Medical Sciences Commons^™

Mbnl Loss Of Function In Smooth Muscle As A Model For Myotonic Dystrophy Associated Gastrointestinal Dysmotility, Janel A M Peterson, Jesus A Frias, Andrew N Miller, Krishnakant G Soni, Yi Zhang, Zheng Xia, John W Day, Geoffrey A Preidis, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy and severely affects multiple organ systems, including the brain, heart, skeletal muscle, and gastrointestinal (GI) tract. Despite 80% of individuals with DM1 experiencing GI dysfunction that affects their daily life, the mechanisms of GI dysmotility in DM1 remain an understudied aspect of the disease. DM1 is caused by a CTG repeat expansion in the DMPK gene that, when expressed as an expanded CUG repeat RNA, sequesters and reduces the activity of the muscleblind-like (MBNL) RNA-binding protein family. We developed a mouse line with conditional, smooth muscle-specific knockout of …

Accurate Imputation Of Pathway-Specific Gene Expression In Spatial Transcriptomics With Pasta, Ruoxing Li, Peng Yang, Mauro Di Pilato, Jianjun Zhang, Christopher R Flowers, Lulu Shang, Ziyi Li

Faculty, Staff and Student Publications

Mapping the entire transcriptome at single-cell resolution under its natural spatial context is essential for investigating the oncogenesis and progression of diseases. The recently emerged targeted in-situ technologies retain the spatial organization of cells at high resolution, although they remain limited in the number of genes that can be simultaneously measured. To overcome this obstacle, numerous computational methods have been developed to predict unmeasured gene expression in spatial transcriptomics data by leveraging scRNA-seq data. Most of these methods focus on the expression of individual genes and usually generate highly variable predictions. In this study, we introduce PASTA (PAthway-oriented Spatial gene …

Lung Adenocarcinoma Surfaceome Remodeling With Egfr Inhibitors Uncovers Placental Alkaline Phosphatase As A Target For Combination Therapy, Yihui Chen, Rongzhang Dou, Monica J Hong, Hanwen Xu, Jody Vykoukal, Ricardo A León-Letelier, Yining Cai, Soyoung Park, Ehsan Irajizad, Fu Chung Hsiao, Jennifer B Dennison, Edwin J Ostrin, Johannes F Fahrmann, Hiroyuki Katayama, Samir M Hanash

Faculty, Staff and Student Publications

Treatment of lung adenocarcinomas (LUADs) that exhibit activated epidermal growth factor receptor (EGFR) with EGFR tyrosine kinase inhibitors (TKIs) has limited efficacy. Assessment of the impact of EGFR TKI on the LUAD surfaceome remodeling reveals potential therapeutic targets. We identify placental type alkaline phosphatase (ALPP), which has restricted expression in normal tissues, among upregulated surface proteins following EGFR TKI treatment of both TKI sensitive as well as resistant cells. EGF treatment represses ALPP expression, whereas EGFR TKIs upregulate its expression through dephosphorylation and activation of FoxO3a, a transcriptional regulator that binds to the promoter region of ALPP. The combination of …

Vesicle-Mediated Mitochondrial Clearance Presents An Actionable Metabolic Vulnerability In Triple-Negative Breast Cancer, Jody Vykoukal, Yihui Chen, Mingxin Zuo, Riccardo Ballarò, Monica J Hong, Hansini Krishna, Daniela B Rodriquez-Perera, Hiroyuki Katayama, Ehsan Irajizad, Ranran Wu, Ricardo A León-Letelier, Jennifer B Dennison, Angelica M Gutierrez, Adriana Paulucci-Holthauzen, Timothy C Thompson, Leona Rusling, Yining Cai, Fu Chung Hsiao, Soyoung Park, Banu Arun, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Selective autophagy of mitochondria is known to promote cancer cell survival and progression, including in triple-negative breast cancer (TNBC). Here, we apply an integrated multi-omics approach together with functional experimental analyses to investigate metabolic adaptations that support mitochondrial quality control in TNBC. We detail a mitochondrial quality control mechanism, complementary to mitophagy, that is enabled by a program of heightened extracellular sphingomyelin salvaging in TNBC coupled with extracellular vesicle-mediated intracellular clearance of mitochondrial damage. Targeting of this onco-metabolic pathway via repurposing of eliglustat, a selective small molecule inhibitor of glucosylceramide synthase, results in ceramide-mediated compensatory mitophagy and cancer cell death …

Intouch Week Of December 15, 2025, New York Medical College

InTouch

• Record Numbers, Remarkable Research Define 30th Medical Student Research Forum
• Wellness Ambassador Program Welcomes New Student Leaders
• New Test Could Revolutionize Lyme Disease Diagnosis
• Meal Plan Launches Through Vemos Pay
• Off Campus, On Craft: Jeanne Chamas Keeps the Department on Track and the Community in Step

Radiogenomic Profiling Of Prostate Tumors Prior To External Beam Radiotherapy Converges On A Transcriptomic Signature Of Tgf-Β Activity Driving Tumor Recurrence, Anson T. Ku, Uma Shankavaram, Shana Y. Trostel, Hong Zhang, Sumeyra Kartal, Houssein A. Sater, Stephanie A. Harmon, Nicole V. Carrabba, Yang Liu, Hyunnam Ryu, James A. Proudfoot, Boon Hao Hong, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Mack Roach, Howard M. Sandler, Stephanie L. Pugh, Kenneth L. Zeitzer, Lucas C. Mendez, Nirav S. Kapadia, William A. Hall, Anand B. Desai, Radka S. Stoyanova, Alan Pollack, Elai Davicioni, Melvin L. K. Chua, Baris Turkbey, Adam G. Sowalsky, Deborah E. Citrin

Einstein Health Papers

PURPOSE: Clinical risk grouping based on PSA, tumor grade, and disease extent guides treatment intensity for localized prostate cancer. However, many patients with intermediate- or high-risk disease treated with external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) still develop biochemical recurrence (BCR). Early identification of patients at high risk for BCR could enable personalized treatment strategies.

EXPERIMENTAL DESIGN: We prospectively enrolled 29 patients with intermediate- or high-risk prostate cancer undergoing EBRT and ADT. Pretreatment biopsies (n = 60) underwent whole-transcriptome microarray and whole-exome sequencing. Patients received multiparametric MRI at baseline and 6 months after treatment, with a median follow-up …

Impact Of Postoperative Intraocular Pressure Spikes On Outcomes Following Goniotomy: A Comparative Study Of Surgical Techniques, Wesam S. Shalaby, Steven L. Chang, Julia Yu, Teresa Horan, Sagar Shah, Shahin Hallaj, Marlene Moster, Reza Razeghinejad, Daniel Lee, Michael Pro, Aakriti Shukla, Ping Huang, Jonathan S. Myers, Tina Xia, Dilru Amarasekera

Wills Eye Hospital Papers

AIM AND BACKGROUND:To compare postoperative intraocular pressure (IOP) spikes and 1-year surgical success among goniotomy procedures: Kahook Dual Blade (KDB), OMNI, bent ab interno needle goniotomy (BANG), and gonioscopy-assisted transluminal trabeculotomy (GATT).

MATERIALS AND METHODS: This single-center, retrospective chart review included glaucoma patients ≥18 years, who underwent goniotomy from January 2021 to December 2022 with ≥3 months of follow-up. Primary outcomes were IOP spikes (≥10 mm Hg increase within 3 months) and 12-month surgical success (≥20% IOP and/or ≥1 medication reduction without further surgery). Secondary outcomes included IOP and medication changes.

RESULTS: Among 247 eyes (107 KDB, 63 OMNI, 77 …

Development Of Broadly Protective Vaccines Against New World Arenaviruses, Brian B. Gowen

Funded Research Records

No abstract provided.

Genomic Ascertainment Of Chek2 -Related Cancer Predisposition, Sunyoung Kim, Jung Kim, Mark Ramos, Jeremy Haley, Diane Smelser, H. Shanker Rao, Uyenlinh L. Mirshahi, Katherine L. Nathanson, Barry I. Graubard, Hormuzd A. Katki, David Carey, Douglas R. Stewart

School of Graduate Studies Faculty Publications

Importance: There is clear evidence that deleterious germline variants in CHEK2 increase risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Objective: To quantify the prevalence of as well as cancer risk and survival associated with CHEK2 germline pathogenic and likely pathogenic variants using genomic ascertainment. Design, Setting, and Participants: This case-control study used 2 electronic health record-linked and exome-sequenced biobanks: UK Biobank (n = 469765) and Geisinger MyCode (adults only; n = 167050). Variants were classified according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Cases …

Mrna Vaccines Encoding Variant Forms Of Sm-Tsp-2 Confer Protective Immunity Against Schistosoma Mansoni, Athos Silva De Oliveira, Sevan Alwan, Philip T Loverde, Ramiz Shaheed, Pranav Mandyam, Rakesh Adhikari, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

This study explored the development and evaluation of mRNA vaccine candidates targeting Schistosoma mansoni tetraspanin-2 (Sm-TSP-2). We designed constructs encoding either full-length Sm-TSP-2, or its large extracellular loop (EC2) domain in secretory, membrane-anchored, or cytosolic forms. In a murine model, the secreted and membrane-anchored versions of Sm-TSP-2-EC2 induced the highest antigen-specific antibody titers. These two construct designs, along with full-length Sm-TSP-2 mRNA, also significantly reduced adult worm and egg burden compared to controls. The membrane-anchored Sm-TSP-2-EC2 mRNA was the most effective, lowering worm and egg burdens by 66.7% and 66.9%, respectively. Protective responses induced by the mRNA vaccines were comparable …

Facts And Hopes Of Chimeric Antigen Receptor-Redirected Nk T Cells, Amy N Courtney, Xin Zhou, Gengwen Tian, Ying Wang, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Chimeric antigen receptor (CAR)-engineered invariant NK T cells (CAR-NKT) are a novel cell platform for cancer immunotherapy. Unlike conventional T cells, NKTs are characterized by innate antitumor properties, minimal alloreactivity, and a unique ability to modulate the tumor microenvironment. This article provides a comprehensive overview of preclinical and early clinical studies evaluating CAR-NKTs in both autologous and allogeneic clinical settings. We discuss the contributions of CAR signaling domains, cytokine coexpression, and other functional measures that correlate with CAR-NKT persistence, function, and metabolic fitness. We also discuss the critical role of immunocompetent animal models in elucidating the interactions of CAR-NKTs with …

Mitochondrial Complex Ii Orchestrates Divergent Effects In Cd4+ And Cd8+ T Cells, Keisuke Seike, Shih-Chun A Chu, Yuichi Sumii, Takashi Ikeda, Meng-Chih Wu, Laure Maneix, Dongchang Zhao, Yaping Sun, Marcin Cieslik, Pavan Reddy

Faculty, Staff and Students Publications

Mitochondrial metabolism orchestrates T cell functions, yet the role of specific mitochondrial components in distinct T cell subsets remains poorly understood. Here, we explored the role of mitochondrial complex II (MC II), the only complex from the electron transport chain (ETC) that plays a role in both ETC and metabolism, in regulating T cell functions. Surprisingly, MC II exerts divergent effects on CD4+ and CD8+ T cell activation and function. Using T cell-specific MC II subunit, succinate dehydrogenase A-deficient (SDHA-deficient) mice, we integrated single-cell RNA-seq and metabolic profiling, with in vitro and in vivo T cell functional assays to illuminate …

Spinach (Spinacia Oleracea L) Flavonoids Are Hydrolyzed During Digestion And Their Bioaccessibility Is Under Stronger Genetic Control Than Raw Material Content, Michael P Dzakovich, Alvin L Tak, Elaine A Le, Rachel P Dang, Benjamin W Redan, Geoffrey A Dubrow

Children’s Nutrition Research Center Staff Publications

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Current Insight Into Ldlr And Pcsk9 Genetic Variants: Investigating Genetic Keys To Cholesterol In A Cohort Of Stroke Patients From Yogyakarta, Indonesia, Loury Priskila, Lenggana Relung Atmadi, Arya Taksya Bagaskara, Andreas Mercyan Anggitama

Makara Journal of Health Research

Background: Stroke is the second leading cause of mortality worldwide. In Yogyakarta, Indonesia, the incidence of stroke (14%) is higher than the national average. We therefore investigated the roles of LDLR rs688 (C/T) and PCSK9 rs562565 (A/G) polymorphisms in familial hypercholesterolemia as predictors of first-time ischemic stroke.

Methods: In this case-control study, 119 first-time ischemic stroke patients were divided into dyslipidemia (N = 71) and non-dyslipidemia groups (N = 48). The DNA of the nucleotide polymorphisms LDLR rs688 (C/T) and PCSK9 rs562556 (A/G) was extracted and analyzed using the PCR-RFLP method, and statistical analyses were performed to evaluate …

Acute And Chronic Effects Of Neuroinflammation On Hippocampus And Anterior Cingulate Cortex Network Dynamics, Lauren A. Crew

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neuroinflammation has emerged as a critical modulator of cognitive function and neural circuit dynamics, yet the distinct contributions of acute and chronic neuroinflammation to brain function remain poorly defined. This dissertation examines how inflammation independently alters large-scale neural activity and behavior, focusing on interactions between the hippocampus (HPC) and anterior cingulate cortex (ACC), regions essential for memory and executive processes. Using in vivo electrophysiological techniques in a rodent model, this study compares the effects of short-term (acute) and prolonged (chronic) neuroinflammatory states, induced via Poly I:C, on neural oscillations, regional coherence, and spatial coding. Findings reveal that even transient inflammation …

Targeting Kinesin Family Member 20a Sensitizes Stem-Like Triple-Negative Breast Cancer Cells To Standard Chemotherapy, Yayoi Adachi, Weilong Chen, Cheng Zhang, Tao Wang, Nina Gildor, Rachel Shi, Haoyong Fu, Masashi Takeda, Qian Liang, Fangzhou Zhao, Hongyi Liu, Jun Fang, Jin Zhou, Hongwei Yao, Lianxin Hu, Shina Li, Lei Guo, Lin Xu, Ling Xie, Xian Chen, Chengheng Liao, Qing Zhang

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC), being both aggressive and highly lethal, poses a major clinical challenge in terms of treatment. Its heterogeneity and lack of hormone receptors or HER2 expression further restrict the availability of targeted therapy. Breast cancer stem cells (BCSCs), known to fuel TNBC malignancy, are now being exploited as a vulnerability for TNBC treatment. Here, we dissected the transcriptome of BCSCs and identified kinesin family member 20A (KIF20A) as a key regulator of BCSC survival and TNBC tumorigenesis. Genetic depletion or pharmacological inhibition of KIF20A impairs BCSC viability and tumor initiation and development in vitro and in vivo. …

Itpr1 Autoantibody-Associated Autoimmunity As A Cause Of Newly Emerging Cognitive Decline Mimicking Alzheimer's Disease: Case Report And Brief Review Of The Literature, Nicolas Kunath, Hermod Arne Bollandsås Ramfjord, Elisabeth Volden Kvisvik, Marton Konyves-Kolonics, Gøril Rolfseng Grøntvedt, Irina I Serysheva, Lars Komorowski, Brigitte Wildemann, Sven Jarius

Faculty, Staff and Student Publications

Background: Since its first description in 2014, anti-inositol 1,4,5-trisphosphate receptor type 1 (ITPR1, also termed IP3R1) autoimmunity has been recognized as causing a clinically heterogeneous spectrum of symptoms. While first described in patients with autoimmune cerebellar ataxia, this facultative paraneoplastic disease has been associated also with peripheral neuropathy, dysautonomia, sleep disorders, neuropsychiatric/psychotic symptoms, and cognitive decline.

Methods: Retrospective case study.

Results: We report the case of a 58-year-old patient who was admitted with acute confusion, rapidly progressive cognitive decline, and hallucinations. A history of mild cognitive impairment over several years and low cerebrospinal fluid (CSF) amyloid beta-42 and elevated CSF …

Low-Dimensional Signatures Of Neuronal Activity Associated With Long-Term Operant Conditioning In Aplysia, Sara Vanaki, Nicholas O Gonzalez, Curtis L Neveu, Yuto Momohara, Behnaam Aazhang, John H Byrne

Faculty, Staff and Student Publications

Operant conditioning is a form of learning in which a behavior is reinforced by reward. Operant conditioning has multiple temporal domains, ranging from short-term, lasting a few minutes, to long-term, persisting for at least 24 h. The extent to which short- and long-term operant conditioning memories rely on shared or separate neural mechanisms is poorly understood. Voltage-sensitive dye (VSD) imaging has been used previously to record the activity of a large number of neurons simultaneously in the buccal ganglion to measure changes in neuronal activity during short-term operant conditioning. We examined neuronal activity using VSD 24 h after operant conditioning …

Protocol For Isolation Of Lipid Droplets And Mitochondria From Acute Myeloid Leukemia Cells For Lipidomic Analysis, Ran Zhao, Liang Zhang, Shuxin Dong, Kazuharu Kamachi, Saurabh Kumar Gupta, Hiroki Akiyama, Jalen Nguyen, G Lavender Hackman, Michael Andreeff, Alessia Lodi, Jo Ishizawa

Faculty, Staff and Student Publications

Lipid droplets (LDs) are dynamic organelles critical for lipid and energy homeostasis. LD dysregulation is implicated in various diseases, including acute myeloid leukemia (AML), which exhibits aberrant lipid metabolism and chemoresistance. Here, we describe an effective protocol for the co-isolation of LDs and mitochondria from lipid-deficient cell types, e.g., AML cells. We detail procedures for the isolation, quality verification, and results from mass spectrometry-based lipidomic analysis. This protocol enables the functional study of organellar lipidomic regulation in AML.

A Long Non-Coding Rna Leat1 Mediates The Hormone Responsiveness Of Efnb2 During Male Urogenital Development, Deidre Mattiske, Pascal Bernard, Paul E Gradie, Richard R Behringer, Paul A Overbeek, Rachel J O'Neill, Tiffany Phillips, Melanie Stewart, Neil Youngson, Gerard Tarulli, Andrew J Pask

Faculty, Staff and Students Publications

The novel long non-coding RNA (lncRNA) Leat1 is extraordinarily conserved in both its location (syntenic with EfnB2, an essential gene in anogenital patterning) and sequence. Here we show that Leat1 is upregulated following the production of testosterone from the developing testis in mice and interacts with EfnB2, positively regulating its expression. Leat1 expression is suppressed by estrogen, which in turn suppresses the expression of EfnB2. Moreover, the loss of Leat1 leads to reduced EfnB2, resulting in a severe hypospadias phenotype. The human LEAT1 gene is also co-expressed with EFNB2 in the developing human penis, suggesting a conserved function for this …

Methodology For The Pediatric Dose Optimization For Seizures In Emergency Medical Services (Pedidose) Study, Manish I Shah, Kathleen M Adelgais, James M Chamberlain, Henry E Wang, Lindsey A Morgan, James J Riviello, Rana R Said, Joseph E Sullivan, Kimia F Ghaffari, Kathryn M Kothari, Mohsen Saidinejad, Robert A Lowe, Raymond L Fowler, Catherine R Counts, Claudia R Morris, Jonathan R Studnek, Nancy K Glober, Caleb E Ward, Brian M Clemency, Nicholas Patrick, Rachel D Munn, Graham M Brant-Zawadzki, Christian Martin-Gill, Daniel K Nishijima, Kevin Li, Neomi Sepulveda, John M Vanburen

Faculty, Staff and Student Publications

Background: Seizures are one of the most common reasons for emergency medical services (EMS) activation for children, and current EMS practice results in underdosing and delayed delivery of anti-seizure medication. A prehospital evidence-based guideline recommends using intranasal or intramuscular midazolam as first-line treatment for pediatric seizures. Despite attempts to implement these guidelines, one-third of children having a paramedic-witnessed seizure have ongoing seizures on emergency department (ED) arrival; this may be due to inadequate or delayed midazolam dosing. Replacing the error-prone, sequential calculations with age-based midazolam dosing may be simpler, faster, and more effective without compromising safety. The objective of this …

Fecal Showdown - Fit Vs. Colonoscopy: Which Is Better In Colorectal Cancer Detection?, Vanessa A. Arenas, Virn Warndahl

Physician Assistant Capstones, 2020-current

Abstract

Objectives

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States, with most cases occurring in individuals aged 50 years and older. Effective screening is essential for early detection and improved patient outcomes. This paper compares two widely used CRC screening methods—fecal immunochemical testing (FIT) and colonoscopy—primarily in terms of colorectal cancer detection, but also considers adherence and diagnostic yield.

Methods

A search was conducted using PubMed and CINAHL to identify relevant studies comparing FIT and colonoscopy. Articles were included if they were randomized controlled trials (RCTs) or clinical trials published after 2020, involved subjects …

Patient-Derived Ovarian Cancer Models Provide Insight Into Cancer Cell-Intrinsic And Immune Cell-Dependent Effects On Therapeutic Response, Parisa Nikeghbal

Biomedical Sciences ETDs

Ovarian cancer is the most lethal gynecologic malignancy, largely due to late diagnosis and resistance to chemotherapy. This dissertation applies patient-derived organoids (PDOs), xenograft-derived organoids (PDXOs), and humanized xenografts (huPDX) to investigate therapeutic responses and immune interactions. Organoids were shown to retain critical features of the original malignancy. Across platinum-sensitive, -resistant, and -refractory cases, both PDOs and PDXOs exhibited drug sensitivities that aligned with patients’ clinical classifications. Building on this foundation, a drug screen revealed novel strategies. Auranofin restored platinum sensitivity in Notch3-active models, afatinib broadly reduced viability, and adavosertib–gemcitabine and sorafenib–topotecan combinations produced synergy. Extending this work, immune interactions …

Protein-Nucleic Acid Language Model-Assisted Design Of Precise And Compact Adenine Base Editor, Jingxuan Ren, Jiawei Yao, Qiuyu Cao, Yinuo Li, Yang Li, Ziyi Zhang, Xiyu Ge, Shengfang Wang, Yang Zhang, Xiaogang Wang, Xiaohui Zhang

Faculty, Staff and Students Publications

Adenine base editors (ABEs) are powerful tools for gene therapy. However, efficient version of ABEs (e.g. ABE8e) always induce excessive bystander and off-target editing events and are large in size, hindering their potential in clinical disease treatment. Here, we develop a pre-trained Protein-Nucleic Acid Constrained Language Model to design ABE8e with high activity, reduced editing window and decreased size. By further engineering, the smallest ABE8e- PNLM-pcABE- with a 27% size reduction, exhibits high activity, precise 3-nt editing window, and reduced off-target events near background level in HEK293T cells. Compared to ABE8e, PNLM-pcABE has up to 133.5-fold precision improvement in pathogenic …

Dermal Lymphatic Carcinomatosis As A Cutaneous Metastasis From Epidermal Growth Factor Receptor-Positive Lung Adenocarcinoma: A Case Report, Sarah A. Hemelt, Jonathan M. Joseph, Nicholas Culotta

School of Medicine Faculty Publications

Cutaneous metastases are an uncommon but clinically significant manifestation of internal malignancies. We present a rare case of dermal lymphatic carcinomatosis arising from epidermal growth factor receptor (EGFR)-positive lung adenocarcinoma, a presentation that may closely mimic inflammatory dermatoses and indicate therapeutic resistance or disease progression. We describe the clinical course of a 65-year-old woman who developed a violaceous cutaneous metastatic lesion beneath the left breast during treatment for metastatic lung adenocarcinoma. This case highlights the importance of recognizing cutaneous signs as indicators of disease progression and emphasizes the diagnostic challenges and prognostic implications of cutaneous metastases in lung cancer.

Krasg12d Mutation Promotes Pancreatic Tumorigenesis By Suppressing Sirtuin Three Via The Guanine Nucleotide Exchange Factor Rcc1, Taoyi Mai, Mengwen Wang, Ya Qiu, Wenhua Lu, Hongyu Wu, Shuna Chen, Paul J Chiao, Peng Huang

Faculty, Staff and Student Publications

KRASG12D mutation is a prevalent gain-of-function mutation that drives pancreatic cancer tumorigenesis, but the underlying mechanisms that promote KRAS-induced cell proliferation and tumor formation remain elusive. To uncover the molecular pathways that facilitate KRASG12D-driven malignant transformation, we measured the transcriptomic alterations at various time points after induction of KRASG12D expression in human pancreatic normal epithelial cells. KEGG pathway enrichment of the differentially expressed genes (DEGs) showed that the major DEGs were located in pathways that regulate nicotinate/nicotinamide metabolism, TNF signaling, and microRNAs associated with cancer. Among these molecular alterations, the NAD-dependent deacetylase gene SIRT3 was significantly down-regulated by KRASG12D. Conversely, …

The Pathophysiological Role Of Mitochondrial Acid-Sensing Ion Channel 1a In Hypoxic Pulmonary Hypertension, Megan N. Tuineau

Biomedical Sciences ETDs

Pulmonary hypertension (PH) is characterized by increased pulmonary arterial constriction, pulmonary arterial remodeling, and right ventricular dysfunction. While metabolic and mitochondrial derangements are increasingly recognized as central pathogenic features, the underlying mechanisms and effectors are not yet fully understood. Acid-sensing ion channel 1a (ASIC1a) is a proton-gated cation channel involved in the development of chronic hypoxia (CH)-induced PH. ASIC1a represents a potential candidate involved in metabolic-mitochondrial dysfunction, as metabolic byproducts can act as ligands for ASIC1a. Additionally, ASIC1a has recently been identified as a mitochondrial ion channel involved in neuronal death following oxidative stress. Therefore, we hypothesize that ASIC1a functions …

When Clotting And Bleeding Collide: A Case Of Bilateral Pe And Concurrent Upper Gi Hemorrhage, Tabitha D. Baca, David Rayburn, Daniel Castro, Jessica Aird

Florida Journal of Emergency Medicine (FJEM)

Introduction

Concurrent episodes of pulmonary emboli and gastrointestinal bleeding in one patient are not commonly seen. When a patient presents with both, it presents a challenge to manage as they are opposite ends of the same disease spectrum associated with the coagulation system.

Case Report

We present the case of a 65-year-old male who presented to our hospital via EMS with unknown prior history after a witnessed cardiac arrest, who on evaluation also had a concurrent bilateral pulmonary emboli with right heart strain.

Why should an emergency physician be aware of this?

While there is extensive research on the management …

In Recent Research: Exosomal And Molecular Regulators Of Browning And Thermogenesis In Adipose Tissues, Merve İnel, Bahadir Öztürk

Turkish Journal of Medical Sciences

This review synthesizes current knowledge on the molecular mechanisms regulating brown, white, and beige adipose tissues, with particular emphasis on the browning process of white adipose tissue. Rather than considering adipose tissue as a passive energy reservoir, this review underscores its active role as a dynamic endocrine and metabolic organ. Brown and beige adipose tissues, recognized for their thermogenic capacity and contribution to energy expenditure, have emerged as promising therapeutic targets for the treatment of obesity, type 2 diabetes, and related metabolic disorders. The review draws upon recent findings on adrenergic signaling, transcription factors, exosomal microRNAs, and other novel regulatory …

Telemedicine Versus Conventional Care For Nonspecific Neck Pain: A Randomized Controlled Study, Selki̇n Yilmaz Muluk, Sevtap Badil Güloğlu, Begüm Ünlütaşkiran

Turkish Journal of Medical Sciences

Background/aim: Telemedicine (TM) can overcome travel barriers in nonspecific neck pain (NNP), yet a comprehensive, physiatrist-supervised TM model has not been directly compared to standard in-clinic care. The aim of this study was to determine whether a video-based exercise and remote follow-up program is as effective as conventional follow-up in reducing pain and disability in NNP.

Materials and methods: This parallel-group randomized controlled trial (registered in ClinicalTrials.gov) included 68 adults (mean age = 40.52 years) with NNP who were randomly allocated 1:1 to the TM group (TG, n = 34) or control group (CG, n = 34). Both received identical …