Medical Specialties Commons^™

Factors Influencing Match Success In Integrated Vascular Surgery Residency Programs From 2019 To 2023, Antony A. Fuleihan, Melissa C. Xu, Scott H. Koeneman, Paul J. Dimuzio, Babak Abai, Michael Nooromid

Department of Surgery Faculty Papers

INTRODUCTION: Integrated vascular surgery residency (IVSR) programs have grown increasingly competitive. However, the factors influencing successful matching remain unclear. This study evaluates the impact of medical school and applicant characteristics on IVSR match outcomes.

METHODS: A list of ACGME-accredited IVSRs was obtained from the Society for Vascular Surgery, and resident data from the 2019-2023 match cycles were collected from publicly available sources. Applicant characteristics consisted of additional graduate degrees, Alpha Omega Alpha (AOA) status, and research productivity. Medical school characteristics consisted of ranking, research funding, vascular surgery interest group (VSIG) presence, and vascular surgery faculty size. Logistic regression models were …

Two Lysosomal Genes Atp13a2 And Gba1 Interact To Drive Neurodegeneration, Mingxue Gu, Jinghan Zhao, Mingxi Deng, Guang Lin, Xueyang Pan, Wenwen Lin, Mengqi Ma, Jinyong Kim, Seul Kee Byeon, Akhilesh Pandey, Lara M Lange, Chad A Shaw, Jonggeol Kim, Joanne Trinh, Christine Klein, Oguz Kanca, Joshua M Shulman, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Background: Parkinson’s disease (PD) is a genetically complex disorder in which combinations of heterozygous risk variants may contribute to pathogenesis. Many PD risk loci encode lysosomal genes, such as GBA1, a common and potent risk factor, conferring at least a 5-fold increase. However, the mechanisms of GBA1 penetrance remain poorly understood.

Methods: Using Drosophila melanogaster, we performed a genetic interaction screen of lysosomal storage disorder (LSD) genes to identify dominant modifiers of Gba1b (fly homolog of GBA1). Age-dependent locomotor assessments, electroretinograms (ERG), transmission electron microscopy (TEM) analyses and quantification of dopaminergic (DA) neurons were used to assess …

Upper Hemisternotomy Vs. Full Sternotomy For Hemiarch And Proximal Aortic Replacement, Jeffrey A. Zucker, Vishal N. Shah, Joshua R. Chen, Christopher Pritting, Colin King, Jacqueline Mcgee, Megary Mccoy, Konstadinos A. Plestis

Department of Surgery Faculty Papers

Introduction: Hemiarch replacement with proximal aortic replacement is seldom performed via upper hemisternotomy (UHS). We report our surgical technique and postoperative outcomes in 11 patients who underwent UHS for hemiarch and proximal aortic replacement, compared with 15 patients who underwent the procedure via full sternotomy (FS).

Methods: A UHS was performed at the right third or fourth intercostal space. Cardiopulmonary bypass (CPB) was established via the distal ascending aorta or right axillary artery and right common femoral vein. After aortic cross-clamping (ACC), the heart was arrested with single-dose antegrade crystalloid cardioplegia. After proximal aortic replacement, hypothermic circulatory arrest (HCA) between …

High-Throughput Proteomic Profiling To Evaluate Differentiation Syndrome With Menin Inhibition, Miriam B Garcia, Bofei Wang, Irtiza Sheikh, Georgina El Hajjar, David Mccall, Cesar Nunez, Amber Gibson, Philip L Lorenzi, Ghayas C Issa, Branko Cuglievan, Hussein A Abbas

Faculty, Staff and Student Publications

High-throughput proteomic profiling provides a comprehensive analysis of systemic cancer effects and tumor microenvironment interactions. Characterizing soluble proteins driving inflammation in acute myeloid leukemia (AML) offers insight into inflammatory diseases like differentiation syndrome (DS) related to AML therapies like menin inhibitors. We present our application of NUcleic acid-Linked Immuno-Sandwich Assay (NULISA), a novel technology leveraging next-generation sequencing (NGS) for high-throughput, ultra-sensitive characterization of secreted inflammatory proteins in plasma or serum. Here we report its use to identify dynamic soluble protein changes during treatment and at the time of suspected DS in pediatric AML patients treated with the menin inhibitor revumenib …

Supercharging-Enhanced Ndia-Ms Enables Global Profiling Of Drug-Induced Proteome Solubility Shifts, Yun Xiong, Huimin Zhang, Lin Tan, Bo Wei, John N Weinstein, Philip L Lorenzi

Faculty, Staff and Student Publications

Mass spectrometry (MS) is indispensable for high-throughput quantitation of protein expression. But protein function is regulated by factors beyond abundance alone. Here, we evaluate two supercharging reagents, dimethyl sulfoxide (DMSO) and m-nitrobenzyl alcohol (mNBA), in narrow-window data-independent acquisition (nDIA)-MS. DMSO markedly enhances MS signal and protein identification, whereas mNBA primarily increases peptide identifications. Optimizating nDIA-MS with 3% DMSO boosts signal intensity by up to 56%, enabling identification of ~9,600 proteins from 1 µg HeLa digest in 15 min. Using this methodology, we quantify solubility and abundance changes in 8,694 proteins across three cell lines following short-term treatment with the proteasome …

Comparing Educational Pathways For Denturists To Become Maxillofacial Prosthetic Specialists In The Us And The Uk, Minseok Kim

Oral Health

Abstract

In the absence of formal training, licensure, and professionalism, this scientific literature review will seek to include denturists in the American maxillofacial prosthetics industry. Denturists are oral health professionals who perform oral examination, design, manufacture, and place removable oral prostheses. In other regions of the world, they are also known as clinical dental technologists and dental prosthetists. This practice is not widespread in the US. The review can also be assessed on the model mediated by PRISMA, which is concentrated on the experiences of international education in the United Kingdom, Canada, and Australia, where the concentration further revolves around …

Clinical Outcomes Of Patients Hospitalized For Conventional Pacemaker Implantation With Protein-Energy Malnutrition, Phuuwadith Wattanachayakul, Pojsakorn Danpanichkul, Chalothorn Wannaphut, Hamza Tahir, John Malin, Thanathip Suenghataiphorn, Kanokphong Suparan, Aman Amanullah

Einstein Health Papers

INTRODUCTION: The impact of protein-energy malnutrition (PEM) on patients hospitalized for conventional pacemaker implantation remains poorly understood.

METHODS: We utilized the 2020 U.S. National Inpatient Sample (NIS) database to evaluate the impact of PEM on the in-hospital outcomes of patients who underwent conventional pacemaker implantation. Patients aged 18 and older were identified by ICD-10 CM and PCS codes. Multivariable survey logistic and linear regression analyses were employed to examine in-hospital outcomes, including in-patient mortality, system-based outcomes, and post-procedural complications.

RESULTS: A total of 108 020 patients were identified with 4315 (3.99%) diagnosed with PEM. The mean age of the cohort …

Retrospective Comparison Of Outcomes Of Osteochondral Allograft Transplantation Of The Knee Using Extended Storage Modality Missouri Osteochondral Preservation System Versus Standard Preservation, Henson Destine, Gaston Davis, Harrison S. Fellheimer, Azra Dees, Nathaniel Kern, Bradford Tucker, Kevin Freedman

Rothman Institute Papers

BACKGROUND: Osteochondral allograft (OCA) transplantation is an established surgical intervention for full-thickness chondral defects. Standard preservation (SP) protocols currently allow for OCAs to be stored for a maximum of 28 days after procurement before significant chondrocyte death. An alternative protocol, the Missouri Osteochondral Allograft Preservation System (MOPS), has been shown to allow for grafts to be stored for twice the maximum time allotment as SP.

PURPOSE: To compare clinical outcomes in patients who have undergone OCA transplantation utilizing the extended storage capabilities of the MOPS versus SP protocols.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: Patients who underwent …

Partial Versus Full Revision In Cementless Single-Stage Exchange For Hip Periprosthetic Joint Infection: A Multicenter Comparative Study With 10-Year Survivorship Analysis, Wenbo Mu, Atthakorn Jarusriwanna, Boyong Xu, Scot A. Brown, Xiaogang Zhang, Alexander Dawes, Javad Parvizi Md, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty (THA). Traditional management typically involves full revision to ensure comprehensive infection eradication. However, for patients with well-fixed implants, partial revision in a single-stage cementless approach may provide a viable alternative, potentially preserving bone stock and reducing operative time. The relative efficacy of this approach compared with full revision remains to be fully explored. This multicenter study aims to determine whether partial revision in cementless single-stage exchange surgery offers comparable infection control outcomes to full revision for select patients with well-fixed implants.

METHODS: We conducted …

Use Of Electrocardiograms To Identify Coronary Artery Disease: Cross-Validation Of An Artificial Intelligence Model, Michael Leasure, Indu Poornima, Adam Butchy, Utkars Jain, Devin Vasoya, Michael Warnick, Brent Williams, John Rehder, Prahlad Menon, Veronica A. Covalesky, Gary S. Mintz

Department of Medicine Faculty Papers

BACKGROUND: The current gold standard for the diagnosis of coronary artery disease (CAD) is invasive angiography; however, it is an invasive procedure. Therefore, we developed an artificial intelligence model designed to predict significant CAD from a resting digital 12-lead electrocardiogram (ECG).

OBJECTIVES: This retrospective study assessed the model's ability to predict clinically significant CAD in a patient population presenting for coronary angiography.

METHODS: From 2019 to 2021, 16,476 patients had a resting 12-lead digital ECG recorded within 90 days prior to coronary angiography. The artificial intelligence model was developed using 10-fold cross-validation methodology. Clinically significant disease was defined as angiographic …

Oncofetal Reprogramming: A New Frontier In Cancer Therapy Resistance, Anh Nguyen, Molly Lausten, Bruce M. Boman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Oncofetal reprogramming has recently emerged as a critical concept in translational cancer research, particularly for its role in driving therapeutic resistance across a variety of malignancies. This biological process refers to a pattern of gene expression that is restricted to embryogenesis, but becomes expressed again in a subpopulation of cancer cells. These genes are typically suppressed after embryogenesis, and their aberrant re-expression in tumors endows cancer cells with stem-like properties and enhanced adaptability. The goal of this review is the following: (i) comprehensively examine the multifaceted nature of oncofetal reprogramming; (ii) elucidate its underlying molecular mechanisms, including its regulators and …

Seipin Expression In Hepatocytes Impairs The Assembly Of Vldls And Exacerbates Steatohepatitis, Qianqian Dong, Yidan Ma, Xin Chen, Xiaowei Wang, Ziwei Liu, Chenxi Liang, Liwen Qiu, Jinye Tang, Jin Wu, Yang Liu, Xiaoqin Wu, Yaru Zhou, Mingming Gao, Hongyuan Yang

Faculty, Staff and Student Publications

VLDLs are crucial for maintaining liver and whole-body lipid homeostasis. Limited knowledge exists regarding the lipidation process of VLDL. Endoplasmic reticulum (ER) luminal lipid droplets (LLDs) have been suggested to provide lipids for VLDL lipidation and maturation. Seipin, an integral membrane protein of the ER, plays key roles in the formation of cytoplasmic LDs (CLDs) and adipocyte differentiation. Surprisingly, seipin is hardly detectable in hepatocytes. Given the critical contribution of seipin in forming CLDs, we hypothesize that the absence of seipin in hepatocytes might ensure the proper formation of LLDs and the lipidation and assembly of VLDLs. To explore the …

Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu

Faculty, Staff and Student Publications

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

A Robust Convnext-Based Framework For Efficient, Generalizable, And Explainable Brain Tumor Classification On Mri, Kirti Pant, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Background: Accurate and dependable brain tumor classification from magnetic resonance imaging (MRI) is essential for clinical decision support, yet remains challenging due to inter-dataset variability, heterogeneous tumor appearances, and limited generalization of many deep learning models. Existing studies often rely on single-dataset evaluation, insufficient statistical validation, or lack interpretability, which restricts their clinical reliability and real-world deployment.

Methods: This study proposes a robust brain tumor classification framework based on the ConvNeXt Base architecture. The model is evaluated across three independent MRI datasets comprising four classes-glioma, meningioma, pituitary tumor, and no tumor. Performance is assessed using class-wise and aggregate metrics, including …

Kdm4a Promotes Nepc Progression Through Regulation Of Myc Expression, Celia Sze Ling Mak, Ming Zhu, Jie Fu, Xin Liang, Xiaoxuan Wang, Fei Yuan, Feng Wang, Anh G Hoang, Xingzhi Song, Peter Shepherd, Derek Liang, Jessica Suh, Jordan Contreras, Thisawin Dang, Cindy Yan, Brandon Figueroa, Mathias Mazzocco, Athena Luo, Bijeta Pradhan, Jiwon Park, Mirrah Bashir, Miao Zhang, Eric Metzger, Roland Schüle, Abhinav K Jain, Ellen Karasik, Daniel Frigo, Barbara A Foster, Min Gyu Lee, Paul Corn, Christopher J Logothetis, Ana Aparicio, Nora Navone, Patricia Troncoso, Zhi Tan, Jianhua Zhang, Sue-Hwa Lin, Guocan Wang

Faculty, Staff and Students Publications

Neuroendocrine prostate cancer (NEPC) is a highly aggressive and lethal subtype of prostate cancer (PCa) that often emerges in response to androgen receptor pathway inhibitors (ARPIs), which are widely used in treating metastatic castration-resistant and hormone-sensitive prostate cancer. The incidence of NEPC is increasing, yet effective therapeutic strategies remain limited due to an incomplete understanding of its molecular drivers. Through transcriptomic analyses of human prostate tumor samples, we identified the histone lysine demethylase KDM4A as uniquely overexpressed in human and mouse NEPC compared to prostate adenocarcinoma. Functional validation demonstrated that KDM4A is a key regulator of NEPC progression and a …

Identification Of Slc3a2 As A Potential Therapeutic Target Of Ferroptosis In Bladder Cancer, Qi Yang, Dewang Zhou, Aaron Beasley, Yujun Liu, Zeqin Yan, Hu Fang, Yuqing Li, Elin S. Gray

Research outputs 2022 to 2026

Bladder cancer (BC) represents the most prevalent malignancy within the urinary system. Mounting evidence underscores the critical involvement of ferroptosis in cancer pathogenesis; Consequently, this study delves into its molecular underpinnings and therapeutic potential specifically in BC. Methods: We analyzed gene expression profiles from The Cancer Genome Atlas (TCGA) and the Gene Expression Om-nibus (GEO) repositories. Ferroptosis-related genes (FRGs) were selected from the FerrDb database. Utilizing systematic bioinformatics analyses, we identify differentially expressed and prognostic FRGs and construct an FRGs prognostic model. Combined with protein-protein interaction (PPI) analysis, solute carrier family 3 member 2 (SLC3A2) was selected for further study. …

The Cortico-Cortical And Subcortical Circuits Of The Human Brain Language Centers Including The Dual Limbic And Language Functioning Fiber Tracts, Arash Kamali, Nithya P Narayana, Anastasia Loiko, Anusha Gandhi, Paul E Schulz, Nitin Tandon, Manish N Shah, Vinodh A Kumar, Larry A Kramer, Jay-Jiguang Zhu, Haris Sair, Roy F Riascos, Khader M Hasan

Faculty, Staff and Student Publications

Background/Objectives: In recent years, MRI-based diffusion-weighted tractography techniques have uncovered additional white matter pathways that have significant roles in language processing and production. In this review, we aim to outline the major language centers of the brain and major language pathways along with association tracts that serve dual roles in both the language and limbic systems. According to the current dual-stream model of language processing, the brain's language network is organized into a dorsal stream, responsible for mapping sound to articulation, and a ventral stream, which maps sound to meaning.

Materials and Methods: The literature cited in this …

Beyond The Rash: Cutaneous Peripheral T-Cell Lymphoma As A Diagnostic Pitfall In Primary Care, Jared Hensley, Aura Calderon, Blake Martin, Cristina Kochi, Andres Suarez Parraga

School of Medicine Publications

Cutaneous manifestations of T-cell lymphomas may resemble common dermatologic or infectious conditions, increasing the risk of delayed recognition. We report a 78-year-old woman with known peripheral T-cell lymphoma (PTCL) who presented with a rapidly progressive, diffuse erythematous rash accompanied by cervical lymphadenopathy. Initial evaluation prioritized more common etiologies; however, inpatient medicine broadened the differential diagnosis, prompting early hematology and oncology consultation. Contrast-enhanced CT of the neck demonstrated multiple enlarged, partially necrotic left cervical lymph nodes consistent with disease progression. After multidisciplinary discussions and consideration of prognosis, the patient elected palliative-focused management with oncology follow-up. This case underscores the importance of …

N-Acetylcysteine Is Associated With Changes In Functional Connectivity In Patients With Parkinson's Disease, Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Faezeh Vedaei, Emily Navarreto, Monisha Gupta, Alicia Steinmetz, Anthony J. Bazzan, Feroze Mohamed, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

INTRODUCTION: This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.

METHODS: Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of …

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …

Race And Patient-Physician Communication On Blood Pressure Management: Helping Improve Care, Samar A. Nasser, Ashley Pender, Ayan Ali, Kardie Tobb, Keith C. Ferdinand

Division of Cardiology Faculty Papers

PURPOSE OF REVIEW: To provide an overview of the relationship of race and ethnicity and patient-physician/clinician communication on blood pressure management.

RECENT FINDINGS: The suboptimal interactions experienced by patients from underrepresented racial and ethnic populations may be improved by enriching relationships among clinicians, population health scientists, policymakers, and community members/leaders. Current care communication and policies for managing hypertension appear to be insufficient. Implementing and disseminating effective strategies to efficiently improve the quality of hypertension care and recognize social determinants of health among minoritized populations is intertwined with enhanced communication.

SUMMARY: Approaches such as self-affirmation—encouraging patients to reflect on their strengths …

Targeting Interleukin-6 Trans-Signaling To Improve Post-Stroke Inflammation: A Precision Immunotherapy Perspective, Kate Mendoza, Dustin T Nguyen, Anjali Chauhan

Faculty, Staff and Student Publications

No abstract provided.

Structures Of Invertebrate Pezo-1 Isoforms With A Compact Architecture And A Dispensable Pore-Distal N-Terminal Blade, Briar Bell, Angela M Jaramillo-Granada, Daniel J Orlin, Wei-Hsiang Weng, Haosheng Wen, Marcos Sotomayor, Alexander T Chesler, Matthew L Baker, Julio F Cordero-Morales, Valeria Vásquez

Faculty, Staff and Student Publications

PIEZO channels are mechanosensitive ion channels conserved from plants to humans, yet structures exist for only a few mammalian orthologs. We define the structural and functional diversity of Caenorhabditis elegans PEZO-1, a single gene with extensive alternative splicing, by determining cryo-electron microscopy structures of three representative isoforms: G (full length), K (lacking the pore-distal N-terminal blade), and L (missing most of the blade). PEZO-1G displays mechanically evoked currents yet adopts a compact, semi-flattened conformation that significantly differs from the mammalian domes. The blades exhibit a three-step slope architecture stabilized by inter-blade latching among transmembrane helical units, yielding a circular, steering-wheel-like …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Structures Of Trpv1 Bound By Hyperthermia-Inducing Analgesics, Yu-Hao Gao, Yi-Zhe Huang, Zhao-Xing Li, Xiao-Ying Chen, Chang-Yan Shao, Han-Wen Li, Bin Liu, Fán Yang, Mei-Rong Chen, Mei-Ling Lu, Michael X Zhu, Fan Yang, Yi-Bei Xiao, Ye Yu

Faculty, Staff and Student Publications

TRPV1, a member of the transient receptor potential vanilloid subfamily, mediates nociception and thermoregulation. TRPV1-targeting analgesics frequently induce hyperthermia, underscoring the need for structural insights to guide the development of safer compounds. Here, we determined the structures of rat TRPV1 bound to the clinical candidate analgesics AMG517, AMG9810, and SB366791. AMG517 and AMG9810 are deeply situated within the S3-S4 interface of the vanilloid pocket, where they interact with residues from the S3-S6 helices, as well as the S4-S5 linker. These interactions induce local deformations in the TRP-box and lower S6 helix, accompanied by a modest rotation of the S1-S4 bundle, …

Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin

Faculty, Staff and Student Publications

Background/Objectives: The bacterial cell division machinery is emerging as an attractive target for antimicrobial compounds. FtsZ, a highly conserved essential division protein, is the target for a number of small molecules such as benzamides. Recent studies show that benzodioxane-benzamides (BDOBs) are among the most potent inhibitors of FtsZ function in Gram-positive bacteria, although their ability to inhibit Gram-negative FtsZ, in particular Escherichia coli FtsZ, has been more controversial.

Methods: Here, we use genetic and cytological methods to demonstrate that FtsZ of efflux pump-disabled E. coli can be efficiently targeted by BDOBs.

Results: We show that engineered mutants …

Beyond Neurons: Impact Of Cannabidiol On Glial Cells In Ischemic Stroke, Victória Linden De Rezende, Khiany Mathias, Cinara Ludvig Gonçalves, Rafael Mariano De Bitencourt, Tatiana Barichello, Fabricia Petronilho

Faculty, Staff and Student Publications

Ischemic stroke triggers a complex cascade of events involving inflammation, oxidative stress, and glial cell dysfunction, all of which contribute to neuronal damage and impaired recovery. Glial cells (e.g., astrocytes, microglia, and oligodendrocytes) play key roles in neuroinflammatory responses, making them attractive targets for therapeutic modulation. Cannabidiol, a non-psychoactive phytocannabinoid from Cannabis sativa, exhibits anti-inflammatory, antioxidant, and neuroprotective properties. Preclinical evidence indicates that cannabidiol attenuates glial reactivity, reduces pro-inflammatory signaling, mitigates oxidative stress, and preserves blood-brain and intestinal barrier integrity in stroke models. Moreover, cannabidiol modulates key molecular pathways (e.g., nuclear factor-κB, tumor necrosis factor, and calcium-related signaling), contributing to …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Analysis Of The Effect Of Neuro-Developmental Treatment (Ndt) On Gross Motor Function In Children With Spastic Diplegic Cerebral Palsy: A Systematic Review, Haunan Naja Izdihar, Aditya Denny Pratama

Jurnal Vokasi Indonesia

Effectiveness of Neurodevelopmental Treatment (NDT) in Children with Spastic Diplegia Cerebral Palsy: A Systematic Review

Background:
Neurodevelopmental Treatment (NDT) is commonly used in pediatric rehabilitation to improve motor function in children with cerebral palsy, particularly those with spastic diplegia.

Methods:
This systematic review followed PRISMA 2020 guidelines. Seven studies published between 2018 and 2024 were identified through electronic databases, including PubMed, Scopus, ProQuest, ScienceDirect, SpringerLink, Cochrane Library, Google Scholar, and Crossref.

Results:
The included studies reported improvements in gross motor function, posture, balance, and daily functional independence following NDT, particularly when combined with other therapeutic interventions. However, outcome measures and …