Faculty Bibliography
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Department/Unit:Cell Biology
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14229
Establishing dermatopathology encyclopedia DermpathNet with Artificial Intelligence-Based Workflow
Accessing high-quality, open-access dermatopathology image datasets for learning and cross-referencing is a common challenge for clinicians and trainees. To establish a comprehensive open-access dermatopathology dataset for educational, cross-referencing, and machine-learning purposes, we employed a hybrid workflow to curate and categorize images from the PubMed Central (PMC) repository. We used specific keywords to extract relevant images, and classified them using a novel hybrid method that combined deep learning-based image modality classification with figure caption analyses. Validation on 651 manually annotated images demonstrated the robustness of our workflow, with an F-score of 89.6% for the deep learning approach, 61.0% for the keyword-based retrieval method, and 90.4% for the hybrid approach. We retrieved over 7,772 images across 166 diagnoses and released this fully annotated dataset, reviewed by board-certified dermatopathologists. Using our dataset as a challenging task, we found the current image analysis algorithm from OpenAI inadequate for analyzing dermatopathology images. In conclusion, we have developed a large, peer-reviewed, open-access dermatopathology image dataset, DermpathNet, which features a semi-automated curation workflow.
PMID: 41651886
ISSN: 2052-4463
CID: 6000722
The International Guideline for the Definition, Classification, Diagnosis and Management of Urticaria
This update and revision of the international guideline for urticaria was developed in accordance with the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is an initiative of the Global Allergy and Asthma Excellence Network (GA2LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), with the participation of 210 delegates from 107 national and international societies, from 59 countries. The consensus conference was held on December 6th, 2024. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, defined by a rapid appearance of wheals, angioedema, or both. The lifetime prevalence of acute urticaria is estimated to be approximately 20%. Chronic urticaria, categorized as either chronic spontaneous urticaria or chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school, however, novel therapies are available. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
PMID: 41649409
ISSN: 1398-9995
CID: 6000592
LetA defines a structurally distinct transporter family
Membrane transport proteins translocate diverse cargos, ranging from small sugars to entire proteins, across cellular membranes1-3. A few structurally distinct protein families have been described that account for most of the known membrane transport processes4-6. However, many membrane proteins with predicted transporter functions remain uncharacterized. Here we determined the structure of Escherichia coli LetAB, a phospholipid transporter involved in outer membrane integrity, and found that LetA adopts a distinct architecture that is structurally and evolutionarily unrelated to known transporter families. LetA localizes to the inner membrane, where it is poised to load lipids into its binding partner, LetB, a mammalian cell entry (MCE) protein that forms an approximately 225 Å long tunnel for lipid transport across the cell envelope. Unexpectedly, the LetA transmembrane domains adopt a fold that is evolutionarily related to the eukaryotic tetraspanin family of membrane proteins, including transmembrane AMPA receptor regulatory proteins (TARPs) and claudins. Through a combination of deep mutational scanning, molecular dynamics simulations, AlphaFold-predicted alternative states and functional studies, we present a model for how the LetA-like family of membrane transporters facilitates the transport of lipids across the bacterial cell envelope.
PMID: 41565823
ISSN: 1476-4687
CID: 5988502
A Road Map to Understanding Cardiovascular Disease in Diabetes: From the AHA Strategically Focused Research Network in Cardiometabolic Health and Type 2 Diabetes
Despite major advances in medical therapies and prevention strategies, the risk of cardiovascular complications in patients with both type I and type II diabetes remains substantially elevated. In 2019, the American Heart Association sought applications for a Strategically Focused Research Network on Cardiometabolic Health and Type 2 Diabetes. In 2020, 4 centers were named, including Brigham and Women's Hospital, Johns Hopkins University, New York University, and the University of Iowa. These centers performed basic, translational, and clinical studies to provide insights to explain the over 2-fold risk of cardiovascular complications in diabetes. Clinical studies and studies in cells and animals aimed to uncover new mechanisms responsible for disease development. Studies using human populations sought to uncover new biomarkers to prognosticate risk. In this review, we discuss several key issues and current and developing methods to understand why diabetes drives atherosclerotic cardiovascular disease and heart failure. Both human data and experimental models are considered. We integrate a review of these topics with work from the Strategically Focused Research Network and conclude with suggestions for identifying novel risk factors and future experimental research.
PMID: 41538415
ISSN: 1524-4571
CID: 5986562
Population analysis and immunologic landscape of melanoma in people living with HIV
PURPOSE/OBJECTIVE:To dissect the clinical and immunological features of people living with HIV (PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer. EXPERIMENTAL DESIGN/METHODS:We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n=11), with downstream validation using multiplex immunofluorescence (n=15 PLWH, n=14 PLw/oH). RESULTS:PLWH were diagnosed at a younger age, had greater representation of Hispanic and Black individuals, and showed reduced survival. They also had a markedly increased risk of brain metastases. PLWH experienced significant delays in initiating immune checkpoint inhibitor (ICI) therapy and had worse post-ICI survival, even after balancing covariates. Spatial transcriptomics revealed a more immunosuppressive tumor microenvironment in PLWH, with increased transcription of immune checkpoints (PD1, LAG3) and reduced antigen-presentation markers (HLA-DRB, B2M), with distinct spatial distributions in tumors and surrounding microenvironments. Multiplex immunofluorescence demonstrated features of an exhausted CD8⁺ T cell compartment, including enrichment of PD1intLAG3⁻ and PD1intLAG3⁺ subpopulations, and a significant accumulation of myeloid-derived suppressor cells (CD11b⁺ HLA-DR⁻ CD33⁺). CONCLUSIONS:Melanoma in PLWH is associated with distinct clinical and immunological features, including delayed ICI treatment, reduced survival, and an immunosuppressive microenvironment with exhausted CD8⁺ T cells and expanded myeloid-derived suppressor cells. These findings suggest that chronic HIV infection may impair antitumor immunity in melanoma. Targeting the pathways identified here may improve therapeutic responses and outcomes in this population.
PMID: 41504629
ISSN: 1557-3265
CID: 5981192
European journal of orthopaedic surgery & traumatology = orthopedie traumatologie. 2026:36(1).DOI: 10.1007/s00590-025-04588-8
Inpatient mortality following hip fracture in the United States: an updated analysis of over one million cases
BACKGROUND:Understanding the current risk of inpatient mortality following hip fracture in the United States is of significant value to patient families and the health system. Currently, the literature lacks a national representation of the inpatient mortality following hip fracture. PURPOSE/OBJECTIVE:The purpose of this study was to investigate the incidence of inpatient mortality following hip fracture using Epic Cosmos-an aggregated, de-identified, multi-institutional data that includes over 280 million patients in the United States. METHODS:A "Cosmos hip fracture cohort" that included all adults (18 years or older) who sustained a femoral neck, intertrochanteric, or subtrochanteric hip fracture (ICD 72.0, S72.1, S72.2) between January 2019 and December 2024 was created. The dataset was queried for demographic data including age, sex, geographic location, incidence of inpatient mortality, and bone health medication use at the time of admission. RESULTS:The Cosmos database included 284,455,033 patients, of which 1,232,250 hip fracture hospital admissions between January 2019 and December 2024 were identified. Of these patients, 47,773 (3.9%) expired during their hip fracture hospital admission. The most common age bracket was 85 years or older (39.8%), followed by 75-85 (30.0%), and 65-75 (17.8%). Most patients were white (91%) females (55.5%). Most inpatient mortalities occurred in the South (38.4%), followed by the Midwest (31.8%), followed by the Northeast (23.6%), and last by the West (6.2%). CONCLUSION/CONCLUSIONS:The current inpatient mortality following hip fracture is 3.9%. Most inpatient mortalities occurred in white females above the age of 85 in the South of the country. LEVEL OF EVIDENCE/METHODS:Level III.
PMID: 41493636
ISSN: 1432-1068
CID: 5980802
Proximal Implant Breakage after Cephalomedullary Nailing of Extra-capsular Proximal Femur Fractures: A Multi-Center Retrospective Comparative Analysis
OBJECTIVE:To compare rates of nail breakage of three common cephalomedullary nails (CMNs) for the treatment of AO/OTA 31A1-3 femur fractures. METHODS:Design: multi-center retrospective study. SETTING/METHODS:13 Level I trauma centers. PATIENT SELECTION CRITERIA/UNASSIGNED:Adult patients with AO/OTA 31A1-3 femur fractures treated between 2014 and 2021with the Trochanteric Fixation Nail-Advanced (TFNA), Gamma3, or Trigen InterTAN were included. OUTCOME MEASUREMENTS AND COMPARISONS/UNASSIGNED:The primary outcome was implant (nail or head element) breakage. The secondary outcomes included nonunion, cut-out/cut-through and overall reoperation rate. Univariate and multivariable analyses were performed to compare breakage rates between implants while controlling for age, sex, AO/OTA 31A1-2 vs 31A3 fracture patterns, low vs high-energy mechanisms and post-operative neck shaft angle (NSA). RESULTS:2,130 patients were included: 770 (36.2%) TFNA, 1,073 (50.4%) Gamma3 and 287 (13.5%) InterTAN. The InterTAN group had younger patients (median age: InterTan: 74, TFNA: 77, Gamma3: 80, p<0.001), more high-energy mechanisms (InterTan: 23%, TFNA: 14%, Gamma3: 10%, p=0.001), and more varus malreductions (NSA<128.5: InterTan: 46%, Gamma3: 39%, TFNA: 34%, p=0.001). The TFNA group was more likely to have an AO/OTA 31A3 fracture pattern than the Gamma3 (TFNA: 17.3%, InterTAN: 14.3%, Gamma3: 12.1%, p=0.002). The overall rate of implant breakage was 1.4% in the InterTAN group, 1.2% in the TFNA group, and 0% in the Gamma3 group. All breakages occurred in the presence of a nonunion or delayed union. Only two of the 31A3 fracture patterns resulted in breakage, both in the TFNA group, while the remainder occurred in 31A1-2 fracture patterns (p = 1.0). After controlling for confounding factors listed above, the TFNA and InterTAN groups were associated with a marginally increased odds of implant breakage compared to the Gamma3 (TFNA vs Gamma3: OR 0.04, 95% CI <0.01-0.5, p=0.034; InterTAN vs Gamma3: OR 0.04, 95% CI <0.01-0.5, p=0.037), while there was no difference between the TFNA and InterTAN (p=0.991). Post-operative neck shaft angle was not independently predictive of breakage (p = 0.55). CONCLUSIONS:This study suggests that the TFNA may be slightly more prone to breakage than the Gamma3 when used for extracapsular proximal femur fractures. However, breakage is a rare event after cephalomedullary nailing with all implants evaluated, is always associated with nonunion or delayed union, and the magnitude of this difference may not be clinically relevant. LEVEL OF EVIDENCE/METHODS:III.
PMID: 41493187
ISSN: 1531-2291
CID: 5980762
Lichen planopilaris in children: Clinical characteristics, comorbidities, and treatment outcomes in a single-center case series [Case Report]
PMCID:12769417
PMID: 41502839
ISSN: 2352-5126
CID: 5981102
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2026:123(2).DOI: 10.1073/pnas.2500723123
Elevator mechanism dynamics in a sodium-coupled dicarboxylate transporter
VcINDY, the sodium-dependent dicarboxylate transporter from
PMID: 41490488
ISSN: 1091-6490
CID: 5980652
Palaeometabolomes yield biological and ecological profiles at early human sites
The science of metabolic profiling exploits chemical compound byproducts of metabolism called metabolites1 that explain internal biological functions, physiological health and disease, and provide evidence of external influences specific to an organism's habitat. Here we assess palaeometabolomes from fossilized mammalian hard tissues as a molecular ecological strategy to provide evidence of an ancient organism's relationship with its environment. From eastern, central and southern African Plio-Pleistocene localities of palaeoanthropological significance, we study six fossils from Olduvai Gorge, Tanzania, one from the Chiwondo Beds, Malawi, and one from Makapansgat, South Africa. We perform endogeneity assessments by analysing palaeometabolomes of palaeosols and the effects of owl digestion on rodent bones to enable prudent ecological inferences. Diagenesis is indicated by metabolites of collagenase-producing bacteria2, whereas the preservation of peptides including those of collagen are identified by proteomics. Endogenous metabolites document biological functions and exogenous metabolites render environmental details including soil characteristics and woody cover, and enable annual minimum and maximum rainfall and temperature reconstructions at Olduvai Gorge, supporting the freshwater woodland and grasslands of Olduvai Gorge Bed I3-5, and the dry woodlands and marsh of Olduvai Gorge Upper Bed II6. All sites denote wetter and/or warmer conditions than today. We infer that metabolites preserved in hard tissues derive from an extravasated vasculature serum filtrate that becomes entombed within developing mineralized matrices, and most probably survive palaeontological timeframes in the nanoscopic 'pool' of structural-bound water that occurs in hard tissue niches7.
PMID: 41407854
ISSN: 1476-4687
CID: 5979502
