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Neural sensitivity to peer hierarchies: Risks for depressive symptoms for low status adolescents
Full text linkPopularity is increasingly salient and impactful in adolescence, and unpopular youth are at significantly greater risk of experiencing depressive symptoms. However, adolescents can vary in their neural sensitivity to social stimuli, such that some adolescents may be more impacted by social status than others. We examined whether adolescents' neural sensitivity to popular and unpopular peers moderates the extent that their own social status is related to trajectories of depressive symptoms across 5 years (6th–10th grades). During an fMRI scan, adolescents from the southeastern United States (n = 116, 61 female, 29% White Non‐Hispanic, 36% Hispanic, 22% Black/African American, 11% multiracial, 2% other; M age = 13.59, SD = 0.59) viewed pictures of their popular and unpopular classmates based on sociometric nominations from their social networks. Results indicated that heightened amygdala sensitivity to unpopular peers moderated the relations between participants' own popularity and their depressive symptoms, leading to increased depressive symptoms for unpopular youth. These findings suggest that individual differences in sensitivity to peer hierarchies impact the degree to which adolescents are negatively impacted by their own level of popularity
The Clinical Utility of Strength Measures in Predicting Patient Progression Following ACLR
Full text linkBackground: Prognostic indicators of lack of strength progression or poor self-reported function may alter rehabilitation decision-making following anterior cruciate ligament reconstruction (ACLR). The torque-velocity relationship is a noninvasive measure of muscle function that is altered following ACLR, but its prognostic value has not been explored. Purpose: To compare the torque-velocity relationship of knee extensors (quadriceps) and flexors (hamstrings) between the ACLR and uninvolved limbs and to determine whether the torque-velocity relationship was prognostic of subsequent achievement of satisfactory strength. Study Design: Cohort study; Level of evidence, 3. Methods: Participants following ACLR with bone–patellar tendon–bone or hamstring autografts completed isokinetic knee extension and flexion at 90°/s and 180°/s bilaterally, the International Knee Documentation Committee (IKDC) form, and Knee injury and Osteoarthritis Outcome Score (KOOS) at approximately 5.5 and 8.3 months post-ACLR. The torque-velocity relationship was defined as the difference in torque production across velocities, and relationships were analyzed using 2 × 2 analyses of variance. Binomial logistic regressions were used to determine the association between the torque-velocity relationship, age, sex, and time postsurgery with satisfactory knee extension strength, IKDC, and KOOS at visit 2. Results: This study included 189 participants (22.4 ± 9.3 years; 55.0% female). There were significant increases in the quadriceps torque-velocity relationship from visit 1 (0.22 Nm/kg) to visit 2 (0.34 Nm/kg, P < .001) but no differences in the uninvolved limb (P = .46) or for the hamstrings (P = .20). When controlling for sex, age, and graft type, higher visit 1 quadriceps torque-velocity relationships were predictive of a higher likelihood of achieving satisfactory knee extension strength (≥1.23 Nm/kg; odds ratio [OR], 1.05; P = .04). The model was associated with an acceptable IKDC score (≥75.9, P = .01), but the only significant individual predictor was age (OR, 0.94; P < .01). The model was not associated with KOOS Sport score at visit 2 (P = .24). Conclusion: Quadriceps torque-velocity relationships of the ACLR limbs increased across time but remained less than uninvolved limbs. Hamstrings torque-velocity relationships remained similar between limbs and across time. These findings indicate that the torque-velocity relationship of the quadriceps changed over time and was predictive of future satisfactory strength. Clinical Relevance: Clinicians may use a greater quadriceps torque-velocity relationship as a positive indication of a patient's ability to achieve satisfactory strength later in rehabilitation
Crowdsourcing is Acceptable to Develop Pre-Exposure Prophylaxis Promotions in Alabama: A Qualitative Study with Sexual Minority Men and Sexual Health Providers
Full text linkPlain Language Summary Crowdsourcing is a way to engage community members to participate in solving problems and sharing the solutions back with the community. Pre-exposure prophylaxis (PrEP) effectively prevents HIV. Crowdsourcing to promote PrEP may be a way to better communicate about PrEP to community members, but we do not know how acceptable this would be the community. This study explores how gay, bisexual, and other men who have sex with men and sexual health providers would feel about using crowdsourcing to promote PrEP. To determine this, we conducted FGDs and interviews with participants. We audio-recorded, transcribed, and studied their answers to understand what were the most important aspects. We found that 1) a person's background influences their participation, 2) community members would be motivated to participate, 3) community members would need resources, like funding or time, to participate, and 4) shame related to sexual health, HIV, LGBTQ+ identity as well as other barriers may prevent some community members from being able to participate. Overall, we found that community members and sexual health providers feel that crowdsourcing could be a good idea to better promote PrEP in the community.Introduction Crowdsourcing engages the community to create and share solutions; this participatory method could be used to create effective pre-exposure prophylaxis (PrEP) promotions. We explored acceptability of using crowdsourcing to develop PrEP promotions among sexual minority men (SMM) and sexual health providers in Alabama. Methods We conducted focus group discussions (FGDs) with SMM and interviews with sexual health providers with guides grounded in the Theoretical Framework of Acceptability. We employed thematic analysis through deductive and inductive coding. Results Ten SMM (60% Black, 50% younger than 30 years) participated in FGDs, and six providers completed interviews. We found four themes: 1) Personal identity and background inform the participation and products of crowdsourcing, 2) SMM and providers are motivated to participate in crowdsourcing, 3) Crowdsourcing participants require resources to effectively engage, and 4) Logistic and social factors are barriers to crowdsourcing participation. Discussion Crowdsourcing as a strategy to create PrEP promotions in the Southern United states would be acceptable and feasible in the correct context. These formative, yet novel, findings demonstrate that SMM and sexual health providers would be willing to participate in crowdsourcing events and also provide key insight to design crowdsourcing events
The Debt-Financed Diet: A Critical Analysis of the Unjustified Exclusion of Financial Liability from United States Food Security Measurement
Full text linkThe measurement of food security in the United States, as operationalized by the United States Department of Agriculture (USDA), stands as the nation’s principal barometer for social well-being and the efficacy of the safety net. Defined formally as "access by all people at all times to enough food for an active, healthy life," the concept is theoretically robust.1 However, the practical application of this definition, through the 18-item Household Food Security Survey Module (HFSSM), suffers from a critical epistemological and economic oversight: it measures the physiological and behavioral consequences of resource deprivation (e.g., skipping meals) while systematically ignoring the financial mechanisms employed to avert these consequences
A systematic assessment of large language models' knowledge of rare diseases: How much do large language models know about rare disease?
Full text linkLarge language models (LLMs) perform well on general medical benchmarks, but their ability to reason about rare diseases (RDs) remains unclear. Rather than challenge LLMs to diagnose a limited number of cases that are unlikely to represent all RDs or RD-associated genes, we instead sought to comprehensively probe LLM understanding of RD-associated genes and phenotypes. We systematically evaluated six leading general-domain LLMs (GPT-4, Claude 3.7, Llama-3.3 70B, Gemma-2 27B, Llama-3.2, and Phi-4) for their ability to generate core phenotypic features and causal genes required to support reasoning for 10,892 Orphanet diseases. Outputs were mapped to Human Phenotype Ontology (HPO) terms and HGNC gene symbols and compared with curated references using set overlap, semantic similarity, and disease ranking via the likelihood ratio interpretation of clinical abnormality (LIRICAL) framework applied to 8,000 patient Phenopackets. LLM recall of curated RD knowledge was generally low, with gene associations retrieved more accurately than phenotypes. Commercial models, particularly GPT-4 and Claude, achieved over 60% recall for gene associations but struggled with precise phenotype recovery. Despite low exact overlaps, moderate semantic similarity scores indicated partial alignment with curated data. When used in LIRICAL, LLM-derived phenotypic profiles yielded ranking performance close to that of gold standard profiles, although direct diagnostic accuracy remained limited. Interestingly, convergent non-curated terms across models suggest potential for hypothesis generation. Current generalist LLMs lack the precision to replace curated RD knowledge bases but offer complementary, semantically relevant information. Our results support hybrid approaches that combine expert curation with selectively integrated LLM outputs to enhance and scale ontology-driven RD diagnostics
The Cognitive Architecture of Anorexia Nervosa and Associated Eating Disorders: A Meta-Analytic Review of Intelligence, Neuropsychology, and Genetic Correlations
Full text linkThe relationship between high intellectual potential and the pathology of eating disorders (EDs), particularly anorexia nervosa (AN), has captivated clinical attention for nearly a century. From the earliest descriptive psychopathologies to modern genomic inquiries, a consistent thread runs through the literature: the observation that individuals who starve themselves often possess extraordinary cognitive resources. Hilde Bruch, a pioneer in the field, famously observed that her patients were often coined "high achievers" of their families; often discussed as perfectionists, and academically gifted. Yet, this apparent advantage presents a clinical paradox. How can individuals with such high cognitive capacity engage in behaviors that are so objectively destructive? Furthermore, does this "genius" persist through the ravages of starvation, or is the "superior intelligence" merely a premorbid trait that is eroded by the metabolic demands of the disorder
Summary of Research: Pregnancy and Infant Outcomes in Multiple Sclerosis: Findings from the Global MAPLE-MS Pharmacovigilance Program
Full text linkInformation on pregnancy and infant outcomes after cladribine tablets exposure is limited, as its use is not recommended during pregnancy. This is a summary of the original published article ‘Pregnancy and infant outcomes in multiple sclerosis: findings from the Global MAPLE-MS Pharmacovigilance Program’. The primary outcome is the prevalence of major congenital anomalies (MCAs) in babies. Secondary outcomes include other pregnancy outcomes (live birth, elective termination, spontaneous abortion, ectopic pregnancy, and stillbirth)
Vascular Reconstruction in Extremity Soft Tissue Sarcomas: A Systematic Review and Single‐Arm Meta‐Analysis
Full text linkINTRODUCTION: The management of extremity soft tissue sarcomas (STS) involving major vessels presents unique challenges, historically leading to amputation. Advances in vascular reconstruction have enabled limb-sparing surgery (LSS), but outcomes and perioperative risks remain uncertain. This systematic review and meta-analysis aimed to evaluate oncologic results following LSS with vascular reconstruction in extremity STS. METHODS: A systematic review and single-arm meta-analysis were performed according to PRISMA guidelines, with registration in PROSPERO. PubMed, Embase, and Cochrane Library were searched from inception to June 2025 for studies reporting outcomes in patients with extremity STS undergoing LSS with vascular reconstruction. Pooled analyses estimated limb salvage, survival, and complication rates using random-effects models. RESULTS: Thirty-one studies comprising 520 patients were included. Approximately 58% were male, with a mean age ranging from 29.3 to 59 years. The most common tumor localizations were the thigh (59.5%), inguinal region (15.9%), and popliteal fossa (8.6%). Liposarcoma (24.0%), synovial sarcoma (19.6%), and osteosarcoma (14.8%) were the most frequent histological subtypes. The pooled limb salvage rate was 89% (95% CI, 86%-92%), while amputation occurred in 10% (95% CI, 8%-14%). One- and 5-year overall survival rates were 89% and 62%, respectively, with disease-free survival rates of 74% and 55%. Major complications included graft thrombosis (19%), wound complications (29%), and wound infection (22%). CONCLUSIONS: Limb-sparing surgery with vascular reconstruction is effective for extremity STS involving major vessels, enabling high limb salvage and favorable long-term survival without compromising oncologic outcomes. However, substantial perioperative morbidity persists, underscoring the need for multidisciplinary care, careful patient selection, and prospective studies to refine indications and enhance quality of life
Improvements in Perceived Abilities and Speech Recognition in Quiet and Noise for Older Adults With Single-sided Deafness or Asymmetric Hearing Loss: A Multi-center Investigation.
Full text linkOBJECTIVE: Cochlear implantation is an effective treatment option for individuals with single-sided deafness (SSD) and asymmetric hearing loss (AHL). Most data are from young and middle-aged adults. This study assessed the outcomes of cochlear implant (CI) use for older adults. STUDY DESIGN: Multi-center, prospective, repeated-measures. SETTING: Five academic centers. PATIENTS: A total of 39 older adult (60 yr or older) CI users with SSD or AHL. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: Procedures were completed preoperatively with a rerouting device and 3, 6, and 12 months postactivation with the CI. Speech recognition for the affected ear was assessed with CNC words. Speech recognition in noise was assessed with the AzBio sentences. The target was presented from the front loudspeaker and the masker was co-located with the target, 90 degrees toward the better hearing ear, or 90 degrees toward the affected ear. Perceived abilities were assessed with the Speech, Spatial, and Qualities of hearing scale. RESULTS: Participants demonstrated significant improvements over time on all measures (p<0.001). There was no significant effect of age on CNC scores (p=0.493) or perceived abilities (p=0.314). Age (p=0.031) and contralateral hearing level (p<0.001) significantly influenced speech recognition in noise. The majority of participants experienced similar or improved performance in noise compared with their own preoperative abilities. CONCLUSIONS: Older adults with SSD and AHL demonstrate significant benefit from cochlear implantation, supporting its effectiveness for Centers for Medicare and Medicaid Services beneficiaries. Candidates should be counseled on how age and hearing level in the better hearing ear may affect outcomes, particularly in noisy environments
Single-cell landscape of peripheral and tumor-infiltrating immune cells in HPV-negative HNSCC
Full text linkHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HPV-negative HNSCC, arising in diverse upper airway mucosal niches, is particularly aggressive, with poor 5-y survival and a limited response to immune checkpoint inhibitors. A deeper understanding of the tumor-localized immune landscape is essential to uncover actionable immunotherapeutic targets. Here, we integrated two single-cell RNA sequencing (scRNA-seq) datasets from 29 samples totaling nearly 300,000 immune cells to dissect immune rewiring during tumor progression and lymph node metastasis in HPV-negative HNSCC. We identified distinct shifts in adaptive immune cell populations across 14 peripheral blood mononuclear cell (PBMC) and 21 tumor-infiltrating immune cell (TIC) states. Notably, TICs exhibited enriched interferon response and immunomodulatory gene signatures, in contrast to PBMCs, indicating tumor-specific immune imprinting. Ligand-receptor analysis revealed that immunosuppressive crosstalk between macrophages and cytotoxic cells was associated with advanced disease. To spatially validate these transcriptional states, we conducted multiplexed immunofluorescence profiling on nine locally invasive HPV-negative HNSCCs, all from the ventrolateral tongue mucosa. Spatial proteomics confirmed peritumoral enrichment of activated (CD107a+, ICOS+) NK and CD8+ T cells and intratumoral accumulation of exhausted (PD-1+, PD-L1+) phenotypes, mirroring pseudotime trajectories inferred from scRNA-seq. These findings highlight spatially localized cytotoxic cell exhaustion as a key immune evasion mechanism in HPV-negative HNSCC and underscore the value of integrating spatial and single-cell data to reveal therapeutic vulnerabilities