JAMA Intern Med. 2025 May 12. doi: 10.1001/jamainternmed.2025.0964. Online ahead of print.
NO ABSTRACT
PMID:40354074 | DOI:10.1001/jamainternmed.2025.0964
Tag: pubmed
JAMA Pediatr. 2025 May 12. doi: 10.1001/jamapediatrics.2025.0676. Online ahead of print.
ABSTRACT
IMPORTANCE: Research documenting the pregnancy experiences of transgender boys and nonbinary youth assigned female at birth (AFAB) in the US is lacking.
OBJECTIVE: To examine AFAB youth sexual health indicators by gender.
DESIGN, SETTING, PARTICIPANTS: Self-reported data were collected cross-sectionally from 2018 through 2020. Initial analyses were conducted in 2023 and analyses were finalized in September 2024. The study took place online, across the 50 US states and Washington, DC. Eligible participants were 14 to 16 years old, read English, and had internet access.
MAIN OUTCOME: Sexual health (ie, self-reported pregnancy and sexually transmitted infections [STIs] lifetime prevalence, condom use, and use of other forms of birth control at last penile-vaginal or penile-anal sex).
RESULTS: Based on weighted data (sample sizes are unweighted), 2109 cisgender girls, 348 transgender boys, and 458 nonbinary AFAB youth were included in analyses. There were 44 transgender boys (14%; 95% CI, 9.4-20.1; P = .24), 67 AFAB nonbinary youth (14%; 95% CI, 10.8-18.8; P = .18), and 397 cisgender girls (18%; 95% CI, 16.0-19.7) who reported ever having penile-vaginal sex. Rates for penile-anal sex were also similar by gender (4% to 6%). Lifetime pregnancy rates were higher for transgender boys (5 [9%]; 95% CI, 2.7-27.1; P = .23) than cisgender (18 [4%]; 95% CI, 2.5-7.1) girls, although not statistically significantly so. Pregnancy rates were similar for AFAB nonbinary youth (5 [5%]; 95% CI, 1.9-13.3; P = .73) compared with cisgender girls. Lifetime STI rates were universally low for all AFAB youth (0.5% to 2.0%). Mean age at first penile-vaginal sex was lower for AFAB nonbinary youth (mean age, 13.6 years; SE, 0.4; P = .003) and transgender boys (mean age, 13.9 years; SE, 0.3; P = .06) compared with cisgender girls (mean age, 14.4 years; SE, 0.1). Condom use at last penile-anal or penile-vaginal sex for transgender boys (24 [16%]; 95% CI, 9.5-27.0; P < .001) and AFAB nonbinary youth (33 [24%]; 95% CI, 16.4-34.2; P < .001) was half that of cisgender girls (245 [49%]; 95% CI, 44.1-54.2). Use of birth control other than condoms at last sex was lower for AFAB nonbinary youth (18 [28%]; 95% CI, 16.2-44.5; P = .14), but similar for transgender boys (20 [42%]; 95% CI, 23.4-62.4; P = .69) compared with cisgender girls (167 [44%]; 95% CI, 38.6-50.0).
CONCLUSION AND RELEVANCE: In this cross-sectional study of sexual health among AFAB youth with a diversity of gender identities, transgender boys were more likely, and nonbinary youth, similarly likely, as cisgender girls to be pregnant during adolescence. Even though overall rates of penile-vaginal sex were similar for transgender boys and AFAB nonbinary youth compared with cisgender girls, half as many transgender boys and AFAB nonbinary youth who had this type of sex used a condom at last sex compared with cisgender girls. As with cisgender girls, transgender boys and AFAB nonbinary youth need to be engaged in affirming and inclusive sexual health education.
PMID:40354068 | DOI:10.1001/jamapediatrics.2025.0676
JAMA Intern Med. 2025 May 12. doi: 10.1001/jamainternmed.2025.1140. Online ahead of print.
ABSTRACT
IMPORTANCE: Promoting social connection among older adults is a public health priority. Addressing hearing loss may reduce social isolation and loneliness among older adults.
OBJECTIVE: To describe the effect of a best-practice hearing intervention vs health education control on social isolation and loneliness over a 3-year period in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study.
DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a multicenter randomized controlled trial with 3-year follow-up was completed in 2022 and conducted at 4 field sites in the US (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; Washington County, Maryland). Data were analyzed in 2024. Participants included 977 adults (aged 70-84 years who had untreated hearing loss without substantial cognitive impairment) recruited from the Atherosclerosis Risk in Communities study (238 [24.4%]) and newly recruited (de novo; 739 [75.6%]). Participants were randomized (1:1) to hearing intervention or health education control and followed up every 6 months.
INTERVENTIONS: Hearing intervention (4 sessions with certified study audiologist, hearing aids, counseling, and education) and health education control (4 sessions with a certified health educator on chronic disease, disability prevention).
MAIN OUTCOMES AND MEASURES: Social isolation (Cohen Social Network Index score) and loneliness (UCLA Loneliness Scale score) were exploratory outcomes measured at baseline and at 6 months and 1, 2, and 3 years postintervention. The intervention effect was estimated using a 2-level linear mixed-effects model under the intention-to-treat principle.
RESULTS: Among the 977 participants, the mean (SD) age was 76.3 (4.0) years; 523 (53.5%) were female, 112 (11.5%) were Black, 858 (87.8%) were White, and 521 (53.4%) had a Bachelor’s degree or higher. The mean (SD) better-ear pure-tone average was 39.4 dB (6.9). Over 3 years, mean (SD) social network size reduced from 22.6 (11.1) to 21.3 (11.0) and 22.3 (10.2) to 19.8 (10.2) people over 2 weeks in the hearing intervention and health education control arms, respectively. In fully adjusted models, hearing intervention (vs health education control) reduced social isolation (social network size [difference, 1.05; 95% CI, 0.01-2.09], diversity [difference, 0.19; 95% CI, 0.02-0.36], embeddedness [difference, 0.27; 95% CI, 0.09-0.44], and reduced loneliness [difference, -0.94; 95% CI, -1.78 to -0.11]) over 3 years. Results were substantively unchanged in sensitivity analyses that incorporated models that were stratified by recruitment source, analyzed per protocol and complier average causal effect, or that varied covariate adjustment.
CONCLUSIONS AND RELEVANCE: This secondary analysis of a randomized clinical trial indicated that older adults with hearing loss retained 1 additional person in their social network relative to a health education control over 3 years. While statistically significant, it is unknown whether observed changes in social network are clinically meaningful, and loneliness measure changes do not represent clinically meaningful changes. Hearing intervention is a low-risk strategy that may help promote social connection among older adults.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03243422.
PMID:40354063 | DOI:10.1001/jamainternmed.2025.1140
JAMA Neurol. 2025 May 12. doi: 10.1001/jamaneurol.2025.0992. Online ahead of print.
ABSTRACT
IMPORTANCE: Delandistrogene moxeparvovec is a recombinant adeno-associated virus rhesus isolate serotype 74 vector-based gene transfer therapy for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed pathogenic variant of the DMD gene. In a subset of patients in the EMBARK (A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec [SRP-9001] in Participants With DMD) randomized clinical trial, changes in muscle health and pathology were assessed to evaluate the therapeutic impact of the treatment on disease progression.
OBJECTIVE: To determine the effect of delandistrogene moxeparvovec on muscle quantitative magnetic resonance (QMR) measures of disease progression in patients in the EMBARK trial.
DESIGN, SETTING, AND PARTICIPANTS: This was a phase 3, double-blind, placebo-controlled (October 2021-September 2023; week 52 cutoff date: September 13, 2023), multicenter randomized clinical trial that included 131 patients. Patients were randomized, and 125 were treated with either delandistrogene moxeparvovec (n = 63) or placebo (n = 62). The current study focused on a subset of patients who underwent muscle QMR imaging.
INTERVENTION: Single-administration intravenous delandistrogene moxeparvovec (1.33 × 1014 vector genome/kg) or placebo.
MAIN OUTCOMES AND MEASURES: Change from baseline to week 52 in muscle MR was a prespecified exploratory end point. Proton MR spectroscopy (MRS) and 8-point Dixon MR imaging (MRI) measured muscle fat fraction (FF); multislice spin echo MRI measured transverse relaxation time (T2). MRS FF was measured in the soleus and vastus lateralis. MRI FF and T2 were measured in 5 leg muscle locations important for ambulation. A post hoc global statistical test combining all muscles and modalities assessed overall treatment effect.
RESULTS: In this exploratory EMBARK analysis, 39 male participants (delandistrogene moxeparvovec, n = 19; placebo, n = 20; mean [SD] age, 6.10 [1.04] years; mean [SD] baseline North Star Ambulatory Assessment total score, 22.99 [3.71] points) underwent muscle MRI. Treated patients showed less disease progression vs placebo on MR measures. Across muscles and modalities, magnitudes of FF change favored delandistrogene moxeparvovec; between-group differences in least-squares mean change ranged from -1.01 (95% CI, -2.79 to 0.77; soleus) to -0.71 (95% CI, -3.21 to 1.80; vastus lateralis) for MRS FF and -3.09 (95% CI, -7.62 to 1.45; vastus lateralis) to -0.44 (95% CI, -4.01 to 3.12; hamstrings) for MRI FF. T2 reductions (improvements; 4 of 5 muscles) were observed in treated patients vs increases (worsening; all muscles) in placebo patients; within-group differences in least-squares mean change ranged from -1.06 (95% CI, -2.10 to -0.02; soleus) to 0.17 (95% CI, -1.76 to 2.10; biceps femoris) in the delandistrogene moxeparvovec group and from 1.12 (95% CI, 0.08-2.16; soleus) to 2.94 (95% CI, 0.84-5.03; quadriceps) in the placebo group. The global statistical test supported treatment benefit (P = .03).
CONCLUSIONS AND RELEVANCE: Results reveal that QMR outcomes consistently favored delandistrogene moxeparvovec across muscle groups, with treatment leading to decreased fat accumulation and improved T2 vs placebo over 52 weeks. Consistent with treatment effects on functional outcomes observed in the EMBARK trial, these results suggest stabilization or less progression of muscle pathology with delandistrogene moxeparvovec-adding to the totality of evidence supporting disease stabilization or slowing of disease progression with delandistrogene moxeparvovec.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05096221.
PMID:40354061 | DOI:10.1001/jamaneurol.2025.0992
JAMA Netw Open. 2025 May 1;8(5):e259119. doi: 10.1001/jamanetworkopen.2025.9119.
ABSTRACT
IMPORTANCE: National guidelines recommend next-generation sequencing (NGS) of tumors in patients diagnosed with metastatic prostate cancer (mPCa) to identify potential actionable alterations. Non-Hispanic Black men are poorly represented in precision oncology cohorts, and therefore differences in alterations frequencies between non-Hispanic Black and White men remain poorly characterized.
OBJECTIVES: To describe the spectrum and frequency of alterations in PCa-related genes and pathways, as well as associations with self-identified race and ethnicity and overall survival in US veterans.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study compared alteration frequencies between non-Hispanic Black and White men who underwent NGS testing from January 23, 2019, to November 2, 2023, adjusted by NGS analyte and clinicopathologic covariates. The analytic data file was locked on December 8, 2023. NGS testing was performed through the Department of Veterans Affairs (VA) National Precision Oncology Program, part of the largest near-equal access integrated health care system in the US.
EXPOSURES: Pathogenic alterations identified by NGS testing with a commercially available NGS platform.
MAIN OUTCOMES AND MEASURES: The primary outcome consisted of alteration frequencies in individual genes, actionable targets, and canonical prostate cancer pathways. Associations between alteration frequency and race and ethnicity as well as survival were also examined.
RESULTS: A total of 5015 veterans with mPCa who underwent NGS were included (1784 non-Hispanic Black [35.6%] and 3231 non-Hispanic White [64.4%]; mean [SD] age, 67.4 [9.0] years). Non-Hispanic Black veterans were younger, had higher prostate-specific antigen levels at diagnosis, were less likely to report Agent Orange exposure, and resided in more deprived neighborhoods compared with non-Hispanic White veterans. Nine of the top 10 most commonly altered genes were the same in non-Hispanic Black and non-Hispanic White veterans; however, the frequencies of alterations varied by race and ethnicity. Non-Hispanic Black race and ethnicity was associated with higher odds of genomic alterations in SPOP (odds ratio [OR], 1.7; 95% CI, 1.2-2.6) as well as immunotherapy targets (OR, 1.7; 95% CI, 1.1-2.5) including high microsatellite instability status (OR, 3.1; 95% CI, 1.1-9.4). Furthermore, non-Hispanic Black race and ethnicity was associated with lower odds of genomic alterations in the AKT/PI3K pathway (OR, 0.6; 95% CI, 0.4-0.7), androgen receptor axis (OR, 0.7; 95% CI, 0.5-0.9), and tumor suppressor genes (OR, 0.7; 95% CI, 0.5-0.8). Cox proportional hazards modeling stratified by race and ethnicity found that alterations in tumor suppressor genes, including TP53, were associated with shorter overall survival in both non-Hispanic Black (hazards ratio [HR], 1.54; 95% CI, 1.13-2.11) and non-Hispanic White (HR, 1.52; 95% CI, 1.25-1.85) veterans.
CONCLUSIONS AND RELEVANCE: This retrospective clinical genomic profiling cohort study with a large total and proportional representation of non-Hispanic Black men with mPCa reported significant differences in alteration frequencies from key oncogenic pathways but similar survival rates in the near equal-access VA health care setting. This analysis suggests the utility of genomic testing for identifying candidates irrespective of race and ethnicity for precision oncology treatments, which could contribute to equitable outcomes in patients with mPCa.
PMID:40354055 | DOI:10.1001/jamanetworkopen.2025.9119
JAMA Netw Open. 2025 May 1;8(5):e259792. doi: 10.1001/jamanetworkopen.2025.9792.
ABSTRACT
IMPORTANCE: Intrinsic capacity (IC) is a core component of the World Health Organization’s healthy aging framework. Yet, despite multiple validations of IC across various settings, there is still a lack of longitudinal cross-national analysis.
OBJECTIVE: To validate the IC construct, describe variance between key demographic groups, and create population centile curves across 15 countries using data from the Survey of Health, Aging, and Retirement in Europe (SHARE).
DESIGN, SETTING, AND PARTICIPANTS: In this population-based multicenter cohort study, data from SHARE wave 5 (January to November 30, 2013) were analyzed, and subsequent care dependence in wave 6 (January to November 30, 2015) was determined. Adults 50 years and older from SHARE wave 5 with at least 1 available measure and follow-up data in SHARE wave 6 were included. Data analyses were conducted between December 11, 2022, and June 7, 2024.
EXPOSURE: SHARE waves 5 and 6.
MAIN OUTCOMES AND MEASURES: Changes in activities of daily living (ADL) and instrumental activities of daily living (IADL). Methods included structural equation modeling, bifactor analysis, and path analysis. Construct validity was tested through multiple linear regression and validity of estimates through mediation analysis. Centile curves were established using the generalized additive models for location, scale, and shape.
RESULTS: The sample included 64 872 eligible participants aged 50 to 104 years, with a mean (SD) age of 67.24 (10.01) years, of whom 35 976 (55.46%) were women. The bifactor confirmatory factor analysis model achieved good fit (comparative fit index, 0.986; Tucker-Lewis index, 0.981), suggesting an IC structure consisting of 1 general factor and 5 subdomains. Mediation analysis indicated that IC was associated with subsequent declining performance in ADL (standard coefficient [SD], -0.213 [0.002]; P < .001) and IADL (standard coefficient [SD], -0.209 [0.002]; P < .001) after adjusting for age, gender, educational attainment, socioeconomic status, and country. Socioeconomic status was associated with IC both within and between countries. Centile curves for IC by gender and country (5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles) were constructed.
CONCLUSIONS AND RELEVANCE: Results of this cohort study of older adults suggest that IC was a valid and reliable measure that effectively captured individual-level aspects of functional ability. The centile curves developed during the study suggest that IC has the potential to serve as a benchmark for health status in older populations.
PMID:40354051 | DOI:10.1001/jamanetworkopen.2025.9792
Biomater Sci. 2025 May 12. doi: 10.1039/d5bm00033e. Online ahead of print.
ABSTRACT
Inflammation plays a key role in cartilage damage that occurs in osteoarthritis (OA). However, in vitro assessments of tissue-engineered constructs for cartilage regeneration generally do not consider their performance in the presence of inflammation. In this work, the chondrogenic differentiation potential of mesenchymal stromal cells (MSCs) was evaluated in the presence of both chondrogenic factors and inflammatory cytokines, and cartilage formation, degradative response, and inflammatory response were characterized. The addition of cytokines reduced cartilage production, increased cell proliferation, and resulted in an increase in inflammatory markers. Incorporation of hyaluronic acid (HA) had little impact on both collagen fibril microstructure and mechanical properties, two gel properties known to affect cell response, and thus allows the work to probe the biological impact of HA without the confounding effect of these gel properties. Regardless of in vitro environment, HA did not change cartilage production. The inflammatory response was similar with or without HA in terms of IL-6 and IL-10 secretion whereas IL-8 production exhibited some correlation with HA concentration as observed via a linear regression model. Additionally, in the presence of cytokines, inclusion of HA statistically decreased the gene- and protein-level expression of matrix metalloproteinase-13 (MMP-13). Thus, when exposed to both chondrogenic growth factors and inflammatory cytokines within a chondrogenic-promoting collagen I/II blended hydrogel, chondrogenic differentiation of MSCs was limited by the inflammatory environment. These findings emphasize the importance of understanding how biomaterials affect cell responses within disease-relevant inflammatory environments.
PMID:40354044 | DOI:10.1039/d5bm00033e
Eur Arch Paediatr Dent. 2025 May 12. doi: 10.1007/s40368-025-01046-1. Online ahead of print.
ABSTRACT
PURPOSE: An effective Deep learning (DL) based Early Childhood Caries (ECC) prediction model is crucial for early detection of ECC. This study aims to develop and evaluate a deep learning (DL) based hybrid statistical model for ECC prediction.
METHODS: The study employed a computational cross-sectional design, conducted over a three-year period from March 2021 to March 2024. Data analysis was carried out using a hybrid statistical approach that integrated bootstrap methods, Logistic Regression Modelling (LRM), and Multilayer Feed-Forward Neural Networks (MLFFNN). The sample comprised 157 parent-child pairs, providing a robust dataset for examining the research questions.
RESULTS: In the current study, the predictors named, “mother’s education” (β1: 0.423; p < 0.25), “parent’s knowledge of bottle-feeding habit during sleep can cause tooth decay” (β2: -1.264; p < 0.25), “attitude towards the importance of oral health as general health” (β4: -1.052; p < 0.25) and “parent’s self-reported oral pain among their children” (β5: -2.107; p < 0.25) showed significant association with ECC. For this model, the Mean Absolute Deviation (MAD) was 0.02211, Predictive Mean Squared Error (PMSE) was 0.07909, and the accuracy level was 99.98%. No significant difference was observed from the t-test between the actual values and the predicted values of the model (p > 0.05).
CONCLUSION: It has been shown that this unique deep learning-based ECC prediction model appears an effective tool with high accuracy and interpretability for ECC prediction. After implementing the oral health intervention program, focusing on the potential predictors of ECC obtained from this innovative model, policymakers could be able to evaluate their prediction models comparing their results with the findings of the current study. This comparison will guide them in understanding, designing, and implementing a more effective intervention program for ECC prevention.
PMID:40354021 | DOI:10.1007/s40368-025-01046-1
Cogn Process. 2025 May 12. doi: 10.1007/s10339-025-01275-8. Online ahead of print.
ABSTRACT
The human brain operates as a complex network, and understanding its functional connectivity is a core challenge in neuroscience. Functional near-infrared spectroscopy (fNIRS) offers a non-invasive, portable method for studying brain activity and connectivity, providing valuable insights into the brain’s network dynamics. In this study, we used fNIRS to examine the functional connectivity of the human brain during the Dual n-back task, a cognitive challenge that varies in memory load (0-back, 1-back, and 2-back). Data were collected from 24 channels in the frontal cortex and pre-processed with discrete wavelet transform. Functional connectivity matrices for each task level were calculated using correlation analysis, and graph theory metrics such as clustering coefficient and local and global efficiency were assessed. Statistical comparisons (t-tests and ANOVA) revealed significant differences in these metrics across memory load levels, with higher memory loads leading to altered brain connectivity patterns (p < 0.05 for clustering coefficient and local efficiency, p < 0.04 for global efficiency). These findings suggest that as cognitive demand increases, the functional connectivity of the brain’s frontal network changes, reflecting the dynamic nature of brain activity during complex tasks. This research highlights the potential of fNIRS for exploring brain network functions and has broader implications for understanding cognitive processes and developing neurocognitive diagnostics and interventions.
PMID:40354005 | DOI:10.1007/s10339-025-01275-8
Discov Oncol. 2025 May 12;16(1):735. doi: 10.1007/s12672-025-02523-1.
ABSTRACT
The growing burden of cancer and recent surge in healthcare data availability call for new ways of analysing this multifactorial disease and improving patient outcomes. The aim of this study is to develop and evaluate prognostic cancer survival models across ten common cancer types based on a large patient sample. We compare the performance of different machine learning algorithms and assess the added value of genetic information in cancer prognosis. We also provide ways to improve model explainabilty which is critical for model adoption in clinical practice. This study included data from 9977 patients with bladder, breast, colorectal, endometrial, glioma, leukaemia, lung, ovarian, prostate, and renal cancers. Genetic data collected through the 100,000 Genomes Project was linked with clinical and demographic data provided by the National Cancer Registration and Analysis Service, Hospital Episode Statistics and Office for National Statistics. More than 500 prognostic features were assessed and four machine learning algorithms including Elastic Net Cox proportional hazards regression, random survival forest, gradient boosting survival and DeepSurv neural network were developed in this study. Most models achieved good performance varying from 60% in bladder cancer to 80% in glioma with the average C-index of 72% across all cancer types. Different machine learning methods achieved similar performance with DeepSurv model slightly underperforming compared to other methods. Addition of genetic data improved performance in endometrial, glioma, ovarian and prostate cancers, showing its potential importance for cancer prognosis. Patient’s age, stage, grade, referral route, waiting times, pre-existing conditions, previous hospital utilisation, tumour mutational burden and mutations in gene TP53 were among the most important features in cancer survival modelling. By offering a comprehensive set of predictive models for cancer survival, this study fills a critical gap in our understanding of cancer prognosis and provides new tools for informing cancer treatment and consequently improving patient outcomes.
PMID:40353995 | DOI:10.1007/s12672-025-02523-1