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Importance Ensuring access to accommodations is critical for resident physicians and their patients. Studies show that a large proportion of medical trainees with disabilities do not request needed accommodations; however, drivers of nonrequests are unknown. Objective To assess the frequency of accommodation requests among first-year resident physicians (ie, interns) with disabilities and to identify possible drivers of nonrequest for needed accommodations. Design, Setting, and Participants As part of the Intern Health Study, a longitudinal cohort study of first-year resident physicians, residents at 86 surgical and nonsurgical residency programs in 64 US institutions provided demographic and training characteristics 2 months prior to matriculation (April-May 2021). At the end of their intern year (June 2022), participants completed a new survey with questions about disability-related information, including disability status, disability type, whether they received accommodations, and if not, reasons for nonaccommodation. Poststratification and attrition weights were used to estimate the frequency of accommodation requests and reasons for not requesting accommodations. Interns reporting at least 1 disability were included in the analysis. Main Outcomes and Measures Prevalence of reported disabilities, residency specialties distribution, frequency of accommodation requests, and reasons for nonaccommodation among resident physicians with disabilities. Results Among the 1486 resident physicians who completed the baseline survey, 799 (53.8%) replied to the disability questions. Of those, 94 interns (11.8%; weighted number, 173 [11.9%]) reported at least 1 disability and were included in the present study (weighted numbers, 91 [52.6%] men, 82 [47.4%] women, mean [SD] age, 28.6 [3.0] years). Among interns with reported disability and need for accommodations (83 of 173 [48.0%]), more than half (42 [50.6%]) did not request them. The most frequently reported reasons for not requesting needed accommodations were fear of stigma or bias (25 [59.5%]), lack of a clear institutional process for requesting accommodations (10 [23.8%]), and lack of documentation (5 [11.9%]). Conclusions and Relevance Program directors should investigate cultural and structural factors within their programs that contribute to an environment where residents do not feel safe or supported in disclosing disability and requesting accommodation and review their disability policies for clarity.

This cohort study uses data from a survey of US medical interns to assess the prevalence of self-reported disability and program accommodations and the association between accommodations, depressive symptoms, and self-reported medical errors among resident physicians.

Low numeracy may skew patient perceptions of information about cancer. This paper examines the relationship between self-reported measures of perceived numeracy and cancer knowledge, beliefs, and affect, using results from 3,052 respondents to the 2007 Health Information National Trends Survey (HINTS-3). Chi-squared tests were used to identify differences in responses between high- and low-numeracy groups using three measures of perceived numeracy. Multivariable logistic regression models were used to evaluate the association between the three perceived numeracy measures and cancer information overload, cancer fatalism, cancer prevention knowledge, and cancer worry. Respondents with low perceived numeracy as expressed by discomfort with medical statistics were more likely to report information overload, to display fatalistic attitudes towards cancer, to lack knowledge about cancer prevention, and to indicate that they worried about cancer more frequently. After controlling for sociodemographic characteristics, this measure of perceived numeracy remained significantly associated with information overload, fatalism, lower prevention knowledge, and worry. The other measures of perceived numeracy, which measured understanding and use of health statistics, were not associated with cancer perceptions. Our findings suggest that individuals with low perceived numeracy broadly differ from individuals with high perceived numeracy in their perceptions of cancer and cancer prevention. By improving our understanding of how perceived numeracy affects patient perceptions of cancer, health providers can improve educational strategies and targeted health messaging.

Headaches are a nearly universal human experience traditionally diagnosed based solely on symptoms. Recent advances in imaging techniques and artificial intelligence (AI) have enabled the development of automated headache detection systems, which can enhance clinical diagnosis, especially when symptom-based evaluations are insufficient. Current AI models often require extensive data, limiting their clinical applicability where data availability is low. However, deep learning models, particularly pre-trained ones and fine-tuned with smaller, targeted datasets can potentially overcome this limitation. By leveraging BioMedCLIP, a pre-trained foundational model combining a vision transformer (ViT) image encoder with PubMedBERT text encoder, we fine-tuned the pre-trained ViT model for the specific purpose of classifying headaches and detecting biomarkers from brain MRI data. The dataset consisted of 721 individuals: 424 healthy controls (HC) from the IXI dataset and 297 local participants, including migraine sufferers ( n  = 96), individuals with acute post-traumatic headache (APTH, n  = 48), persistent post-traumatic headache (PPTH, n  = 49), and additional HC ( n  = 104). The model achieved high accuracy across multiple balanced test sets, including 89.96% accuracy for migraine versus HC, 88.13% for APTH versus HC, and 83.13% for PPTH versus HC, all validated through five-fold cross-validation for robustness. Brain regions identified by Gradient-weighted Class Activation Mapping analysis as responsible for migraine classification included the postcentral cortex, supramarginal gyrus, superior temporal cortex, and precuneus cortex; for APTH, rostral middle frontal and precentral cortices; and, for PPTH, cerebellar cortex and precentral cortex. To our knowledge, this is the first study to leverage a multimodal biomedical foundation model in the context of headache classification and biomarker detection using structural MRI, offering complementary insights into the causes and brain changes associated with headache disorders.

Increased climatic variability can impact tree physiological processes beyond what is predicted from changes in mean conditions. We assessed the sensitivity of conifer saplings to spatial and temporal variability in meteorological conditions, taking advantage of the end of California’s historic drought and the exceedingly wet winter of 2017. We sought to understand how very dry and very wet conditions constrain photosynthesis and growth in four regionally dominant conifers and whether sensitivity in these processes changes across a 500 m gradient in elevation. All species demonstrated phenotypic plasticity in response to temporal differences in precipitation on both inter-annual and seasonal timescales. Net photosynthesis in Pinus contorta decreased from an early season 2016 average of 12.4 to 6.89 μmol CO2 m−2 s−1 later in the summer, but increased 14.1% between seasons in the wet year. By contrast, elevation had almost no effect on instantaneous photosynthetic gas exchange, CO2 response curve parameters, or stem water potential in any of the years for any of the species. Effects of the heavy snow year (2017) on needle growth differed between elevations. Pinus contorta showed a 38.9% increase in average needle length at the lower two elevations but a 31.6% decrease at the highest site compared to the height of the drought. Despite these differences, biological variation was dampened compared to the physical variation between years, suggesting these trees can effectively withstand substantial meteorological variability. Our results show that these species demonstrated considerable ability to tolerate and recover from an extreme drought event.

Background The purpose of this study was to interrogate brain iron accumulation in participants with acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and to determine if functional connectivity is affected in areas with iron accumulation. We aimed to examine the correlations between iron accumulation and headache frequency, post-concussion symptom severity, number of mTBIs, and time since most recent TBI. Methods Sixty participants with acute PTH and 60 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging including quantitative T 2 * maps and resting-state functional connectivity imaging. Between group T 2 * differences were determined using T-tests ( p  < 0.005, cluster size threshold of 90 voxels). For regions with T 2 * differences, two analyses were conducted. First, the correlations with clinical variables including headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) symptom severity scale scores were investigated using linear regression. Second, the functional connectivity of these regions with the rest of the brain was examined (significance of p  < 0.05 with family wise error correction for multiple comparisons). Results The acute PTH group consisted of 60 participants (22 male, 38 female) with average age of 42 ± 14 years. The HC group consisted of 60 age-matched controls (17 male, 43 female, average age of 42 ± 13). PTH participants had lower T 2 * values compared to HC in the left posterior cingulate and the bilateral cuneus. Stronger functional connectivity was observed between bilateral cuneus and right cerebellar areas in PTH compared to HC. Within the PTH group, linear regression showed negative associations of T 2 * in the left posterior cingulate with SCAT symptom severity score ( p  = 0.05) and T 2 * in the left cuneus with headache frequency ( p  = 0.04). Conclusions Iron accumulation in posterior cingulate and cuneus was observed in those with acute PTH relative to HC; stronger functional connectivity was detected between the bilateral cuneus and the right cerebellum. The correlations of decreased T 2 * (suggesting higher iron content) with headache frequency and post mTBI symptom severity suggest that the iron accumulation that results from mTBI might reflect the severity of underlying mTBI pathophysiology and associate with post-mTBI symptom severity including PTH.

Background The Women Informed to Screen Depending On Measures of risk (WISDOM) Study is the first prospective, population-wide application of personalized breast cancer screening. We aim to demonstrate the feasibility of the study’s novel use of polygenic risk scores (PRSs) to tailor screening, evaluate our strategy for adapting PRSs to diverse populations, and quantify the impact of incorporating PRS on the study’s screening recommendations. Methods WISDOM is a randomized, preference-tolerant screening trial in the USA testing the safety and morbidity of risk-based versus annual screening in women aged 40–74 without a prior history of breast cancer. This early report includes participants in the risk-based arm only and compares screening recommendations generated by the Breast Cancer Surveillance Consortium (BCSC) clinical risk model alone versus the BCSC model modified by a PRS (BCSC-PRS). The main outcome of interest is the proportion of participants with a change in screening recommendation after integrating PRS for risk stratification. Results In the risk-based arm, 21,631 participants received a PRS. Small but statistically significant differences in the PRS were seen between major racial and ethnic groups ( p  < 0.001), and higher PRS was associated with greater extent of family history ( p  < 0.001) and denser breasts ( p  < 0.001). BCSC-PRS risk estimates changed the screening recommendations for 14% of women aged 40–49 compared to BCSC alone and for 10% of women aged 50–74. Projected net screening encounters at the population level were similar for both age groups. Conclusions In a first-in-kind application of PRS to inform breast cancer screening approaches, we demonstrate feasibility for scaled implementation, moderate changes to individual screening recommendations, and minimal projected downstream burden on the healthcare system. Trial registration Prospectively registered on ClinicalTrials.gov as NCT02620852 on 12/2/2015.

Background Post-traumatic headache (PTH) is a common acute and persistent symptom following mild traumatic brain injury (mTBI). Symptoms of cutaneous allodynia and presence of nociceptive sensitization might be associated with acute PTH and its persistence. The objectives of this study were to compare allodynia symptoms and cutaneous heat pain thresholds amongst males and females with acute PTH to healthy controls (HC) and determine if pain thresholds and allodynia symptoms are associated with PTH outcomes. Methods This prospective longitudinal study enrolled 139 adults with acute PTH attributed to mTBI as defined by the International Classification of Headache Disorders and 95 HC. All PTH participants completed a baseline research visit near PTH onset and a follow-up visit three to four months later. All PTH participants and a subset of HC completed the Allodynia Symptom Checklist (ASC-12) at each research visit. A different subset of the PTH participants ( n  = 37) and HC ( n  = 36) underwent quantitative sensory testing (QST) during baseline, 4-week, and 16-week research visits to quantify cutaneous heat pain thresholds at the forehead and forearms. Data from daily headache diaries were used to determine longitudinal PTH improvement versus non-improvement at three months. ASC-12 score and pain threshold comparisons were made between PTH and HC groups, PTH improved versus non-improved cohorts, and between PTH males and females. Results Participants with PTH had an average age of 42.6 years and 64.0% were female. HC had an average age of 40.0 years and 65.3% were female. At the first visit, PTH participant ASC-12 scores averaged 3.6 versus 0.1 amongst HC, p  < 0.001. 57.1% of PTH participants had headache improvement at 3 months. ASC-12 scores were higher in the PTH non-improved versus improved group at baseline (4 versus 2.7, p  = 0.046) and 3-month follow-up (3.8 versus 1.9, p  = 0.004). ASC-12 scores were higher in females than males at baseline (4.7 versus 1.6, p  < 0.001) and 3-months (3.9 versus 1.2, p  < 0.001). Cutaneous heat pain thresholds at the forehead and forearm did not differ between any group. Conclusions PTH attributed to mTBI is associated with symptoms of cutaneous allodynia. Greater allodynia symptoms are present in females with PTH compared to males and may be associated with PTH non-improvement.

BackgroundMyocardial infarction (MI) is the leading cause of heart failure. The adult human heart, unlike mouse or early neonatal hearts, lacks the capability to undergo extensive regeneration. Rapid re-establishment of blood flow post MI is vital for limiting tissue damage and preserving cardiac function. A better understanding of the mechanisms underpinning cardiovascular regeneration in adult hearts is needed. Recent technologies including single cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have empowered studies of healthy and diseased tissue at unprecedented resolution.Methods and ResultsFirst, we established an EC-specific multispectral lineage-tracing mouse model (Pdgfb-iCreERT2-R26R-Brainbow2.1) and assessed EC clonal proliferation in the adult heart post MI. We discovered a significant increase in clone size in the MI hearts compared to the healthy controls (cells per clone = 4.0 ± 2.1 vs. 10.3 ± 10.6, P < 0.0001), demonstrating that the structural integrity of adult endothelium following MI was maintained through clonal proliferation by resident ECs in the infarct border region. We then isolated the Pdgfb-lineage ECs from the healthy (12,780) and injured (15,818) hearts through FACS, performed scRNA-seq and downstream analysis, and defined ten transcriptionally discrete heterogeneous EC states and associated pathways that might impact upon cardiovascular regeneration. Next, high-quality scRNA-seq data from 10 curated studies of the mouse and human hearts were integrated for a cross-species systematic meta-analysis. Coronary ECs were enriched in silico based on the expression of 45 endothelial markers and analysed using Seurat. Unsupervised clustering of integrated neonatal and adult mouse coronary ECs revealed 15 transcriptionally distinct clusters. The subsequent DEG analysis identified the Vegfc pathway as a program that can potentially augment adult cardiovascular regeneration in the neonatal heart. The integration of the mouse and human coronary EC data and the DEG analysis identified 41 commonly upregulated genes after ischaemic injuries, including KLF4, EGR1 and ZFP36. Further, spatial transcriptomics analysis of MI patient-derived heart tissues revealed the elevation of these conserved targets in the damaged tissues in the acute phase. We validated the upregulation of these targets in the injured human coronary ECs (% KLF4+ CD31+ EC = 29.7 ± 7.5% versus 7.3 ± 6.4%, P = 0.0009;% EGR1+ CD31+ EC = versus 10.1 ± 3.5% versus 3.4 ± 2.5%, P = 0.004; ZFP36 expression was high the diseased tissue but minimal in control hearts). In vitro siRNA knockdown of ZFP36 in cultured human cardiac microvascular endothelial cells (HCMECs) showed that cell proliferation was significantly inhibited compared to the control siRNA treatment (Fold change of%EdU+ HCMECs = 0.84 ± 0.19 vs 0.25 ± 0.12, P = 0.0007). In vivo, we used the multi-spectral MI mouse model and showed that the administration of rhVEGF-C significantly increased neovascularisation in the infarct border in the adult mouse heart compared to the PBS treated controls (vascular clone volume (μm3) = 3072 ± 491.2 versus 426 ± 105, P = 0.02).ConclusionWe have successfully developed and implemented a robust framework, using meta-analysis of scRNA-seq, spatial transcriptomics, tissue section immunofluorescence, primary human cell culture, and multispectral MI mouse model, to collectively identify, assess, and validate novel mechanisms and targets potential to promote vascular regeneration.