Medical Specialties Commons^™

Antibody-Directed Evolution Reveals A Mechanism For Enhanced Neutralization At The Hiv-1 Fusion Peptide Site, Bailey B Banach, Sergei Pletnev, Adam S Olia, Kai Xu, Baoshan Zhang, Reda Rawi, Tatsiana Bylund, Nicole A Doria-Rose, Thuy Duong Nguyen, Ahmed S Fahad, Myungjin Lee, Bob C Lin, Tracy Liu, Mark K Louder, Bharat Madan, Krisha Mckee, Sijy O'Dell, Mallika Sastry, Arne Schön, Natalie Bui, Chen-Hsiang Shen, Jacy R Wolfe, Gwo-Yu Chuang, John R Mascola, Peter D Kwong, Brandon J Dekosky

Faculty, Staff and Student Publications

The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to …

Qa-Snare Syntaxin 18 Mediates Lipid Droplet Fusion With Snap23 And Sec22b, Yuhui Fu, Binbin Ding, Xiaoxia Liu, Shangang Zhao, Fang Chen, Linsen Li, Yi Zhu, Jingxuan Zhao, Zhen Yuan, Yafeng Shen, Chaofeng Yang, Mengle Shao, She Chen, Perry E Bickel, Qing Zhong

Faculty, Staff and Students Publications

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)-SNAP23-SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18-SNAP23-SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, …

Widespread Brca1/2-Independent Homologous Recombination Defects Are Caused By Alterations In Rna-Binding Proteins, Daniel J Mcgrail, Yang Li, Roger S Smith, Bin Feng, Hui Dai, Limei Hu, Briana Dennehey, Sharad Awasthi, Marc L Mendillo, Anil K Sood, Gordon B Mills, Shiaw-Yih Lin, S Stephen Yi, Nidhi Sahni

Faculty, Staff and Student Publications

Defects in homologous recombination DNA repair (HRD) both predispose to cancer development and produce therapeutic vulnerabilities, making it critical to define the spectrum of genetic events that cause HRD. However, we found that mutations in BRCA1/2 and other canonical HR genes only identified 10%-20% of tumors that display genomic evidence of HRD. Using a networks-based approach, we discovered that over half of putative genes causing HRD originated outside of canonical DNA damage response genes, with a particular enrichment for RNA-binding protein (RBP)-encoding genes. These putative drivers of HRD were experimentally validated, cross-validated in an independent cohort, and enriched in cancer-associated …

Mediation Of The Association Between Social Environmental Characteristics Of Family Childcare Home And Weight Status In Children By Diet Quality., Qianxia Jiang, Patricia Markham Risica, Alison Tovar, Kristen Cooksey Stowers, Marlene B. Schwartz, Caitlin Lombardi, Kim M. Gans

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The food and beverages served in family childcare homes (FCCHs) may play an important role in the development of childhood overweight and obesity. This analysis examines whether children's diet quality mediates the relationship between foods and beverages served in FCCHs and preschool-aged children's weight status.

METHODS: Trained and certified staff conducted observations for two days in each FCCH, using the Environment and Policy Assessment and Observation (EPAO) measure to determine the foods and beverages served to children (N = 370) in FCCHs (N = 120). They also used the Dietary Observation in Child Care (DOCC) protocol to assess children's …

Safety And Efficacy Of Direct Oral Anticoagulants In Stroke Prevention In Patients With Atrial Fibrillation Complicated With Anemia And/Or Thrombocytopenia: A Retrospective Cohort Study, Wenlin Xu, Jiana Chen, Shuyi Wu, Nianxu Huang, Xia Chen, Wang Zhang, Wei Hu, Jun Su, Hengfen Dai, Ping Gu, Xiaohong Huang, Xiaoming Du, Ruijuan Li, Qiaowei Zheng, Xiangsheng Lin, Yanxia Zhang, Lang Zou, Yuxin Liu, Min Zhang, Xiumei Liu, Zhu Zhu, Jinhua Zhang

Faculty, Staff and Student Publications

BACKGROUND: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia.

METHODS: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 10

RESULTS: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any …

Early And Empirical High-Dose Cryoprecipitate For Hemorrhage After Traumatic Injury: The Cryostat-2 Randomized Clinical Trial, Ross Davenport, Nicola Curry, Erin E Fox, Helen Thomas, Joanne Lucas, Amy Evans, Shaminie Shanmugaranjan, Rupa Sharma, Alison Deary, Antoinette Edwards, Laura Green, Charles E Wade, Jonathan R Benger, Bryan A Cotton, Simon J Stanworth, Karim Brohi, Cryostat-2 Principal Investigators

Faculty, Staff and Student Publications

IMPORTANCE: Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.

OBJECTIVE: To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.

DESIGN, SETTING, AND PARTICIPANTS: CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US …

Silencing Of Genes By Promoter Hypermethylation Shapes Tumor Microenvironment And Resistance To Immunotherapy In Clear-Cell Renal Cell Carcinomas, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Alexandra Helleux, Véronique Lindner, Roger Mouawad, Jean-Philippe Spano, Morgan Rouprêt, Eva Compérat, Virginie Verkarre, Cheng-Ming Sun, Mostefa Bennamoun, Hervé Lang, Philippe Barthelemy, Wenxuan Cheng, Li Xu, Irwin Davidson, Fangrong Yan, Wolf Hervé Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

The efficacy of immune checkpoint inhibitors varies in clear-cell renal cell carcinoma (ccRCC), with notable primary resistance among patients. Here, we integrate epigenetic (DNA methylation) and transcriptome data to identify a ccRCC subtype characterized by cancer-specific promoter hypermethylation and epigenetic silencing of Polycomb targets. We develop and validate an index of methylation-based epigenetic silencing (iMES) that predicts primary resistance to immune checkpoint inhibition (ICI) in the BIONIKK trial. High iMES is associated with VEGF pathway silencing, endothelial cell depletion, immune activation/suppression, EZH2 activation, BAP1/SETD2 deficiency, and resistance to ICI. Combination therapy with hypomethylating agents or tyrosine kinase inhibitors may benefit …

A Conceptual Framework For Nomenclatural Stability And Validity Of Medically Important Fungi: A Proposed Global Consensus Guideline For Fungal Name Changes Supported By Abp, Asm, Clsi, Ecmm, Escmid-Efisg, Eucast-Afst, Fdlc, Idsa, Isham, Mmsa, And Msgerc, Sybren De Hoog, Thomas J Walsh, Sarah A Ahmed, Ana Alastruey-Izquierdo, Barbara D Alexander, Maiken Cavling Arendrup, Esther Babady, Feng-Yan Bai, Joan-Miquel Balada-Llasat, Andrew Borman, Anuradha Chowdhary, Andrew Clark, Robert C Colgrove, Oliver A Cornely, Tanis C Dingle, Philippe J Dufresne, Jeff Fuller, Jean-Pierre Gangneux, Connie Gibas, Heather Glasgow, Yvonne Gräser, Jacques Guillot, Andreas H Groll, Gerhard Haase, Kimberly Hanson, Amanda Harrington, David L Hawksworth, Randall T Hayden, Martin Hoenigl, Vit Hubka, Kristie Johnson, Julianne V Kus, Ruoyu Li, Jacques F Meis, Michaela Lackner, Fanny Lanternier, Sixto M Leal, Francesca Lee, Shawn R Lockhart, Paul Luethy, Isabella Martin, Kyung J Kwon-Chung, Wieland Meyer, M Hong Nguyen, Luis Ostrosky-Zeichner, Elizabeth Palavecino, Preeti Pancholi, Peter G Pappas, Gary W Procop, Scott A Redhead, Daniel D Rhoads, Stefan Riedel, Bryan Stevens, Kaede Ota Sullivan, Paschalis Vergidis, Emmanuel Roilides, Amir Seyedmousavi, Lili Tao, Vania A Vicente, Roxana G Vitale, Qi-Ming Wang, Nancy L Wengenack, Lars Westblade, Nathan Wiederhold, Lewis White, Christina M Wojewoda, Sean X Zhang

Faculty, Staff and Student Publications

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the …

New Insights Into Yap/Taz-Tead-Mediated Gene Regulation And Biological Processes In Cancer, Yang Zhao, Marisela Sheldon, Yutong Sun, Li Ma

Faculty, Staff and Student Publications

The Hippo pathway is conserved across species. Key mammalian Hippo pathway kinases, including MST1/2 and LATS1/2, inhibit cellular growth by inactivating the TEAD coactivators, YAP, and TAZ. Extensive research has illuminated the roles of Hippo signaling in cancer, development, and regeneration. Notably, dysregulation of Hippo pathway components not only contributes to tumor growth and metastasis, but also renders tumors resistant to therapies. This review delves into recent research on YAP/TAZ-TEAD-mediated gene regulation and biological processes in cancer. We focus on several key areas: newly identified molecular patterns of YAP/TAZ activation, emerging mechanisms that contribute to metastasis and cancer therapy resistance, …

Position Statement On In-Hospital/Clinic Point-Of-Care Coagulation Testing For Anticoagulation Monitoring In Saudi Arabia, Fakhr Al Ayoubi, Malak Al Mashali, Mohamed Hassan Abdallah, Mohamed Al Sheef, Tarek Owaidah

Journal of the Saudi Heart Association

Objectives: Hospital overload is a persistent occurrence in daily practice. Interventions such as point-of-care testing (POCT) are needed to alleviate the pressure faced by healthcare providers and administrators. Methods: An invited panel of experts from Saudi Arabia was formed under the auspices of the Saudi Heart Association in order to discuss local treatment gaps in the management of patients receiving anticoagulation therapy. This was done in a series of meetings, which resulted in the development of official recommendations for the implementation of POCT for anticoagulation monitoring in the country. Recommendations were based on a comprehensive literature review and international guidelines …

Protracted Respiratory Failure In A Case Of Global Spinal Syringomyelia And Chiari Malformation Following Administration Of Diazepam: Illustrative Case, Luke Bauerle, Brandon Rogowski, Aakash Shingala, Habib Emil Rafka, Timothy Webb, Brian F. Saway, Edward F. Kilb, Julio A. Chalela, Nathan C. Rowland

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Syringomyelia is defined as dilation of the spinal cord's central canal and is often precipitated by skull base herniation disorders. Although respiratory failure (RF) can be associated with skull base abnormalities due to brainstem compression, most cases occur in pediatric patients and quickly resolve. The authors report the case of an adult patient with global spinal syringomyelia and Chiari malformation who developed refractory RF after routine administration of diazepam.

OBSERVATIONS: A 31-year-old female presented with malnutrition, a 1-month history of right-sided weakness, and normal respiratory dynamics. After administration of diazepam prior to magnetic resonance imaging (MRI), she suddenly developed …

Evaluating The Efficacy Of Chatgpt In Navigating The Spanish Medical Residency Entrance Examination (Mir): Promising Horizons For Ai In Clinical Medicine., Francisco Guillen-Grima, Sara Guillen-Aguinaga, Laura Guillen-Aguinaga, Rosa Alas-Brun, Luc Onambele, Wilfrido Ortega, Rocio Montejo, Enrique Aguinaga-Ontoso, Paul Barach, Ines Aguinaga-Ontoso

Department of Medicine Faculty Papers

UNLABELLED: The rapid progress in artificial intelligence, machine learning, and natural language processing has led to increasingly sophisticated large language models (LLMs) for use in healthcare. This study assesses the performance of two LLMs, the GPT-3.5 and GPT-4 models, in passing the MIR medical examination for access to medical specialist training in Spain. Our objectives included gauging the model's overall performance, analyzing discrepancies across different medical specialties, discerning between theoretical and practical questions, estimating error proportions, and assessing the hypothetical severity of errors committed by a physician.

MATERIAL AND METHODS: We studied the 2022 Spanish MIR examination results after excluding …

Large Right Lower Quadrant Abdominal Mass, Isheeta Madeka, Cannon Greco-Hiranaka, Ozlem Kulak, Wilbur Bowne

Jefferson Hospital Staff Papers and Presentations

No abstract provided.

Brain-Derived Neurotrophic Factor – A Key Player In The Gastrointestinal System, Arjun Singh

Jefferson Hospital Staff Papers and Presentations

Brain-derived neurotrophic factor (BDNF) is highly expressed throughout the gastrointestinal (GI) tract and plays a critical role in the regulation of intestinal motility, secretion, sensation, immunity, and mucosal integrity. Dysregulation of BDNF signalling has been implicated in the pathophysiology of various GI disorders including inflammatory bowel disease, irritable bowel syndrome, functional dyspepsia, and diabetic gastroenteropathy. This review provides a comprehensive overview of BDNF localization, synthesis, receptors, and signalling mechanisms in the gut. In addition, current evidence on the diverse physiologic and pathophysiologic roles of BDNF in the control of intestinal peristalsis, mucosal transport processes, visceral sensation, neuroimmune interactions, gastrointestinal mucosal …

A Network Pharmacology And Molecular-Docking-Based Approach To Identify The Probable Targets Of Short-Chain Fatty-Acid-Producing Microbial Metabolites Against Kidney Cancer And Inflammation, Md Rezaul Karim, Md Niaj Morshed, Safia Iqbal, Shahnawaz Mohammad, Ramya Mathiyalagan, Deok Chun Yang, Yeon Ju Kim, Joon Hyun Song, Dong Uk Yang

Faculty, Staff and Student Publications

(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species …

The Role Of Vitamin D In Patients With Inflammatory Bowel Disease Treated With Vedolizumab, Bincy P Abraham, Christopher Fan, Theresa Thurston, Joshua Moskow, Hoda M Malaty

Faculty, Staff and Students Publications

BACKGROUND: Many clinical factors can contribute to the efficacy of medical therapy in Inflammatory Bowel Disease (IBD). We assessed their effects on the efficacy of vedolizumab therapy in a cohort of patients with IBD.

METHODS: We conducted a retrospective study on patients between 18 and 80 years of age with ulcerative colitis (UC) or Crohn's disease (CD) who were seen in the IBD program at Houston Methodist in Houston, TX and treated with vedolizumab for at least 6 months from 2018 to 2022. We investigated factors prior to the initiation of therapy that best predicted treatment response, with an emphasis …

Vaginal Microbial Dynamics And Pathogen Colonization In A Humanized Microbiota Mouse Model, Marlyd E Mejia, Vicki Mercado-Evans, Jacob J Zulk, Samantha Ottinger, Korinna Ruiz, Mallory B Ballard, Stephanie W Fowler, Robert A Britton, Kathryn A Patras

Faculty, Staff and Students Publications

Vaginal microbial composition is associated with differential risk of urogenital infection. Although Lactobacillus spp. are thought to confer protection against infection, the lack of in vivo models resembling the human vaginal microbiota remains a prominent barrier to mechanistic discovery. Using 16S rRNA amplicon sequencing of C57BL/6J female mice, we found that vaginal microbial composition varies within and between colonies across three vivaria. Noting vaginal microbial plasticity in conventional mice, we assessed the vaginal microbiome of humanized microbiota mice (

Trend Of Outcome Metrics In Recent Out-Of-Hospital-Cardiac-Arrest Research: A Narrative Review Of Clinical Trials, Natalie N Htet, Daniel Jafari, Jennifer A Walker, Ali Pourmand, Anna Shaw, Khai Dinh, Quincy K Tran

Faculty, Staff and Student Publications

Cardiopulmonary resuscitation (CPR) research traditionally focuses on survival. In 2018, the International Liaison Committee on Resuscitation (ILCOR) proposed more patient-centered outcomes. Our narrative review assessed clinical trials after 2018 to identify the trends of outcome metrics in the field OHCA research. We performed a search of the PubMed database from 1 January 2019 to 22 September 2023. Prospective clinical trials involving adult humans were eligible. Studies that did not report any patient-related outcomes or were not available in full-text or English language were excluded. The articles were assessed for demographic information and primary and secondary outcomes. We included 89 studies …

Eicosanoid And Eicosanoid-Related Inflammatory Mediators And Exercise Intolerance In Heart Failure With Preserved Ejection Fraction, Emily S Lau, Athar Roshandelpoor, Shahrooz Zarbafian, Dongyu Wang, James S Guseh, Norrina Allen, Vinithra Varadarajan, Matthew Nayor, Ravi V Shah, Joao A C Lima, Sanjiv J Shah, Bing Yu, Mona Alotaibi, Susan Cheng, Mohit Jain, Gregory D Lewis, Jennifer E Ho

Faculty, Staff and Student Publications

Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.

Mechanism Of Stepwise Electron Transfer In Six-Transmembrane Epithelial Antigen Of The Prostate (Steap) 1 And 2, Kehan Chen, Lie Wang, Jiemin Shen, Ah-Lim Tsai, Ming Zhou, Gang Wu

Faculty, Staff and Student Publications

Six transmembrane epithelial antigen of the prostate (STEAP) 1-4 are membrane-embedded hemoproteins that chelate a heme prosthetic group in a transmembrane domain (TMD). STEAP2-4, but not STEAP1, have an intracellular oxidoreductase domain (OxRD) and can mediate cross-membrane electron transfer from NADPH via FAD and heme. However, it is unknown whether STEAP1 can establish a physiologically relevant electron transfer chain. Here, we show that STEAP1 can be reduced by reduced FAD or soluble cytochrome b5 reductase that serves as a surrogate OxRD, providing the first evidence that STEAP1 can support a cross-membrane electron transfer chain. It is not clear whether …

In Vivo Volumetric Depth-Resolved Imaging Of Cilia Metachronal Waves Using Dynamic Optical Coherence Tomography, Tian Xia, Kohei Umezu, Deirdre M Scully, Shang Wang, Irina V Larina

Faculty, Staff and Students Publications

Motile cilia are dynamic hair-like structures covering epithelial surfaces in multiple organs. The periodic coordinated beating of cilia creates waves propagating along the surface, known as the metachronal waves, which transport fluids and mucus along the epithelium. Motile ciliopathies result from disrupted coordinated cilia beating and are associated with serious clinical complications, including reproductive disorders. Despite the recognized clinical significance, research of cilia dynamics is extremely limited. Here, we present quantitative imaging of cilia metachronal waves volumetrically through tissue layers using dynamic optical coherence tomography (OCT). Our method relies on spatiotemporal mapping of the phase of intensity fluctuations in OCT …

Tert Immunohistochemistry As A Surrogate Marker For Tert Promoter Mutations In Infiltrating Gliomas, Gillian Gordon Perue, Hao Ying, Antonio Bustillo, Lili Zhou, Carolina M Gutierrez, Hannah E Gardener, Judith Krigman, Angus Jameson, Chuanhui Dong, Tatjana Rundek, David Z Rose, Jose G Romano, Ayham Alkhachroum, Ralph L Sacco, Negar Asdaghi, Sebastian Koch

Faculty, Staff and Student Publications

BACKGROUND: Guideline-based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescriber's blood pressure (BP) medication choice adheres to clinical practice guidelines (BP-guideline adherence).

METHODS AND RESULTS: The FSR (Florida Stroke Registry) uses statewide data prospectively collected for all acute stroke admissions. Based on established guidelines, we defined optimal BP-guideline adherence using the following hierarchy of rules: (1) use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker as first-line antihypertensive among diabetics; (2) use of thiazide-type diuretics or calcium channel blockers among Black patients; (3) …

Prediagnostic Selenium Status, Selenoprotein Gene Variants And Association With Breast Cancer Risk In A European Cohort Study, David J Hughes, Lutz Schomburg, Mazda Jenab, Carine Biessy, Catherine Méplan, Aurelie Moskal, Qian Sun, Kamil Demircan, Veronika Fedirko, Elisabete Weiderpass, Maryam Mukhtar, Anja Olsen, Anne Tjønneland, Kim Overvad, Matthias Schulze, Therese Haugdahl Nøst, Guri Skeie, Karina Standahl Olsen, Fulvio Ricceri, Sara Grioni, Domenico Palli, Giovanna Masala, Rosario Tumino, Fabrizio Pasanisi, Pilar Amiano, Sandra M Colorado Yohar, Antonio Agudo, Maria-Jose Sánchez, Eva Ardanaz, Malin Sund, Anne Andersson, Aurora Perez-Cornago, Ruth Travis, Alicia K Heath, Laure Dossus

Faculty, Staff and Student Publications

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional …

Pakistan Study Of Premature Coronary Atherosclerosis In Young Adults (Pak-Sehat): A Prospective Longitudinal Study Protocol Investigating The Prevalence, Severity And Determinants Of Atherosclerotic Cardiovascular Disease In The Young Adult Pakistani Population, Bashir Hanif, Sana Sheikh, Ghazal Peerwani, Miguel Cainzos-Achirica, Wajiha Javed, Jaffer Bin Baqar, Zainab Samad, Faiza Bashir, Salim S. Virani, Khurram Nasir

Section of Cardiology

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity, mortality and health expenditures worldwide. Despite having higher ASCVD in the Pakistani population, data on subclinical coronary atherosclerosis in young Pakistanis remain scarce. The PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT) aims to assess the prevalence, severity and determinants of subclinical coronary atherosclerosis among Pakistani men (35-60 years) and women (35-65 years) free of clinically symptomatic ASCVD and will assess 5-year rates of ASCVD events.
Methods and analysis: PAK-SEHAT is an ongoing prospective cohort study with 2000 participants from all provinces of Pakistan who will be …

Angiotensin Ii In Liver Transplantation (Anglt-1): Protocol Of A Randomised, Double-Blind, Placebo-Controlled Trial., Michael Bokoch, Amy Tran, Erika Brinson, Sivan Marcus, Meghana Reddy, Elizabeth Sun, Garrett Roll, Manuel Pardo, Scott Fields, Dieter Adelmann, Rishi Kothari, Matthieu Legrand

Department of Anesthesiology Faculty Papers

INTRODUCTION: Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in …

Molecular Basis Of Retinal Remodeling In A Zebrafish Model Of Retinitis Pigmentosa, Abirami Santhanam, Eyad Shihabeddin, Haichao Wei, Jiaqian Wu, John O'Brien

Faculty, Staff and Student Publications

A hallmark of inherited retinal degenerative diseases such as retinitis pigmentosa (RP) is progressive structural and functional remodeling of the remaining retinal cells as photoreceptors degenerate. Extensive remodeling of the retina stands as a barrier for the successful implementation of strategies to restore vision. To understand the molecular basis of remodeling, we performed analyses of single-cell transcriptome data from adult zebrafish retina of wild type AB strain (WT) and a P23H mutant rhodopsin transgenic model of RP with continuous degeneration and regeneration. Retinas from both female and male fish were pooled to generate each library, combining data from both sexes. …

Dietary Analysis For Hashimoto’S Thyroiditis: An Integrative Review, Evan Thompson, Alison Hultquist

Master of Science in Nursing Final Projects

Abstract

Hashimoto’s Thyroiditis (HT) is the leading cause of primary hypothyroidism in the United States. In HT, there is an infiltration by lymphocytes which leads to the production of autoantibodies against the thyroid gland. Throughout this integrative review, the aim was to evaluate the effectiveness of micronutrient supplementation and dietary management as adjunct treatments in HT. The purpose was to assist primary care providers in the development of a more holistic plan of care. Literature published within the past seven years was gathered and reviewed from PubMed, CINAHL, and Cochrane Library. Findings indicate that many patients with HT may benefit …

Association Between Microbiome And The Development Of Adverse Posttraumatic Neuropsychiatric Sequelae After Traumatic Stress Exposure, Abigail L. Zeamer, Marie-Claire Salive, Xinming An, Francesca L. Beaudoin, Stacey L. House, Jennifer S. Stevens, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Sarah D. Linnstaedt, Scott L. Rauch, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Erica Harris, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Ronald C. Kessler, Karestan C. Koenen, Samuel A. Mclean, Vanni Bucci, John P. Haran

Einstein Health Papers

Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA …

Efficacy Of Futibatinib, An Irreversible Fibroblast Growth Factor Receptor Inhibitor, In Fgfr-Altered Breast Cancer, Turcin Saridogan, Argun Akcakanat, Ming Zhao, Kurt W Evans, Erkan Yuca, Stephen Scott, Bryce P Kirby, Xiaofeng Zheng, Min Jin Ha, Huiqin Chen, Patrick K S Ng, Timothy P Diperi, Gordon B Mills, Jordi Rodon Ahnert, Senthil Damodaran, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib's efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and …

Architecture Of The Baculovirus Nucleocapsid Revealed By Cryo-Em, Xudong Jia, Yuanzhu Gao, Yuxuan Huang, Linjun Sun, Siduo Li, Hongmei Li, Xueqing Zhang, Yinyin Li, Jian He, Wenbi Wu, Harikanth Venkannagari, Kai Yang, Matthew L Baker, Qinfen Zhang

Faculty, Staff and Student Publications

Baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has been widely used as a bioinsecticide and a protein expression vector. Despite their importance, very little is known about the structure of most baculovirus proteins. Here, we show a 3.2 Å resolution structure of helical cylindrical body of the AcMNPV nucleocapsid, composed of VP39, as well as 4.3 Å resolution structures of both the head and the base of the nucleocapsid composed of over 100 protein subunits. AcMNPV VP39 demonstrates some features of the HK97-like fold and utilizes disulfide-bonds and a set of interactions at its C-termini to mediate nucleocapsid assembly and stability. …