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Abstract Objectives This study aims to develop an innovative approach for monitoring and assessing labor pain through ECG waveform analysis, utilizing machine learning techniques to monitor pain resulting from uterine contractions. Methods The study was conducted at National Taiwan University Hospital between January and July 2020. We collected a dataset of 6010 ECG samples from women preparing for natural spontaneous delivery (NSD). The ECG data was used to develop an ECG waveform-based Nociception Monitoring Index (NoM). The dataset was divided into training (80%) and validation (20%) sets. Multiple machine learning models, including LightGBM, XGBoost, SnapLogisticRegression, and SnapDecisionTree, were developed and evaluated. Hyperparameter optimization was performed using grid search and five-fold cross-validation to enhance model performance. Results The LightGBM model demonstrated superior performance with an AUC of 0.96 and an accuracy of 90%, making it the optimal model for monitoring labor pain based on ECG data. Other models, such as XGBoost and SnapLogisticRegression, also showed strong performance, with AUC values ranging from 0.88 to 0.95. Conclusions This study demonstrates that the integration of machine learning algorithms with ECG data significantly enhances the accuracy and reliability of labor pain monitoring. Specifically, the LightGBM model exhibits exceptional precision and robustness in continuous pain monitoring during labor, with potential applicability extending to broader healthcare settings. Trial registration ClinicalTrials.gov Identifier: NCT04461704.

Abstract Genome-wide association studies (GWAS) have revolutionized our understanding of the genetic architecture of complex traits and diseases. GWAS summary statistics have become essential tools for various genetic analyses, including meta-analysis, fine-mapping, and risk prediction. However, the increasing number of GWAS summary statistics and the diversity of software tools available for their analysis can make it challenging for researchers to select the most appropriate tools for their specific needs. This systematic review aims to provide a comprehensive overview of the currently available software tools and databases for GWAS summary statistics analysis. We conducted a comprehensive literature search to identify relevant software tools and databases. We categorized the tools and databases by their functionality, including data management, quality control, single-trait analysis, and multiple-trait analysis. We also compared the tools and databases based on their features, limitations, and user-friendliness. Our review identified a total of 305 functioning software tools and databases dedicated to GWAS summary statistics, each with unique strengths and limitations. We provide descriptions of the key features of each tool and database, including their input/output formats, data types, and computational requirements. We also discuss the overall usability and applicability of each tool for different research scenarios. This comprehensive review will serve as a valuable resource for researchers who are interested in using GWAS summary statistics to investigate the genetic basis of complex traits and diseases. By providing a detailed overview of the available tools and databases, we aim to facilitate informed tool selection and maximize the effectiveness of GWAS summary statistics analysis.

Abstract Objective Data imbalance is a pervasive issue in medical data mining, often leading to biased and unreliable predictive models. This study aims to address the urgent need for effective strategies to mitigate the impact of data imbalance on classification models. We focus on quantifying the effects of different imbalance degrees and sample sizes on model performance, identifying optimal cut-off values, and evaluating the efficacy of various methods to enhance model accuracy in highly imbalanced and small sample size scenarios. Methods We collected medical records of patients receiving assisted reproductive treatment in a reproductive medicine center. Random forest was used to screen the key variables for the prediction target. Various datasets with different imbalance degrees and sample sizes were constructed to compare the classification performance of logistic regression models. Metrics such as AUC, G-mean, F1-Score, Accuracy, Recall, and Precision were used for evaluation. Four imbalance treatment methods (SMOTE, ADASYN, OSS, and CNN) were applied to datasets with low positive rates and small sample sizes to assess their effectiveness. Results The logistic model’s performance was low when the positive rate was below 10% but stabilized beyond this threshold. Similarly, sample sizes below 1200 yielded poor results, with improvement seen above this threshold. For robustness, the optimal cut-offs for positive rate and sample size were identified as 15% and 1500, respectively. SMOTE and ADASYN oversampling significantly improved classification performance in datasets with low positive rates and small sample sizes. Conclusions The study identifies a positive rate of 15% and a sample size of 1500 as optimal cut-offs for stable logistic model performance. For datasets with low positive rates and small sample sizes, SMOTE and ADASYN are recommended to improve balance and model accuracy.

Abstract Pangenomics is a relatively new scientific field which investigates the union of all the genomes of a clade. The word pan means everything in ancient Greek; the term pangenomics originally regarded genomes of bacteria and was later intended to refer to human genomes as well. Modern bioinformatics offers several tools to analyze pangenomics data, paving the way to an emerging field that we can call computational pangenomics. Current computational power available for the bioinformatics community has made computational pangenomic analyses easy to perform, but this higher accessibility to pangenomics analysis also increases the chances to make mistakes and to produce misleading or inflated results, especially by beginners. To handle this problem, we present here a few quick tips for efficient and correct computational pangenomic analyses with a focus on bacterial pangenomics, by describing common mistakes to avoid and experienced best practices to follow in this field. We believe our recommendations can help the readers perform more robust and sound pangenomic analyses and to generate more reliable results.

Abstract Background Identifying critical genes is important for understanding the pathogenesis of complex diseases. Traditional studies typically comparing the change of biomecules between normal and disease samples or detecting important vertices from a single static biomolecular network, which often overlook the dynamic changes that occur between different disease stages. However, investigating temporal changes in biomolecular networks and identifying critical genes is critical for understanding the occurrence and development of diseases. Methods A novel method called Quantifying Importance of Genes with Tensor Decomposition (QIGTD) was proposed in this study. It first constructs a time series network by integrating both the intra and inter temporal network information, which preserving connections between networks at adjacent stages according to the local similarities. A tensor is employed to describe the connections of this time series network, and a 3-order tensor decomposition method was proposed to capture both the topological information of each network snapshot and the time series characteristics of the whole network. QIGTD is also a learning-free and efficient method that can be applied to datasets with a small number of samples. Results The effectiveness of QIGTD was evaluated using lung adenocarcinoma (LUAD) datasets and three state-of-the-art methods: T-degree, T-closeness, and T-betweenness were employed as benchmark methods. Numerical experimental results demonstrate that QIGTD outperforms these methods in terms of the indices of both precision and mAP. Notably, out of the top 50 genes, 29 have been verified to be highly related to LUAD according to the DisGeNET Database, and 36 are significantly enriched in LUAD related Gene Ontology (GO) terms, including nuclear division, mitotic nuclear division, chromosome segregation, organelle fission, and mitotic sister chromatid segregation. Conclusion In conclusion, QIGTD effectively captures the temporal changes in gene networks and identifies critical genes. It provides a valuable tool for studying temporal dynamics in biological networks and can aid in understanding the underlying mechanisms of diseases such as LUAD.

Abstract The Covid-19 pandemic, caused by the SARS-Cov2- virus, has transformed our lives. To combat the spread of the infection, remote work has become a widespread practice. However, this shift has led to various work-related problems, including prolonged working hours, mental health issues, and communication difficulties. One particular challenge faced by team members is the inability to accurately gauge the work engagement (WE) levels of subordinates, such as their absorption, dedication, and vigor, due to the limited number of in-person interactions that occur in remote work settings. To address this issue, online communication systems utilizing text-based chat tools such as Slack and Microsoft Teams have gained popularity as substitutes for face-to-face communication. In this paper, we propose a novel approach that uses graph neural networks (GNNs) to estimate the work engagement levels (WELs) of users on text-based chat platforms. Specifically, our method involves embedding users in a feature space based solely on the structural information of the utilized communication network, without considering the contents of the conversations that take place. We conduct two studies using Slack data to evaluate our proposal. The first study reveals that the properties of communication networks play a more significant role when estimating WELs than do conversation contents. Building upon this result, the second study involves the development of a machine learning model that estimates WELs using only the architectural features of the employed communication network. In this network representation, each node corresponds to a human user, and edges represent communication logs; i.e., if person A talks to person B, the edge between node A and node B is stretched. Notably, our model achieves a correlation coefficient of 0.60 between the observed and predicted WEL values. Importantly, our proposed approach relies solely on communication network data and does not require linguistic information. This makes it particularly valuable for real-world business situations.

Abstract There are examples of how unconscious bias can influence actions of people. In the judiciary, however, despite some examples there is no general theory on whether different demographic attributes such as gender, seniority or ethnicity affect case sentencing. We aim to gain insight into this issue by analyzing over 100k decisions of three different areas of law with the goal of understanding whether judge identity or judge attributes such as gender and seniority can be inferred from decision documents. We find that stylistic features of decisions are predictive of judge identities, their gender and their seniority, a finding that is aligned with results from analysis of written texts outside the judiciary. Surprisingly, we find that features based on legislation cited are also predictive of judge identities and attributes. While own content reuse by judges can explain our ability to predict judge identities, no specific reduced set of features can explain the differences we find in the legislation cited of decisions when we group judges by gender or seniority. Our findings open the door for further research on how these differences translate into how judges apply the law and, ultimately, to promote a more transparent and fair judiciary system.

Abstract Background Data quality in health information systems has a complex structure and consists of several dimensions. This research conducted for identify Common data quality elements for health information systems. Methods A literature review was conducted and search strategies run in Web of Knowledge, Science Direct, Emerald, PubMed, Scopus and Google Scholar search engine as an additional source for tracing references. We found 760 papers, excluded 314 duplicates, 339 on abstract review and 167 on full-text review; leaving 58 papers for critical appraisal. Results Current review shown that 14 criteria are categorized as the main dimensions for data quality for health information system include: Accuracy, Consistency, Security, Timeliness, Completeness, Reliability, Accessibility, Objectivity, Relevancy, Understandability, Navigation, Reputation, Efficiency and Value- added. Accuracy, Completeness, and Timeliness, were the three most-used dimensions in literature. Conclusions At present, there is a lack of uniformity and potential applicability in the dimensions employed to evaluate the data quality of health information system. Typically, different approaches (qualitative, quantitative and mixed methods) were utilized to evaluate data quality for health information system in the publications that were reviewed. Consequently, due to the inconsistency in defining dimensions and assessing methods, it became imperative to categorize the dimensions of data quality into a limited set of primary dimensions.

Abstract Background Artificial intelligence (AI) is increasingly used for prevention, diagnosis, monitoring, and treatment of cardiovascular diseases. Despite the potential for AI to improve care, ethical concerns and mistrust in AI-enabled healthcare exist among the public and medical community. Given the rapid and transformative recent growth of AI in cardiovascular care, to inform practice guidelines and regulatory policies that facilitate ethical and trustworthy use of AI in medicine, we conducted a literature review to identify key ethical and trust barriers and facilitators from patients’ and healthcare providers’ perspectives when using AI in cardiovascular care. Methods In this rapid literature review, we searched six bibliographic databases to identify publications discussing transparency, trust, or ethical concerns (outcomes of interest) associated with AI-based medical devices (interventions of interest) in the context of cardiovascular care from patients’, caregivers’, or healthcare providers’ perspectives. The search was completed on May 24, 2022 and was not limited by date or study design. Results After reviewing 7,925 papers from six databases and 3,603 papers identified through citation chasing, 145 articles were included. Key ethical concerns included privacy, security, or confidentiality issues (n = 59, 40.7%); risk of healthcare inequity or disparity (n = 36, 24.8%); risk of patient harm (n = 24, 16.6%); accountability and responsibility concerns (n = 19, 13.1%); problematic informed consent and potential loss of patient autonomy (n = 17, 11.7%); and issues related to data ownership (n = 11, 7.6%). Major trust barriers included data privacy and security concerns, potential risk of patient harm, perceived lack of transparency about AI-enabled medical devices, concerns about AI replacing human aspects of care, concerns about prioritizing profits over patients’ interests, and lack of robust evidence related to the accuracy and limitations of AI-based medical devices. Ethical and trust facilitators included ensuring data privacy and data validation, conducting clinical trials in diverse cohorts, providing appropriate training and resources to patients and healthcare providers and improving their engagement in different phases of AI implementation, and establishing further regulatory oversights. Conclusion This review revealed key ethical concerns and barriers and facilitators of trust in AI-enabled medical devices from patients’ and healthcare providers’ perspectives. Successful integration of AI into cardiovascular care necessitates implementation of mitigation strategies. These strategies should focus on enhanced regulatory oversight on the use of patient data and promoting transparency around the use of AI in patient care.

Abstract Background Successful deployment of clinical prediction models for clinical deterioration relates not only to predictive performance but to integration into the decision making process. Models may demonstrate good discrimination and calibration, but fail to match the needs of practising acute care clinicians who receive, interpret, and act upon model outputs or alerts. We sought to understand how prediction models for clinical deterioration, also known as early warning scores (EWS), influence the decision-making of clinicians who regularly use them and elicit their perspectives on model design to guide future deterioration model development and implementation. Methods Nurses and doctors who regularly receive or respond to EWS alerts in two digital metropolitan hospitals were interviewed for up to one hour between February 2022 and March 2023 using semi-structured formats. We grouped interview data into sub-themes and then into general themes using reflexive thematic analysis. Themes were then mapped to a model of clinical decision making using deductive framework mapping to develop a set of practical recommendations for future deterioration model development and deployment. Results Fifteen nurses (n = 8) and doctors (n = 7) were interviewed for a mean duration of 42 min. Participants emphasised the importance of using predictive tools for supporting rather than supplanting critical thinking, avoiding over-protocolising care, incorporating important contextual information and focusing on how clinicians generate, test, and select diagnostic hypotheses when managing deteriorating patients. These themes were incorporated into a conceptual model which informed recommendations that clinical deterioration prediction models demonstrate transparency and interactivity, generate outputs tailored to the tasks and responsibilities of end-users, avoid priming clinicians with potential diagnoses before patients were physically assessed, and support the process of deciding upon subsequent management. Conclusions Prediction models for deteriorating inpatients may be more impactful if they are designed in accordance with the decision-making processes of acute care clinicians. Models should produce actionable outputs that assist with, rather than supplant, critical thinking.

Abstract Background The integrity of clinical research and machine learning models in healthcare heavily relies on the quality of underlying clinical laboratory data. However, the preprocessing of this data to ensure its reliability and accuracy remains a significant challenge due to variations in data recording and reporting standards. Methods We developed lab2clean, a novel algorithm aimed at automating and standardizing the cleaning of retrospective clinical laboratory results data. lab2clean was implemented as two R functions specifically designed to enhance data conformance and plausibility by standardizing result formats and validating result values. The functionality and performance of the algorithm were evaluated using two extensive electronic medical record (EMR) databases, encompassing various clinical settings. Results lab2clean effectively reduced the variability of laboratory results and identified potentially erroneous records. Upon deployment, it demonstrated effective and fast standardization and validation of substantial laboratory data records. The evaluation highlighted significant improvements in the conformance and plausibility of lab results, confirming the algorithm’s efficacy in handling large-scale data sets. Conclusions lab2clean addresses the challenge of preprocessing and cleaning clinical laboratory data, a critical step in ensuring high-quality data for research outcomes. It offers a straightforward, efficient tool for researchers, improving the quality of clinical laboratory data, a major portion of healthcare data. Thereby, enhancing the reliability and reproducibility of clinical research outcomes and clinical machine learning models. Future developments aim to broaden its functionality and accessibility, solidifying its vital role in healthcare data management. Graphical Abstract

Abstract Background Modeling patient data, particularly electronic health records (EHR), is one of the major focuses of machine learning studies in healthcare, as these records provide clinicians with valuable information that can potentially assist them in disease diagnosis and decision-making. Methods In this study, we present a multi-level graph-based framework called MedMGF, which models both patient medical profiles extracted from EHR data and their relationship network of health profiles in a single architecture. The medical profiles consist of several layers of data embedding derived from interval records obtained during hospitalization, and the patient-patient network is created by measuring the similarities between these profiles. We also propose a modification to the Focal Loss (FL) function to improve classification performance in imbalanced datasets without the need to imputate the data. MedMGF’s performance was evaluated against several Graphical Convolutional Network (GCN) baseline models implemented with Binary Cross Entropy (BCE), FL, class balancing parameter $$\alpha$$ α , and Synthetic Minority Oversampling Technique (SMOTE). Results Our proposed framework achieved high classification performance (AUC: 0.8098, ACC: 0.7503, SEN: 0.8750, SPE: 0.7445, NPV: 0.9923, PPV: 0.1367) on an extreme imbalanced pediatric sepsis dataset (n=3,014, imbalance ratio of 0.047). It yielded a classification improvement of 3.81% for AUC, 15% for SEN compared to the baseline GCN+ $$\alpha$$ α FL (AUC: 0.7717, ACC: 0.8144, SEN: 0.7250, SPE: 0.8185, PPV: 0.1559, NPV: 0.9847), and an improvement of 5.88% in AUC and 22.5% compared to GCN+FL+SMOTE (AUC: 0.7510, ACC: 0.8431, SEN: 0.6500, SPE: 0.8520, PPV: 0.1688, NPV: 0.9814). It also showed a classification improvement of 3.86% for AUC, 15% for SEN compared to the baseline GCN+ $$\alpha$$ α BCE (AUC: 0.7712, ACC: 0.8133, SEN: 0.7250, SPE: 0.8173, PPV: 0.1551, NPV: 0.9847), and an improvement of 14.33% in AUC and 27.5% in comparison to GCN+BCE+SMOTE (AUC: 0.6665, ACC: 0.7271, SEN: 0.6000, SPE: 0.7329, PPV: 0.0941, NPV: 0.9754). Conclusion When compared to all baseline models, MedMGF achieved the highest SEN and AUC results, demonstrating the potential for several healthcare applications.

Abstract The healthcare industry has been put to test the need to manage enormous amounts of data provided by various sources, which are renowned for providing enormous quantities of heterogeneous information. The data are collected and analyzed with different Data Analytic (DA) and machine learning algorithm approaches. Researchers, scientists, and industrialists must manage or select the best approach associated with DA in healthcare. This scientific study is based on decision analysis between the DA factors and alternatives. The information affects the whole system in a rational manner. This information is very important in healthcare sector for appropriate prediction and analysis. The evaluation discusses its benefits and presents an analytic framework. The Fuzzy Analytic Hierarchy Process (Fuzzy AHP) approach is used to address the weight of the factors. The Fuzzy Techniques for Order Preference by Similarity to Ideal Solution (Fuzzy TOPSIS) address the rank of the data analytic alternatives used in healthcare sector. The models used in the article briefly discuss the challenges of DA and approaches to address those challenges. The assorted factors of DA are capture, cleaning, storage, security, stewardship, reporting, visualization, updating, sharing, and querying. The DA alternatives include descriptive, diagnostic, predictive, prescriptive, discovery, regression, cohort and inferential analyses. The most influential factors of the DA and the most suitable approach for the DA are evaluated. The ‘cleaning’ factor has the highest weight, and ‘updating’ is achieved at least by the Fuzzy-AHP approach. The regression approach of data analysis had the highest rank, and the diagnostic analysis had the lowest rank. Decision analyses are necessary for data scientists and medical providers to predict diseases appropriately in the healthcare domain. This analysis also revealed the cost benefits to hospitals.

Abstract Background Predictive modeling based on multi-omics data, which incorporates several types of omics data for the same patients, has shown potential to outperform single-omics predictive modeling. Most research in this domain focuses on incorporating numerous data types, despite the complexity and cost of acquiring them. The prevailing assumption is that increasing the number of data types necessarily improves predictive performance. However, the integration of less informative or redundant data types could potentially hinder this performance. Therefore, identifying the most effective combinations of omics data types that enhance predictive performance is critical for cost-effective and accurate predictions. Methods In this study, we systematically evaluated the predictive performance of all 31 possible combinations including at least one of five genomic data types (mRNA, miRNA, methylation, DNAseq, and copy number variation) using 14 cancer datasets with right-censored survival outcomes, publicly available from the TCGA database. We employed various prediction methods and up-weighted clinical data in every model to leverage their predictive importance. Harrell’s C-index and the integrated Brier Score were used as performance measures. To assess the robustness of our findings, we performed a bootstrap analysis at the level of the included datasets. Statistical testing was conducted for key results, limiting the number of tests to ensure a low risk of false positives. Results Contrary to expectations, we found that using only mRNA data or a combination of mRNA and miRNA data was sufficient for most cancer types. For some cancer types, the additional inclusion of methylation data led to improved prediction results. Far from enhancing performance, the introduction of more data types most often resulted in a decline in performance, which varied between the two performance measures. Conclusions Our findings challenge the prevailing notion that combining multiple omics data types in multi-omics survival prediction improves predictive performance. Thus, the widespread approach in multi-omics prediction of incorporating as many data types as possible should be reconsidered to avoid suboptimal prediction results and unnecessary expenditure.

Abstract Problem Pancreatic ductal adenocarcinoma (PDAC) is considered a highly lethal cancer due to its advanced stage diagnosis. The five-year survival rate after diagnosis is less than 10%. However, if diagnosed early, the five-year survival rate can reach up to 70%. Early diagnosis of PDAC can aid treatment and improve survival rates by taking necessary precautions. The challenge is to develop a reliable, data privacy-aware machine learning approach that can accurately diagnose pancreatic cancer with biomarkers. Aim The study aims to diagnose a patient’s pancreatic cancer while ensuring the confidentiality of patient records. In addition, the study aims to guide researchers and clinicians in developing innovative methods for diagnosing pancreatic cancer. Methods Machine learning, a branch of artificial intelligence, can identify patterns by analyzing large datasets. The study pre-processed a dataset containing urine biomarkers with operations such as filling in missing values, cleaning outliers, and feature selection. The data was encrypted using the Fernet encryption algorithm to ensure confidentiality. Ten separate machine learning models were applied to predict individuals with PDAC. Performance metrics such as F1 score, recall, precision, and accuracy were used in the modeling process. Results Among the 590 clinical records analyzed, 199 (33.7%) belonged to patients with pancreatic cancer, 208 (35.3%) to patients with non-cancerous pancreatic disorders (such as benign hepatobiliary disease), and 183 (31%) to healthy individuals. The LGBM algorithm showed the highest efficiency by achieving an accuracy of 98.8%. The accuracy of the other algorithms ranged from 98 to 86%. In order to understand which features are more critical and which data the model is based on, the analysis found that the features “plasma_CA19_9”, REG1A, TFF1, and LYVE1 have high importance levels. The LIME analysis also analyzed which features of the model are important in the decision-making process. Conclusions This research outlines a data privacy-aware machine learning tool for predicting PDAC. The results show that a promising approach can be presented for clinical application. Future research should expand the dataset and focus on validation by applying it to various populations.

Abstract Background The worldwide prevalence of type 2 diabetes mellitus in adults is experiencing a rapid increase. This study aimed to identify the factors affecting the survival of prediabetic patients using a comparison of the Cox proportional hazards model (CPH) and the Random survival forest (RSF). Method This prospective cohort study was performed on 746 prediabetics in southwest Iran. The demographic, lifestyle, and clinical data of the participants were recorded. The CPH and RSF models were used to determine the patients’ survival. Furthermore, the concordance index (C-index) and time-dependent receiver operating characteristic (ROC) curve were employed to compare the performance of the Cox proportional hazards (CPH) model and the random survival forest (RSF) model. Results The 5-year cumulative T2DM incidence was 12.73%. Based on the results of the CPH model, NAFLD (HR = 1.74, 95% CI: 1.06, 2.85), FBS (HR = 1.008, 95% CI: 1.005, 1.012) and increased abdominal fat (HR = 1.02, 95% CI: 1.01, 1.04) were directly associated with diabetes occurrence in prediabetic patients. The RSF model suggests that factors including FBS, waist circumference, depression, NAFLD, afternoon sleep, and female gender are the most important variables that predict diabetes. The C-index indicated that the RSF model has a higher percentage of agreement than the CPH model, and in the weighted Brier Score index, the RSF model had less error than the Kaplan-Meier and CPH model. Conclusion Our findings show that the incidence of diabetes was alarmingly high in Iran. The results suggested that several demographic and clinical factors are associated with diabetes occurrence in prediabetic patients. The high-risk population needs special measures for screening and care programs.

Abstract In 2016, the Bloomberg Philanthropies Data for Health initiative assisted the Philippine Statistical Authority in implementing Iris, an automated coding software program that enables medical death certificates to be coded according to international standards. Iris was implemented to improve the quality, timeliness, and consistency of coded data as part of broader activities to strengthen the country’s civil registration and vital statistics system. This study was conducted as part of the routine implementation of Iris to ensure that automatically coded cause of death data was of sufficient quality to be released and disseminated as national mortality statistics. Data from medical death certificates coded with Iris between 2017 and 2019 were analysed and evaluated for apparent errors and inconsistencies, and trends were examined for plausibility. Cause-specific mortality distributions were calculated for each of the 3 years and compared for consistency, and annual numeric and percentage changes were calculated and compared for all age groups. The typology, reasons, and proportions of records that could not be coded (Iris ‘rejects’) were also studied. Overall, the study found that the Philippine Statistical Authority successfully operates Iris. The cause-specific mortality fractions for the 20 leading causes of death showed reassuring stability after the introduction of Iris, and the type and proportion of rejects were similar to international experience. Broadly, this study demonstrates how an automated coding system can improve the accuracy and timeliness of cause of death data—providing critical country experiences to help build the evidence base on the topic.

Abstract Background The Decade of Healthy Aging (2021–2030) emerges as a 10 years strategy to improve the lives of older adults, their families, and the communities in which they live. One of the actions defined in this framework is related to improving the measurement, monitoring, and understanding of characteristics, factors, and needs related to aging and health. The aim was to analyze and assess the process of construction and development of the Strategic Information System on Health, Funcional Dependence and Aging (SIESDE, for its acronym in Spanish). SIESDE will provide strategic information in Mexico at the municipal, state, and national levels that support the public policies on healthy aging. Methods The system processes and analyzes the data sources of the Health Information Systems and the National System of Statistical and Geographical Information. SIESDE comprises three components: (1) Design, construction, and evaluation of the indicators; (2) storage, management, and visualization, and (3) diffusion and translation of information. Results A total of 135 indicators were built on seven themes: (1) demographic, socioeconomic, and aging conditions, (2) health, (3) functional dependence, (4) healthy aging, (5) health services, (6) social and physical environments, and (7) complex indicators. Conclusions SIESDE is an effective system for providing an overall view of health, aging, and functional dependence.

Abstract Background and aim Digital interventions for depression and anxiety can be as effective as face-to-face therapy. One in six workers experience some form of mental health problems, making the workplace a potential avenue to deliver mental health interventions as part of a stepped care model. This study aimed to assess the acceptability, feasibility, and preliminary efficacy of a digital cognitive behavioural therapy (dCBT) on depression and anxiety for employees in the workplace. Methods A mixed-methods evaluation of employees allocated to dCBT (n=25), or a waitlist control group (n=27) was used to assess five feasibility objectives related to recruitment of employers and employees, engagement, study procedure and preliminary efficacy of the intervention. Quantitative outcome measures and qualitative interviews at 8 weeks post-randomisation were used. Quantitative outcomes were also assessed within subject at 3-, 6-, and 12-month follow-up. Qualitative data was analysed using thematic and framework analysis in Nvivo, whilst quantitative outcomes were analysed using mixed effect linear models between and within subject in R and SPSS. Results Thirty-Three businesses agreed to facilitate the delivery of three trials run by the University of Warwick in their workplaces. 52 participants consented into the REST trial. Adherence/usage of participants of the treatment platform was just over 50% across the whole sample. There was a reduction in depression and anxiety symptoms post-intervention and at follow-up timepoints across all participants and over time although there were no statistically significant between group differences. High acceptability and satisfaction of the intervention were reported by participants based on qualitative interview data at post-intervention. Conclusions Results from this feasibility study suggests that the dCBT programme (REST) was acceptable and shows improvement in depression and anxiety symptoms, albeit not over and above the treatment effects in the control group. Recruitment of participants and engagement with the intervention made the feasibility of the delivery somewhat challenging. With better recruitment promotion and engagement strategies, as well as implementing the learnings from the feasibility trial, a fully powered study can inform the efficacy of the REST intervention. Trial registration The study is registered in the BMC Springer Nature ISRCTN registry ISRCTN31161020 (registered on 08/06/2021).

Abstract Background Duchenne muscular dystrophy (DMD) is a genetic disease resulting in progressive muscle weakness, loss of ambulation, and cardiorespiratory complications. Direct estimation of health-related quality of life for patients with DMD is challenging, highlighting the need for proxy measures. This study aims to catalog and compare existing published health state utility estimates for DMD and related conditions. Methods Using two search strategies, relevant utilities were extracted from the Tufts Cost-Effectiveness Analysis Registry, including health states, utility estimates, and study and patient characteristics. Analysis One identified health states with comparable utility estimates to a set of published US patient population utility estimates for DMD. A minimal clinically important difference of ± 0.03 was applied to each DMD utility estimate to establish a range, and the registry was searched to identify other health states with associated utilities that fell within each range. Analysis Two used pre-defined search terms to identify health states clinically similar to DMD. Mapping was based on the degree of clinical similarity. Results Analysis One identified 4,308 unique utilities across 2,322 cost-effectiveness publications. The health states captured a wide range of acute and chronic conditions; 34% of utility records were extrapolated for US populations (n = 1,451); 1% were related to pediatric populations (n = 61). Analysis Two identified 153 utilities with health states clinically similar to DMD. The median utility estimates varied among identified health states. Health states similar to the early non-ambulatory DMD phase exhibited the greatest difference between the median estimate of the sample (0.39) and the existing estimate from published literature (0.21). Conclusions When available estimates are limited, using novel search strategies to identify utilities of clinically similar conditions could be an approach for overcoming the information gap. However, it requires careful evaluation of the utility instruments, tariffs, and raters (proxy or self).

Abstract Background Diabetes-specific quality of life (QoL) questionnaires are commonly used to assess the impact of diabetes and its management on an individual’s quality of life. While several valid and reliable measures of diabetes-specific QoL exist, there is no consensus on which to use and in what setting. Furthermore, there is limited evidence of their acceptability to people with diabetes. Our aim was to explore perceptions of adults with type 1 diabetes (T1D) toward five diabetes-specific QoL measures. Methods Adults (aged 18 + years) with T1D living in Australia or the United Kingdom (UK) were eligible to take part in ‘YourSAY: QoL’, an online cross-sectional survey. Recruitment involved study promotion on diabetes-related websites and social media, as well as direct invitation of people with T1D via a hospital client list (UK only). In random order, participants completed five diabetes-specific QoL measures: Audit of Diabetes-Dependent Quality of Life (ADDQoL-19); Diabetes Care Profile: Social and Personal Factors subscale (DCP); DAWN Impact of Diabetes Profile (DIDP); Diabetes-Specific Quality of Life Scale: Burden Subscale (DSQoLS); Diabetes Quality of Life Questionnaire (Diabetes QOL-Q). They were invited to provide feedback on each questionnaire in the form of a brief free-text response. Responses were analysed using inductive, thematic template analysis. Results Of the N = 1,946 adults with T1D who completed the survey, 20% (UK: n = 216, Australia: n = 168) provided qualitative responses about ≥ 1 measure. All measures received both positive and negative feedback, across four themes: (1) clarity and ease of completion, e.g., difficulty isolating impact of diabetes, dislike of hypothetical questions, and preference for ‘not applicable’ response options; (2) relevance and comprehensiveness, e.g., inclusion of a wide range of aspects of life to improve personal relevance; (3) length and repetition, e.g., length to be balanced against respondent burden; (4) framing and tone, e.g., preference for respectful language and avoidance of extremes. Conclusions These findings suggest opportunities to improve the relevance and acceptability of existing diabetes-specific QoL measures, and offer considerations for developing new measures, which need to be better informed by the preferences of people living with diabetes.

Abstract Background Computerized adaptive testing (CAT) is an effective way to reduce time, repetitious redundancy, and respond burden, and has been used to measure outcomes in many diseases. This study aimed to develop and validate a comprehensive disease-specific CAT for chronic obstructive pulmonary disease (COPD) patient-reported outcome measurement. Methods The discrimination and difficulty of the items from the modified patient-reported outcome scale for COPD (mCOPD-PRO) were analyzed using item response theory. Then the initial item, item selection method, ability estimation method, and stopping criteria were further set based on Concerto platform to form the CAT. Finally, the reliability and validity were validated. Results The item discrimination ranged from 1.05 to 2.71, and the item difficulty ranged from − 3.08 to 3.65. The measurement reliability of the CAT ranged from 0.910 to 0.922 using random method, while that ranged from 0.910 to 0.924 using maximum Fisher information (MFI) method. The content validity was good. The correlation coefficient between theta of the CAT and COPD assessment test and modified Medical Research Council dyspnea scale scores using random method was 0.628 and 0.540 (P

Abstract Background Incorporating principles of family-centered care into pediatric weight management interventions can improve the effectiveness and quality of treatment and reduce attrition rates. To assess the family-centeredness of interventions, reliable, valid, and easy-to-administer scales are needed. The purpose of the study was to develop a shortened version of the modified Family Centered Care Assessment (mFCCA) and assess its psychometric properties. Methods The mFCCA, a scale to assess the family-centeredness of interventions for childhood obesity, was administered to families following the Connect for Health randomized control trial evaluating the effectiveness of a primary care-based pediatric weight management intervention. We iteratively removed items from the mFCCA and used Rasch modeling to examine the reliability and validity of the shortened scale. Results We included data from 318 parents and the exploratory factor analysis showed the presence of a single factor. The results of the Rasch modeling demonstrated acceptable internal consistency of the scale (0.7) and strong validity as evidenced by the overall model fit and range of item difficulty. Following the psychometric analyses, we reduced the number of items from 24 to 8 items. Conclusion The mFCCA short version demonstrates good psychometrics and can be used to evaluate the family-centeredness of childhood obesity interventions with reduced participant burden, thereby improving outcomes for children with obesity. Trial registration Clinicaltrials.gov NCT02124460 registered on April 24, 2014.

Abstract Background This study aimed to synthesize and quantitatively examine Health State Utility Values (HSUVs) for Type 2 Diabetes Mellitus (T2DM) and its complications, providing a robust meta-regression framework for selecting appropriate HSUV estimates. Method We conducted a systematic review to extract HSUVs for T2DM and its complications, encompassing various influencing factors. Relevant literature was sourced from a review spanning 2000-2020, supplemented by literature from PubMed, Embase, and the Web of Science (up to March 2024). Multivariate meta-regression was performed to evaluate the impact of measurement tools, tariffs, health status, and clinical and demographic variables on HSUVs. Results Our search yielded 118 studies, contributing 1044 HSUVs. The HSUVs for T2DM with complications varied, from 0.65 for cerebrovascular disease to 0.77 for neuropathy. The EQ-5D-3L emerged as the most frequently employed valuation method. HSUV differences across instruments were observed; 15-D had the highest (0.89), while HUI-3 had the lowest (0.70) values. Regression analysis elucidated the significant effects of instrument and tariff choice on HSUVs. Complication-related utility decrement, especially in diabetic foot, was quantified. Age

The newly adopted EU AI Act represents a pivotal milestone that heralds a new era of AI regulation across industries. With its broad territorial scope and applicability, this comprehensive legislation establishes stringent requirements for AI systems. In this article, we analyze the AI Act’s impact on digital medical products, such as medical devices: How does the AI Act apply to AI/ML-enabled medical devices? How are they classified? What are the compliance requirements? And, what are the obligations of ‘providers’ of these AI systems? After addressing these foundational questions, we discuss the AI Act’s broader implications for the future of regulated digital medical products.

Abstract Understanding the evolving nature of coronary hemodynamics is crucial for early disease detection and monitoring progression. We require digital twins that mimic a patient’s circulatory system by integrating continuous physiological data and computing hemodynamic patterns over months. Current models match clinical flow measurements but are limited to single heartbeats. To this end, we introduced the longitudinal hemodynamic mapping framework (LHMF), designed to tackle critical challenges: (1) computational intractability of explicit methods; (2) boundary conditions reflecting varying activity states; and (3) accessible computing resources for clinical translation. We show negligible error (0.0002–0.004%) between LHMF and explicit data of 750 heartbeats. We deployed LHMF across traditional and cloud-based platforms, demonstrating high-throughput simulations on heterogeneous systems. Additionally, we established LHMFC, where hemodynamically similar heartbeats are clustered to avoid redundant simulations, accurately reconstructing longitudinal hemodynamic maps (LHMs). This study captured 3D hemodynamics over 4.5 million heartbeats, paving the way for cardiovascular digital twins.

Abstract Deep learning for computer vision can be leveraged for interpreting surgical scenes and providing surgeons with real-time guidance to avoid complications. However, neither generalizability nor scalability of computer-vision-based surgical guidance systems have been demonstrated, especially to geographic locations that lack hardware and infrastructure necessary for real-time inference. We propose a new equipment-agnostic framework for real-time use in operating suites. Using laparoscopic cholecystectomy and semantic segmentation models for predicting safe/dangerous (“Go”/”No-Go”) zones of dissection as an example use case, this study aimed to develop and test the performance of a novel data pipeline linked to a web-platform that enables real-time deployment from any edge device. To test this infrastructure and demonstrate its scalability and generalizability, lightweight U-Net and SegFormer models were trained on annotated frames from a large and diverse multicenter dataset from 136 institutions, and then tested on a separate prospectively collected dataset. A web-platform was created to enable real-time inference on any surgical video stream, and performance was tested on and optimized for a range of network speeds. The U-Net and SegFormer models respectively achieved mean Dice scores of 57% and 60%, precision 45% and 53%, and recall 82% and 75% for predicting the Go zone, and mean Dice scores of 76% and 76%, precision 68% and 68%, and recall 92% and 92% for predicting the No-Go zone. After optimization of the client-server interaction over the network, we deliver a prediction stream of at least 60 fps and with a maximum round-trip delay of 70 ms for speeds above 8 Mbps. Clinical deployment of machine learning models for surgical guidance is feasible and cost-effective using a generalizable, scalable and equipment-agnostic framework that lacks dependency on hardware with high computing performance or ultra-fast internet connection speed.

Abstract Parkinson’s disease (PD) presents diverse symptoms and comorbidities, complicating its diagnosis and management. The primary objective of this cross-sectional, monocentric study was to assess digital gait sensor data’s utility for monitoring and diagnosis of motor and gait impairment in PD. As a secondary objective, for the more challenging tasks of detecting comorbidities, non-motor outcomes, and disease progression subgroups, we evaluated for the first time the integration of digital markers with metabolomics and clinical data. Using shoe-attached digital sensors, we collected gait measurements from 162 patients and 129 controls in a single visit. Machine learning models showed significant diagnostic power, with AUC scores of 83–92% for PD vs. control and up to 75% for motor severity classification. Integrating gait data with metabolomics and clinical data improved predictions for challenging-to-detect comorbidities such as hallucinations. Overall, this approach using digital biomarkers and multimodal data integration can assist in objective disease monitoring, diagnosis, and comorbidity detection.

Abstract Distributed collaborative learning is a promising approach for building predictive models for privacy-sensitive biomedical images. Here, several data owners (clients) train a joint model without sharing their original data. However, concealed systematic biases can compromise model performance and fairness. This study presents MyThisYourThat (MyTH) approach, which adapts an interpretable prototypical part learning network to a distributed setting, enabling each client to visualize feature differences learned by others on their own image: comparing one client’s 'This’ with others’ 'That’. Our setting demonstrates four clients collaboratively training two diagnostic classifiers on a benchmark X-ray dataset. Without data bias, the global model reaches 74.14% balanced accuracy for cardiomegaly and 74.08% for pleural effusion. We show that with systematic visual bias in one client, the performance of global models drops to near-random. We demonstrate how differences between local and global prototypes reveal biases and allow their visualization on each client’s data without compromising privacy.

Abstract The application of artificial intelligence (AI) algorithms to 12-lead electrocardiogram (ECG) provides promising age prediction models. We explored whether the gap between the pre-procedural AI-ECG age and chronological age can predict atrial fibrillation (AF) recurrence after catheter ablation. We validated a pre-trained residual network-based model for age prediction on four multinational datasets. Then we estimated AI-ECG age using a pre-procedural sinus rhythm ECG among individuals on anti-arrhythmic drugs who underwent de-novo AF catheter ablation from two independent AF ablation cohorts. We categorized the AI-ECG age gap based on the mean absolute error of the AI-ECG age gap obtained from four model validation datasets; aged-ECG (≥10 years) and normal ECG age (

The Remote Assessment of Disease and Relapse – Alzheimer’s Disease (RADAR-AD) consortium evaluated remote measurement technologies (RMTs) for assessing functional status in AD. The consortium engaged with the European Medicines Agency (EMA) to obtain feedback on identification of meaningful functional domains, selection of RMTs and clinical study design to assess the feasibility of using RMTs in AD clinical studies. We summarized the feedback and the lessons learned to guide future projects.

Abstract Increased intracranial pressure (ICP) ≥15 mmHg is associated with adverse neurological outcomes, but needs invasive intracranial monitoring. Using the publicly available MIMIC-III Waveform Database (2000–2013) from Boston, we developed an artificial intelligence-derived biomarker for elevated ICP (aICP) for adult patients. aICP uses routinely collected extracranial waveform data as input, reducing the need for invasive monitoring. We externally validated aICP with an independent dataset from the Mount Sinai Hospital (2020–2022) in New York City. The AUROC, accuracy, sensitivity, and specificity on the external validation dataset were 0.80 (95% CI, 0.80–0.80), 73.8% (95% CI, 72.0–75.6%), 73.5% (95% CI 72.5–74.5%), and 73.0% (95% CI, 72.0–74.0%), respectively. We also present an exploratory analysis showing aICP predictions are associated with clinical phenotypes. A ten-percentile increment was associated with brain malignancy (OR = 1.68; 95% CI, 1.09-2.60), intracerebral hemorrhage (OR = 1.18; 95% CI, 1.07–1.32), and craniotomy (OR = 1.43; 95% CI, 1.12–1.84; P

Abstract Background SmithRNAs (Small MITochondrial Highly-transcribed RNAs) are a novel class of small RNA molecules that are encoded in the mitochondrial genome and regulate the expression of nuclear transcripts. Initial evidence for their existence came from the Manila clam Ruditapes philippinarum, where they have been described and whose activity has been biologically validated through RNA injection experiments. Current evidence on the existence of these RNAs in other species is based only on small RNA sequencing. As a preliminary step to characterize smithRNAs across different metazoan lineages, a dedicated, unified, analytical workflow is needed. Results We propose a novel workflow specifically designed for smithRNAs. Sequence data (from small RNA sequencing) uniquely mapping to the mitochondrial genome are clustered into putative smithRNAs and prefiltered based on their abundance, presence in replicate libraries and 5′ and 3′ transcription boundary conservation. The surviving sequences are subsequently compared to the untranslated regions of nuclear transcripts based on seed pairing, overall match and thermodynamic stability to identify possible targets. Ample collateral information and graphics are produced to help characterize these molecules in the species of choice and guide the operator through the analysis. The workflow was tested on the original Manila clam data. Under basic settings, the results of the original study are largely replicated. The effect of additional parameter customization (clustering threshold, stringency, minimum number of replicates, seed matching) was further evaluated. Conclusions The study of smithRNAs is still in its infancy and no dedicated analytical workflow is currently available. At its core, the SmithHunter workflow builds over the bioinformatic procedure originally applied to identify candidate smithRNAs in the Manila clam. In fact, this is currently the only evidence for smithRNAs that has been biologically validated and, therefore, the elective starting point for characterizing smithRNAs in other species. The original analysis was readapted using current software implementations and some minor issues were solved. Moreover, the workflow was improved by allowing the customization of different analytical parameters, mostly focusing on stringency and the possibility of accounting for a minimal level of genetic differentiation among samples.

Abstract Background Advancements over the past decade in DNA sequencing technology and computing power have created the potential to revolutionize medicine. There has been a marked increase in genetic data available, allowing for the advancement of areas such as personalized medicine. A crucial type of data in this context is genetic variant data which is stored in variant call format (VCF) files. However, the rapid growth in genomics has presented challenges in analyzing and comparing VCF files. Results In response to the limitations of existing tools, this paper introduces a novel web application that provides a user-friendly solution for VCF file analyses and comparisons. The software tool enables researchers and clinicians to perform high-level analysis with ease and enhances productivity. The application’s interface allows users to conveniently upload, analyze, and visualize their VCF files using simple drag-and-drop and point-and-click operations. Essential visualizations such as Venn diagrams, clustergrams, and precision–recall plots are provided to users. A key feature of the application is its support for metadata-based file grouping, accomplished through flexible data matrix uploads, streamlining organization and analysis of user-defined categories. Additionally, the application facilitates standardized benchmarking of VCF files by integrating user-provided ground truth regions and variant lists. Conclusions By providing a user-friendly interface and supporting essential visualizations, this software enhances the accessibility of VCF file analysis and assists researchers and clinicians in their scientific inquiries.

Abstract Background Gene expression and alternative splicing are strictly regulated processes that shape brain development and determine the cellular identity of differentiated neural cell populations. Despite the availability of multiple valuable datasets, many functional implications, especially those related to alternative splicing, remain poorly understood. Moreover, neuroscientists working primarily experimentally often lack the bioinformatics expertise required to process alternative splicing data and produce meaningful and interpretable results. Notably, re-analyzing publicly available datasets and integrating them with in-house data can provide substantial novel insights. However, such analyses necessitate developing harmonized data handling and processing pipelines which in turn require considerable computational resources and in-depth bioinformatics expertise. Results Here, we present Cortexa—a comprehensive web portal that incorporates RNA-sequencing datasets from the mouse cerebral cortex (longitudinal or cell-specific) and the hippocampus. Cortexa facilitates understandable visualization of the expression and alternative splicing patterns of individual genes. Our platform provides SplicePCA—a tool that allows users to integrate their alternative splicing dataset and compare it to cell-specific or developmental neocortical splicing patterns. All standardized gene expression and alternative splicing datasets can be downloaded for further in-depth downstream analysis without the need for extensive preprocessing. Conclusions Cortexa provides a robust and readily available resource for unraveling the complexity of gene expression and alternative splicing regulatory processes in the mouse brain. The data portal is available at https://cortexa-rna.com/

Abstract Background With the advance in single-cell RNA sequencing (scRNA-seq) technology, deriving inherent biological system information from expression profiles at a single-cell resolution has become possible. It has been known that network modeling by estimating the associations between genes could better reveal dynamic changes in biological systems. However, accurately constructing a single-cell network (SCN) to capture the network architecture of each cell and further explore cell-to-cell heterogeneity remains challenging. Results We introduce SINUM, a method for constructing the SIngle-cell Network Using Mutual information, which estimates mutual information between any two genes from scRNA-seq data to determine whether they are dependent or independent in a specific cell. Experiments on various scRNA-seq datasets with different cell numbers based on eight performance indexes (e.g., adjusted rand index and F-measure index) validated the accuracy and robustness of SINUM in cell type identification, superior to the state-of-the-art SCN inference method. Additionally, the SINUM SCNs exhibit high overlap with the human interactome and possess the scale-free property. Conclusions SINUM presents a view of biological systems at the network level to detect cell-type marker genes/gene pairs and investigate time-dependent changes in gene associations during embryo development. Codes for SINUM are freely available at https://github.com/SysMednet/SINUM .

Abstract Background A variant can be pathogenic or benign with relation to a human disease. Current classification categories from benign to pathogenic reflect a probabilistic summary of the current understanding. A primary metric of clinical utility for multiplexed assays of variant effect (MAVE) is the number of variants that can be reclassified from uncertain significance (VUS). However, a gap in this measure of utility is that it underrepresents the information gained from MAVEs. The aim of this study was to develop an improved quantification metric for MAVE utility. We propose adopting an information content approach that includes data that does not reclassify variants will better reflect true information gain. We adopted an information content approach to evaluate the information gain, in bits, for MAVEs of BRCA1, PTEN, and TP53. Here, one bit represents the amount of information required to completely classify a single variant starting from no information. Results BRCA1 MAVEs produced a total of 831.2 bits of information, 6.58% of the total missense information in BRCA1 and a 22-fold increase over the information that only contributed to VUS reclassification. PTEN MAVEs produced 2059.6 bits of information which represents 32.8% of the total missense information in PTEN and an 85-fold increase over the information that contributed to VUS reclassification. TP53 MAVEs produced 277.8 bits of information which represents 6.22% of the total missense information in TP53 and a 3.5-fold increase over the information that contributed to VUS reclassification. Conclusions An information content approach will more accurately portray information gained through MAVE mapping efforts than by counting the number of variants reclassified. This information content approach may also help define the impact of guideline changes that modify the information definitions used to classify groups of variants.

Abstract Genomics methods have uncovered patterns in a range of biological systems, but obscure important aspects of cell behavior: the shapes, relative locations, movement, and interactions of cells in space. Spatial technologies that collect genomic or epigenomic data while preserving spatial information have begun to overcome these limitations. These new data promise a deeper understanding of the factors that affect cellular behavior, and in particular the ability to directly test existing theories about cell state and variation in the context of morphology, location, motility, and signaling that could not be tested before. Rapid advancements in resolution, ease-of-use, and scale of spatial genomics technologies to address these questions also require an updated toolkit of statistical methods with which to interrogate these data. We present a framework to respond to this new avenue of research: four open biological questions that can now be answered using spatial genomics data paired with methods for analysis. We outline spatial data modalities for each open question that may yield specific insights, discuss how conflicting theories may be tested by comparing the data to conceptual models of biological behavior, and highlight statistical and machine learning-based tools that may prove particularly helpful to recover biological understanding.

Abstract Background The variant call format (VCF) file is a structured and comprehensive text file crucial for researchers and clinicians in interpreting and understanding genomic variation data. It contains essential information about variant positions in the genome, along with alleles, genotype calls, and quality scores. Analyzing and visualizing these files, however, poses significant challenges due to the need for diverse resources and robust features for in-depth exploration. Results To address these challenges, we introduce variant graph craft (VGC), a VCF file visualization and analysis tool. VGC offers a wide range of features for exploring genetic variations, including extraction of variant data, intuitive visualization, and graphical representation of samples with genotype information. VGC is designed primarily for the analysis of patient cohorts, but it can also be adapted for use with individual probands or families. It integrates seamlessly with external resources, providing insights into gene function and variant frequencies in sample data. VGC includes gene function and pathway information from Molecular Signatures Database (MSigDB) for GO terms, KEGG, Biocarta, Pathway Interaction Database, and Reactome. Additionally, it dynamically links to gnomAD for variant information and incorporates ClinVar data for pathogenic variant information. VGC supports the Human Genome Assembly Hg37 and Hg38, ensuring compatibility with a wide range of data sets, and accommodates various approaches to exploring genetic variation data. It can be tailored to specific user needs with optional phenotype input data. Conclusions In summary, VGC provides a comprehensive set of features tailored to researchers working with genomic variation data. Its intuitive interface, rapid filtering capabilities, and the flexibility to perform queries using custom groups make it an effective tool in identifying variants potentially associated with diseases. VGC operates locally, ensuring data security and privacy by eliminating the need for cloud-based VCF uploads, making it a secure and user-friendly tool. It is freely available at https://github.com/alperuzun/VGC .

Abstract Mouse (Mus musculus) models have been heavily utilized in developmental biology research to understand mammalian embryonic development, as mice share many genetic, physiological, and developmental characteristics with humans. New explorations into the integration of temporal (stage-specific) and transcriptional (tissue-specific) data have expanded our knowledge of mouse embryo tissue-specific gene functions. To better understand the substantial impact of synonymous mutational variations in the cell-state-specific transcriptome on a tissue’s codon and codon pair usage landscape, we have established a novel resource—Mouse Embryo Codon and Codon Pair Usage Tables (Mouse Embryo CoCoPUTs). This webpage not only offers codon and codon pair usage, but also GC, dinucleotide, and junction dinucleotide usage, encompassing four strains, 15 murine embryonic tissue groups, 18 Theiler stages, and 26 embryonic days. Here, we leverage Mouse Embryo CoCoPUTs and employ the use of heatmaps to depict usage changes over time and a comparison to human usage for each strain and embryonic time point, highlighting unique differences and similarities. The usage similarities found between mouse and human central nervous system data highlight the translation for projects leveraging mouse models. Data for this analysis can be directly retrieved from Mouse Embryo CoCoPUTs. This cutting-edge resource plays a crucial role in deciphering the complex interplay between usage patterns and embryonic development, offering valuable insights into variation across diverse tissues, strains, and stages. Its applications extend across multiple domains, with notable advantages for biotherapeutic development, where optimizing codon usage can enhance protein expression; one can compare strains, tissues, and mouse embryonic stages in one query. Additionally, Mouse Embryo CoCoPUTs holds great potential in the field of tissue-specific genetic engineering, providing insights for tailoring gene expression to specific tissues for targeted interventions. Furthermore, this resource may enhance our understanding of the nuanced connections between usage biases and tissue-specific gene function, contributing to the development of more accurate predictive models for genetic disorders.

Abstract Background Recently, the process of evolution information and the deep learning network has promoted the improvement of protein contact prediction methods. Nevertheless, still remain some bottleneck: (1) One of the bottlenecks is the prediction of orphans and other fewer evolution information proteins. (2) The other bottleneck is the method of predicting single-sequence-based proteins mainly focuses on selecting protein sequence features and tuning the neural network architecture, However, while the deeper neural networks improve prediction accuracy, there is still the problem of increasing the computational burden. Compared with other neural networks in the field of protein prediction, the graph neural network has the following advantages: due to the advantage of revealing the topology structure via graph neural network and being able to take advantage of the hierarchical structure and local connectivity of graph neural networks has certain advantages in capturing the features of different levels of abstraction in protein molecules. When using protein sequence and structure information for joint training, the dependencies between the two kinds of information can be better captured. And it can process protein molecular structures of different lengths and shapes, while traditional neural networks need to convert proteins into fixed-size vectors or matrices for processing. Results Here, we propose a single-sequence-based protein contact map predictor PCP-GC-LM, with dual-level graph neural networks and convolution networks. Our method performs better with other single-sequence-based predictors in different independent tests. In addition, to verify the validity of our method against complex protein structures, we will also compare it with other methods in two homodimers protein test sets (DeepHomo test dataset and CASP-CAPRI target dataset). Furthermore, we also perform ablation experiments to demonstrate the necessity of a dual graph network. In all, our framework presents new modules to accurately predict inter-chain contact maps in protein and it’s also useful to analyze interactions in other types of protein complexes.

Abstract We consider a problem of inferring contact network from nodal states observed during an epidemiological process. In a black-box Bayesian optimisation framework this problem reduces to a discrete likelihood optimisation over the set of possible networks. The cardinality of this set grows combinatorially with the number of network nodes, which makes this optimisation computationally challenging. For each network, its likelihood is the probability for the observed data to appear during the evolution of the epidemiological process on this network. This probability can be very small, particularly if the network is significantly different from the ground truth network, from which the observed data actually appear. A commonly used stochastic simulation algorithm struggles to recover rare events and hence to estimate small probabilities and likelihoods. In this paper we replace the stochastic simulation with solving the chemical master equation for the probabilities of all network states. Since this equation also suffers from the curse of dimensionality, we apply tensor train approximations to overcome it and enable fast and accurate computations. Numerical simulations demonstrate efficient black-box Bayesian inference of the network.

Objective: To learn more about the effect of virtual reality videos on patients’ symptoms near the end of life, including which are most effective, how long the effect lasts, and which patients benefit the most. Patients and Methods: We conducted a prospective study of 30 patients in a regional hospice and palliative care program from March 11, 2022, through July 14, 2023. Using a head-mounted display virtual reality, all participants viewed a 15-minute video of serene nature scenes with ambient sounds. Fifteen patients also participated in a second session of viewing bucket-list video clips they selected. Symptoms were measured with the revised Edmonton Symptom Assessment Scale before, immediately after, and 2 days after each experience. Participants rated their bucket-list selections by level of previous experience, strength of connection, and overall video quality. Functional status was also recorded. Results: Nature scenes significantly improved total symptom scores (30% decrease, P

Objective: To develop an artificial intelligence deep neural network (AI-DNN) algorithm to analyze 12-lead electrocardiogram (ECG) for detection of acute pulmonary embolism (PE) and PE categories. Patients and Methods: A cohort of patients seen between January 1, 1999, and December 31, 2020, from across the Mayo Clinic Enterprise with computed tomography pulmonary angiogram (CTPA) and ECG performed ±6 hours was identified. Natural language processing algorithms were applied to radiology reports to determine the diagnosis of acute PE, acute right ventricular strain pulmonary embolism (RVSPE), saddle pulmonary embolism (SADPE), or no PE. Diagnostic performance parameters of the AI-DNN reported were area under the receiver operating characteristics curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: A cohort of patients with CTPA report and ECG consisted of 79,894 patients including 7423 (9.3%) with acute PE, among whom 1138 patients had RVSPE or SADPE. Artificial intelligence deep neural network predicted acute PE with a modest accuracy of AUROC of 0.69 (95% CI, 0.68-0.71), sensitivity of 63.5%, specificity of 64.7%, PPV of 15.6%, and NPV of 94.5%. The AI-DNN prediction using the same algorithm for RVSPE or SADPE was higher (AUROC, 0.84; 95% CI, 0.81-0.86) with a sensitivity of 80.8%, specificity of 64.7.8%, PPV of 3.5%, and NPV of 99.5%. Conclusion: An AI-based analysis of 12-lead ECG shows modest detection power for acute PE in patients who underwent CTPA, with higher accuracy for high-risk PE. Moreover, with the high NPV, it has the clinical potential to exclude high-risk PE quickly and correctly.

Artificial intelligence (AI)-enabled technology has the potential to expand access to high-quality health information and health care services. Learning how diverse users interact with technology enables improvements to the AI model and the user interface, maximizing its potential benefit for a greater number of people. This narrative describes how technology developers, academic researchers, and representatives from a community-based organization collaborated to conduct a community-centered project on emerging health technologies. Our project team comprised representatives from Stanford Medicine, Google, and Santa Clara Family Health Plan’s Blanca Alvarado Community Resource Center. We aimed to understand the usability and acceptability of an AI-driven dermatology tool among East San Jose, California, community members. Specifically, our objectives were as follows: to test a model for cross-sector research of AI-based health technology; to determine the utility of the tool in an ethnically and age-diverse population; to obtain in-depth user experience feedback from participants recruited during community events; to offer free skin health consultations; and to provide resources for receiving follow-up care. We describe a collaborative approach in which each party contributed expertise: knowledge of the community from the community health partner, clinical expertise from the academic research institution, and software and AI expertise from the technology company. Through an iterative process, we identified important community needs, including technological, language, and privacy support. Our approach allowed us to recruit and engage a diverse cohort of participants, over 70% of whom preferred a language other than English. We distill learnings from planning and executing this case study that may help other collaborators bridge the gap between academia, industry, and community in AI health care innovation.

Objective: To evaluate the impact of Information and Communication Technology (ICT) on the implementation of Integrated Management of Childhood Illness (IMCI) and integrated Community Case Management (iCCM) through a systematic review and meta-analysis (PROSPERO registration number: CRD42024517375). Methods: We searched MEDLINE, EMBASE, Cochrane Library, and gray literature from January 2010 to February 2024, focusing on IMCI/iCCM-related terms (Integrated Management of Childhood Illness, IMCI, integrated Community Case Management, iCCM) and excluding non-ICT interventions. A meta-analysis synthesized the effect of ICT on clinical assessment, disease classification, therapy, and antibiotic prescription through odds ratio (OR; 95% CI) employing a random effects model for significant heterogeneity (I2>50%) and conducting subgroup analyses. Results: Of 1005 initial studies, 44 were included, covering 8 interventions for IMCI, 7 for iCCM, and 2 for training. All digital interventions except 1 outperformed traditional paper-based methods. Pooling effect sizes from 16 studies found 5.7 OR for more complete clinical assessments (95% CI, 1.7-19.1; I2, 95%); 2.0 for improved disease classification accuracy (95% CI, 0.9-4.4; I2, 93%); 1.4 for more appropriate therapy (95% CI, 0.8-2.2; I2, 93%); and 0.2 for reduced antibiotic use (95% CI, 0.06-0.55; I2 99%). Conclusion: This review is the first to comprehensively quantify the effect of ICT on the implementation of IMCI/iCCM programs, confirming both the benefits and limitations of these technologies. The customization of digital tools for IMCI/iCCM can serve as a model for other health programs. As ICT increasingly supports the achievement of sustainable development goals, the effective digital interventions identified in this review can pave the way for future innovations.

The use of machine learning tools in health care is rapidly expanding. However, the processes that support these tools in deployment, that is, machine learning operations, are still emerging. The purpose of this work was not only to provide a comprehensive synthesis of existing literature in the field but also to identify gaps and offer insights for adoption in clinical practice. A scoping review was conducted using the MEDLINE, PubMed, Google Scholar, Embase, and Scopus databases. We used MeSH and non-MeSH search terms to identify pertinent articles, with the authors performing 2 screening phases and assigning relevance scores: 148 English language articles most salient to the review were eligible for inclusion; 98 offered the most unique information and these were supplemented by 50 additional sources, yielding 148 references. From the 148 references, we distilled 7 key topic areas, based on a synthesis of the available literature and how that aligned with practitioner needs. The 7 topic areas were machine learning model monitoring; automated retraining systems; ethics, equity, and bias; clinical workflow integration; infrastructure, human resources, and technology stack; regulatory considerations; and financial considerations. This review provides an overview of best practices and knowledge gaps of this domain in health care and identifies the strengths and weaknesses of the literature, which may be useful to health care machine learning practitioners and consumers.

Objective: To develop natural language processing (NLP) solutions for identifying patients’ unmet social needs to enable timely intervention. Patients and Methods: Design: A retrospective cohort study with review and annotation of clinical notes to identify unmet social needs, followed by using the annotations to develop and evaluate NLP solutions. Participants: A total of 1103 primary care patients seen at a large academic medical center from June 1, 2019, to May 31, 2021 and referred to a community health worker (CHW) program. Clinical notes and portal messages of 200 age and sex-stratified patients were sampled for annotation of unmet social needs. Systems: Two NLP solutions were developed and compared. The first solution employed similarity-based classification on top of sentences represented as semantic embedding vectors. The second solution involved designing of terms and patterns for identifying each domain of unmet social needs in the clinical text. Measures: Precision, recall, and f1-score of the NLP solutions. Results: A total of 5675 clinical notes and 475 portal messages were annotated, with an inter-annotator agreement of 0.938. The best NLP solution achieved an f1-score of 0.95 and was applied to the entire CHW-referred cohort (n=1103), of whom >80% had at least 1 unmet social need within the 6 months before the first CHW referral. Financial strain and health literacy were the top 2 domains of unmet social needs across most of the sex and age strata. Conclusion: Clinical text contains rich information about patients’ unmet social needs. The NLP can achieve good performance in identifying those needs for CHW referral and facilitate data-driven research on social determinants of health.

To assess the current real-world applications of machine learning (ML) and artificial intelligence (AI) as functionality of digital behavior change interventions (DBCIs) that influence patient or consumer health behaviors. A scoping review was done across the EMBASE, PsycInfo, PsycNet, PubMed, and Web of Science databases using search terms related to ML/AI, behavioral science, and digital health to find live DBCIs using ML or AI to influence real-world health behaviors in patients or consumers. A total of 32 articles met inclusion criteria. Evidence regarding behavioral domains, target real-world behaviors, and type and purpose of ML and AI used were extracted. The types and quality of research evaluations done on the DBCIs and limitations of the research were also reviewed. Research occurred between October 9, 2023, and January 20, 2024. Twenty-three DBCIs used AI to influence real-world health behaviors. Most common domains were cardiometabolic health (n=5, 21.7%) and lifestyle interventions (n=4, 17.4%). The most common types of ML and AI used were classical ML algorithms (n=10, 43.5%), reinforcement learning (n=8, 34.8%), natural language understanding (n=8, 34.8%), and conversational AI (n=5, 21.7%). Evidence was generally positive, but had limitations such as inability to detect causation, low generalizability, or insufficient study duration to understand long-term outcomes. Despite evidence gaps related to the novelty of the technology, research supports the promise of using AI in DBCIs to manage complex input data and offer personalized, contextualized support for people changing real-world behaviors. Key opportunities are standardizing terminology and improving understanding of what ML and AI are.

Hospital-based digital care and virtual care are becoming increasingly common and their reach and scope are expanding in terms of patient groups and technological sophistication. The objective of this viewpoint is to provide guidance on design and factors that can be decisive for the organization of virtual care from a hospital’s perspective. Relevant aspects to be taken into account are as follows: characteristics of the technology, in a broader sense, the nature and intensity of provider involvement and supervision, the degree of self-management by the patient and his environment, the relation and cooperation mechanisms with other providers as home care, general practitioner ’s and other specialist care, the matter of (economies of) scale and finally the uniformity of processes over geographic regions and providers. We provide suggestions for further research and future policy related to these aspects.