Citations

Abstract Exposure to asbestos is the primary cause of mesothelioma, however the processes underpinning its initiation and evolutionary trajectory remain elusive. To address this knowledge gap, we conducted whole exome sequencing and phylogenetic analysis of 277 mesotheliomas. Using multidimensional Dirichlet process clustering we inferred phylogenies, uncovering mutation order dominated by early 13q,1p, 8p, 6q and 22q somatic copy number alterations. Mesotheliomas exhibit a spectrum of genomic intra-tumor heterogeneity spanning linear (L) to highly branched (B) tree topologies, quantifiable by the Weighted Shannon Entropy (WSE). Somatic copy number alterations emerge earlier than single nucleotide variants (SNVs), and at a much faster relative rate in L-mesotheliomas. BAP1 is the only positively selected driver in L-mesotheliomas, whereas, B-mesotheliomas harbor multiple positively selected drivers and an aggressive phenotype, including a bias of loss of RPL5, and MTAP deletion linked to breakpoint enriched with long interspersed nuclear elements. L-trees had lower WSE, but greater T-cell inflammation and tertiary lymphoid structures, despite having a lower neoantigen burden. WSE is higher in larger volume, immunologically cold mesotheliomas, and is associated with shorter survival. In summary, progressive genomic heterogeneity is a defining feature of more aggressive mesothelioma yet illuminates opportunities for precision therapeutic intervention.

ABSTRACT Femoral nerve block is an essential regional anesthetic technique for surgery and analgesia of the anterior thigh, hip, and knee. Its effectiveness depends on understanding the femoral nerve's origin, branching pattern, fascial relationships, and common anatomical variations. This review summarizes current anatomical, cadaveric, and imaging studies to clarify the course of the femoral nerve and highlight variations such as high divisions, accessory branches, and vascular overlap that may influence block success. Approaches including landmark, nerve stimulator, and ultrasound‐guided techniques are reviewed with emphasis on procedural anatomy. Ultrasound features of the femoral nerve and fascia iliaca are correlated with cadaveric findings to outline optimal needle placement and spread of injectate. Continuous catheter methods, anesthetic selection, and volume considerations are also described. Comparative evidence indicates that ultrasound guidance improves accuracy, reduces vascular puncture, and decreases local anesthetic requirements compared with blind or stimulator‐based approaches. Clinical applications across orthopedic surgery, trauma care, and multimodal perioperative pathways are discussed, along with potential complications such as nerve injury, hematoma, systemic toxicity, and quadriceps weakness. Specifically, detailed knowledge of the femoral nerve's course beneath the fascia iliaca, its shifting proximity to the femoral vessels, and its variable early branching is the key to accurate needle placement, dependable block success, and fewer procedure‐related complications.

Tumor-associated antigens (TAAs) are non-mutated antigenic peptides expressed in cancer tissue at abnormally high levels but in normal tissue either at negligible levels, during only particular developmental stages, or in a tissue-restricted manner. The shared nature of TAAs across patients makes them attractive targets for off-the-shelf immunotherapies. However, no studies have comprehensively surveyed the TAA potential of all possible wild-type peptides originating from cancer-associated genes. In this study of 16 cancer tissue types and 39 normal tissue types, we analyzed the expression profiles of protein-coding genes to identify those with aberrantly high RNA levels across multiple solid tumor types and low RNA levels across all normal tissue types examined. We then developed a score to quantify tumor specificity of gene expression. Compared to previously reported TAA genes, those we identified exhibited substantially greater tumor specificity. Seven of these genes demonstrated consistently elevated expression in at least five tumor types and minimal expression across all non-immune-privileged normal tissues. To assess Human Leukocyte Antigen (HLA) class I presentation potential of the multi-cancer-associated genes, we computationally predicted the binding affinities between the most common class I HLA alleles and all possible wild-type TAA epitopes of 8–11 amino acids arising from those genes. We then applied rigorous filtering criteria to prioritize the most promising multi-cancer TAA peptide candidates and evaluated their HLA binding and cell-surface presentation using T2 and immunopeptidome analysis. Our results highlight new potential targets for multi-cancer immunotherapies.

Racial minorities remain underrepresented among allied health providers. Pathway programs address this gap by fostering career exposure and mentorship for underrepresented students. A pilot program was designed to increase underrepresented minority (URM) students entering health professions through career exploration and mentorship. High school students were enrolled into a pre-post survey study through a healthcare magnet school having higher proportions of economically disadvantaged students. Career exploration included healthcare presentations and skills sessions. Students were matched with mentors based on career interests. 22 students participated. The program facilitated career exploration sessions, mentor-mentee meetings, and workshops with diverse healthcare professionals. Participants reported increased likelihood towards pursuing healthcare careers. Preliminary findings suggest similar pilot pathway programs may increase URM student interest in healthcare careers.

Reasonable accommodations in higher education are being more frequently requested by graduate occupational and physical therapy students within didactic and clinical contexts. Researchers aimed to describe the experiences of clinical educators in occupational and physical therapy mentoring graduate students with a disclosed accommodation during terminal clinical education, employing a qualitative design. Semi-structured interviews and one-time electronic survey were completed. Reflexive thematic analysis was conducted following the approach described by Braun and Clarke. Twelve occupational or physical therapy clinical educators participated in semi-structured interviews, each having mentored 1–2 students with a disclosed disability accommodation during a terminal clinical education experience. Four major thematic categories regarding accommodation use in terminal clinical emerged: 1) accommodation process, 2) team approach to accommodating, 3) fostering accommodations, and 4) ambiguity in facilitating accommodations. Clinical educators emphasized the importance of being informed about accommodations well in advance, adapting teaching methods, and maintaining regular communication between academic institutions, clinical sites, and students. Training for clinical educators on the disclosure process, legal obligations, and strategies for effective mentorship to ensure alignment of accommodation, academic requirements, and site expectations is essential.

AIMS: Evidence-based medicine (EBM) is a necessary attribute required for quality medical practice. Despite being integral in advancing medicine and improving patient outcomes, research and quality improvement (QI) rarely integrate into medical education. We present our curricular course design and reveal students' perceptions of the implementation of this course. In addition, we compared physician assistant (PA) student perceptions from the first two traditional cohorts (4 years undergraduate before entry to PA program) to the accelerated 3+2 pathway cohorts (3 years pre-PA coursework followed by 2 years PA program). METHODS: Faculty developed an EBM course taught through student participation in QI projects and assessed students' perceptions of discovery, collaboration, cognitive ownership, and global sense toward general outcomes through the implementation and analysis of validated survey instruments. RESULTS: All students contributed to QI projects, achieved Quality Academy Bronze certification and Silver assessment and disseminated their work at peer-reviewed conferences. Over 56.4% earned Silver certification, and 36.2% of students had their project published in a journal. Student perception of experiential impact was positive overall, with 83.3% of students minimally responding 'true' to the prompts. All students indicated that after the experience, they possessed a basic understanding of QI approaches. The accelerated students selected 'true' for all other prompts more frequently than the traditional student population. DISCUSSION: This manuscript presents vital educational strategies, highlighting an approach and plan to extrapolate EBM principles beyond PA students and to generalize to other healthcare professionals and students. Through course completion, students met educational objectives and reaped additional benefits that positively impacted their resume building and future job prospects. By honing these skills, students are better prepared to contribute to patient care and advance the field of medicine. The accelerated students perceived greater course benefit likely due to the life-experience differences between the two cohorts, whereby the traditional students matriculated into the program with a breadth of prior knowledge obtained through years of contributions to education and careers.

The 2026 ASAHP (Association of Schools Advancing Health Professions) Clinical Education Committee recommendations present a framework for advancing clinical education across health professions. This report emphasizes the importance of expanding clinical education settings, integrating artificial intelligence and telehealth into curricula, ensuring alignment of interprofessional competencies with accreditation standards, and continuing to facilitate collaborative practice across disciplines. These efforts are essential to training a workforce that is not only clinically competent but also adaptable, mindful of equity, and capable of thriving in diverse, team-based care settings. Equally critical is the call to elevate research and scholarly activity within clinical education. The report emphasizes the need for academic-clinical partnerships that support and complete an inquiry into the value, effectiveness, and innovation of clinical training. These recommendations aim to advance a responsive, inclusive, and outcomes-driven clinical education system that benefits students, educators, healthcare systems, and the communities they serve. These efforts reflect ASAHP's name and mission to advance health professions.

Abstract Antidepressants are widely prescribed for major depressive disorder, yet only one-third of patients achieve remission after initial treatment. Previous genome-wide association studies (GWAS) of clinically assessed antidepressant response combined multiple antidepressant classes, potentially obscuring class-specific effects. This study focused on selective serotonin reuptake inhibitors (SSRIs), often first-line due to better tolerability. Data from 15 cohorts across four ancestries were integrated: European (N = 3887; 11 studies), East Asian (N = 1068; 4), African (N = 277; 1), and Admixed American (N = 250; 1). GWAS of non-remission and percentage improvement were conducted within cohorts, followed by ancestry-specific meta-analyses and trans-ancestry meta-regression. Single nucleotide polymorphism (SNP)-based heritability was estimated in European samples. Polygenic scores were used for leave-one-out prediction and to assess shared genetic architecture with psychiatric traits. Gene-level and gene-set enrichment analyses were also performed. No genome-wide significant variants were identified for either outcome in any ancestry-specific or trans-ancestry analyses. However, trans-ancestry meta-regression yielded eight independent loci with suggestive associations (p < 1 × 10 −5 ) for non-remission and 17 for percentage improvement. Gene-set analyses revealed nominal enrichment of the serotonergic synapse pathway for non-remission. SNP-based heritability estimates were not significantly different from zero for either outcome. Better SSRI response was nominally associated with lower genetic predisposition to major depressive disorder, post-traumatic stress disorder, and schizophrenia. This study represents the largest trans-ancestry GWAS of SSRI response, highlighting emerging biological signals. Limited power emphasises the need for larger and ancestrally diverse cohorts to better characterise the genetic architecture of antidepressant response.

BACKGROUND/OBJECTIVES Pediatric hospital medicine (PHM) is a growing field with a unique scholarly perspective and evolving role in academic leadership. Since the last systematic assessment of PHM research in 2009, predating subspecialty certification in 2016 and fellowship accreditation in 2020, the research infrastructure within PHM has not been reevaluated. We sought to assess the current state of PHM research by assessing the number, scope, and scholarly domains of research faculty, as well as research funding and support. METHODS Using the Pediatrics Research in Inpatient Settings Network, we distributed a cross-sectional survey to PHM group leaders across the United States and Canada. The 16-item instrument, adapted from prior PHM and adult hospital medicine surveys, assessed program demographics, faculty effort allocation, research support, funding, and scholarly domains. Surveys were distributed via REDCap with follow-up reminders. Descriptive statistics were used. RESULTS 49 programs responded (51% response rate), representing 1702 faculty (∼40% of US pediatric hospitalists). Fewer than half of programs (n = 21, 43%) reported faculty with more than 50% research effort. One-hundred and ninety faculty members (11%) had dedicated research time, and 72% of those conducting quality improvement research did so without any protected effort. Most PHM programs (n = 27, 55%) received less than $100 000 in total annual research funding. CONCLUSIONS Despite recent PHM subspecialty designation and pediatric hospitalist desire to conduct research, dedicated time and associated supports are uncommon in PHM groups. Improvements in the PHM research pipeline will require understanding institutional financial constraints and diversifying and strengthening research funding.

Abstract Effective filtration and concentration of stool specimens is an essential pre-analytical step for reducing fecal debris and improving organism recovery using microscopy-based ova and parasite (O&P) examination. This study evaluated three commercially available fecal sedimentation-based filtration/concentration systems – ParaPak SpinCon® (Meridian Bioscience), Mini Parasep SF® (Apacor), and the newly-available Paradevice® (Reingenuity) – for qualitative parasite detection and workflow logistics using conventional and artificial intelligence (AI)-assisted microscopy. Forty clinical stool specimens (20 parasite-positive and 20 parasite-negative) were processed with the 3 devices, and the resultant 120 wet mount and 120 trichrome-stained smear preparations were examined using conventional microscopy. Trichrome-stained slides were also scanned at 40x magnification using a Hamamatsu® NanoZoomerS360® flatbed digital slide scanner and images were analyzed using the Techcyte® Fusion Human Fecal Trichrome AI algorithm. Positive and indeterminate digital findings were confirmed by conventional glass slide microscopy. Slides and digital images were reviewed in a blinded manner. Concordance was assessed among the 360 initial evaluations (microscopy and AI-assisted), and discrepant parasitology results were resolved through re-review and specimen reprocessing as needed. Final qualitative agreement across slide/image evaluations using all three concentration systems was 100%. Minor discrepancies in protozoan and white/red blood cell detection/identification were noted in 5 and 7 cases, respectively, and likely reflected sampling and observer variability. While the three concentration systems produced equivalent qualitative results, the Paradevice® and Mini Parasep SF® offered the most streamlined workflows. These findings support the Paradevice® and Mini Parasep SF® as efficient, analytically equivalent systems that are compatible with traditional and AI-assisted O&P workflows. Importance Microscopy-based examination of stool specimens remains an important diagnostic tool for intestinal parasitic infections. Filtration and concentration methods improve test performance by increasing organism recovery and reducing obscuring fecal debris prior to evaluation. These methods may also facilitate the preparation of thin monolayer trichrome-stained slides for digital scanning and automated parasite detection. Because many clinical laboratories rely on commercial filtration and concentration systems, supply chain disruptions, product shortages, and manufacturer recalls threaten testing continuity, underscoring the need for validated alternatives. This study demonstrates that multiple commercially available concentration systems provide equivalent parasite detection while supporting both conventional microscopy and emerging digital workflows. These findings provide laboratories with evidence-based alternatives that enhance operational resilience without compromising diagnostic performance.