
}


@Article{info:doi/10.2196/51381,
author="Aye, Sin Phyu
and Barnes, Joanne
and Laking, George
and Cameron, Laird
and Anderson, Malcolm
and Luey, Brendan
and Delany, Stephen
and Harris, Dean
and McLaren, Blair
and Brenman, Elliott
and Wong, Jayden
and Lawrenson, Ross
and Arendse, Michael
and Tin Tin, Sandar
and Elwood, Mark
and Hope, Philip
and McKeage, James Mark",
title="Erlotinib or Gefitinib for Treating Advanced Epidermal Growth Factor Receptor Mutation--Positive Lung Cancer in Aotearoa New Zealand: Protocol for a National Whole-of-Patient-Population Retrospective Cohort Study and Results of a Validation Substudy",
journal="JMIR Res Protoc",
year="2024",
month="Jul",
day="2",
volume="13",
pages="e51381",
keywords="epidermal growth factor receptor",
keywords="erlotinib",
keywords="gefitinib",
keywords="lung cancer",
keywords="retrospective cohort",
keywords="study protocol",
keywords="validation",
abstract="Background: Starting in 2010, the epidermal growth factor receptor (EGFR) kinase inhibitors erlotinib and gefitinib were introduced into routine use in Aotearoa New Zealand (NZ) for treating advanced lung cancer, but their impact in this setting is unknown. Objective: The study described in this protocol aims to understand the effectiveness and safety of these new personalized lung cancer treatments and the contributions made by concomitant medicines and other factors to adverse outcomes in the general NZ patient population. A substudy aimed to validate national electronic health databases as the data source and the methods for determining patient eligibility and identifying outcomes and variables. Methods: This study will include all NZ patients with advanced EGFR mutation--positive lung cancer who were first dispensed erlotinib or gefitinib before October 1, 2020, and followed until death or for at least 1 year. Routinely collected health administrative and clinical data will be collated from national electronic cancer registration, hospital discharge, mortality registration, and pharmaceutical dispensing databases by deterministic data linkage using National Health Index numbers. The primary effectiveness and safety outcomes will be time to treatment discontinuation and serious adverse events, respectively. The primary variable will be high-risk concomitant medicines use with erlotinib or gefitinib. For the validation substudy (n=100), data from clinical records were compared to those from national electronic health databases and analyzed by agreement analysis for categorical data and by paired 2-tailed t tests for numerical data. Results: In the validation substudy, national electronic health databases and clinical records agreed in determining patient eligibility and for identifying serious adverse events, high-risk concomitant medicines use, and other categorical data with overall agreement and $\kappa$ statistic of >90\% and >0.8000, respectively; for example, for the determination of patient eligibility, the comparison of proxy and standard eligibility criteria applied to national electronic health databases and clinical records, respectively, showed overall agreement and $\kappa$ statistic of 96\% and 0.8936, respectively. Dates for estimating time to treatment discontinuation and other numerical variables and outcomes showed small differences, mostly with nonsignificant P values and 95\% CIs overlapping with zero difference; for example, for the dates of the first dispensing of erlotinib or gefitinib, national electronic health databases and clinical records differed on average by approximately 4 days with a nonsignificant P value of .33 and 95\% CIs overlapping with zero difference. As of May 2024, the main study is ongoing. Conclusions: A protocol is presented for a national whole-of-patient-population retrospective cohort study designed to describe the safety and effectiveness of erlotinib and gefitinib during their first decade of routine use in NZ for treating EGFR mutation--positive lung cancer. The validation substudy demonstrated the feasibility and validity of using national electronic health databases and the methods for determining patient eligibility and identifying the study outcomes and variables proposed in the study protocol. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12615000998549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368928 International Registered Report Identifier (IRRID): DERR1-10.2196/51381 ",
doi="10.2196/51381",
url="https://www.researchprotocols.org/2024/1/e51381"
}


@Article{info:doi/10.2196/56593,
author="He, Yan
and Tang, Ying
and Hua, Qun
and Li, Xin
and Ge, You
and Liu, Yangyang
and Tang, Rong
and Tian, Ye
and Li, Wei",
title="Exploring Dynamic Changes in HIV-1 Molecular Transmission Networks and Key Influencing Factors: Cross-Sectional Study",
journal="JMIR Public Health Surveill",
year="2024",
month="May",
day="29",
volume="10",
pages="e56593",
keywords="HIV",
keywords="dynamic",
keywords="molecular transmission network",
keywords="influence factors",
keywords="HIV-1",
keywords="molecular network",
keywords="real-time analysis",
keywords="transmission",
keywords="Nanjing",
keywords="infection",
keywords="gene distance",
keywords="heterosexual",
keywords="homosexual",
keywords="dynamic alteration",
keywords="dynamic alterations",
keywords="risk factor",
abstract="Background: The HIV-1 molecular network is an innovative tool, using gene sequences to understand transmission attributes and complementing social and sexual network studies. While previous research focused on static network characteristics, recent studies' emphasis on dynamic features enhances our understanding of real-time changes, offering insights for targeted interventions and efficient allocation of public health resources. Objective: This study aims to identify the dynamic changes occurring in HIV-1 molecular transmission networks and analyze the primary influencing factors driving the dynamics of HIV-1 molecular networks. Methods: We analyzed and compared the dynamic changes in the molecular network over a specific time period between the baseline and observed end point. The primary factors influencing the dynamic changes in the HIV-1 molecular network were identified through univariate analysis and multivariate analysis. Results: A total of 955 HIV-1 polymerase fragments were successfully amplified from 1013 specimens; CRF01\_AE and CRF07\_BC were the predominant subtypes, accounting for 40.8\% (n=390) and 33.6\% (n=321) of the specimens, respectively. Through the analysis and comparison of the basic and terminal molecular networks, it was discovered that 144 sequences constituted static molecular networks, and 487 sequences contributed to the formation of dynamic molecular networks. The findings of the multivariate analysis indicated that the factors occupation as a student, floating population, Han ethnicity, engagement in occasional or multiple sexual partnerships, participation in anal sex, and being single were independent risk factors for the dynamic changes observed in the HIV-1 molecular network, and the odds ratio (OR; 95\% CIs) values were 2.63 (1.54-4.47), 1.83 (1.17-2.84), 2.91 (1.09-7.79), 1.75 (1.06-2.90), 4.12 (2.48-6.87), 5.58 (2.43-12.80), and 2.10 (1.25-3.54), respectively. Heterosexuality and homosexuality seem to exhibit protective effects when compared to bisexuality, with OR values of 0.12 (95\% CI 0.05-0.32) and 0.26 (95\% CI 0.11-0.64), respectively. Additionally, the National Eight-Item score and sex education experience were also identified as protective factors against dynamic changes in the HIV-1 molecular network, with OR values of 0.12 (95\% CI 0.05-0.32) and 0.26 (95\% CI 0.11-0.64), respectively. Conclusions: The HIV-1 molecular network analysis showed 144 sequences in static networks and 487 in dynamic networks. Multivariate analysis revealed that occupation as a student, floating population, Han ethnicity, and risky sexual behavior were independent risk factors for dynamic changes, while heterosexuality and homosexuality were protective compared to bisexuality. A higher National Eight-Item score and sex education experience were also protective factors. The identification of HIV dynamic molecular networks has provided valuable insights into the characteristics of individuals undergoing dynamic alterations. These findings contribute to a better understanding of HIV-1 transmission dynamics and could inform targeted prevention strategies. ",
doi="10.2196/56593",
url="https://publichealth.jmir.org/2024/1/e56593",
url="http://www.ncbi.nlm.nih.gov/pubmed/38810253"
}


@Article{info:doi/10.2196/54042,
author="Seeger, Nico
and Gutknecht, Stefan
and Zschokke, Irin
and Fleischmann, Isabella
and Roth, Nadja
and Metzger, J{\"u}rg
and Weber, Markus
and Breitenstein, Stefan
and Grochola, Filip Lukasz",
title="A Predictive Noninvasive Single-Nucleotide Variation--Based Biomarker Signature for Resectable Pancreatic Cancer: Protocol for a Prospective Validation Study",
journal="JMIR Res Protoc",
year="2024",
month="May",
day="13",
volume="13",
pages="e54042",
keywords="single-nucleotide polymorphism",
keywords="SNP",
keywords="single-nucleotide variation",
keywords="SNV",
keywords="pancreatic ductal adenocarcinoma",
keywords="PDAC",
keywords="noninvasive biomarker",
keywords="survival",
keywords="resection",
keywords="prospective validation",
abstract="Background: Single-nucleotide variations (SNVs; formerly SNPs) are inherited genetic variants that can be easily determined in routine clinical practice using a simple blood or saliva test. SNVs have potential to serve as noninvasive biomarkers for predicting cancer-specific patient outcomes after resection of pancreatic ductal adenocarcinoma (PDAC). Two recent analyses led to the identification and validation of three SNVs in the CD44 and CHI3L2 genes (rs187115, rs353630, and rs684559), which can be used as predictive biomarkers to help select patients most likely to benefit from pancreatic resection. These variants were associated with an over 2-fold increased risk for tumor-related death in three independent PDAC study cohorts from Europe and the United States, including The Cancer Genome Atlas cohorts (reaching a P value of 1{\texttimes}10--8). However, these analyses were limited by the inherent biases of a retrospective study design, such as selection and publication biases, thereby limiting the clinical use of these promising biomarkers in guiding PDAC therapy. Objective: To overcome the limitations of previous retrospectively designed studies and translate the findings into clinical practice, we aim to validate the association of the identified SNVs with survival in a controlled setting using a prospective cohort of patients with PDAC following pancreatic resection. Methods: All patients with PDAC who will undergo pancreatic resection at three participating hospitals in Switzerland and fulfill the inclusion criteria will be included in the study consecutively. The SNV genotypes will be determined using standard genotyping techniques from patient blood samples. For each genotyped locus, log-rank and Cox multivariate regression tests will be performed, accounting for the relevant covariates American Joint Committee on Cancer stage and resection status. Clinical follow-up data will be collected for at least 3 years. Sample size calculation resulted in a required sample of 150 patients to sufficiently power the analysis. Results: The follow-up data collection started in August 2019 and the estimated end of data collection will be in May 2027. The study is still recruiting participants and 142 patients have been recruited as of November 2023. The DNA extraction and genotyping of the SNVs will be performed after inclusion of the last patient. Since no SNV genotypes have been determined, no data analysis has been performed to date. The results are expected to be published in 2027. Conclusions: This is the first prospective study of the CD44 and CHI3L2 SNV--based biomarker signature in PDAC. A prospective validation of this signature would enable its clinical use as a noninvasive predictive biomarker of survival after pancreatic resection that is readily available at the time of diagnosis and can assist in guiding PDAC therapy. The results of this study may help to individualize treatment decisions and potentially improve patient outcomes. International Registered Report Identifier (IRRID): DERR1-10.2196/54042 ",
doi="10.2196/54042",
url="https://www.researchprotocols.org/2024/1/e54042",
url="http://www.ncbi.nlm.nih.gov/pubmed/38635586"
}


@Article{info:doi/10.2196/56884,
author="Bui, Thu Huong Thi
and Nguy?n Th? Ph??ng, Qu?nh
and Cam Tu, Ho
and Nguyen Phuong, Sinh
and Pham, Thi Thuy
and Vu, Thu
and Nguyen Thi Thu, Huyen
and Khanh Ho, Lam
and Nguyen Tien, Dung",
title="The Roles of NOTCH3 p.R544C and Thrombophilia Genes in Vietnamese Patients With Ischemic Stroke: Study Involving a Hierarchical Cluster Analysis",
journal="JMIR Bioinform Biotech",
year="2024",
month="May",
day="7",
volume="5",
pages="e56884",
keywords="Glasgow Coma Scale",
keywords="ischemic stroke",
keywords="hierarchical cluster analysis",
keywords="clustering",
keywords="machine learning",
keywords="MTHFR",
keywords="NOTCH3",
keywords="modified Rankin scale",
keywords="National Institutes of Health Stroke Scale",
keywords="prothrombin",
keywords="thrombophilia",
keywords="mutations",
keywords="genetics",
keywords="genomics",
keywords="ischemia",
keywords="risk",
keywords="risk analysis",
abstract="Background: The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms. Objective: We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors. Methods: We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models. Results: We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) {\textmu}mol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50\% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively. Conclusions: The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95\% CI 1.53-15.04) and 3.13 (95\% CI 1.60-6.11), respectively (Pfisher<.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients. ",
doi="10.2196/56884",
url="https://bioinform.jmir.org/2024/1/e56884",
url="http://www.ncbi.nlm.nih.gov/pubmed/38935968"
}


@Article{info:doi/10.2196/47911,
author="Ramli, Safura Anis
and Qureshi, Nadeem
and Abdul-Hamid, Hasidah
and Kamal, Aisyah
and Kanchau, Dedi Johanes
and Shahuri, Syahirah Nur
and Akyea, Kwame Ralph
and Silva, Luisa
and Condon, Laura
and Abdul-Razak, Suraya
and Al-Khateeb, Alyaa
and Chua, Yung-An
and Mohamed-Yassin, Mohamed-Syarif
and Baharudin, Noorhida
and Badlishah-Sham, Fatimah Siti
and Abdul Aziz, Firzah Aznida
and Mohd Kasim, Alicezah Noor
and Sheikh Abdul Kadir, Hamimah Siti
and Kai, Joe
and Leonardi-Bee, Jo
and Nawawi, Hapizah",
title="Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study",
journal="JMIR Res Protoc",
year="2023",
month="Jun",
day="2",
volume="12",
pages="e47911",
keywords="mixed methods evaluation",
keywords="study protocol",
keywords="familial hypercholesterolemia",
keywords="diagnostic accuracy",
keywords="qualitative methods",
keywords="FAMCAT",
keywords="Simon Broome criteria",
keywords="Dutch Lipid Clinic Criteria",
keywords="genetic diagnosis",
keywords="primary care",
keywords="Malaysia",
abstract="Background: Familial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. FH can be clinically diagnosed using established clinical criteria, namely, Simon Broome (SB) and Dutch Lipid Clinic Criteria (DLCC), and can be identified using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), a primary care screening tool. Objective: This study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting. Methods: This is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the ``think-aloud'' methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool. Results: The recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023. Conclusions: This study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients' perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease. International Registered Report Identifier (IRRID): DERR1-10.2196/47911 ",
doi="10.2196/47911",
url="https://www.researchprotocols.org/2023/1/e47911",
url="http://www.ncbi.nlm.nih.gov/pubmed/37137823"
}


@Article{info:doi/10.2196/34055,
author="Coffin, Tara
and Bowen, Deborah
and Swisher, Elizabeth
and Lu, Karen
and Rayes, Nadine
and Norquist, Barbara
and Blank, Stephanie
and Levine, Douglas
and Bakkum-Gamez, Jamie
and Fleming, Gini
and Olopade, Olufunmilayo
and D'Andrea, Alan
and Nebgen, Denise
and Peterson, Christine
and Munsell, Mark
and Gavin, Kathleen
and Lechner, Rebecca
and Crase, Jamie
and Polinsky, Deborah
and Romero, Iris",
title="An Accessible Communication System for Population-Based Genetic Testing: Development and Usability Study",
journal="JMIR Form Res",
year="2022",
month="Oct",
day="17",
volume="6",
number="10",
pages="e34055",
keywords="genetic testing",
keywords="internet",
keywords="social media",
keywords="accessibility",
abstract="Background: Genetic testing uptake is low, despite the well-established connection between pathogenic variants in certain cancer-linked susceptibility genes and ovarian cancer risk. Given that most major insurers cover genetic testing for those with a family history suggestive of hereditary cancer, the issue may lie in access to genetic testing. Remotely accessible web-based communication systems may improve awareness, and uptake, of genetic testing services. Objective: This study aims to present the development and formative evaluation of the multistep web-based communication system required to support the implementation of, and access to, genetic testing. Methods: While designing the multistep web-based communication system, we considered various barriers and facilitators to genetic testing, guided by dimensions of accessibility. In addition to conducting usability testing, we performed ongoing assessments focusing on the function of the web-based system and participant response rates, with the goal of continuing to make modifications to the web-based communication system as it is in use. Results: The combined approach of usability testing and expert user experience consultation resulted in several modifications to the multistep web-based communication system, including changes that related to imagery and content, web accessibility, and general organization of the web-based system. All recommendations were made with the goal of improving the overall accessibility of the web-based communication system. Conclusions: A multistep web-based communication system appears to be an effective way to address many potential barriers to access, which may otherwise make genetic testing difficult for at-risk individuals to participate in. Importantly, some dimensions of access were easy to assess before study recruitment, but other aspects of the communication system required ongoing assessment during the implementation process of the Making Genetic Testing Accessible study. ",
doi="10.2196/34055",
url="https://formative.jmir.org/2022/10/e34055",
url="http://www.ncbi.nlm.nih.gov/pubmed/36251350"
}


@Article{info:doi/10.2196/35702,
author="Liu, Yongtai
and Yin, Zhijun
and Wan, Zhiyu
and Yan, Chao
and Xia, Weiyi
and Ni, Congning
and Clayton, Wright Ellen
and Vorobeychik, Yevgeniy
and Kantarcioglu, Murat
and Malin, A. Bradley",
title="Implicit Incentives Among Reddit Users to Prioritize Attention Over Privacy and Reveal Their Faces When Discussing Direct-to-Consumer Genetic Test Results: Topic and Attention Analysis",
journal="JMIR Infodemiology",
year="2022",
month="Aug",
day="3",
volume="2",
number="2",
pages="e35702",
keywords="direct-to-consumer genetic testing",
keywords="topic modeling",
keywords="social media",
abstract="Background: As direct-to-consumer genetic testing services have grown in popularity, the public has increasingly relied upon online forums to discuss and share their test results. Initially, users did so anonymously, but more recently, they have included face images when discussing their results. Various studies have shown that sharing images on social media tends to elicit more replies. However, users who do this forgo their privacy. When these images truthfully represent a user, they have the potential to disclose that user's identity. Objective: This study investigates the face image sharing behavior of direct-to-consumer genetic testing users in an online environment to determine if there exists an association between face image sharing and the attention received from other users. Methods: This study focused on r/23andme, a subreddit dedicated to discussing direct-to-consumer genetic testing results and their implications. We applied natural language processing to infer the themes associated with posts that included a face image. We applied a regression analysis to characterize the association between the attention that a post received, in terms of the number of comments, the karma score (defined as the number of upvotes minus the number of downvotes), and whether the post contained a face image. Results: We collected over 15,000 posts from the r/23andme subreddit, published between 2012 and 2020. Face image posting began in late 2019 and grew rapidly, with over 800 individuals revealing their faces by early 2020. The topics in posts including a face were primarily about sharing, discussing ancestry composition, or sharing family reunion photos with relatives discovered via direct-to-consumer genetic testing. On average, posts including a face image received 60\% (5/8) more comments and had karma scores 2.4 times higher than other posts. Conclusions: Direct-to-consumer genetic testing consumers in the r/23andme subreddit are increasingly posting face images and testing reports on social platforms. The association between face image posting and a greater level of attention suggests that people are forgoing their privacy in exchange for attention from others. To mitigate this risk, platform organizers and moderators could inform users about the risk of posting face images in a direct, explicit manner to make it clear that their privacy may be compromised if personal images are shared. ",
doi="10.2196/35702",
url="https://infodemiology.jmir.org/2022/2/e35702",
url="http://www.ncbi.nlm.nih.gov/pubmed/37113452"
}


@Article{info:doi/10.2196/29706,
author="Korngiebel, M. Diane
and West, McGlone Kathleen",
title="Patient Recommendations for the Content and Design of Electronic Returns of Genetic Test Results: Interview Study Among Patients Who Accessed Their Genetic Test Results via the Internet",
journal="JMIRx Med",
year="2022",
month="May",
day="31",
volume="3",
number="2",
pages="e29706",
keywords="user-centered design",
keywords="genomic medicine",
keywords="patient portals",
keywords="electronic health records",
keywords="return of results",
keywords="bioethics",
keywords="genetics",
keywords="genetic testing",
keywords="patient preferences",
keywords="design",
keywords="human factors",
keywords="mobile phone",
abstract="Background: Genetic test results will be increasingly made available electronically as more patient-facing tools are developed; however, little research has been done that collects data on patient preferences for content and design before creating results templates. Objective: This study identifies patient preferences for the electronic return of genetic test results, including what considerations should be prioritized for content and design. Methods: Following user-centered design methods, 59 interviews were conducted by using semistructured protocols. The interviews explored the content and design issues of patient portals that facilitated the return of test results to patients. We interviewed patients who received electronic results for specific types of genetics tests (pharmacogenetic tests, hereditary blood disorder tests, and tests for the risk of heritable cancers) or electronically received any type of genetic or nongenetic test results. Results: In general, many of participants felt that there always needed to be some clinician involvement in electronic result returns and that electronic coversheets with simple summaries would be helpful for facilitating this. Coversheet summaries could accompany, but not replace, the more detailed report. Participants had specific suggestions for such results summaries, such as only reporting the information that was the most important for patients to understand, including next steps, and doing so by using clear language that is free of medical jargon. Electronic result returns should also include explicit encouragement for patients to contact health care providers about questions. Finally, many participants preferred to manage their care by using their smartphones, particularly in instances when they needed to access health information on the go. Conclusions: Participants recommended that a patient-friendly front section should accompany the more detailed report and made suggestions for organization, content, and wording. Many used their smartphones regularly to access test results; therefore, health systems and patient portal software vendors should accommodate smartphone app design and web portal design concomitantly when developing platforms for returning results. ",
doi="10.2196/29706",
url="https://med.jmirx.org/2022/2/e29706/",
url="http://www.ncbi.nlm.nih.gov/pubmed/37725563"
}


@Article{info:doi/10.2196/27898,
author="Zolk, Oliver
and von dem Knesebeck, Annika
and Graf, Norbert
and Simon, Thorsten
and Hero, Barbara
and Abdul-Khaliq, Hashim
and Abd El Rahman, Mohamed
and Spix, Claudia
and Mayer, Benjamin
and Elsner, Susanne
and Gebauer, Judith
and Langer, Thorsten",
title="Cardiovascular Health Status And Genetic Risk In Survivors of Childhood Neuroblastoma and Nephroblastoma Treated With Doxorubicin: Protocol of the Pharmacogenetic Part of the LESS-Anthra Cross-Sectional Cohort Study",
journal="JMIR Res Protoc",
year="2022",
month="Feb",
day="17",
volume="11",
number="2",
pages="e27898",
keywords="cardiotoxicity",
keywords="anthracyclines",
keywords="childhood cancer survivors",
keywords="genetics",
keywords="polymorphisms",
keywords="cardiology",
keywords="cardiac health",
keywords="cancer",
keywords="survivors",
keywords="childhood",
keywords="children",
keywords="risk monitoring",
keywords="cardiovascular health",
keywords="pediatrics",
abstract="Background: In childhood cancer survivors (survival of 5 years or more after diagnosis), cardiac toxicity is the most common nonmalignant cause of death attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. The use of genetic markers has been proposed, together with clinical risk factors, to predict individual risk of cardiac toxicity from cancer therapies, such as doxorubicin. Objective: The primary aim of this study is to evaluate the value of multimarker genetic testing for RARG rs2229774, UGT1A6 rs17863783, and SLC28A3 rs7853758 for predicting doxorubicin-induced cardiotoxicity. The secondary aim is to replicate previously described associations of candidate genetic markers with doxorubicin-induced cardiotoxicity. Moreover, we will evaluate the prevalence of cardiovascular dysfunction in childhood cancer survivors after neuroblastoma or nephroblastoma. Methods: This is the pharmacogenetic substudy of the research project Structural Optimization for Children With Cancer After Anthracycline Therapy (LESS-Anthra). We invited 2158 survivors of childhood neuroblastoma or nephroblastoma treated with doxorubicin according to the trial protocols of SIOP 9/GPOH, SIOP 93-01/GPOH, SIOP 2001/GPOH, NB 90, NB 97, or NB 2004 to participate in this prospective cross-sectional cohort study. The study participants underwent a cardiological examination and were asked to provide a blood or saliva sample for genotyping. The study participants' health statuses and cardiovascular diagnoses were recorded using a questionnaire completed by the cardiologist. Digital echocardiographic data were centrally evaluated to determine the contractile function parameters. Medical data on the tumor diagnosis and treatment protocol were taken from the study documentation. Survivors were screened for variants of several candidate genes by TaqMan genotyping. Results: This study includes 657 survivors treated with doxorubicin for childhood cancer, the largest German cohort assembled to date to investigate cardiovascular late effects. Data analyses are yet to be completed. Conclusions: This study will define the genetic risk related to 3 marker genes proposed in a pharmacogenetic guideline for risk assessment. Moreover, the results of this study will show the prevalence of cardiovascular dysfunction in survivors of pediatric neuroblastoma or nephroblastoma who were treated with doxorubicin. The results will help to improve primary treatment and follow-up care, thus reducing cardiovascular late effects in the growing population of childhood cancer survivors. Trial Registration: German Clinical Trials Register DRKS00015084; https://www.drks.de/drks\_web/navigate.do?navigationId=trial.HTML\&TRIAL\_ID=DRKS00015084 International Registered Report Identifier (IRRID): DERR1-10.2196/27898 ",
doi="10.2196/27898",
url="https://www.researchprotocols.org/2022/2/e27898",
url="http://www.ncbi.nlm.nih.gov/pubmed/35175211"
}


@Article{info:doi/10.2196/32568,
author="Bangash, Hana
and Makkawy, Ahmed
and Gundelach, H. Justin
and Miller, A. Alexandra
and Jacobson, A. Kimberly
and Kullo, J. Iftikhar",
title="Web-Based Tool (FH Family Share) to Increase Uptake of Cascade Testing for Familial Hypercholesterolemia: Development and Evaluation",
journal="JMIR Hum Factors",
year="2022",
month="Feb",
day="15",
volume="9",
number="1",
pages="e32568",
keywords="familial hypercholesterolemia",
keywords="cascade testing",
keywords="communication",
keywords="genetic counselors",
keywords="digital tools",
keywords="website",
keywords="usability",
keywords="user experience",
keywords="public health",
abstract="Background: Familial hypercholesterolemia, a prevalent genetic disorder, remains significantly underdiagnosed in the United States. Cascade testing, wherein individuals diagnosed with familial hypercholesterolemia--- probands---contact their family members to inform them of their risk for familial hypercholesterolemia, has low uptake in the United States. Digital tools are needed to facilitate communication between familial hypercholesterolemia probands and their family members and to promote sharing of familial hypercholesterolemia--related risk information. Objective: We aimed to create and evaluate a web-based tool designed to enhance familial communication and promote cascade testing for familial hypercholesterolemia. Methods: A hybrid type 1 implementation science framework and a user-centered design process were used to develop an interactive web-based tool---FH Family Share---that enables familial hypercholesterolemia probands to communicate information about their familial hypercholesterolemia diagnosis with at-risk relatives. Probands can also use the tool to draw a family pedigree and learn more about familial hypercholesterolemia through education modules and curated knowledge resources. Usability guidelines and standards were taken into account during the design and development of the tool. The initial prototype underwent a cognitive walkthrough, which was followed by usability testing with key stakeholders including genetic counselors and patients with familial hypercholesterolemia. Participants navigated the prototype using the think-aloud technique, and their feedback was used to refine features of the tool. Results: Key themes that emerged from the cognitive walkthrough were design, format, navigation, terminology, instructions, and learnability. Expert feedback from the cognitive walkthrough resulted in a rebuild of the web-based tool to align it with institutional standards. Usability testing with genetic counselors and patients with familial hypercholesterolemia provided insights on user experience, satisfaction and interface design and highlighted specific modifications that were made to refine the features of FH Family Share. Genetic counselors and patients with familial hypercholesterolemia suggested inclusion of the following features in the web-based tool: (1) a letter-to-family-member email template, (2) education modules, and (3) knowledge resources. Surveys revealed that 6 of 9 (67\%) genetic counselors found information within FH Family Share very easy to find, and 5 of 9 (56\%) genetic counselors found information very easy to understand; 5 of 9 (56\%) patients found information very easy to find within the website, and 7 of 9 (78\%) patients found information very easy to understand. All genetic counselors and patients indicated that FH Family Share was a resource worth returning to. Conclusions: FH Family Share facilitates communication between probands and their relatives. Once informed, at-risk family members have the option to seek testing and treatment for familial hypercholesterolemia. ",
doi="10.2196/32568",
url="https://humanfactors.jmir.org/2022/1/e32568",
url="http://www.ncbi.nlm.nih.gov/pubmed/35166678"
}


@Article{info:doi/10.2196/31885,
author="Chowdhury, Rajiv
and Noh, Md Mohd Fairulnizal
and Ismail, Rasheeqa Sophia
and van Daalen, Robin Kim
and Kamaruddin, Megat Puteri Sofia Nadira
and Zulkiply, Hafizah Siti
and Azizul, Hayati Nur
and Khalid, Mustafa Norhayati
and Ali, Azizan
and Idris, Mohd Izyan
and Mei, Shih Yong
and Abdullah, Rifham Shazana
and Faridus, Norfashihah
and Yusof, Md Nur Azirah
and Yusoff, M. Nur Najwa Farahin
and Jamal, Rahman
and Rahim, Abdul Aizai Azan
and Ghapar, Abdul Abdul Kahar
and Radhakrishnan, Kutty Ammu
and Fong, Yip Alan Yean
and Ismail, Omar
and Krishinan, Saravanan
and Lee, Yan Chuey
and Bang, Houng Liew
and Mageswaren, Eashwary
and Mahendran, Kauthaman
and Amin, Mohd Nor Hanim
and Muthusamy, Gunavathy
and Jin, Hean Aaron Ong
and Ramli, Wazi Ahmad
and Ross, Thomas Noel
and Ruhani, Irawan Anwar
and Yahya, Mansor
and Yusoff, Yusniza
and Abidin, Zainal Siti Khairani
and Amado, Laryssa
and Bolton, Thomas
and Weston, Sophie
and Crawte, Jason
and Ovenden, Niko
and Michielsen, Ank
and Monower, Mostafa Md
and Mahiyuddin, Wan Wan Rozita
and Wood, Angela
and Di Angelantonio, Emanuele
and Sulaiman, Suffia Nur
and Danesh, John
and Butterworth, S. Adam",
title="Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study",
journal="JMIR Res Protoc",
year="2022",
month="Feb",
day="10",
volume="11",
number="2",
pages="e31885",
keywords="myocardial infarction",
keywords="cardiovascular disease",
keywords="case-control study",
keywords="Malaysia",
abstract="Background: Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse. Objective: The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results. Methods: By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire. Results: Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95\% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95\% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95\% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95\% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95\% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95\% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models. Conclusions: The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action. International Registered Report Identifier (IRRID): RR1-10.2196/31885 ",
doi="10.2196/31885",
url="https://www.researchprotocols.org/2022/2/e31885",
url="http://www.ncbi.nlm.nih.gov/pubmed/35142634"
}


@Article{info:doi/10.2196/29447,
author="Chavez-Yenter, Daniel
and Kimball, E. Kadyn
and Kohlmann, Wendy
and Lorenz Chambers, Rachelle
and Bradshaw, L. Richard
and Espinel, F. Whitney
and Flynn, Michael
and Gammon, Amanda
and Goldberg, Eric
and Hagerty, J. Kelsi
and Hess, Rachel
and Kessler, Cecilia
and Monahan, Rachel
and Temares, Danielle
and Tobik, Katie
and Mann, M. Devin
and Kawamoto, Kensaku
and Del Fiol, Guilherme
and Buys, S. Saundra
and Ginsburg, Ophira
and Kaphingst, A. Kimberly",
title="Patient Interactions With an Automated Conversational Agent Delivering Pretest Genetics Education: Descriptive Study",
journal="J Med Internet Res",
year="2021",
month="Nov",
day="18",
volume="23",
number="11",
pages="e29447",
keywords="cancer",
keywords="genetic testing",
keywords="virtual conversational agent",
keywords="user interaction",
keywords="smartphone",
keywords="mobile phone",
abstract="Background: Cancer genetic testing to assess an individual's cancer risk and to enable genomics-informed cancer treatment has grown exponentially in the past decade. Because of this continued growth and a shortage of health care workers, there is a need for automated strategies that provide high-quality genetics services to patients to reduce the clinical demand for genetics providers. Conversational agents have shown promise in managing mental health, pain, and other chronic conditions and are increasingly being used in cancer genetic services. However, research on how patients interact with these agents to satisfy their information needs is limited. Objective: Our primary aim is to assess user interactions with a conversational agent for pretest genetics education. Methods: We conducted a feasibility study of user interactions with a conversational agent who delivers pretest genetics education to primary care patients without cancer who are eligible for cancer genetic evaluation. The conversational agent provided scripted content similar to that delivered in a pretest genetic counseling visit for cancer genetic testing. Outside of a core set of information delivered to all patients, users were able to navigate within the chat to request additional content in their areas of interest. An artificial intelligence--based preprogrammed library was also established to allow users to ask open-ended questions to the conversational agent. Transcripts of the interactions were recorded. Here, we describe the information selected, time spent to complete the chat, and use of the open-ended question feature. Descriptive statistics were used for quantitative measures, and thematic analyses were used for qualitative responses. Results: We invited 103 patients to participate, of which 88.3\% (91/103) were offered access to the conversational agent, 39\% (36/91) started the chat, and 32\% (30/91) completed the chat. Most users who completed the chat indicated that they wanted to continue with genetic testing (21/30, 70\%), few were unsure (9/30, 30\%), and no patient declined to move forward with testing. Those who decided to test spent an average of 10 (SD 2.57) minutes on the chat, selected an average of 1.87 (SD 1.2) additional pieces of information, and generally did not ask open-ended questions. Those who were unsure spent 4 more minutes on average (mean 14.1, SD 7.41; P=.03) on the chat, selected an average of 3.67 (SD 2.9) additional pieces of information, and asked at least one open-ended question. Conclusions: The pretest chat provided enough information for most patients to decide on cancer genetic testing, as indicated by the small number of open-ended questions. A subset of participants were still unsure about receiving genetic testing and may require additional education or interpersonal support before making a testing decision. Conversational agents have the potential to become a scalable alternative for pretest genetics education, reducing the clinical demand on genetics providers. ",
doi="10.2196/29447",
url="https://www.jmir.org/2021/11/e29447",
url="http://www.ncbi.nlm.nih.gov/pubmed/34792472"
}


@Article{info:doi/10.2196/32729,
author="Henrique, Bazzanello Patr{\'i}cia Paula
and Perez, Pelle Fabr{\'i}zzio Martin
and Becker, Cemin Osvaldo Henrique
and Bellei, Andrei Ericles
and Biduski, Daiana
and Korb, Arthiese
and Pochmann, Daniela
and Dani, Caroline
and Elsner, Rostirola Viviane
and De Marchi, Bertoletti Ana Carolina",
title="Kinesiotherapy With Exergaming as a Potential Modulator of Epigenetic Marks and Clinical Functional Variables of Older Women: Protocol for a Mixed Methods Study",
journal="JMIR Res Protoc",
year="2021",
month="Oct",
day="13",
volume="10",
number="10",
pages="e32729",
keywords="elderly women",
keywords="exergame",
keywords="epigenome",
keywords="cognition",
keywords="kinesiotherapy",
abstract="Background: Kinesiotherapy is an option to mitigate worsening neuropsychomotor function due to human aging. Moreover, exergames are beneficial for the practice of physical therapy by older patients. Physical exercise interventions are known to alter the epigenome, but little is known about their association with exergames. Objective: We aim to evaluate the effects of kinesiotherapy with exergaming on older women's epigenetic marks and cognitive ability, as well as on their clinical functional variables. Our hypothesis states that this kind of therapy can elicit equal or even better outcomes than conventional therapy. Methods: We will develop a virtual clinic exergame with 8 types of kinesiotherapy exercises. Afterward, we will conduct a 1:1 randomized clinical trial to compare the practice of kinesiotherapy with exergames (intervention group) against conventional kinesiotherapy (control group). A total of 24 older women will be enrolled for 1-hour sessions performed twice a week, for 6 weeks, totaling 12 sessions. We will assess outcomes using epigenetic blood tests, the Montreal Cognitive Assessment test, the Timed Up and Go test, muscle strength grading in a hydraulic dynamometer, and the Game Experience Questionnaire at various stages. Results: The project was funded in October 2019. Game development took place in 2020. Patient recruitment and a clinical trial are planned for 2021. Conclusions: Research on this topic is likely to significantly expand the understanding of kinesiotherapy and the impact of exergames. To the best of our knowledge, this may be one of the first studies exploring epigenetic outcomes of exergaming interventions. Trial Registration: Brazilian Clinical Trials Registry/Registro Brasileiro de Ensaios Cl{\'i}nicos (ReBEC) RBR-9tdrmw; https://ensaiosclinicos.gov.br/rg/RBR-9tdrmw. International Registered Report Identifier (IRRID): DERR1-10.2196/32729 ",
doi="10.2196/32729",
url="https://www.researchprotocols.org/2021/10/e32729",
url="http://www.ncbi.nlm.nih.gov/pubmed/34643543"
}


@Article{info:doi/10.2196/31150,
author="Alshammari, O. Fatemah O. F.
and Al-saraireh, M. Yousef
and Youssef, M. Ahmed M.
and Al-Sarayra, M. Yahya
and Alrawashdeh, Mohammad Hamzeh",
title="Cytochrome P450 1B1 Overexpression in Cervical Cancers: Cross-sectional Study",
journal="Interact J Med Res",
year="2021",
month="Oct",
day="12",
volume="10",
number="4",
pages="e31150",
keywords="cancer",
keywords="cervical cancer",
keywords="cytochrome P450",
keywords="cytochrome 1B1",
keywords="immunohistochemistry",
keywords="toxicity",
keywords="therapies",
keywords="molecular",
keywords="tumor",
keywords="cytochrome",
keywords="cervix",
abstract="Background: Current standard treatments for patients with recurrent cervical cancer are not very effective and are associated with severe toxicity. Recently, the rational approach for the discovery of new therapies for cervical cancer is based on the alterations in the molecular biology of cancer cells. One of the emerging molecular changes in cancer cells is the aberrant expression of cytochrome P450 1B1 (CYP1B1). This unique enzyme has been reported to be selectively overexpressed in several cancers. Objective: The aim of this study was to examine CYP1B1 expression in cervical cancers and to assess the enzyme's relationship with several clinicopathological features. Methods: Immunohistochemistry was performed to examine CYP1B1 expression in 100 patient samples with cervical cancer and 10 patient samples with normal healthy cervical tissues. Results: CYP1B1 was expressed in the majority of the cervical cancer samples (91/100, 91.0\%) but not in normal healthy cervical samples. The difference in the expression of CYP1B1 between healthy and tumorous cervical tissues was significant (P=.01). Moreover, the frequency of CYP1B1 expression was found to be significantly higher in patients with advanced grades of the disease (P=.03) and in patients having metastasis to the lymph nodes (P=.01). Surprisingly, there was a significantly higher expression of CYP1B1 in patients with a high prevalence of human papilloma virus 16/18 (P=.04). Conclusions: The differential profile of CYP1B1 expression between cervical cancer tissues and normal cervical tissues suggests that CYP1B1 may be used as a target for future therapeutic exploitations. ",
doi="10.2196/31150",
url="https://www.i-jmr.org/2021/4/e31150",
url="http://www.ncbi.nlm.nih.gov/pubmed/34636736"
}


@Article{info:doi/10.2196/29123,
author="Naeim, Arash
and Dry, Sarah
and Elashoff, David
and Xie, Zhuoer
and Petruse, Antonia
and Magyar, Clara
and Johansen, Liliana
and Werre, Gabriela
and Lajonchere, Clara
and Wenger, Neil",
title="Electronic Video Consent to Power Precision Health Research: A Pilot Cohort Study",
journal="JMIR Form Res",
year="2021",
month="Sep",
day="8",
volume="5",
number="9",
pages="e29123",
keywords="biobanking",
keywords="precision medicine",
keywords="electronic consent",
keywords="privacy",
keywords="pilot study",
keywords="video",
keywords="consent",
keywords="precision",
keywords="innovation",
keywords="efficient",
keywords="cancer",
keywords="education",
keywords="barrier",
keywords="engagement",
keywords="participation",
abstract="Background: Developing innovative, efficient, and institutionally scalable biospecimen consent for remnant tissue that meets the National Institutes of Health consent guidelines for genomic and molecular analysis is essential for precision medicine efforts in cancer. Objective: This study aims to pilot-test an electronic video consent that individuals could complete largely on their own. Methods: The University of California, Los Angeles developed a video consenting approach designed to be comprehensive yet fast (around 5 minutes) for providing universal consent for remnant biospecimen collection for research. The approach was piloted in 175 patients who were coming in for routine services in laboratory medicine, radiology, oncology, and hospital admissions. The pilot yielded 164 completed postconsent surveys. The pilot assessed the usefulness, ease, and trustworthiness of the video consent. In addition, we explored drivers for opting in or opting out. Results: The pilot demonstrated that the electronic video consent was well received by patients, with high scores for usefulness, ease, and trustworthiness even among patients that opted out of participation. The revised more animated video pilot test in phase 2 was better received in terms of ease of use (P=.005) and the ability to understand the information (P<.001). There were significant differences between those who opted in and opted out in their beliefs concerning the usefulness of tissue, trusting researchers, the importance of contributing to science, and privacy risk (P<.001). The results showed that ``I trust researchers to use leftover biological specimens to promote the public's health'' and ``Sharing a biological sample for research is safe because of the privacy protections in place'' discriminated opt-in statuses were the strongest predictors (both areas under the curve were 0.88). Privacy concerns seemed universal in individuals who opted out. Conclusions: Efforts to better educate the community may be needed to help overcome some of the barriers in engaging individuals to participate in precision health initiatives. ",
doi="10.2196/29123",
url="https://formative.jmir.org/2021/9/e29123",
url="http://www.ncbi.nlm.nih.gov/pubmed/34313247"
}


@Article{info:doi/10.2196/25789,
author="Wang, Quan
and Yang, Ke-Lu
and Zhang, Zhen
and Wang, Zhu
and Li, Chen
and Li, Lun
and Tian, Jin-Hui
and Ye, Ying-Jiang
and Wang, Shan
and Jiang, Ke-Wei",
title="Characterization of Global Research Trends and Prospects on Single-Cell Sequencing Technology: Bibliometric Analysis",
journal="J Med Internet Res",
year="2021",
month="Aug",
day="10",
volume="23",
number="8",
pages="e25789",
keywords="single-cell sequencing",
keywords="bibliometric analysis",
keywords="cancer",
keywords="cancer genomics",
keywords="bioinformatics",
keywords="cancer subtyping",
keywords="tumor dissociation",
keywords="tumor microenvironment",
keywords="precision medicine",
keywords="immunology",
keywords="development trends",
keywords="hotspots",
keywords="research topics",
keywords="Web of Science",
keywords="CiteSpace",
keywords="VOSviewer",
keywords="network",
abstract="Background: As single-cell sequencing technology has been gradually introduced, it is essential to characterize global collaboration networks and map development trends over the past 20 years. Objective: The aim of this paper was to illustrate collaboration in the field of single-cell sequencing methods and explore key topics and future directions. Methods: Bibliometric analyses were conducted with CiteSpace and VOSviewer software on publications prior to November 2019 from the Web of Science Core Collection about single-cell sequencing methods. Results: Ultimately, we identified 2489 records, which were published in 495 journals by 14,202 authors from 1970 institutes in 61 countries. There was a noticeable increase in publications in 2014. The United States and high-income countries in Europe contributed to most of the records included. Harvard University, Stanford University, Karolinska Institutes, Peking University, and the University of Washington were the biggest nodes in every cluster of the collaboration network, and SA Teichmann, JC Marioni, A Regev, and FC Tang were the top-producing authors. Keywords co-occurrence analysis suggested applications in immunology as a developing research trend. Conclusions: We concluded that the global collaboration network was unformed and that high-income countries contributed more to the rapidly growth of publications of single-cell sequencing technology. Furthermore, the application in immunology might be the next research hotspot and developmental direction. ",
doi="10.2196/25789",
url="https://www.jmir.org/2021/8/e25789",
url="http://www.ncbi.nlm.nih.gov/pubmed/34014832"
}


@Article{info:doi/10.2196/25670,
author="He, Kai
and Yao, Lixia
and Zhang, JiaWei
and Li, Yufei
and Li, Chen",
title="Construction of Genealogical Knowledge Graphs From Obituaries: Multitask Neural Network Extraction System",
journal="J Med Internet Res",
year="2021",
month="Aug",
day="4",
volume="23",
number="8",
pages="e25670",
keywords="genealogical knowledge graph",
keywords="EHR",
keywords="information extraction",
keywords="genealogy",
keywords="neural network",
abstract="Background: Genealogical information, such as that found in family trees, is imperative for biomedical research such as disease heritability and risk prediction. Researchers have used policyholder and their dependent information in medical claims data and emergency contacts in electronic health records (EHRs) to infer family relationships at a large scale. We have previously demonstrated that online obituaries can be a novel data source for building more complete and accurate family trees. Objective: Aiming at supplementing EHR data with family relationships for biomedical research, we built an end-to-end information extraction system using a multitask-based artificial neural network model to construct genealogical knowledge graphs (GKGs) from online obituaries. GKGs are enriched family trees with detailed information including age, gender, death and birth dates, and residence. Methods: Built on a predefined family relationship map consisting of 4 types of entities (eg, people's name, residence, birth date, and death date) and 71 types of relationships, we curated a corpus containing 1700 online obituaries from the metropolitan area of Minneapolis and St Paul in Minnesota. We also adopted data augmentation technology to generate additional synthetic data to alleviate the issue of data scarcity for rare family relationships. A multitask-based artificial neural network model was then built to simultaneously detect names, extract relationships between them, and assign attributes (eg, birth dates and death dates, residence, age, and gender) to each individual. In the end, we assemble related GKGs into larger ones by identifying people appearing in multiple obituaries. Results: Our system achieved satisfying precision (94.79\%), recall (91.45\%), and F-1 measures (93.09\%) on 10-fold cross-validation. We also constructed 12,407 GKGs, with the largest one made up of 4 generations and 30 people. Conclusions: In this work, we discussed the meaning of GKGs for biomedical research, presented a new version of a corpus with a predefined family relationship map and augmented training data, and proposed a multitask deep neural system to construct and assemble GKGs. The results show our system can extract and demonstrate the potential of enriching EHR data for more genetic research. We share the source codes and system with the entire scientific community on GitHub without the corpus for privacy protection. ",
doi="10.2196/25670",
url="https://www.jmir.org/2021/8/e25670",
url="http://www.ncbi.nlm.nih.gov/pubmed/34346903"
}


@Article{info:doi/10.2196/28527,
author="Yin, Kanhua
and Zhou, Jingan
and Singh, Preeti
and Wang, Jin
and Braun, Danielle
and Hughes, S. Kevin",
title="Search Behavior Regarding Cancer Susceptibility Genes Using a Clinical Decision Support Tool for Gene-Specific Penetrance: Content Analysis",
journal="JMIR Cancer",
year="2021",
month="Jul",
day="13",
volume="7",
number="3",
pages="e28527",
keywords="genetic testing",
keywords="pathogenic variant",
keywords="germline",
keywords="risk communication",
keywords="online health",
keywords="digital health",
keywords="cancer data",
keywords="genetics",
keywords="online tool",
keywords="bioinformatics",
keywords="web tool",
keywords="cancer",
abstract="Background: Genetic testing for germline cancer susceptibility genes is widely available. The Ask2Me.org (All Syndromes Known to Man Evaluator) tool is a clinical decision support tool that provides evidence-based risk predictions for individuals with pathogenic variants in cancer susceptibility genes. Objective: The aim of this study was to understand the search behavior of the Ask2Me.org tool users, identify the patterns of queries entered, and discuss how to further improve the tool. Methods: We analyzed the Ask2Me.org user-generated queries collected between December 12, 2018, and October 8, 2019. The gene frequencies of the user-generated queries were compared with previously published panel testing data to assess the correspondence between usage and prevalence of pathogenic variants. The frequencies of prior cancer in the user-generated queries were compared with the most recent US population--based cancer incidence. Results: A total of 10,085 search queries were evaluated. The average age submitted in the queries was 48.8 (SD 16.5) years, and 84.1\% (8478/10,085) of the submitted queries were for females. BRCA2 (1671/10,085, 16.6\%), BRCA1 (1627/10,085, 16.1\%), CHEK2 (994/10,085, 9.9\%), ATM (662/10,085, 6.6\%), and APC (492/10,085, 4.9\%) were the top 5 genes searched by users. There was a strong linear correlation between genes queried by users and the frequency of pathogenic variants reported in published panel testing data (r=0.95, r2=0.90, P<.001). Over half of the queries (5343/10,085, 53.0\%) included a prior personal history of cancer. The frequencies of prior cancers in the queries on females were strongly correlated with US cancer incidences (r=0.97, r2=0.95, P<.001), while the same correlation was weaker among the queries on males (r=0.69, r2=0.47, P=.02). Conclusions: The patients entered in the Ask2Me.org tool are a representative cohort of patients with pathogenic variants in cancer susceptibility genes in the United States. While a majority of the queries were on breast cancer susceptibility genes, users also queried susceptibility genes with lower prevalence, which may represent a transformation from single gene testing to multigene panel testing. Owing to these changing tides, more efforts are needed to improve evidence-based clinical decision support tools to better aid clinicians and their practice. ",
doi="10.2196/28527",
url="https://cancer.jmir.org/2021/3/e28527",
url="http://www.ncbi.nlm.nih.gov/pubmed/34255640"
}


@Article{info:doi/10.2196/27980,
author="Lantoine, Jos{\'e}phine
and Brysse, Anne
and Dideberg, Vinciane
and Claes, Kathleen
and Symoens, Sofie
and Coucke, Wim
and Benoit, Val{\'e}rie
and Rombout, Sonia
and De Rycke, Martine
and Seneca, Sara
and Van Laer, Lut
and Wuyts, Wim
and Corveleyn, Anniek
and Van Den Bogaert, Kris
and Rydlewski, Catherine
and Wilkin, Fran{\c{c}}oise
and Ravoet, Marie
and Fastr{\'e}, Elodie
and Capron, Arnaud
and Vandevelde, Monique Nathalie",
title="Frequency of Participation in External Quality Assessment Programs Focused on Rare Diseases: Belgian Guidelines for Human Genetics Centers",
journal="JMIR Med Inform",
year="2021",
month="Jul",
day="12",
volume="9",
number="7",
pages="e27980",
keywords="human genetics",
keywords="external quality assessment",
keywords="quality control",
keywords="proficiency testing",
keywords="frequency",
keywords="genetic testing",
keywords="rare diseases",
keywords="cost-effectiveness",
keywords="surveillance, public health authorities",
keywords="public health",
keywords="health informatics",
keywords="medical informatics",
keywords="genetics",
keywords="algorithm",
abstract="Background: Participation in quality controls, also called external quality assessment (EQA) schemes, is required for the ISO15189 accreditation of the Medical Centers of Human Genetics. However, directives on the minimal frequency of participation in genetic quality control schemes are lacking or too heterogeneous, with a possible impact on health care quality. Objective: The aim of this project is to develop Belgian guidelines on the frequency of participation in quality controls for genetic testing in the context of rare diseases. Methods: A group of experts analyzed 90 EQA schemes offered by accredited providers and focused on analyses used for the diagnosis of rare diseases. On that basis, the experts developed practical recommendations about the minimal frequencies of participation of the Medical Centers of Human Genetics in quality controls and how to deal with poor performances and change management. These guidelines were submitted to the Belgian Accreditation Body and then reviewed and approved by the Belgian College of Human Genetics and Rare Diseases and by the National Institute for Health and Disability Insurance. Results: The guidelines offer a decisional algorithm for the minimal frequency of participation in human genetics EQA schemes. This algorithm has been developed taking into account the scopes of the EQA schemes, the levels of experience, and the annual volumes of the Centers of Human Genetics in the performance of the tests considered. They include three key principles: (1) the recommended annual assessment of all genetic techniques and technological platforms, if possible through EQAs covering the technique, genotyping, and clinical interpretation; (2) the triennial assessment of the genotyping and interpretation of specific germline mutations and pharmacogenomics analyses; and (3) the documentation of actions undertaken in the case of poor performances and the participation to quality control the following year. The use of a Bayesian statistical model has been proposed to help the Centers of Human Genetics to determine the theoretical number of tests that should be annually performed to achieve a certain threshold of performance (eg, a maximal error rate of 1\%). Besides, the guidelines insist on the role and responsibility of the national public health authorities in the follow-up of the quality of analyses performed by the Medical Centers of Human Genetics and in demonstrating the cost-effectiveness and rationalization of participation frequency in these quality controls. Conclusions: These guidelines have been developed based on the analysis of a large panel of EQA schemes and data collected from the Belgian Medical Centers of Human Genetics. They are applicable to other countries and will facilitate and improve the quality management and financing systems of the Medical Centers of Human Genetics. ",
doi="10.2196/27980",
url="https://medinform.jmir.org/2021/7/e27980",
url="http://www.ncbi.nlm.nih.gov/pubmed/34255700"
}


@Article{info:doi/10.2196/17137,
author="An, Ning
and Mattison, John
and Chen, Xinyu
and Alterovitz, Gil",
title="Team Science in Precision Medicine: Study of Coleadership and Coauthorship Across Health Organizations",
journal="J Med Internet Res",
year="2021",
month="Jun",
day="14",
volume="23",
number="6",
pages="e17137",
keywords="precision medicine",
keywords="team science",
abstract="Background: Interdisciplinary collaborations bring lots of benefits to researchers in multiple areas, including precision medicine. Objective: This viewpoint aims at studying how cross-institution team science would affect the development of precision medicine. Methods: Publications of organizations on the eHealth Catalogue of Activities were collected in 2015 and 2017. The significance of the correlation between coleadership and coauthorship among different organizations was calculated using the Pearson chi-square test of independence. Other nonparametric tests examined whether organizations with coleaders publish more and better papers than organizations without coleaders. Results: A total of 374 publications from 69 organizations were analyzed in 2015, and 7064 papers from 87 organizations were analyzed in 2017. Organizations with coleadership published more papers (P<.001, 2015 and 2017), which received higher citations (Z=--13.547, P<.001, 2017), compared to those without coleadership. Organizations with coleaders tended to publish papers together (P<.001, 2015 and 2017). Conclusions: Our findings suggest that organizations in the field of precision medicine could greatly benefit from institutional-level team science. As a result, stronger collaboration is recommended. ",
doi="10.2196/17137",
url="https://www.jmir.org/2021/6/e17137",
url="http://www.ncbi.nlm.nih.gov/pubmed/34125070"
}


@Article{info:doi/10.2196/26264,
author="Kim, Sue
and Aceti, Monica
and Baroutsou, Vasiliki
and B{\"u}rki, Nicole
and Caiata-Zufferey, Maria
and Cattaneo, Marco
and Chappuis, O. Pierre
and Ciorba, M. Florina
and Graffeo-Galbiati, Rossella
and Heinzelmann-Schwarz, Viola
and Jeong, Joon
and Jung, M. MiSook
and Kim, Sung-Won
and Kim, Jisun
and Lim, Cheol Myong
and Ming, Chang
and Monnerat, Christian
and Park, Seok Hyung
and Park, Hyung Sang
and Pedrazzani, A. Carla
and Rabaglio, Manuela
and Ryu, Min Jai
and Saccilotto, Ramon
and Wieser, Simon
and Z{\"u}rrer-H{\"a}rdi, Ursina
and Katapodi, C. Maria",
title="Using a Tailored Digital Health Intervention for Family Communication and Cascade Genetic Testing in Swiss and Korean Families With Hereditary Breast and Ovarian Cancer: Protocol for the DIALOGUE Study",
journal="JMIR Res Protoc",
year="2021",
month="Jun",
day="11",
volume="10",
number="6",
pages="e26264",
keywords="HBOC",
keywords="proportion of informed at-risk relatives",
keywords="coping",
keywords="communicating",
keywords="decisional conflict",
keywords="cultural and linguistic adaptation",
keywords="implementation",
keywords="RE-AIM",
keywords="mobile phone",
abstract="Background: In hereditary breast and ovarian cancer (HBOC), family communication of genetic test results is essential for cascade genetic screening, that is, identifying and testing blood relatives of known mutation carriers to determine whether they also carry the pathogenic variant, and to propose preventive and clinical management options. However, up to 50\% of blood relatives are unaware of relevant genetic information, suggesting that potential benefits of genetic testing are not communicated effectively within family networks. Technology can facilitate communication and genetic education within HBOC families. Objective: The aims of this study are to develop the K-CASCADE (Korean--Cancer Predisposition Cascade Genetic Testing) cohort in Korea by expanding an infrastructure developed by the CASCADE (Cancer Predisposition Cascade Genetic Testing) Consortium in Switzerland; develop a digital health intervention to support the communication of cancer predisposition for Swiss and Korean HBOC families, based on linguistic and cultural adaptation of the Family Gene Toolkit; evaluate its efficacy on primary (family communication of genetic results and cascade testing) and secondary (psychological distress, genetic literacy, active coping, and decision making) outcomes; and explore its translatability using the reach, effectiveness, adoption, implementation, and maintenance framework. Methods: The digital health intervention will be available in French, German, Italian, Korean, and English and can be accessed via the web, mobile phone, or tablet (ie, device-agnostic). K-CASCADE cohort of Korean HBOC mutation carriers and relatives will be based on the CASCADE infrastructure. Narrative data collected through individual interviews or mini focus groups from 20 to 24 HBOC family members per linguistic region and 6-10 health care providers involved in genetic services will identify the local cultures and context, and inform the content of the tailored messages. The efficacy of the digital health intervention against a comparison website will be assessed in a randomized trial with 104 HBOC mutation carriers (52 in each study arm). The translatability of the digital health intervention will be assessed using survey data collected from HBOC families and health care providers. Results: Funding was received in October 2019. It is projected that data collection will be completed by January 2023 and results will be published in fall 2023. Conclusions: This study addresses the continuum of translational research, from developing an international research infrastructure and adapting an existing digital health intervention to testing its efficacy in a randomized controlled trial and exploring its translatability using an established framework. Adapting existing interventions, rather than developing new ones, takes advantage of previous valid experiences without duplicating efforts. Culturally sensitive web-based interventions that enhance family communication and understanding of genetic cancer risk are timely. This collaboration creates a research infrastructure between Switzerland and Korea that can be scaled up to cover other hereditary cancer syndromes. Trial Registration: ClinicalTrials.gov NCT04214210; https://clinicaltrials.gov/ct2/show/NCT04214210 and CRiS KCT0005643; https://cris.nih.go.kr/cris/ International Registered Report Identifier (IRRID): PRR1-10.2196/26264 ",
doi="10.2196/26264",
url="https://www.researchprotocols.org/2021/6/e26264",
url="http://www.ncbi.nlm.nih.gov/pubmed/34114954"
}


@Article{info:doi/10.2196/23586,
author="Zong, Nansu
and Ngo, Victoria
and Stone, J. Daniel
and Wen, Andrew
and Zhao, Yiqing
and Yu, Yue
and Liu, Sijia
and Huang, Ming
and Wang, Chen
and Jiang, Guoqian",
title="Leveraging Genetic Reports and Electronic Health Records for the Prediction of Primary Cancers: Algorithm Development and Validation Study",
journal="JMIR Med Inform",
year="2021",
month="May",
day="25",
volume="9",
number="5",
pages="e23586",
keywords="genetic reports",
keywords="electronic health records",
keywords="predicting primary cancers",
keywords="Fast Healthcare Interoperability Resources",
keywords="FHIR",
keywords="Resource Description Framework",
keywords="RDF",
abstract="Background: Precision oncology has the potential to leverage clinical and genomic data in advancing disease prevention, diagnosis, and treatment. A key research area focuses on the early detection of primary cancers and potential prediction of cancers of unknown primary in order to facilitate optimal treatment decisions. Objective: This study presents a methodology to harmonize phenotypic and genetic data features to classify primary cancer types and predict cancers of unknown primaries. Methods: We extracted genetic data elements from oncology genetic reports of 1011 patients with cancer and their corresponding phenotypical data from Mayo Clinic's electronic health records. We modeled both genetic and electronic health record data with HL7 Fast Healthcare Interoperability Resources. The semantic web Resource Description Framework was employed to generate the network-based data representation (ie, patient-phenotypic-genetic network). Based on the Resource Description Framework data graph, Node2vec graph-embedding algorithm was applied to generate features. Multiple machine learning and deep learning backbone models were compared for cancer prediction performance. Results: With 6 machine learning tasks designed in the experiment, we demonstrated the proposed method achieved favorable results in classifying primary cancer types (area under the receiver operating characteristic curve [AUROC] 96.56\% for all 9 cancer predictions on average based on the cross-validation) and predicting unknown primaries (AUROC 80.77\% for all 8 cancer predictions on average for real-patient validation). To demonstrate the interpretability, 17 phenotypic and genetic features that contributed the most to the prediction of each cancer were identified and validated based on a literature review. Conclusions: Accurate prediction of cancer types can be achieved with existing electronic health record data with satisfactory precision. The integration of genetic reports improves prediction, illustrating the translational values of incorporating genetic tests early at the diagnosis stage for patients with cancer. ",
doi="10.2196/23586",
url="https://medinform.jmir.org/2021/5/e23586",
url="http://www.ncbi.nlm.nih.gov/pubmed/34032581"
}


@Article{info:doi/10.2196/25401,
author="Sinha, Ranjan
and Kachru, Dashyanng
and Ricchetti, Ray Roshni
and Singh-Rambiritch, Simitha
and Muthukumar, Marimuthu Karthik
and Singaravel, Vidhya
and Irudayanathan, Carmel
and Reddy-Sinha, Chandana
and Junaid, Imran
and Sharma, Garima
and Francis-Lyon, Alice Patricia",
title="Leveraging Genomic Associations in Precision Digital Care for Weight Loss: Cohort Study",
journal="J Med Internet Res",
year="2021",
month="May",
day="19",
volume="23",
number="5",
pages="e25401",
keywords="obesity",
keywords="digital therapeutics",
keywords="precision nutrition",
keywords="nutrigenomics",
keywords="personalized nutrition",
keywords="mHealth",
keywords="mobile apps",
keywords="gut microbiota",
keywords="machine learning",
keywords="health coaching",
keywords="lifestyle medicine",
keywords="mobile phone",
abstract="Background: The COVID-19 pandemic has highlighted the urgency of addressing an epidemic of obesity and associated inflammatory illnesses. Previous studies have demonstrated that interactions between single-nucleotide polymorphisms (SNPs) and lifestyle interventions such as food and exercise may vary metabolic outcomes, contributing to obesity. However, there is a paucity of research relating outcomes from digital therapeutics to the inclusion of genetic data in care interventions. Objective: This study aims to describe and model the weight loss of participants enrolled in a precision digital weight loss program informed by the machine learning analysis of their data, including genomic data. It was hypothesized that weight loss models would exhibit a better fit when incorporating genomic data versus demographic and engagement variables alone. Methods: A cohort of 393 participants enrolled in Digbi Health's personalized digital care program for 120 days was analyzed retrospectively. The care protocol used participant data to inform precision coaching by mobile app and personal coach. Linear regression models were fit of weight loss (pounds lost and percentage lost) as a function of demographic and behavioral engagement variables. Genomic-enhanced models were built by adding 197 SNPs from participant genomic data as predictors and refitted using Lasso regression on SNPs for variable selection. Success or failure logistic regression models were also fit with and without genomic data. Results: Overall, 72.0\% (n=283) of the 393 participants in this cohort lost weight, whereas 17.3\% (n=68) maintained stable weight. A total of 142 participants lost 5\% bodyweight within 120 days. Models described the impact of demographic and clinical factors, behavioral engagement, and genomic risk on weight loss. Incorporating genomic predictors improved the mean squared error of weight loss models (pounds lost and percent) from 70 to 60 and 16 to 13, respectively. The logistic model improved the pseudo R2 value from 0.193 to 0.285. Gender, engagement, and specific SNPs were significantly associated with weight loss. SNPs within genes involved in metabolic pathways processing food and regulating fat storage were associated with weight loss in this cohort: rs17300539\_G (insulin resistance and monounsaturated fat metabolism), rs2016520\_C (BMI, waist circumference, and cholesterol metabolism), and rs4074995\_A (calcium-potassium transport and serum calcium levels). The models described greater average weight loss for participants with more risk alleles. Notably, coaching for dietary modification was personalized to these genetic risks. Conclusions: Including genomic information when modeling outcomes of a digital precision weight loss program greatly enhanced the model accuracy. Interpretable weight loss models indicated the efficacy of coaching informed by participants' genomic risk, accompanied by active engagement of participants in their own success. Although large-scale validation is needed, our study preliminarily supports precision dietary interventions for weight loss using genetic risk, with digitally delivered recommendations alongside health coaching to improve intervention efficacy. ",
doi="10.2196/25401",
url="https://www.jmir.org/2021/5/e25401",
url="http://www.ncbi.nlm.nih.gov/pubmed/33849843"
}


@Article{info:doi/10.2196/24754,
author="Wang, Haishuai
and Avillach, Paul",
title="Retracted: Diagnostic Classification and Prognostic Prediction Using Common Genetic Variants in Autism Spectrum Disorder: Genotype-Based Deep Learning",
journal="JMIR Med Inform",
year="2021",
month="Apr",
day="7",
volume="9",
number="4",
pages="e24754",
keywords="deep learning",
keywords="autism spectrum disorder",
keywords="common genetic variants, diagnostic classification",
abstract="Background: In the United States, about 3 million people have autism spectrum disorder (ASD), and around 1 out of 59 children are diagnosed with ASD. People with ASD have characteristic social communication deficits and repetitive behaviors. The causes of this disorder remain unknown; however, in up to 25\% of cases, a genetic cause can be identified. Detecting ASD as early as possible is desirable because early detection of ASD enables timely interventions in children with ASD. Identification of ASD based on objective pathogenic mutation screening is the major first step toward early intervention and effective treatment of affected children. Objective: Recent investigation interrogated genomics data for detecting and treating autism disorders, in addition to the conventional clinical interview as a diagnostic test. Since deep neural networks perform better than shallow machine learning models on complex and high-dimensional data, in this study, we sought to apply deep learning to genetic data obtained across thousands of simplex families at risk for ASD to identify contributory mutations and to create an advanced diagnostic classifier for autism screening. Methods: After preprocessing the genomics data from the Simons Simplex Collection, we extracted top ranking common variants that may be protective or pathogenic for autism based on a chi-square test. A convolutional neural network--based diagnostic classifier was then designed using the identified significant common variants to predict autism. The performance was then compared with shallow machine learning--based classifiers and randomly selected common variants. Results: The selected contributory common variants were significantly enriched in chromosome X while chromosome Y was also discriminatory in determining the identification of autistic individuals from nonautistic individuals. The ARSD, MAGEB16, and MXRA5 genes had the largest effect in the contributory variants. Thus, screening algorithms were adapted to include these common variants. The deep learning model yielded an area under the receiver operating characteristic curve of 0.955 and an accuracy of 88\% for identifying autistic individuals from nonautistic individuals. Our classifier demonstrated a considerable improvement of {\textasciitilde}13\% in terms of classification accuracy compared to standard autism screening tools. Conclusions: Common variants are informative for autism identification. Our findings also suggest that the deep learning process is a reliable method for distinguishing the diseased group from the control group based on the common variants of autism. ",
doi="10.2196/24754",
url="https://medinform.jmir.org/2021/4/e24754",
url="http://www.ncbi.nlm.nih.gov/pubmed/33714937"
}


@Article{info:doi/10.2196/21023,
author="Li, Jianqiao
and Hojlo, A. Margaret
and Chennuri, Sampath
and Gujral, Nitin
and Paterson, L. Heather
and Shefchek, A. Kent
and Genetti, A. Casie
and Cohn, L. Emily
and Sewalk, C. Kara
and Garvey, A. Emily
and Buttermore, D. Elizabeth
and Anderson, C. Nickesha
and Beggs, H. Alan
and Agrawal, B. Pankaj
and Brownstein, S. John
and Haendel, A. Melissa
and Holm, A. Ingrid
and Gonzalez-Heydrich, Joseph
and Brownstein, A. Catherine",
title="Underrepresentation of Phenotypic Variability of 16p13.11 Microduplication Syndrome Assessed With an Online Self-Phenotyping Tool (Phenotypr): Cohort Study",
journal="J Med Internet Res",
year="2021",
month="Mar",
day="16",
volume="23",
number="3",
pages="e21023",
keywords="self-phenotyping",
keywords="16p13.11 microduplication syndrome",
keywords="copy number variation",
keywords="genetics",
keywords="incomplete penetrance",
keywords="phenotype",
keywords="variable presentation",
keywords="human phenotype ontology",
keywords="online survey",
keywords="digital health",
abstract="Background: 16p13.11 microduplication syndrome has a variable presentation and is characterized primarily by neurodevelopmental and physical phenotypes resulting from copy number variation at chromosome 16p13.11. Given its variability, there may be features that have not yet been reported. The goal of this study was to use a patient ``self-phenotyping'' survey to collect data directly from patients to further characterize the phenotypes of 16p13.11 microduplication syndrome. Objective: This study aimed to (1) discover self-identified phenotypes in 16p13.11 microduplication syndrome that have been underrepresented in the scientific literature and (2) demonstrate that self-phenotyping tools are valuable sources of data for the medical and scientific communities. Methods: As part of a large study to compare and evaluate patient self-phenotyping surveys, an online survey tool, Phenotypr, was developed for patients with rare disorders to self-report phenotypes. Participants with 16p13.11 microduplication syndrome were recruited through the Boston Children's Hospital 16p13.11 Registry. Either the caregiver, parent, or legal guardian of an affected child or the affected person (if aged 18 years or above) completed the survey. Results were securely transferred to a Research Electronic Data Capture database and aggregated for analysis. Results: A total of 19 participants enrolled in the study. Notably, among the 19 participants, aggression and anxiety were mentioned by 3 (16\%) and 4 (21\%) participants, respectively, which is an increase over the numbers in previously published literature. Additionally, among the 19 participants, 3 (16\%) had asthma and 2 (11\%) had other immunological disorders, both of which have not been previously described in the syndrome. Conclusions: Several phenotypes might be underrepresented in the previous 16p13.11 microduplication literature, and new possible phenotypes have been identified. Whenever possible, patients should continue to be referenced as a source of complete phenotyping data on their condition. Self-phenotyping may lead to a better understanding of the prevalence of phenotypes in genetic disorders and may identify previously unreported phenotypes. ",
doi="10.2196/21023",
url="https://www.jmir.org/2021/3/e21023",
url="http://www.ncbi.nlm.nih.gov/pubmed/33724192"
}


@Article{info:doi/10.2196/23523,
author="Raspa, Melissa
and Moultrie, Rebecca
and Toth, Danielle
and Haque, Naim Saira",
title="Barriers and Facilitators to Genetic Service Delivery Models: Scoping Review",
journal="Interact J Med Res",
year="2021",
month="Feb",
day="25",
volume="10",
number="1",
pages="e23523",
keywords="genetics",
keywords="telehealth",
keywords="genetic services",
keywords="rare diseases",
abstract="Background: Advances in diagnostics testing and treatment of genetic conditions have led to increased demand for genetic services in the United States. At the same time, there is a shortage of genetic services professionals. Thus, understanding the models of service delivery currently in use can help increase access and improve outcomes for individuals identified with genetic conditions. Objective: This review aims to provide an overview of barriers and facilitators to genetic service delivery models to inform future service delivery. Methods: We conducted a scoping literature review of the evidence to more fully understand barriers and facilitators around the provision of genetic services. Results: There were a number of challenges identified, including the limited number of genetics specialists, wait time for appointments, delivery of services by nongenetics providers, reimbursement, and licensure. The ways to address these challenges include the use of health information technology such as telehealth, group genetic counseling, provider-to-provider education, partnership models, and training; expanding genetic provider types; and embedding genetic counselors in clinical settings. Conclusions: The literature review highlighted the need to expand access to genetic services. Ways to expand services include telehealth, technical assistance, and changing staffing models. In addition, using technology to improve knowledge among related professionals can help expand access. ",
doi="10.2196/23523",
url="https://www.i-jmr.org/2021/1/e23523",
url="http://www.ncbi.nlm.nih.gov/pubmed/33629958"
}


@Article{info:doi/10.2196/21787,
author="Myers, Madeleine
and Bloss, Cinnamon",
title="The Need for Education and Clinical Best Practice Guidelines in the Era of Direct-to-Consumer Genomic Testing",
journal="JMIR Med Educ",
year="2020",
month="Dec",
day="8",
volume="6",
number="2",
pages="e21787",
keywords="personal genome testing",
keywords="direct-to-consumer",
keywords="primary care",
keywords="patient-physician relationship",
keywords="medical education",
doi="10.2196/21787",
url="http://mededu.jmir.org/2020/2/e21787/",
url="http://www.ncbi.nlm.nih.gov/pubmed/33289492"
}


@Article{info:doi/10.2196/23596,
author="Rubanovich, Kseniya Caryn
and Zhang, Wendy
and Bloss, S. Cinnamon",
title="Direct-to-Consumer Genetic Ancestry Testing in Clinical Encounters: Perspectives From Psychotherapy Cases",
journal="JMIR Ment Health",
year="2020",
month="Nov",
day="26",
volume="7",
number="11",
pages="e23596",
keywords="direct-to-consumer",
keywords="genetic ancestry testing",
keywords="therapeutic alliance",
keywords="psychotherapy",
doi="10.2196/23596",
url="http://mental.jmir.org/2020/11/e23596/",
url="http://www.ncbi.nlm.nih.gov/pubmed/33242016"
}


@Article{info:doi/10.2196/19040,
author="Mendoza-Alvarez, Alejandro
and Mu{\~n}oz-Barrera, Adri{\'a}n
and Rubio-Rodr{\'i}guez, Alberto Luis
and Marcelino-Rodriguez, Itahisa
and Corrales, Almudena
and I{\~n}igo-Campos, Antonio
and Callero, Ariel
and Perez-Rodriguez, Eva
and Garcia-Robaina, Carlos Jose
and Gonz{\'a}lez-Montelongo, Rafaela
and Lorenzo-Salazar, Miguel Jose
and Flores, Carlos",
title="Interactive Web-Based Resource for Annotation of Genetic Variants Causing Hereditary Angioedema (HADA): Database Development, Implementation, and Validation",
journal="J Med Internet Res",
year="2020",
month="Oct",
day="9",
volume="22",
number="10",
pages="e19040",
keywords="genetic cause",
keywords="hereditary angioedema",
keywords="knowledge database",
keywords="precision medicine",
keywords="variant interpretation",
abstract="Background: Hereditary angioedema is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, leading to an increased bradykinin plasma concentration. Hereditary angioedema is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, first-line genetic screening is not integrated in routine diagnosis. Consequently, a delay in the diagnosis, and inaccurate or incomplete diagnosis and treatment of hereditary angioedema are common. Objective: In agreement with recent recommendations from the International Consensus on the Use of Genetics in the Management of Hereditary Angioedema, to facilitate the clinical diagnosis and adapt it to the paradigm of precision medicine and next-generation sequencing--based genetic tests, we aimed to develop a genetic annotation tool, termed Hereditary Angioedema Database Annotation (HADA). Methods: HADA is built on top of a database of known variants affecting function, including precomputed pathogenic assessment of each variant and a ranked classification according to the current guidelines from the American College of Medical Genetics and Genomics. Results: HADA is provided as a freely accessible, user-friendly web-based interface with versatility for the entry of genetic information. The underlying database can also be incorporated into automated command-line stand-alone annotation tools. Conclusions: HADA can achieve the rapid detection of variants affecting function for different hereditary angioedema types, and further integrates useful information to reduce the diagnosis odyssey and improve its delay. ",
doi="10.2196/19040",
url="http://www.jmir.org/2020/10/e19040/",
url="http://www.ncbi.nlm.nih.gov/pubmed/33034563"
}


@Article{info:doi/10.2196/18044,
author="Cahan, M. Eli
and Khatri, Purvesh",
title="Data Heterogeneity: The Enzyme to Catalyze Translational Bioinformatics?",
journal="J Med Internet Res",
year="2020",
month="Aug",
day="12",
volume="22",
number="8",
pages="e18044",
keywords="medical Informatics",
keywords="health equity",
keywords="health care disparities",
keywords="population health",
keywords="quality improvement",
keywords="precision medicine",
doi="10.2196/18044",
url="https://www.jmir.org/2020/8/e18044",
url="http://www.ncbi.nlm.nih.gov/pubmed/32784182"
}


@Article{info:doi/10.2196/18387,
author="Kweon, Solbi
and Lee, Hoon Jeong
and Lee, Younghee
and Park, Rang Yu",
title="Personal Health Information Inference Using Machine Learning on RNA Expression Data from Patients With Cancer: Algorithm Validation Study",
journal="J Med Internet Res",
year="2020",
month="Aug",
day="10",
volume="22",
number="8",
pages="e18387",
keywords="cancer",
keywords="privacy issue",
keywords="personal information",
keywords="prediction",
keywords="RNA sequencing",
keywords="machine learning",
abstract="Background: As the need for sharing genomic data grows, privacy issues and concerns, such as the ethics surrounding data sharing and disclosure of personal information, are raised. Objective: The main purpose of this study was to verify whether genomic data is sufficient to predict a patient's personal information. Methods: RNA expression data and matched patient personal information were collected from 9538 patients in The Cancer Genome Atlas program. Five personal information variables (age, gender, race, cancer type, and cancer stage) were recorded for each patient. Four different machine learning algorithms (support vector machine, decision tree, random forest, and artificial neural network) were used to determine whether a patient's personal information could be accurately predicted from RNA expression data. Performance measurement of the prediction models was based on the accuracy and area under the receiver operating characteristic curve. We selected five cancer types (breast carcinoma, kidney renal clear cell carcinoma, head and neck squamous cell carcinoma, low-grade glioma, and lung adenocarcinoma) with large samples sizes to verify whether predictive accuracy would differ between them. We also validated the efficacy of our four machine learning models in analyzing normal samples from 593 cancer patients. Results: In most samples, personal information with high genetic relevance, such as gender and cancer type, could be predicted from RNA expression data alone. The prediction accuracies for gender and cancer type, which were the best models, were 0.93-0.99 and 0.78-0.94, respectively. Other aspects of personal information, such as age, race, and cancer stage, were difficult to predict from RNA expression data, with accuracies ranging from 0.0026-0.29, 0.76-0.96, and 0.45-0.79, respectively. Among the tested machine learning methods, the highest predictive accuracy was obtained using the support vector machine algorithm (mean accuracy 0.77), while the lowest accuracy was obtained using the random forest method (mean accuracy 0.65). Gender and race were predicted more accurately than other variables in the samples. On average, the accuracy of cancer stage prediction ranged between 0.71-0.67, while the age prediction accuracy ranged between 0.18-0.23 for the five cancer types. Conclusions: We attempted to predict patient information using RNA expression data. We found that some identifiers could be predicted, but most others could not. This study showed that personal information available from RNA expression data is limited and this information cannot be used to identify specific patients. ",
doi="10.2196/18387",
url="https://www.jmir.org/2020/8/e18387",
url="http://www.ncbi.nlm.nih.gov/pubmed/32773372"
}


@Article{info:doi/10.2196/16886,
author="Chuang, Li-Yeh
and Yang, Cheng-San
and Yang, Huai-Shuo
and Yang, Cheng-Hong",
title="Identification of High-Order Single-Nucleotide Polymorphism Barcodes in Breast Cancer Using a Hybrid Taguchi-Genetic Algorithm: Case-Control Study",
journal="JMIR Med Inform",
year="2020",
month="Jun",
day="17",
volume="8",
number="6",
pages="e16886",
keywords="genetic algorithm",
keywords="single-nucleotide polymorphism",
keywords="breast cancer",
keywords="case-control study",
abstract="Background: Breast cancer has a major disease burden in the female population, and it is a highly genome-associated human disease. However, in genetic studies of complex diseases, modern geneticists face challenges in detecting interactions among loci. Objective: This study aimed to investigate whether variations of single-nucleotide polymorphisms (SNPs) are associated with histopathological tumor characteristics in breast cancer patients. Methods: A hybrid Taguchi-genetic algorithm (HTGA) was proposed to identify the high-order SNP barcodes in a breast cancer case-control study. A Taguchi method was used to enhance a genetic algorithm (GA) for identifying high-order SNP barcodes. The Taguchi method was integrated into the GA after the crossover operations in order to optimize the generated offspring systematically for enhancing the GA search ability. Results: The proposed HTGA effectively converged to a promising region within the problem space and provided excellent SNP barcode identification. Regression analysis was used to validate the association between breast cancer and the identified high-order SNP barcodes. The maximum OR was less than 1 (range 0.870-0.755) for two- to seven-order SNP barcodes. Conclusions: We systematically evaluated the interaction effects of 26 SNPs within growth factor--related genes for breast carcinogenesis pathways. The HTGA could successfully identify relevant high-order SNP barcodes by evaluating the differences between cases and controls. The validation results showed that the HTGA can provide better fitness values as compared with other methods for the identification of high-order SNP barcodes using breast cancer case-control data sets. ",
doi="10.2196/16886",
url="https://medinform.jmir.org/2020/6/e16886",
url="http://www.ncbi.nlm.nih.gov/pubmed/32554381"
}


@Article{info:doi/10.2196/16734,
author="Raspa, Melissa
and Moultrie, Rebecca
and Wagner, Laura
and Edwards, Anne
and Andrews, Sara
and Frisch, Katherine Mary
and Turner-Brown, Lauren
and Wheeler, Anne",
title="Ethical, Legal, and Social Issues Related to the Inclusion of Individuals With Intellectual Disabilities in Electronic Health Record Research: Scoping Review",
journal="J Med Internet Res",
year="2020",
month="May",
day="21",
volume="22",
number="5",
pages="e16734",
keywords="electronic health records",
keywords="privacy",
keywords="informed consent",
keywords="intellectual disability",
keywords="genetics",
abstract="Background: Data from electronic health records (EHRs) are increasingly used in the field of genetic research to further precision medicine initiatives. However, many of these efforts exclude individuals with intellectual disabilities, which often stem from genetic conditions. To include this important subpopulation in EHR research, important ethical, legal, and social issues should be considered. Objective: The goal of this study was to review prior research to better understand what ethical, legal, and social issues may need further investigation when considering the research use of EHRs for individuals with genetic conditions that may result in intellectual disability. This information will be valuable in developing methods and best practices for involving this group in research given they are considered a vulnerable population that may need special research protections. Methods: We conducted a scoping review to examine issues related to the use of EHRs for research purposes and those more broadly associated with genetic research. The initial search yielded a total of 460 unique citations. We used an evaluative coding process to determine relevancy for inclusion. Results: This approach resulted in 59 articles in the following areas: informed consent, privacy and security, return of results, and vulnerable populations. The review included several models of garnering informed consent in EHR or genetic research, including tiered or categorical, blanket or general, open, and opt-out models. Second, studies reported on patients' concerns regarding the privacy and security of EHR or genetic data, such as who has access, type of data use in research, identifiability, and risks associated with privacy breach. The literature on return of research results using biospecimens examined the dissension in the field, particularly when sharing individualized genetic results. Finally, work involving vulnerable populations highlighted special considerations when conducting EHR or genetic research. Conclusions: The results frame important questions for researchers to consider when designing EHR studies, which include individuals with intellectual disabilities, including appropriate safeguards and protections. ",
doi="10.2196/16734",
url="http://www.jmir.org/2020/5/e16734/",
url="http://www.ncbi.nlm.nih.gov/pubmed/32436848"
}


@Article{info:doi/10.2196/17507,
author="Knitza, Johannes
and Knevel, Rachel
and Raza, Karim
and Bruce, Tor
and Eimer, Ekaterina
and Gehring, Isabel
and Mathsson-Alm, Linda
and Poorafshar, Maryam
and Hueber, J. Axel
and Schett, Georg
and Johannesson, Martina
and Catrina, Anca
and Klareskog, Lars
and ",
title="Toward Earlier Diagnosis Using Combined eHealth Tools in Rheumatology: The Joint Pain Assessment Scoring Tool (JPAST) Project",
journal="JMIR Mhealth Uhealth",
year="2020",
month="May",
day="15",
volume="8",
number="5",
pages="e17507",
keywords="rheumatology",
keywords="eHealth",
keywords="mHealth",
keywords="symptom-checkers",
keywords="apps",
doi="10.2196/17507",
url="https://mhealth.jmir.org/2020/5/e17507",
url="http://www.ncbi.nlm.nih.gov/pubmed/32348258"
}


@Article{info:doi/10.2196/16084,
author="Pak, Kyoungjune
and Oh, Sae-Ock
and Goh, Sik Tae
and Heo, Jin Hye
and Han, Myoung-Eun
and Jeong, Cheon Dae
and Lee, Chi-Seung
and Sun, Hokeun
and Kang, Junho
and Choi, Suji
and Lee, Soohwan
and Kwon, Jung Eun
and Kang, Wan Ji
and Kim, Hak Yun",
title="A User-Friendly, Web-Based Integrative Tool (ESurv) for Survival Analysis: Development and Validation Study",
journal="J Med Internet Res",
year="2020",
month="May",
day="5",
volume="22",
number="5",
pages="e16084",
keywords="survival analysis",
keywords="grouped variable selection",
keywords="The Cancer Genome Atlas",
keywords="web-based tool",
keywords="user service",
abstract="Background: Prognostic genes or gene signatures have been widely used to predict patient survival and aid in making decisions pertaining to therapeutic actions. Although some web-based survival analysis tools have been developed, they have several limitations. Objective: Taking these limitations into account, we developed ESurv (Easy, Effective, and Excellent Survival analysis tool), a web-based tool that can perform advanced survival analyses using user-derived data or data from The Cancer Genome Atlas (TCGA). Users can conduct univariate analyses and grouped variable selections using multiomics data from TCGA. Methods: We used R to code survival analyses based on multiomics data from TCGA. To perform these analyses, we excluded patients and genes that had insufficient information. Clinical variables were classified as 0 and 1 when there were two categories (for example, chemotherapy: no or yes), and dummy variables were used where features had 3 or more outcomes (for example, with respect to laterality: right, left, or bilateral). Results: Through univariate analyses, ESurv can identify the prognostic significance for single genes using the survival curve (median or optimal cutoff), area under the curve (AUC) with C statistics, and receiver operating characteristics (ROC). Users can obtain prognostic variable signatures based on multiomics data from clinical variables or grouped variable selections (lasso, elastic net regularization, and network-regularized high-dimensional Cox-regression) and select the same outputs as above. In addition, users can create custom gene signatures for specific cancers using various genes of interest. One of the most important functions of ESurv is that users can perform all survival analyses using their own data. Conclusions: Using advanced statistical techniques suitable for high-dimensional data, including genetic data, and integrated survival analysis, ESurv overcomes the limitations of previous web-based tools and will help biomedical researchers easily perform complex survival analyses. ",
doi="10.2196/16084",
url="https://www.jmir.org/2020/5/e16084",
url="http://www.ncbi.nlm.nih.gov/pubmed/32369034"
}


@Article{info:doi/10.2196/16810,
author="Glicksberg, Scott Benjamin
and Burns, Shohei
and Currie, Rob
and Griffin, Ann
and Wang, Jane Zhen
and Haussler, David
and Goldstein, Theodore
and Collisson, Eric",
title="Blockchain-Authenticated Sharing of Genomic and Clinical Outcomes Data of Patients With Cancer: A Prospective Cohort Study",
journal="J Med Internet Res",
year="2020",
month="Mar",
day="20",
volume="22",
number="3",
pages="e16810",
keywords="data sharing",
keywords="electronic health records",
keywords="genomics",
keywords="medicine",
keywords="blockchain",
keywords="neoplasms",
abstract="Background: Efficiently sharing health data produced during standard care could dramatically accelerate progress in cancer treatments, but various barriers make this difficult. Not sharing these data to ensure patient privacy is at the cost of little to no learning from real-world data produced during cancer care. Furthermore, recent research has demonstrated a willingness of patients with cancer to share their treatment experiences to fuel research, despite potential risks to privacy. Objective: The objective of this study was to design, pilot, and release a decentralized, scalable, efficient, economical, and secure strategy for the dissemination of deidentified clinical and genomic data with a focus on late-stage cancer. Methods: We created and piloted a blockchain-authenticated system to enable secure sharing of deidentified patient data derived from standard of care imaging, genomic testing, and electronic health records (EHRs), called the Cancer Gene Trust (CGT). We prospectively consented and collected data for a pilot cohort (N=18), which we uploaded to the CGT. EHR data were extracted from both a hospital cancer registry and a common data model (CDM) format to identify optimal data extraction and dissemination practices. Specifically, we scored and compared the level of completeness between two EHR data extraction formats against the gold standard source documentation for patients with available data (n=17). Results: Although the total completeness scores were greater for the registry reports than those for the CDM, this difference was not statistically significant. We did find that some specific data fields, such as histology site, were better captured using the registry reports, which can be used to improve the continually adapting CDM. In terms of the overall pilot study, we found that CGT enables rapid integration of real-world data of patients with cancer in a more clinically useful time frame. We also developed an open-source Web application to allow users to seamlessly search, browse, explore, and download CGT data. Conclusions: Our pilot demonstrates the willingness of patients with cancer to participate in data sharing and how blockchain-enabled structures can maintain relationships between individual data elements while preserving patient privacy, empowering findings by third-party researchers and clinicians. We demonstrate the feasibility of CGT as a framework to share health data trapped in silos to further cancer research. Further studies to optimize data representation, stream, and integrity are required. ",
doi="10.2196/16810",
url="http://www.jmir.org/2020/3/e16810/",
url="http://www.ncbi.nlm.nih.gov/pubmed/32196460"
}


@Article{info:doi/10.2196/14890,
author="Thiebes, Scott
and Toussaint, A. Philipp
and Ju, Jaehyeon
and Ahn, Jae-Hyeon
and Lyytinen, Kalle
and Sunyaev, Ali",
title="Valuable Genomes: Taxonomy and Archetypes of Business Models in Direct-to-Consumer Genetic Testing",
journal="J Med Internet Res",
year="2020",
month="Jan",
day="21",
volume="22",
number="1",
pages="e14890",
keywords="genomics",
keywords="genetic testing",
keywords="genetic privacy",
keywords="direct-to-consumer screening and testing",
keywords="taxonomy",
keywords="cluster analysis",
abstract="Background: Recent progress in genome data collection and analysis technologies has led to a surge of direct-to-consumer (DTC) genetic testing services. Owing to the clinical value and sensitivity of genomic data, as well as uncertainty and hearsay surrounding business practices of DTC genetic testing service providers, DTC genetic testing has faced significant criticism by researchers and practitioners. Research in this area has centered on ethical and legal implications of providing genetic tests directly to consumers, but we still lack a more profound understanding of how businesses in the DTC genetic testing markets work and provide value to different stakeholders. Objective: The aim of this study was to address the lack of knowledge concerning business models of DTC genetic testing services by systematically identifying the salient properties of various DTC genetic testing service business models as well as discerning dominant business models in the market. Methods: We employed a 3-phased research approach. In phase 1, we set up a database of 277 DTC genetic testing services. In phase 2, we drew on these data as well as conceptual models of DTC genetic testing services and iteratively developed a taxonomy of DTC genetic testing service business models. In phase 3, we used a 2-stage clustering method to cluster the 277 services that we identified during phase 1 and derived 6 dominant archetypes of DTC genetic testing service business models. Results: The contributions of this research are 2-fold. First, we provided a first of its kind, systematically developed taxonomy of DTC genetic testing service business models consisting of 15 dimensions in 4 categories. Each dimension comprises 2 to 5 characteristics and captures relevant aspects of DTC genetic testing service business models. Second, we derived 6 archetypes of DTC genetic testing service business models named as follows: (1) low-cost DTC genomics for enthusiasts, (2) high-privacy DTC genomics for enthusiasts, (3) specific information tests, (4) simple health tests, (5) basic low-value DTC genomics, and (6) comprehensive tests and low data processing. Conclusions: Our analysis paints a much more complex business landscape in the DTC genetic testing market than previously anticipated. This calls for further research on business models and their effects that underlie DTC genetic testing services and invites specific regulatory interventions to protect consumers and level the playing field. ",
doi="10.2196/14890",
url="https://www.jmir.org/2020/1/e14890",
url="http://www.ncbi.nlm.nih.gov/pubmed/31961329"
}


@Article{info:doi/10.2196/12980,
author="Cahill, J. Tiernan
and Wertz, Blake
and Zhong, Qiankun
and Parlato, Andrew
and Donegan, John
and Forman, Rebecca
and Manot, Supriya
and Wu, Tianyi
and Xu, Yazhu
and Cummings, J. James
and Norkunas Cunningham, Tricia
and Wang, Catharine",
title="The Search for Consumers of Web-Based Raw DNA Interpretation Services: Using Social Media to Target Hard-to-Reach Populations",
journal="J Med Internet Res",
year="2019",
month="Jul",
day="30",
volume="21",
number="7",
pages="e12980",
keywords="research subject recruitment",
keywords="social media",
keywords="survey methods",
keywords="data collection methods",
keywords="advertising as topic",
keywords="algorithms",
abstract="Background: In recent years, there has been a proliferation of third-party Web-based services available to consumers to interpret raw DNA from direct-to-consumer genetic testing companies. Little is known about who uses these services and the downstream health implications. Identifying this hard-to-reach population of consumers for research raised questions about the most effective recruitment methods to undertake. Past studies have found that Web-based social media survey distribution can be cost-effective for targeting hard-to-reach populations, yet comparative efficacy information across platforms is limited. Objective: The aim of this study was to identify the most effective Web-based strategies to identify and recruit the target population of direct-to-consumer genetic testing users who also made use of third-party interpretation services to analyze their raw genetic data. Web-based survey recruitment methods varying by social media platform and advertising method were compared in terms of cost-effectiveness and demographics of survey respondents. Methods: A total of 5 Web-based survey distribution conditions were examined: 4 paid advertising services and 1 unpaid service. For the paid services, a 2x2 quasi-experimental design compared social media platforms (Facebook vs Twitter) and advertising tracking metrics (by click vs by conversion). The fifth unpaid comparison method consisted of study postings on the social media platform, Reddit, without any paid advertising. Links to identical Web-based versions of the study questionnaire were posted for 10 to 14 days for each of the distribution conditions, which allowed tracking the number of respondents that entered and completed the questionnaire by distribution condition. Results: In total, 438 individuals were recruited to the study through all conditions. A nearly equivalent number of participants were recruited from paid campaigns on Facebook (n=159) and Twitter (n=167), with a smaller sample recruited on Reddit (n=112). Significantly more participants were recruited through conversion-tracking (n=222) than through click-tracking campaigns (n=104; Z=6.5, P<.001). Response rates were found to be partially driven by organic sharing of recruitment materials among social media users. Conversion tracking was more cost-effective than click tracking across paid social media platforms. Significant differences in terms of gender and age distributions were noted between the platforms and between the tracking metrics. Conclusions: Web-based recruitment methods were effective at recruiting participants from a hard-to-reach population in a short time frame. There were significant differences in the effectiveness of various paid advertising techniques. Recruitment through Web-based communities also appeared to perform adequately, yet it may be limited by the number of users accessible in open community groups. Future research should evaluate the impact of organic sharing of recruitment materials because this appeared to play a substantial role in the observed effectiveness of different methods. ",
doi="10.2196/12980",
url="http://www.jmir.org/2019/7/e12980/",
url="http://www.ncbi.nlm.nih.gov/pubmed/31364607"
}


@Article{info:doi/10.2196/13043,
author="McPadden, Jacob
and Durant, JS Thomas
and Bunch, R. Dustin
and Coppi, Andreas
and Price, Nathaniel
and Rodgerson, Kris
and Torre Jr, J. Charles
and Byron, William
and Hsiao, L. Allen
and Krumholz, M. Harlan
and Schulz, L. Wade",
title="Health Care and Precision Medicine Research: Analysis of a Scalable Data Science Platform",
journal="J Med Internet Res",
year="2019",
month="Apr",
day="09",
volume="21",
number="4",
pages="e13043",
keywords="data science",
keywords="monitoring, physiologic",
keywords="computational health care",
keywords="medical informatics computing",
keywords="big data",
abstract="Background: Health care data are increasing in volume and complexity. Storing and analyzing these data to implement precision medicine initiatives and data-driven research has exceeded the capabilities of traditional computer systems. Modern big data platforms must be adapted to the specific demands of health care and designed for scalability and growth. Objective: The objectives of our study were to (1) demonstrate the implementation of a data science platform built on open source technology within a large, academic health care system and (2) describe 2 computational health care applications built on such a platform. Methods: We deployed a data science platform based on several open source technologies to support real-time, big data workloads. We developed data-acquisition workflows for Apache Storm and NiFi in Java and Python to capture patient monitoring and laboratory data for downstream analytics. Results: Emerging data management approaches, along with open source technologies such as Hadoop, can be used to create integrated data lakes to store large, real-time datasets. This infrastructure also provides a robust analytics platform where health care and biomedical research data can be analyzed in near real time for precision medicine and computational health care use cases. Conclusions: The implementation and use of integrated data science platforms offer organizations the opportunity to combine traditional datasets, including data from the electronic health record, with emerging big data sources, such as continuous patient monitoring and real-time laboratory results. These platforms can enable cost-effective and scalable analytics for the information that will be key to the delivery of precision medicine initiatives. Organizations that can take advantage of the technical advances found in data science platforms will have the opportunity to provide comprehensive access to health care data for computational health care and precision medicine research. ",
doi="10.2196/13043",
url="https://www.jmir.org/2019/4/e13043/",
url="http://www.ncbi.nlm.nih.gov/pubmed/30964441"
}


@Article{info:doi/10.2196/10297,
author="Westendorf, Lauren
and Shaer, Orit
and Pollalis, Christina
and Verish, Clarissa
and Nov, Oded
and Ball, Price Mad",
title="Exploring Genetic Data Across Individuals: Design and Evaluation of a Novel Comparative Report Tool",
journal="J Med Internet Res",
year="2018",
month="Sep",
day="24",
volume="20",
number="9",
pages="e10297",
keywords="genomics",
keywords="consumer health informatics",
abstract="Background: The growth in the availability of personal genomic data to nonexperts poses multiple challenges to human-computer interaction research; data are highly sensitive, complex, and have health implications for individuals and families. However, there has been little research on how nonexpert users explore their genomic data. Objective: We focus on how to support nonexperts in exploring and comparing their own personal genomic report with those of other people. We designed and evaluated CrossGenomics, a novel tool for comparing personal genetic reports, which enables exploration of shared and unshared genetic variants. Focusing on communicating comparative impact, rarity, and certainty, we evaluated alternative novel interactive prototypes. Methods: We conducted 3 user studies. The first focuses on assessing the usability and understandability of a prototype that facilitates the comparison of reports from 2 family members. Following a design iteration, we studied how various prototypes support the comparison of genetic reports of a 4-person family. Finally, we evaluated the needs of early adopters---people who share their genetic reports publicly for comparing their genetic reports with that of others. Results: In the first study, sunburst- and Venn-based comparisons of two genomes led to significantly higher domain comprehension, compared with the linear comparison and with the commonly used tabular format. However, results show gaps between objective and subjective comprehension, as sunburst users reported significantly lower perceived understanding and higher levels of confusion than the users of the tabular report. In the second study, users who were allowed to switch between the different comparison views presented higher comprehension levels, as well as more complex reasoning than users who were limited to a single comparison view. In the third study, 35\% (17/49) reported learning something new from comparing their own data with another person's data. Users indicated that filtering and toggling between comparison views were the most useful features. Conclusions: Our findings (1) highlight features and visualizations that show strengths in facilitating user comprehension of genomic data, (2) demonstrate the value of affording users the flexibility to examine the same report using multiple views, and (3) emphasize users' needs in comparison of genomic data. We conclude with design implications for engaging nonexperts with complex multidimensional genomic data. ",
doi="10.2196/10297",
url="http://www.jmir.org/2018/9/e10297/",
url="http://www.ncbi.nlm.nih.gov/pubmed/30249582"
}


@Article{info:doi/10.2196/ijmr.5199,
author="Collins, Heather
and Calvo, Sherri
and Greenberg, Kathleen
and Forman Neall, Lisa
and Morrison, Stephanie",
title="Information Needs in the Precision Medicine Era: How Genetics Home Reference Can Help",
journal="Interact J Med Res",
year="2016",
month="Apr",
day="27",
volume="5",
number="2",
pages="e13",
keywords="individualized medicine",
keywords="patient education as topic",
keywords="databases, genetic",
keywords="health resources",
doi="10.2196/ijmr.5199",
url="http://www.i-jmr.org/2016/2/e13/",
url="http://www.ncbi.nlm.nih.gov/pubmed/27122232"
}