Citations

Foundation models, known as the large-scale, pretrained models capable of generalizing across diverse tasks, have significantly advanced the field of medical image analysis. While most early applications focused on 2D modalities, the unique challenges and opportunities associated with volumetric medical imaging have recently attracted growing interest. This study provides a comprehensive overview of the current landscape of foundation models tailored for volumetric medical image analysis, with a focus on CT, MRI, and PET imaging. We examine key components of these models, including 3D architectures, training strategies, and supported modalities. In addition, we highlight their contribution to major clinical tasks such as classification and prediction, segmentation, image registration, quality enhancement, and visual question answering. Critical challenges of these models, including high computational cost, limited and less diverse 3D datasets, and domain adaptation, are discussed alongside the promising solutions and future research directions. By synthesizing recent advances in volumetric foundation models and outlining key technical and clinical challenges, this review provides a thorough roadmap toward the development of scalable, generalizable, and clinically applicable AI systems for volumetric medical images.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of 13.3%. First-line treatment relies on two chemotherapy regimens, FOLFIRINOX (FOLFNX) or gemcitabine plus nab-paclitaxel (GEMPAC). However, direct clinical comparisons between these regimens have yielded inconsistent results across survival and toxicity endpoints, and the molecular basis of heterogeneous treatment responses remains poorly defined. To investigate regimen-specific tumor-cell-intrinsic mechanisms, we performed quantitative proteomic profiling of a primary PDAC-derived MIA PaCa-2 cell line following treatment with FOLFNX or GEMPAC. Differentially expressed proteins were analyzed using Gene Ontology, KEGG, and Ingenuity Pathway Analysis to define pathway-level alterations, and findings were contextualized using TCGA transcriptomic data. Proteomic analyses revealed that FOLFNX and GEMPAC engage in distinct cytotoxic programs. FOLFNX predominantly suppressed ribosome biogenesis and mitochondrial translation, consistent with sustained metabolic and biosynthetic stress, whereas GEMPAC preferentially disrupted mitotic cytokinesis and phosphatidylinositol phosphate biosynthesis, consistent with mitotic failure. Integration with TCGA data showed that FOLFNX-altered proteins aligned with favorable prognostic expression signatures, whereas GEMPAC-associated proteins were enriched among adverse profiles, reflecting engagement of distinct tumor-intrinsic programs. Together, these findings provide mechanistic insight into differential chemotherapy responses and establish a foundation for proteomics-based biomarkers to guide personalized chemotherapy selection in PDAC.

ABSTRACT Background and Aims Women now comprise over half of US medical school matriculants yet remain underrepresented in academic leadership, including emergency medicine (EM). Leadership training within medical education is variable, particularly in communication, conflict management, negotiation, and operations. Concurrently, large language models (LLMs) are emerging as accessible tools to support leadership skill development. This study aimed to develop and evaluate an AI‐augmented leadership skills workshop designed to address the leadership gap for women in academic emergency medicine. Materials and Methods The Academy for Women in Academic Emergency Medicine (AWAEM) developed and piloted a leadership development workshop at the 2025 Society for Academic Emergency Medicine Annual Meeting. The curriculum integrated evidence‐based leadership frameworks with experiential small‐group learning and structured demonstrations of LLM use. Educational strategies included brief didactics, reflection on lived leadership challenges, peer discussion, and guided LLM‐supported simulation of leadership conversations. Pre‐workshop and postworkshop surveys and qualitative feedback were collected to assess participant confidence and perceived utility. Results Participants demonstrated increased confidence in navigating power‐differential conversations and initiating negotiations following the workshop. There was greater reported intent to apply leadership frameworks and to utilize LLMs for leadership‐related tasks. Qualitative feedback highlighted themes of empowerment, practical applicability, and the importance of a psychologically safe, gender‐informed learning environment. Participants identified LLMs as a novel and accessible adjunct to traditional leadership development resources. Discussion and Conclusions An AI‐augmented, experiential leadership workshop is a feasible and scalable approach to addressing persistent leadership development gaps for women in academic emergency medicine. Integrating LLM‐supported practice with established leadership frameworks may enhance learner confidence and engagement. This model offers a practical strategy to support leadership skills for women physicians needed to navigate systemic barriers and advance into leadership roles.

ABSTRACT Introduction/Aims:. Primary Sjögren syndrome (SS) is a chronic autoimmune disease characterized frequently by sensory neuropathy (SN). Carbonic Anhydrase‐6 (CA‐6), Parotid Secretory Protein (PSP), and Salivary Protein‐1 (SP‐1) antibodies (Early Sjögren antibodies [ESA]) are found in 45% of SS patients who lack traditional antibodies (Ro/La). But there is a lack of information regarding whether ESA are associated with SN, and if there are any identifying characteristics associated with ESA in SN. Our goal was to close this knowledge gap. Methods All SN patients tested for ESA from May 2023–October 2024 were retrospectively analyzed for clinical features such as sicca symptoms, onset acuity, small fiber neuropathy (SFN)‐questionnaire scores, and pathological features such as length‐dependence/vasculitis on skin biopsies, as well as lip biopsy confirmation of SS. Seropositive/seronegative groups were separated for statistical analysis. Results Thirty‐three adult patients (73% female) with cryptogenic SN had ESA testing. Eighteen (55%) had abnormal ESA. Twelve (100%) seropositive patients had significant sicca symptoms versus four seronegative patients (29%) ( p = 0.0002). There were no significant associations between ESA seropositivity and SFN‐questionnaires, pathological nonlength dependence (NLD)/vasculitis, or onset acuity. Discussion ESA may be seen in more than half of cryptogenic SN patients, but whether these patients have confirmed SS is unclear. Seropositive patients more frequently have significant sicca symptoms than seronegative patients, but no other significant identifying characteristics were seen. Further work on a larger population should be done to confirm these findings, but this study suggests the utility of checking ESA in cryptogenic SN patients with significant sicca symptoms.

ABSTRACT Glucagon‐like peptide‐1 (GLP‐1) receptor agonists (GLP‐1 RAs) improve glycaemia and reduce body weight, yet their organ‐level actions on skeletal muscle remain incompletely defined. Framing skeletal muscle as an integrated unit of vasculature and muscle cells, we synthesize evidence with emphasis on glucose and protein metabolism. GLP‐1 and GLP‐1 RAs recruit microvasculature in muscle, expanding capillary surface area and increasing delivery of insulin, glucose, and amino acids. Microvascular recruitment increases interstitial insulin availability and potentiates insulin‐stimulated glucose uptake and glycogen synthesis, whereas direct effects of GLP‐1 on muscle cells remain under investigation. For protein metabolism, microvascular recruitment can enhance muscle protein synthesis when plasma amino acid availability is elevated, whereas effects under basal (fasted) conditions remain unclear. Elucidating the uncertainty regarding GLP‐1 receptor localization in human muscle cells will clarify whether direct signaling occurs within muscle cells, thereby improving our understanding of the relative contribution of direct versus perfusion‐mediated actions of GLP‐1 RAs. Clinically, GLP‐1 RAs reduce lean body mass, likely reflecting energy‐deficit–mediated effects, but studies directly assessing muscle mass are still limited. Overall, current evidence indicates that GLP‐1 RAs exert beneficial effects on muscle vasculature and muscle glucose metabolism. However, their influence on muscle protein turnover remains unclear—primarily due to observed reductions in muscle mass—despite preclinical data suggesting potential favorable effects on muscle protein metabolism that remain to be confirmed in humans.

Abstract Creating a People-Centered Organization: 12 Organizational Actions to Reduce Burnout and Foster Professional Fulfillment tells the story of the evolving journey to create a better work environment for health care professionals. It dwells not on the story of occupational distress, burnout, moral injury, and cognitive dissonance but rather on a narrative of hope, well-being, camaraderie, values alignment, and meaning. Achieving this aspiration requires health care professionals and operational leaders working together to create 10 “Ideal Work Elements”: community at work and camaraderie; intrinsic motivation and rewards; control and flexibility; fairness and equity; professional development and mentorship; partnership; safety; trust and respect; gratitude; and work–life Integration. The ultimate aspiration is a people-centered organization with a culture that inspires enthusiasm, loyalty, engagement, and strong regard for the welfare of the team and the best interests of patients. Creating a People-Centered Organization: 12 Organizational Actions to Reduce Burnout and Foster Professional Fulfillment provides a road map for you to create such an environment for your team and organization. The map is paved with information about reliable, thoughtfully designed systems built on a psychologically safe and just culture. The authors drew on their extensive research on the well-being of health care professionals and their executive leadership experience in staff wellness, quality improvement, organization development, and operations management.

Elucidating the structure and function of enteropeptidase (EP) is essential for advancing our understanding of its biological significance, particularly in regulating trypsinogen activation. Using cryo-EM and enzymatic activity, we uncovered the significance of the CUB2 domain in mediating the cleavage of macromolecular substrates. We identified crucial binding loops and key residues for EP’s proteolytic function. The mutation E574A enhanced the proteolytic activity of EP, whereas the mutation N619A diminished its cleavage efficiency, highlighting the importance of surface-charged interactions in modulating EP’s activity. A proteolytic cycle was proposed to deepen our understanding of the trypsinogen activation by EP. This work offers valuable insights into the molecular mechanisms underlying EP’s interaction with its substrate, and opens up avenues for therapeutically modulating EP-mediated proteolysis.

Abstract Spatial transcriptomics links gene expression to tissue architecture, but detecting spatially variable genes at atlas scale remains difficult because biologically relevant patterns are multiscale, sparse, and often non-parametric. Here we show that FlashS, a frequency-domain kernel test using random Fourier features, sparse sketching, and a kurtosis-corrected null, retains Gaussian-kernel flexibility at near-linear per-gene cost without permutation. Across 50 benchmark datasets spanning 9 spatial transcriptomics platforms, F lash S achieves the highest ranking accuracy among 14 compared methods while maintaining calibrated inference under simulation and full-atlas permutation. In human heart tissue, it recovers a mitochondrial biogenesis program that co-localizes with ventricular cardiomyocytes. On the Allen Brain MERFISH atlas containing 3.94 million cells, F lash S completes in minutes on a single workstation and separates biological signal from negative-control barcodes even when p-values saturate.

Background: Femoroacetabular impingement (FAI) is a common injury experienced by basketball players. Surgical management with arthroscopic labral repair and femoral osteochondroplasty can lead to successful outcomes for athletes whose nonoperative management fails. Recent studies have demonstrated that athletes undergoing hip arthroscopy in the setting of FAI had favorable return-to-sport (RTS) and sport continuation outcomes. Purpose: To evaluate patient-reported outcome measures (PROMs) and RTS rates at minimum 5-year follow-up in basketball players after hip arthroscopy for FAI. Study Design: Case series; Level of evidence, 4. Methods: All active basketball players at the recreational, high school, and collegiate levels who underwent primary hip arthroscopy with labral repair for FAI between August 2009 and December 2019 were identified. Postoperative RTS, revision rates, and surgery satisfaction at final follow-up were evaluated. PROMs were also analyzed as follows: visual analog scale, Tegner Activity Scale, modified Harris Hip Score, Hip Outcome Score–Activities of Daily Living, and Hip Outcome Score–Sport. Results: Fifty-three patients (64 hips) were included with a mean ± SD age of 21.2 ± 6.0 years. Most athletes played recreational or high school basketball (85%), while 15% played college basketball. Forty-three patients attempted to return to basketball. Of these patients, 35 (81%) returned to basketball after surgery, with 32 (91%) returning to the same level of play. Patients who returned to basketball had significantly improved outcomes on the modified Harris Hip Score ( P = .006), Hip Outcome Score–Activities of Daily Living ( P = .007), Hip Outcome Score–Sport ( P = .004), Tegner Activity Scale ( P = .010), and visual analog scale with use ( P = .041) as compared with those who did not return. High school athletes had decreased odds of RTS when compared with recreational athletes ( P = .01). There was significant improvement in all PROMs from baseline to minimum 5-year follow-up ( P < .05). Conclusion: At minimum 5-year follow-up, basketball players demonstrated durable improvements in PROMs and an RTS rate of 81% after hip arthroscopy for FAI. The majority of athletes returned to the same level of competition. There were significantly improved PROMs in patients who returned to sport versus those who did not. High school athletes had decreased odds of RTS when compared with recreational athletes. However, body mass index, sex, age, alpha angle, and basketball position did not significantly correlate with RTS outcomes.