Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Cell Biology
Total Results:
14175
Proceedings of the National Academy of Sciences of the United States of America. 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
Clinical cancer research : an official journal of the American Association for Cancer Research. 2026.DOI: 10.1158/1078-0432.CCR-25-3148
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
On the mechanism of K+ transport through the inter-subunit tunnel of KdpFABC
KdpFABC is an ATP-dependent membrane complex that enables prokaryotes to maintain potassium homeostasis under potassium-limited conditions. It features a unique hybrid mechanism combining a channel-like selectivity filter in KdpA with the ATP-driven transport functionality of KdpB. A key unresolved question is whether K+ ions translocate through the inter-subunit tunnel as a queue of ions or individually within a hydrated environment. Using molecular dynamics simulations, metadynamics, anomalous X-ray scattering, and biochemical assays, we demonstrate that the tunnel is predominantly occupied by water molecules rather than multiple K+ ions. Our results identify only one stable intermediate binding site for K+ within the tunnel, apart from the canonical sites in KdpA and KdpB. Free energy calculations reveal a substantial barrier (∼22 kcal/mol) at the KdpA-KdpB interface, making spontaneous K+ translocation unlikely. Furthermore, mutagenesis and functional assays confirm previous findings that Phe232 at this interface plays a key role in coupling ATP hydrolysis to K+ transport. These findings challenge previous models containing a continuous wire of K+ ions through the tunnel and suggest the existence of an as-yet unidentified intermediate state or mechanistic detail that facilitates K+ movement into KdpB.
PMID: 41384914
ISSN: 1540-7748
CID: 5978042
Integrin is required for basement membrane crossing and branching of an invading intracellular tube
The narrowest biological tubes are comprised of cells that hollow to form an intracellular lumen. Here, we examine early lumenogenesis of the C. elegans excretory cell, which branches to form an H-shaped intracellular tube spanning the length of the worm. Using genetically paralyzed embryos to freeze movement, we describe lumen initiation and branching for the first time using time-lapse fluorescence microscopy. We show that the excretory cell lumen forms through a plasma membrane invasion mechanism when a nascent lumen grows from the plasma membrane into the cytoplasm. The lumen subsequently extends along the left-right axis before branching to form anterior-posterior projections. Through a genetic screen, we identify mutations in ina-1/⍺-integrin and pat-3/β-integrin that block lumenogenesis at the anterior-posterior branching step, and we show that integrin function is required within the excretory cell. Finally, we find that the excretory cell crosses the epidermal basement membrane where anterior-posterior branches form and demonstrate that basement membrane crossing fails in integrin mutant embryos. Our findings reveal how an intracellular lumen initiates and branches and identify integrins and basement membrane as key branching regulators.
PMID: 41321174
ISSN: 1477-9129
CID: 5974502
Journal of child psychology & psychiatry & allied disciplines. 2026:67(1):104-114.DOI: 10.1111/jcpp.70023
Motor stereotypies in toddlers with and without autism: A transdiagnostic dimension
BACKGROUND:Motor stereotypies (MS) represent one of the transdiagnostic symptom dimensions identified by the NIMH Research Domain Criteria work group as relevant to psychopathology. MS are common in neurodevelopmental conditions, but they remain poorly understood, particularly in early childhood. The present study examined MS in 648 toddlers with autism spectrum disorder (autism, n = 455) and other neurodevelopmental conditions (non-autism, n = 193) and their concurrent and prospective links with other phenotypic characteristics. METHODS:Toddlers were recruited between February 2000 and October 2018 and evaluated at 24 +/- 5 months (Time 1, N = 648) and 41 +/- 6 months (Time 2, N = 455). The presence of MS was determined based on the Autism Diagnostic Observation Schedule assessment. The phenotypic measures included adaptive socialization skills, severity of social symptoms of autism, and verbal, nonverbal, and motor skills. The analysis was conducted using the general linear models while controlling for age, sex, visit year, group, and other relevant covariates. RESULTS: CONCLUSIONS:Motor stereotypies are present in toddlers with and without autism and may represent a distinct transdiagnostic dimension expressed early in development, associated with core developmental skills and, putatively, characterized by shared pathophysiology across neurodevelopmental conditions.
PMID: 40757458
ISSN: 1469-7610
CID: 5904782
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
Review Article: Extending the Frontiers of Intestinal Ultrasound Knowledge, Performance and Expansion
BACKGROUND:Intestinal ultrasonography (IUS) is increasingly utilised for diagnosing and monitoring IBD. Despite its cost-effectiveness, patient tolerance and suitability for serial bedside assessments, broad adoption has been limited by knowledge gaps in evidence, training and standardisation. AIMS/OBJECTIVE:To summarise key knowledge gaps in the assessment of luminal disease activity, postoperative recurrence, complications, pouch-related disorders and the use of IUS in paediatrics, contrast enhancement, elastography, as well as education, training and future applications involving artificial intelligence. METHODS:We conducted a systematic umbrella review, following PRISMA guidelines, to map the current landscape of high-quality evidence and identify gaps in IUS research relevant to IBD. We searched MEDLINE from inception to February 2025 for systematic reviews, meta-analyses and consensus statements. We extracted data from eligible studies on design, outcomes and identified research gaps. Gaps were categorised by insufficient information, bias, inconsistency or lack of relevant data. RESULTS:Sixty of 507 studies met inclusion criteria. Key gaps included lack of validated and standardised IUS activity indices for Crohn's disease and ulcerative colitis, limited evidence for IUS in post-operative recurrence, paediatric populations and perianal or pouch disease. Data on the use of contrast-enhanced ultrasound and elastography were sparse. Small sample sizes, heterogeneous designs and inadequate follow-up limited most studies. Training, competency assessment and integration of artificial intelligence remain underexplored. CONCLUSIONS:Sizable gaps persist in the evidence base for IUS in IBD. Addressing these gaps through robust, multicentre studies and consensus-driven frameworks is essential to optimise the clinical and research utility of IUS in IBD management.
PMID: 41235810
ISSN: 1365-2036
CID: 5967142
Neural stem cell quiescence is actively maintained by the epigenome
Homeostasis of the nervous system is maintained by a population of resident neural stem cells (NSCs) retained in a state of reversible cell-cycle arrest called quiescence. Quiescent NSCs can resume proliferation in response to different physiological stimuli. Reactivation requires changes in gene expression, much of which is regulated at the epigenomic level. We mapped epigenomic changes in NSC chromatin during stem cell quiescence and reactivation in Drosophila in vivo. Contrary to expectations, chromatin accessibility is increased in quiescent NSCs. Surprisingly, genes crucial for cell-cycle progression are repressed while remaining within permissive H3K36me3-bound euchromatin. At the same time, genes necessary for cell-cell communication are derepressed by eviction of histone H1 and transition to an SWI/SNF-enriched active state. Our results reveal global expansion of accessible chromatin in quiescent NSCs without concomitant transcriptional activation. Strikingly, this process reverses upon reactivation, indicating that opening of chromatin is a quiescence-specific event.
PMID: 41417732
ISSN: 2211-1247
CID: 5979772
