Journal of Personalized Medicine

Patients diagnosed with type 2 diabetes (T2D) are at increased risk of developing cardiovascular disease (CVD), the leading cause of morbidity and mortality in this population. Early detection and glycemic control within the first year after diagnosis reduce CVD risk. However, gaps remain in how to operationalize early detection of T2D using Electronic Health Record (EHR) data and quantify its relationship with subsequent CVD risk using longitudinal observations. We developed a probabilistic graph model to analyze the interdependencies between early detection of T2D, post-diagnosis glycemic control, and CVD occurrence. Using a temporally structured Bayesian Network (BN) learned from EHR data of 9,450 primary care patients between 2017 and 2023, we quantified probabilistic dependencies between demographics, diagnostic delay surrogates, glycemic control, and post-diagnosis CVD occurrence. Percentile based thresholds defined risk groups, where individuals with predicted probabilities in the bottom decile ([≤] 10th percentile) were classified as low risk, and those in the top decile ([≥] 90th percentile) as high risk. Results demonstrated heterogeneity in predicted risks across glycemic and cardiovascular outcomes. Predicted probability of developing CVD within the first year after T2D diagnosis ranged from a mean of 5.2% in the low-risk group to 28.9% in the high-risk group, while predicted probabilities of mean Hemoglobin A1c (HbA1c) [≥] 8% during the first year post-diagnosis ranged from 1.6% in low-risk to 55.1% in high-risk group. Patients with HbA1c at diagnosis [≥] 8% had higher predicted probabilities of first-year post-diagnosis mean HbA1c [≥] 8% (53.3% vs. 1.9%) and high HbA1c coefficient of variation (18.7% vs. 3.1%) compared with those with HbA1c [≤] 6.5%. Incorporating early clinical outcomes refined later risk predictions, with long-term CVD risk reaching 33.5% among high-risk individuals. The proposed model achieved predictive performance comparable to conventional machine learning approaches while providing interpretable relationships for risk stratification in primary care populations.

BackgroundThe variants G1 and G2 within the APOL1 gene confer a higher risk of APOL1-mediated kidney disease (AMKD) whilst associated with an evolutionary advantage against trypanosome-mediated sleeping sickness. MethodsIn this study, we analysed transcriptome data of kidney biopsies from FSGS patients with the APOL1 high-risk (HR) and low-risk (LR) variants and compared it to cellular models based on patient-specific podocytes, HEK cells with engineered over-expressing HR variants and HR variant single-cell-RNA-seq data from kidney organoids. ResultsWe identified a signature of up- and down-regulated genes between biopsies from FSGS patients with APOL1 HR and LR variants. The up-regulated genes are functionally annotated to be associated with Calcium and mTOR signaling, whilst the down-regulated genes with inflammatory and immune response pathways. These pathways were confirmed by comparing with cellular models. Analysis of small molecules reverting the IFN-{gamma} stimulated gene expression to the non-stimulated gene expression in genome-edited APOL-G1 kidney organoids revealed several putative candidates such as the mTOR inhibitor AZD-2014. ConclusionWe have unveiled a signature of up- and down-regulated genes between APOL1 HR and LR kidney biopsies which could be assigned as associated with Calcium and mTOR signaling and down-regulated immune response.

Abstract Background: Immune-mediated inflammatory diseases (IMIDs) are associated with increased risk of cardiometabolic diseases. Investigating genetic overlap among these conditions can provide insights into their clinical management. Methods: Genetic correlation was assessed using linkage disequilibrium score regression (LDSC). Then, a meta-analysis was conducted using Association Analysis Based on SubSETs (ASSET) to pinpoint independent single nucleotide polymorphisms (SNPs) shared across the diseases. Each independent SNP was then used to define a genomic window (+/-500KB) for colocalisation analysis and Local Analysis of [co]Variant Association (LAVA) to offer multiple layers of regional pleiotropic evidence. Over-representation analysis was then run to identify enriched biological pathways, which then were used for drug target analysis. Results: The LDSC analysis showed a significant global genetic correlation for rheumatoid arthritis (RA) and cardiometabolic diseases including hypertension, coronary artery disease (CAD), heart failure (HF), stroke, atrial fibrillation (AF), and type two diabetes mellitus (T2DM) ranging from rg = 0.09 to 0.24. ASSET meta-analysis identified 164 independent SNPs shared across RA and the cardiometabolic diseases with P < 5 x 10- in the overall one-sided meta-analysis P-value, FDR < 0.05 in both individual GWASs, and TRUE phenotype matrix. Colocalisation analysis revealed multiple loci with strong evidence (Posterior probabilities [&ge;] 80) of single causal SNPs between the trait pairs. LAVA analysis was then used as an additional layer of confirmation for the findings generated by ASSET and colocalisation and thus several loci were highlighted. Over-representation analysis showed significant enriched immune-related pathways across RA-hypertension, RA-CAD, RA-AF, and RA-T2DM trait pairs. Drug target analysis highlighted several drugs which could be further tested for their effectiveness in RA and its common comorbidities. Conclusion: The findings revealed a shared genetic architecture and key immune-related biological pathways underlying RA and its associated cardiometabolic comorbidities. The identified genes and drugs provide opportunities for further therapeutic assessment which could improve clinical management strategies.

Abstract Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to obesity and cardiometabolic dysfunction, yet local prevalence data from Mexican first-level care units are scarce. We estimated the prevalence of MASLD by B-mode ultrasonography and characterized the clinical profile of obese adults in a family medicine unit in Leon, Mexico. Methods: Cross-sectional study of 55 adults with obesity (body mass index [BMI] >=30 kg/m2) registered at one medical office of a Mexican Social Security Institute family medicine unit (April-October 2024). Hepatic steatosis was graded by B-mode ultrasonography; MASLD was defined as ultrasonographic steatosis plus at least one cardiometabolic criterion (all participants met the obesity criterion). Prevalence was reported with Wilson 95% confidence intervals (CIs); associations with obesity grade were assessed by Cochran-Armitage trend and Fisher exact tests. Results: MASLD was present in 37 of 55 participants (67.3%; 95% CI, 54.1-78.2). Mild (grade 1) steatosis predominated (45.5%). Prevalence increased across obesity grades: 59.0%, 75.0%, and 100% for grades 1, 2, and 3, respectively (trend P=0.022). Type 2 diabetes and hypertension each affected 50.9% of participants; the sample was predominantly female (74.5%). Conclusion: Two of every three obese adults screened in primary care had ultrasonographic MASLD, with a significant rise across obesity grades. Opportunistic ultrasonography in obese primary-care patients may enable earlier MASLD detection. Keywords: Non-alcoholic Fatty Liver Disease; Fatty Liver; Obesity; Ultrasonography; Primary Health Care; Prevalence

Purpose: Elective genomic sequencing (EGS) returns monogenic disease findings in multiple genes, including potentially novel variants, and may also provide participants with carrier status, pharmacogenomic and other health-related information. The PeopleSeq Study assessed participants' motivations for and concerns about EGS and the associated clinical and psychosocial outcomes across diverse EGS providers. Methods: We administered a shared questionnaire to participants who chose to undergo EGS via 18 academic, clinical, or commercial EGS platforms. Results: We enrolled 1575 participants, of whom 1147 (72.8%) completed a questionnaire after receiving their EGS results. A majority (60.3%) of the participants who completed a post-result questionnaire self-reported receiving results they assessed as important, including negative findings, and 75.9% reported a form of health-related utility. Among a subset (19.4%) who shared their EGS reports, 16.6% (37 of n=223) received a monogenic finding and self-reported results deemed "important" were consistent with EGS reports. Most participants (74.1%) discussed their results with their family, but fewer discussed their results with a healthcare provider other than the site team (41.7%) or had one or more medical visits as a direct result of their EGS testing (23.1%). Participants expressed diverse motivations for EGS, with 91.4% expressing interest in their personal disease risk and 54% who expressed quasi-indication-based motivations related to family medical history. Individuals motivated by family history reported important results at a significantly higher rate. Conclusions: Early adopters of EGS are motivated by general interest in their health as well as quasi-indication-based considerations such as family history. A majority of participants learned results they considered medically important, but a much smaller segment engaged healthcare providers with their results.

Importance Pharmacogenomic (PGx) guidelines can improve medication efficacy and reduce toxicity, but their application in pediatric intensive care units (PICUs) remains largely unexplored. Objective To determine the frequency of medications with established PGx guidelines administered in the PICU and assess the capacity of exome sequencing to capture PGx phenotypes for these medications. Design Retrospective cohort study integrating electronic medical record and exome sequencing data. Setting Morgan Stanley Children's Hospital of NewYork-Presbyterian, a single center tertiary care children's hospital. Participants A total of 4,939 children admitted to the PICU (2020 - 2024), and 192 children admitted to the PICU who underwent exome sequencing for research purposes (2015 - 2023). Exposure Critical illness requiring PICU admission. Main Outcomes and Measures Frequencies of administration of medications with established PGx guidelines in the PICU and the proportion of individuals with exome sequencing with identifiable PGx phenotypes. Results Among 4,939 PICU patients, 37.2% (n=1,837) received at least one medication with established PGx guidelines and 14.4% (n=712) received two or more such medications. Twenty PGx genes were implicated; CYP2C9 was most common (17.3%, n=853). An estimated 8.2% of patients received medications for which PGx-guided recommendations would have altered clinical management. Among 192 patients who underwent exome sequencing, at least one metabolizer phenotype was identified in 62% (n=119). Conclusions and Relevance Many critically ill children receive medications with established PGx guidelines. This study highlights an opportunity for more personalized medicine for critically ill children admitted to a tertiary care hospital and assesses the strengths and weaknesses of exome sequencing to uncover pertinent PGx phenotypes.

Genetic testing for inherited cardiovascular conditions is recommended by multiple national guidelines to inform medical management. However, access to genetic counseling and testing is often limited particularly in the inpatient setting. Cardiologists cite lack of access to genetic counselors as a reason for not pursuing genetic testing. Genetic test education videos have been successfully implemented in the outpatient setting to increase patient volumes and decrease wait times, but they have not been studied in the inpatient setting.

Objectives: To assess how patients with non-valvular atrial fibrillation (NVAF) receiving oral anticoagulants are managed in routine primary care practice in Spain. Methods: This observational, descriptive study included patients with NVAF treated with oral anticoagulants for at least 6 months before enrolment and managed in primary care settings in Spain. The Barthel and ACTS questionnaires were administered to evaluate functional autonomy and treatment satisfaction, respectively. Results: A total of 1,901 patients were included: 428 received vitamin K antagonists (VKAs) and 1,473 direct oral anticoagulants (DOACs). Compared with patients receiving DOACs, those treated with VKAs were significantly older and had a higher prevalence of more hypertension. Mean treatment duration was 7.6 years for VKAs and 3.8 years for DOACs. Among patients receiving VKAs, 56.2% and 59.0% achieved good anticoagulation control according to the direct and Rosendaal methods, respectively. Patients in the DOAC group reported greater satisfaction across several domains, including perceived treatment benefits, lower impact on daily life, and overall positive treatment effect. Event incidence rates (per 1,000 person-years) were higher with DOACs than with VKAs for stroke (1.75; 95% CI 1.05-2.92), ischemic stroke (1.78; 95% CI 1.06-3.00), acute myocardial infarction (1.64; 95% CI 0.97-2.79), and major bleeding (3.68; 95% CI 1.81-7.46). Conclusions: In routine primary care practice in Spain, patient profiles and treatment duration varied by oral anticoagulant type. These differences may partly explain the higher rates of stroke and major bleeding observed with DOACs versus VKAs, despite greater treatment satisfaction among patients receiving DOACs.

Introduction: Severe hypercholesterolemia has four primary causes: monogenic familial hypercholesterolemia (FH), polygenic hypercholesterolemia (PRS), severely elevated Lp(a) concentration, and hypercholesterolemia due to environmental/lifestyle/behavioral factors (i.e., no known genetic etiology). Here, we explore patient and clinician perspectives about the identification and management of each of these causes. Methods: Patients with severe hypercholesterolemia with a primary language of English or Spanish and clinicians (primary care, genetic counseling, cardiology) across two health systems (Geisinger, Mount Sinai) participated in semi-structured interviews. Analysis was completed using an a priori codebook informed by Proctor?s implementation outcomes to identify themes influencing the identification and management of the underlying causes of severe hypercholesterolemia. Results: A total of 28 patients and 25 clinicians participated. Patients emphasized the importance of receiving results directly from their clinician, requested take-home resources that mirrored the information from their clinician, were motivated to seek multidisciplinary care, and anticipated all results would be actionable, but that high-risk PRS and elevated Lp(a) may require more support (e.g., specialists, education) to act on. Clinicians stressed the importance of integrating workflows (e.g., test ordering) with the electronic health record, highlighted LDL-C levels and multidisciplinary care coordination as key to management, explained how they would tailor care to individual patients, and expressed a more limited understanding of Lp(a) and PRS result types based on their clinical experiences and, therefore, hesitation about the recommended clinical actions. Conclusions: Patients and clinicians identified complementary determinants influencing the identification and management of the underlying cause of severe hypercholesterolemia. Participants welcomed risk information and requested a higher level of informational support and specialty expertise to appropriately manage high Lp(a) and PRS results. Integrating genomic information into risk assessments will require a partnership between general practitioners and specialists to provide a multidisciplinary approach to the identification and management of the underlying causes of severe hypercholesterolemia.

Abstract Fractures in older adults cause high morbidity and mortality. This study aims to identify fracture incidence and risk factors, and to develop the Fracture Risk Model-Abu Dhabi (FRM-AD). Method This retrospective cohort study of 1757 males and females aged 40+ from Abu Dhabi, United Arab Emirates, who participated in a screening program from 2016 to 2020, followed until 2024 for 4.7 years, SD =1.8. It utilized Electronic Medical Records (EMRs) data and telephone interviews. The outcome assessed was the occurrence of fractures. Results There were 58 out of the 1149 females (5.0%) and 26 out of the 608 males (4.3%) who had at least one incident fracture. Hip and vertebral fractures accounted for 12.1% and 11.5%, respectively. There was an annual incidence of 10.5 fractures per 1,000 person-years, 10.7 cases among females and 9.9 among males, rising after age 80 to 39.1 among females and 25.3 among males. Fracture Predictors identified using Poisson regression analysis were older age, smoking, history of previous fracture(s), interaction of history of fracture in a parent with a family history of osteoporosis, positive history of hip fracture in a parent after the age of 40, lack of dyslipidemia diagnosis and the interaction of diabetes mellitus diagnosis and family history of osteoporosis. A higher Body Mass Index (BMI) increased the risk of fractures in this cohort, especially in obese males. Logistic regression of variables at the end of follow-up showed that lower latest vitamin D levels were associated with increased fracture risk. FRM-AD, derived using Poisson regression, performed well in predicting fractures, with Receiver Operating Characteristic (ROC) curves of 0.736 (0.677-0.794) and 0.742 (0.684-0.800) without and with BMD, respectively. The FRAX AUC to predict MOF and hip fracture ranged between 0.624 and 0.683. Conclusion In this Emirati cohort, the locally derived FRM-AD showed moderate discrimination for incident fracture and outperformed FRAX-AD, suggesting that a locally derived model may improve fracture risk stratification. Several risk factors and predictors were identified that can be targeted for prevention.

Introduction: The application of pharmacogenomics (PGx) in pediatrics is limited by the lack of age-oriented interpretation approaches, as algorithms developed for adults do not account for ontogenetic changes in the activity of drug-metabolizing enzymes and transport proteins. The aim of this study was to evaluate the clinical applicability of pharmacogenomic data in Russian children, assess the concordance between genotype-based recommendations and the ontogenetic status of drug-metabolizing enzymes, and develop recommendations for the generation of age-oriented PGx reports. Methods: We analyzed whole-exome sequencing (WES) data from 524 pediatric patients and 635 newborns, filtering pharmacogenomic annotations according to PharmGKB/ClinPGx evidence levels (1A-2B) and the presence of the 'Pediatrics' tag. The concordance between genotype-based recommendations and the ontogenetic status of drug-metabolizing enzymes was assessed in newborns. In a pediatric subgroup of 100 patients, a retrospective analysis of medical records was performed to evaluate the structure of pharmacotherapy and the frequency of adverse drug reactions (ADRs). A 'PGx-ADR-cost' database was created, and the relative population burden index was calculated for 27 gene-variant-drug-ADR associations. Results: Clinically relevant annotations (requiring drug avoidance or dose modification) accounted for only 5% of all initial pharmacogenomic annotations in both cohorts; 67.6% (pediatric cohort) and 67.2% (neonatal cohort) of these were related to alleles with altered function. Concordance between genotype-based recommendations and the ontogenetic status of drug-metabolizing enzymes in newborns was observed in only 5 of 14 (35.71%) gene-drug pairs. ADRs were identified in 21% of the 100 pediatric patients; however, only two cases could be explained by high-evidence PharmGKB/ClinPGx annotations. Ranking by relative population burden identified UGT1A1*28-irinotecan-induced neutropenia and HLA-A*31:01-carbamazepine-induced severe cutaneous reactions as priority associations. Conclusions: Age represents a critical factor in the interpretation of pharmacogenomic data in children, as current approaches to PGx reporting do not adequately incorporate the ontogenetic context. We propose a pediatric PGx interpretation model that includes mandatory reporting of patient age, ontogenetic adjustment, evidence-level stratification, and multidisciplinary clinical assessment. Prospective validation is required to confirm the clinical utility of the proposed approach.

Background Iron deficiency (ID) is a readily treatable condition once identified. Ferritin is the primary diagnostic marker, but cut-offs vary and inflammation complicates interpretation in patients with long-term conditions (LTCs). Aim To describe ferritin distribution and the prevalence of threshold-defined low ferritin in adults with and without LTCs in primary care. Design and setting Cross-sectional observational study using routinely collected electronic health records from a national primary care database in England (1st January 2015 to 31st December 2021). Method Adults with >1 ferritin test in Clinical Practice Research Datalink (CPRD) Aurum were included. LTCs were identified using validated primary-care code lists. Outcomes included ferritin distribution and threshold-defined ID prevalence using World Health Organization (WHO) (<15 ug/L; <70 ug/L if inflammation) and National Institute for Health and Care Excellence (NICE) (<30 ug/L) cut-offs, stratified by sex and, in women, by age <50 versus >=50 as a proxy for menopausal status. Results 4,489,594 individuals were included; 55% (n=2,469,882) had >1 LTC. Ferritin was lowest in women <50 and in LTCs characterised by impaired absorption or blood loss (coeliac disease, inflammatory bowel disease). Among women <50 with an LTC, 80% had ferritin <70 ug/L versus 47% <30 ug/L, leaving 33% in the 30 to 70 ug/L range potentially missed by standard cut-offs; equivalent figures were 28% in women >=50 and 17% in men. Conclusion Threshold-defined low ferritin is very common across LTCs and disproportionately affects women, particularly those under 50. Condition-specific, inflammation-adjusted ferritin thresholds may improve detection, management, and equity in primary care.

Background: Chronic lowgrade inflammation in long standing rheumatoid arthritis (RA) contributes not only to joint damage but also to metabolic dysregulation, endothelial dysfunction, and elevated cardiovascular (CV) risk. Although combination disease modifying anti rheumatic drugs (DMARDs) remain the mainstay of therapy, their long term efficacy in controlling systemic inflammation and preventing metabolic complications appears limited. Phytochemicals such as resveratrol, a polyphenolic compound widely used in traditional and complementary medicine, possess anti inflammatory and immunomodulatory properties. Objectives: To investigate whether resveratrol can complement the immunomodulatory effects of combination DMARDs in long duration RA patients by modulating inflammatory cytokines and the JNK-IRS-Akt insulin signaling axis. Methods: This study enrolled early and late rheumatoid arthritis patients to assess disease activity, vascular markers, and ex vivo PBMC responses. PBMCs were isolated for cytotoxicity testing and resveratrol treatment, followed by ELISA and Western blot analysis. Statistical comparisons evaluated immunomodulatory effects and alterations in inflammatory signaling. Results: Longitudinal follow up of RA patients showed significant first year improvement in disease activity and atherosclerotic markers, correlated with MTX dose. An early versus late RA comparison revealed elevated cytokines and enhanced JNK mediated stress signaling in longstanding disease. Resveratrol maintained PBMC viability, reduced LPS induced TNF&alpha and adipokine levels, and downregulated pJNK and GSK&beta, indicating targeted anti inflammatory modulation independent of Akt activation. Conclusion: Chronic RA showed persistent inflammatory and metabolic dysregulation driven by JNK-NF&kappaB activation. Resveratrol reduced cytokines, corrected adipokine imbalance, and selectively inhibited JNK, suggesting adjunct therapeutic value alongside DMARDs for improving immunometabolic disturbances in long-standing RA.

Advances in high-throughput sequencing and genetic research have expanded the role of genetics in medicine and society. Population-based screening programs, including neonatal and preconception testing, are increasingly implemented globally, alongside the rise of direct-to-consumer (DTC) genetic testing. The "Genetics and the General Public" Ethics Working Group of the French Federation of Human Genetics (FFGH) assessed knowledge and awareness of genetics within the French population through a nationally representative survey (n=3,013) conducted by the polling firm Ipsos bva. Results indicated that 69% of respondents report an interest in genetics, although their level of knowledge remains limited. Most respondents expressed positive attitudes toward genetics, perceiving it as a major source of hope in healthcare. While a majority indicated willingness to undergo genetic testing for medical purposes, they also reported legitimate concerns regarding the potential results. Despite legal restrictions, 12% reported having ordered a DTC genetic test (5% for genealogical; 5% for medical and 2% for both purposes), and 45% of non-users expressed strong interest in this type of test. Notably, there is a substantial lack of awareness regarding the limitations of these tests and the French legal framework governing their use. These findings highlight critical gaps in public knowledge, emphasizing the need for improved genetic education, including incorporating genetics into school curricula and launching targeted awareness campaigns. These initiatives should help clarify the distinctions between clinically validated genetic tests and DTC genetic testing services, addressing both their benefits and their ethical, legal, and scientific limitations, in order to promote informed decision-making.

Objective To determine if it is possible to assess individual patient risk of the development of colorectal cancer (CRC) in people in high-risk groups due to their family history. Design/Method Retrospective observational study of prospectively collected data from consecutive patients referred for a colonoscopy. 2,478 consecutive patients were referred to a single colorectal surgical practice in Sydney, Australia between 1977 and 2018 for a colonoscopy because of a family history of CRC. Of these, 1,963 have been followed for more than 10 years and are the subject of this paper. Histopathological findings categorised as normal (N), non-advanced adenoma (NAA) or advanced neoplasia (AN) with AN proven to be the precursor to CRC. Intervention Colonoscopic screening on the basis of contemporary practice to 2006 and subsequently according to Australian National Health and Medical Research Council guidelines. Results Participants with normal or low-risk findings in the first decade remain at lower risk of CRC for 30 years from the commencement of screening. Conclusion It is possible to stratify individual patients in a high relative risk cohort into those with high or low personal risk of CRC based on colonoscopic findings in the first 10 years of surveillance. Those with no AN in the first ten years have a lower 30-year risk of developing AN than the general community. This offers the possibility of structuring surveillance programs around individual risk rather than group risk, lessening the need for multiple surveillance colonoscopies in the majority of such patients and improving the cost effectiveness of CRC screening at the population level.

Background: The tumor microenvironment (TME) plays a critical role in cancer progression and treatment response. Stromal components, including cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), and angiogenesis, contribute to tumor aggressiveness. However, a comprehensive stromal activity score integrating multiple stromal dimensions for pan-cancer prognosis prediction is lacking. Methods: We developed a Stromal Activity Score (SAS) integrating five stromal dimensions: CAF signature (12 genes), ECM remodeling (15 genes), TGF-{beta} signaling (13 genes), angiogenesis (12 genes), and complement activation (11 genes). SAS was calculated using single-sample Gene Set Enrichment Analysis (ssGSEA) on TCGA pan-cancer data comprising 1,303 samples across 12 cancer types. Prognostic value was evaluated using Kaplan-Meier analysis and Cox regression. Immunotherapy response prediction was validated in two independent cohorts (IMvigor210, n=88; Liu2019, n=105). Results: Pan-cancer Cox regression demonstrated a significant association between SAS and overall survival (HR = 1.165, 95% CI: 1.065-1.275, P = 0.001). Per-cancer analysis identified BRCA (HR = 1.942, P = 0.022), STAD (HR = 1.684, P = 0.024), and LUSC (HR = 1.552, P = 0.038) as significant, though none survived FDR correction. SAS correlated strongly with ESTIMATE Stromal Score (Spearman {rho} = 0.835) and moderately with Immune Score ({rho} = 0.396). Immunotherapy validation showed consistent trends (IMvigor210: AUC = 0.602; Liu2019: AUC = 0.617). Time-dependent ROC analysis showed 1-year AUC = 0.596, 3-year = 0.579, 5-year = 0.559. Leave-one-out analysis identified angiogenesis removal as enhancing prognostic signal (HR = 3.737, P = 0.0002). Three distinct TME subtypes were identified with differential SAS profiles. Conclusions: SAS is a novel pan-cancer stromal activity score that captures TME biology with strong construct validity. Its clinical utility as a standalone biomarker remains modest, but it may complement existing immunotherapy biomarkers.

Introduction: Genetic testing is increasingly central to the diagnosis and management of cardiovascular genetic conditions. However, use and follow-through vary across patient populations. Examining clinician perspectives on sociocultural and structural factors influencing testing is important for understanding these differences and informing public health genomics research and implementation efforts. Methods: We conducted semi-structured interviews with 15 cardiologists from health systems across the United States who have integrated cardiogenetics in their practice. Interviews explored experiences diagnosing cardiovascular genetic conditions among patients from underrepresented backgrounds, as well as approaches to incorporating social and contextual information into care. Data were coded thematically and analyzed using a framework analysis guided by the Health Equity Implementation Framework and Social Determinants of Health domains. Results: Clinicians described multi-level factors shaping genetic testing practices, including patient-provider interactions, clinical workflows, health system infrastructure, and broader policy contexts. Key themes included challenges communicating complex genetic information across language and literacy differences; patient trust shaped by prior healthcare experiences; fragmented insurance coverage separating genetic testing from genetic counseling; and challenges interpreting variants of uncertain significance, particularly for populations underrepresented in genomic reference databases. Clinicians also described adaptive strategies, such as interdisciplinary collaboration, telehealth, and patient assistance programs, that supported testing in some settings but were often inconsistent or resource-dependent. Conclusion: Among cardiologists using genetic testing, system-level and sociocultural factors shape the feasibility and downstream use of cardiovascular genetic testing. Findings highlight considerations for public health-informed genomic infrastructure that accounts for social context, supports communication, and reduces reliance on individual clinician workarounds, with implications for clinical decision support and related public health genomics initiatives.

This study aims to assess women's perceptions of artificial intelligence (AI) used in breast cancer screening in France by examining their knowledge of AI and the barriers to their participation in organized screening. The results of a survey conducted in June 2025 among a national sample of 2000 women (aged 40-75) reveal limited participation and persistent concerns among women. Nevertheless, despite a low awareness of specific AI applications, a large majority of the women surveyed are very favorable to the use of AI in breast cancer diagnosis, even considering it a lever to increase screening participation.

Background: Patient-reported measures (PRMs), including patient-reported outcome and experience measures, capture patients perspectives on their health status and healthcare experiences. In cancer genetics, PRMs have been used to assess genetic knowledge, psychosocial outcomes, and decision-making. However, patients must understand these measures to provide useful information, an ability which is influenced by general and health literacy levels. Readability guidelines recommend that patient-facing materials be written at or below a Grade 6 level. This study evaluated the readability of PRMs used in a cancer genetic testing context. Objective: To assess whether PRMs used in heritable cancer genetic testing meet recommended readability levels using validated indices. Methods: PRMs were identified from a recent systematic review of PRMs used in heritable cancer genetic testing, which reported 83 instruments across eight categories. English-language PRMs containing structured question items and response scales were eligible for extraction and converted into plain text for analysis. Readability was assessed using four validated indices: Flesch Kincaid Grading Level (FKGL), FORd, CAylor, and STicht (FORCAST) formula, Flesch Reading Ease Score (FRES), and Simple Measure of Gobbledygook (SMOG) via an automated readability software. Descriptive analysis and numerical comparison evaluated readability levels across PRM categories and against the recommended Grade 6 reading level. Results: Sixty-five PRMs met the eligibility criteria, with most, including validated instruments, exceeding the recommended Grade 6 reading level. Across the eight categories, genetics-specific PRMs required the highest readability levels, indicating higher readability demands. Conclusions: Most PRMs, particularly those specific to genetics, do not meet readability guidelines. This may limit their accessibility to individuals with limited general and health literacy. Development of PRMs specific to genetics should consider strategies to improve readability, such as plain-language approaches and involvement of individuals with limited general or health literacy. Keywords: readability, patient-reported measures, cancer, genetic testing, health literacy

Background Racial and ethnic minority populations face disproportionate rates of uncontrolled blood pressure (BP) and hypertension-related mortality. Remote hypertension monitoring (RHM) with active clinician-led medication titration has shown promise for improving BP control, but real-world evidence in majority-minority primary care settings remains limited. Methods This retrospective cohort study (January 2022-December 2024) enrolled adults with hypertension in a Bluetooth-integrated RHM program at a single urban academic primary care clinic. Of 550 patients enrolled, 503 with evaluable follow-up data were included. Patients transmitted daily home BP readings; clinicians reviewed readings monthly and titrated anti-hypertensive regimens per 2017 ACC/AHA guidelines. BP control was assessed at baseline and 3, 6, and 9 months. Factors associated with longitudinal BP control were examined using multivariable generalized estimating equations (GEE), with outcomes defined as strict control (<130/80 mmHg), at-least-moderate control (<140/90 mmHg), and uncontrolled (>140/90 mmHg). Results Among 503 participants (mean age 58.3 [SD 12.1] years; 63.6% African American; 52.9% male), BP control increased from 10.1% at baseline to 37.1% at 9 months. Each additional month of enrollment was associated with reduced odds of uncontrolled BP (adjusted odds ratio [aOR] 0.82; 95% CI, 0.80-0.85; P<.001). White race was associated with lower odds of uncontrolled BP versus African American race (aOR 0.57, at-least-moderate control; aOR 0.40, strict control; both P<.001). Male sex (aOR 1.46; P=.02) and congestive heart failure (aOR 2.09, strict control; aOR 2.05, at-least-moderate control; both P<.05) were associated with higher odds of uncontrolled BP. Conclusion Bluetooth-integrated RHM with active clinician-led medication titration was associated with a nearly 4-fold increase in BP control over 9 months in a majority-minority primary care population. Persistent within-program racial disparities underscore the need for equity-centered strategies beyond technology adoption alone. Prospective studies with concurrent usual-care comparators are needed to establish causal inference.