Medical Specialties Commons^™

Clinical Mortality In A Large Covid-19 Cohort: Observational Study., M. Jarrett, S. Schultz, J. Lyall, J. Wang, L. Stier, M. De Geronimo, K. Nelson

Journal Articles

BACKGROUND: Northwell Health, an integrated health system in New York, has treated more than 15,000 inpatients with COVID-19 at the US epicenter of the SARS-CoV-2 pandemic.

OBJECTIVE: We describe the demographic characteristics of patients who died of COVID-19, observation of frequent rapid response team/cardiac arrest (RRT/CA) calls for non-intensive care unit (ICU) patients, and factors that contributed to RRT/CA calls.

METHODS: A team of registered nurses reviewed the medical records of inpatients who tested positive for SARS-CoV-2 via polymerase chain reaction before or on admission and who died between March 13 (first Northwell Health inpatient expiration) and April 30, 2020, …

Delay In Diagnosis Of Barrett's Esophagus Cancer During The Covid-19 Pandemic: Lessons Learned., A. J. Trindade, A. Rishi

Journal Articles

No abstract provided.

Teaching Professional Formation In Response To The Covid-19 Pandemic., L. B. Mccullough, J. Coverdale, F. A. Chervenak

Journal Articles

In response to the COVID-19 pandemic, the Association of American Medical Colleges has called for a temporary suspension of clinical teaching activities for medical students. Planning for the continued involvement of learners in patient care during this pandemic should include teaching learners professional formation. The authors provide an ethical framework to guide such teaching, based on the ethical principle of beneficence and the professional virtues of courage and self-sacrifice from professional ethics in medicine. The authors show that these concepts support the conclusion that learners are ethically obligated to accept reasonable, but not unreasonable, risk. Based on this ethical framework, …

Global Survey On Pancreatic Surgery During The Covid-19 Pandemic., A. Oba, T. F. Stoop, M. Löhr, T. Hackert, N. Zyromski, W. H. Nealon, M. Unno, R. D. Schulick, M. H. Al-Musawi, M. Del Chiaro, +6 Additional Authors

Journal Articles

OBJECTIVE:The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients' and clinicians' safety and safeguard health care capacity. SUMMARY BACKGROUND DATA:The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer. METHODS:An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery …

Current Smoking With Or Without Chronic Bronchitis Is Independently Associated With Goblet Cell Hyperplasia In Healthy Smokers And Copd Subjects, Victor Kim, Stephanie Jeong, Huaqing Zhao, Mehmet Kesimer, Richard C. Boucher, J. Michael Wells, Stephanie A. Christenson, Meilan K. Han, Mark Dransfield, Robert Paine, Christopher B. Cooper, Igor Barjaktarevic, Russell Bowler, Jeffrey L. Curtis, Robert J. Kaner, Sarah L. O'Beirne, Wanda K. O'Neal, Stephen I. Rennard, Fernando J. Martinez, Prescott G. Woodruff

Journal Articles: Pulmonary & Critical Care Med

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, …

Blood Eosinophil Counts In Clinical Trials For Chronic Obstructive Pulmonary Disease, Dave Singh, Mona Bafadhel, Christopher E. Brightling, Frank C. Sciurba, Jeffrey L. Curtis, Fernando J. Martinez, Cara B. Pasquale, Debora D. Merrill, Norbert Metzdorf, Stefano Petruzzelli, Ruth Tal-Singer, Christopher Compton, Stephen I. Rennard, Ubaldo J. Martin

Journal Articles: Pulmonary & Critical Care Med

No abstract provided.

Heme Metabolism Genes Downregulated In Copd Cachexia, Ava C. Wilson, Preeti L. Kumar, Sool Lee, Margaret M. Parker, Itika Arora, Jarrett D. Morrow, Emiel F.M. Wouters, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Alvar Agusti, Ruth Tal-Singer, Mark T. Dransfield, J. Michael Wells, Surya P. Bhatt, George Washko, Victor J. Thannickal, Hemant K. Tiwari, Craig P. Hersh, Peter J. Castaldi, Edwin K. Silverman, Merry-Lynn N. Mcdonald

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Cachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.

METHODS: We analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (<  20 kg/m

RESULTS: The prevalence of …

Improving The Evaluation Of Copd Exacerbation Treatment Effects By Accounting For Early Treatment Discontinuations: A Post-Hoc Analysis Of Randomized Clinical Trials., Agnieszka Król, Robert Palmér, Virginie Rondeau, Stephen I. Rennard, Ulf G. Eriksson, Alexandra Jauhiainen

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) clinical trials aimed at evaluating treatment effects on exacerbations often suffer from early discontinuations of randomized treatment. Treatment discontinuations imply a loss of information and should ideally be considered in the statistical analysis of trial results, particularly if the discontinuations are related to the disease or treatment itself. Here, we explore this issue by investigating (1) whether there exists an association between the risks of exacerbation and treatment discontinuation in COPD clinical trials and (2) whether disregarding this association can cause bias in exacerbation treatment effect estimates. We focus on the hypothetical estimand, i.e. …

Agonist-Specific Desensitization Of Pge2-Stimulated Camp Signaling Due To Upregulated Phosphodiesterase Expression In Human Lung Fibroblasts, Francisco J. Nunez, Nancy Schulte, David M. Fogel, Joel Michalski, Stephen I. Rennard, Raymond B. Penn, Myron L. Toews, Rennolds S. Ostrom

Journal Articles: Pulmonary & Critical Care Med

Pulmonary fibrosis is characterized by fibroblasts persisting in an activated form, producing excessive fibrous material that destroys alveolar structure. The second messenger molecule cyclic 3',5'-adenosine monophosphate (cAMP) has antifibrotic properties, and prostaglandin E2 (PGE2) can stimulate cAMP production through prostaglandin E (EP)2 and EP4 receptors. Although EP receptors are attractive therapeutic targets, the effects of long-term exposure to PGE2 have not been characterized. To determine the effects of long-term exposure of lung fibroblasts to PGE2, human fetal lung (HFL)-1 cells were treated for 24 h with 100 nM PGE2 or other cAMP-elevating agents. cAMP levels stimulated by acute exposure to …

Growth Hormone Deficiency In Megalencephaly-Capillary Malformation Syndrome: An Association With Activating Mutations In Pik3ca, Shanlee Davis, Meredith A Ware, Jordan Zeiger, Matthew A Deardorff, Katheryn Grand, Adda Grimberg, Stephanie Hsu, Megan Kelsey, Shideh Majidi, Revi P Matthew, Melanie Napier, Natalie Nokoff, Chitra Prasad, Andrew C Riggs, Margaret L Mckinnon, Ghayda Mirzaa

Paediatrics Publications

Megalencephaly-capillary malformation syndrome (MCAP) is a brain overgrowth disorder characterized by cortical malformations (specifically polymicrogyria), vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (PIK3CA). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multicenter study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had …

The Pancreas-Specific Form Of Secretory Pathway Calcium Atpase 2 Regulates Multiple Pathways Involved In Calcium Homeostasis, Melissa Fenech, Mckenzie M Carter, Peter B Stathopulos, Christopher Pin

Paediatrics Publications

Acinar cell exocytosis requires spatiotemporal Ca²⁺ signals regulated through endoplasmic reticulum (ER) stores, Ca²⁺ATPases, and store-operated Ca²⁺ entry (SOCE). The secretory pathway Ca²⁺ATPase 2 (SPCA2) interacts with Orai1, which is involved in SOCE and store independent Ca²⁺ entry (SICE). However, in the pancreas, only a C-terminally truncated form of SPCA2 (termed SPAC2C) exists. The goal of this study was to determine if SPCA2C effects Ca²⁺ homeostasis in a similar fashion to the full-length SPCA2. Using epitope-tagged SPCA2C (SPCA2C^FLAG) expressed in HEK293A cells and Fura2 imaging, cytosolic [Ca²⁺] was …

Intranasal Dexmedetomidine For Procedural Distress In Children: A Systematic Review., Naveen Poonai, Joseph Spohn, Ben Vandermeer, Samina Ali, Maala Bhatt, Shawn Hendrikx, Evelyne D Trottier, Vikram Sabhaney, Amit Shah, Gary Joubert, Lisa Hartling

Paediatrics Publications

CONTEXT: Intranasal dexmedetomidine (IND) is an emerging agent for procedural distress in children.

OBJECTIVE: To explore the effectiveness of IND for procedural distress in children.

DATA SOURCES: We performed electronic searches of Medline (1946-2019), Embase (1980-2019), Google Scholar (2019), Cumulative Index to Nursing and Allied Health Literature (1981-2019), and Cochrane Central Register.

STUDY SELECTION: We included randomized trials of IND for procedures in children.

DATA EXTRACTION: Methodologic quality of evidence was evaluated by using the Cochrane Collaboration's risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. The primary outcome was the proportion of participants …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

The President's Emergency Plan For Aids Relief And Adult Mortality: A Replication Study Of Hiv Development Assistance Effects In Sub-Saharan African Countries, Nicholas A. Hein, Danstan Bagenda, Jiangtao Luo

Journal Articles: Anesthesiology

The US budget for global health funding, which was by far the largest of similar funding in the world, increased from US $1.3 billion in 2001 to more than US $10 billion in recent years. More than 54% of this funding was allocated to the Global Fund to Fight HIV/AIDS through the US President's Emergency Plan for AIDS Relief (PEPFAR) in Africa. However, recent studies indicate contradictory results regarding the effectiveness of PEPFAR. One by Bendavid, Holmes, Bhattacharya, and Miller shows positive effects of PEPFAR in reducing adult mortality in Africa, while another by Duber, Coates, Szekeras, Kaji, and Lewis …

Transcriptional And Immunohistological Assessment Of Immune Infiltration In Pancreatic Cancer., Brady Bernard, Venkatesh Rajamanickam, Christopher Dubay, Brian D. Piening, Emilio Alonso, Zeljka Jutric, Ephraim Tang, Pippa Newell, Paul D Hansen, Terry R Medler, Andrew J Gunderson, Kristina H Young, Carlo Bifulco, Joanna Pucilowska, Marka R Crittenden, Michael J. Gough

Articles, Abstracts, and Reports

Pancreatic adenocarcinoma is characterized by a complex tumor environment with a wide diversity of infiltrating stromal and immune cell types that impact the tumor response to conventional treatments. However, even in this poorly responsive tumor the extent of T cell infiltration as determined by quantitative immunohistology is a candidate prognostic factor for patient outcome. As such, even more comprehensive immunophenotyping of the tumor environment, such as immune cell type deconvolution via inference models based on gene expression profiling, holds significant promise. We hypothesized that RNA-Seq can provide a comprehensive alternative to quantitative immunohistology for immunophenotyping pancreatic cancer. We performed RNA-Seq …

A Head-To-Head Comparison Of The Efficacy And Safety Of Ixekizumab And Adalimumab In Biological-Naïve Patients With Active Psoriatic Arthritis: 24-Week Results Of A Randomised, Open-Label, Blinded-Assessor Trial., Philip Mease, Josef S Smolen, Frank Behrens, Peter Nash, Soyi Liu Leage, Lingnan Li, Hasan Tahir, Melinda Gooderham, Eswar Krishnan, Hong Liu-Seifert, Paul Emery, Sreekumar G Pillai, Philip S Helliwell

Articles, Abstracts, and Reports

OBJECTIVES: To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs).

METHODS: Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the …

Unmet Need In Rheumatology: Reports From The Targeted Therapies Meeting 2019., Kevin L Winthrop, Michael E Weinblatt, Joan Bathon, Gerd R Burmester, Philip Mease, Leslie Crofford, Vivian Bykerk, Maxime Dougados, James Todd Rosenbaum, Xavier Mariette, Joachim Sieper, Fritz Melchers, Bruce N Cronstein, Ferry C Breedveld, Joachim Kalden, Josef S Smolen, Daniel Furst

Articles, Abstracts, and Reports

OBJECTIVES: To detail the greatest areas of unmet scientific and clinical needs in rheumatology.

METHODS: The 21st annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. During the meeting, breakout sessions were convened, consisting of 5 disease-specific groups with 20-30 experts assigned to each group based on expertise. Specific groups included: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and other systemic autoimmune rheumatic diseases. In each group, experts were asked to identify unmet clinical and translational research needs in general …

Defining Current Gaps In Quality Measures For Cancer Immunotherapy: Consensus Report From The Society For Immunotherapy Of Cancer (Sitc) 2019 Quality Summit, Sara Pai, David Blaisdell, Rachel Brodie, Robert G. Carlson, Heidi Finnes, Michele Galioto, Roxanne E. Jensen, Tom Valuck, Antonia R. Sepulveda, Howard L. Kaufman

Population and Public Health Sciences Faculty Publications

Background Quality measures are important because they can help improve and standardize the delivery of cancer care among healthcare providers and across tumor types. In an environment characterized by a rapidly shifting immunotherapeutic landscape and lack of associated long-term outcome data, defining quality measures for cancer immunotherapy is a high priority yet fraught with many challenges. Methods Thus, the Society for Immunotherapy of Cancer convened a multistakeholder expert panel to, first, identify the current gaps in measures of quality cancer care delivery as it relates to immunotherapy and to, second, advance priority concepts surrounding quality measures that could be developed …

Dynamic Conformal Arcs For Lung Stereotactic Body Radiation Therapy: A Comparison With Volumetric-Modulated Arc Therapy., Rasmus Bokrantz, Minna Wedenberg, Peter Sandwall

Oncology Articles

This study constitutes a feasibility assessment of dynamic conformal arc (DCA) therapy as an alternative to volumetric-modulated arc therapy (VMAT) for stereotactic body radiation therapy (SBRT) of lung cancer. The rationale for DCA is lower geometric complexity and hence reduced risk for interplay errors induced by respiratory motion. Forward planned DCA and inverse planned DCA based on segment-weight optimization were compared to VMAT for single arc treatments of five lung patients. Analysis of dose-volume histograms and clinical goal fulfillment revealed that DCA can generate satisfactory and near equivalent dosimetric quality to VMAT, except for complex tumor geometries. Segment-weight optimized DCA …

Prospective Molecular Profiling Of Circulating Tumor Cells From Patients With Melanoma Receiving Combinatorial Immunotherapy., Selena Y Lin, Shu-Ching Chang, Stella Lam, Romela Irene Ramos, Kevin Tran, Shuichi Ohe, Matthew P Salomon, Ali Asgar S Bhagat, Chwee Teck Lim, Trevan D Fischer, Leland J Foshag, Christine L Boley, Steven J O'Day, Dave Hoon

Articles, Abstracts, and Reports

BACKGROUND: Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel.

METHODS: Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical …

Ampk In The Ventromedial Nucleus Of The Hypothalamus: A Key Regulator For Thermogenesis, Hailan Liu, Yong Xu, Fang Hu

Children’s Nutrition Research Center Staff Publications

Obesity has become a global health issue, but effective therapies remain very limited. Adaptive thermogenesis promotes weight loss by dissipating energy in the form of heat, thereby representing a promising target to counteract obesity. Notably, the regulation of thermogenesis is tightly orchestrated by complex neuronal networks, especially those in the hypothalamus. Recent evidence highlights the importance of adenosine monophosphate-activated protein kinase (AMPK) within the ventromedial nucleus of the hypothalamus (VMH) in modulating thermogenesis. Various molecules, such as GLP-1, leptin, estradiol, and thyroid hormones, have been reported to act on the VMH to inhibit AMPK, which subsequently increases thermogenesis through the …

Individual And Community Social Determinants Of Health Associated With Diabetes Management In A Mexican American Population, Kehe Zhang, Belinda Reininger, Miryoung Lee, Qian Xiao, Cici Bauer

Faculty, Staff and Student Publications

Background: Diabetes is a major health burden in Mexican American populations, especially among those in the Lower Rio Grande Valley (LRGV) in the border region of Texas. Understanding the roles that social determinants of health (SDOH) play in diabetes management programs, both at the individual and community level, may inform future intervention strategies.

Methods: This study performed a secondary data analysis on 1,568 individuals who participated in Salud y Vida (SyV), a local diabetes and chronic disease management program, between October 2013 and September 2018 recruited from a local clinic. The primary outcome was the reduction of hemoglobin A1C (HbA1C) …

Somatic Symptoms And Binge Eating In Women's Daily Lives, Kelly A. Romano, Kristin E. Heron, Kathryn E. Smith, Ross D. Crosby, Scott G. Engel, Stephen A. Wonderlich, Raina D. Pang, Tyler B. Mason

Psychology Faculty Publications

Objective

The present study aimed to determine whether the momentary severity of women's somatic symptoms was concurrently and prospectively associated with their engagement in binge eating in naturalistic settings.

Method

Thirty women (M_age = 34.13, SD = 13.92) who had engaged in binge eating at least once over the month prior to study entry completed a 14-day ecological momentary assessment (EMA) protocol. During each of the 14 days, participants received five semi-random surveys via text message that assessed momentary somatic symptom severity (i.e., headaches, stomachaches/pain, chest/heart pain, faintness/dizziness, shortness of breath, fatigue) and disordered eating behaviors. Generalized estimating equations …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …

Covid-19 Sampling From The Middle Ear And Mastoid: A Case Report, George B Wanna, Zachary G Schwam, Vivian F Kaul, Maura K Cosetti, Enrique Perez, Peter Filip, Waleed Javaid, Avi Kandel, Alberto Paniz-Mondolfi, Satish Govindaraj, Eric M Genden

Faculty, Staff and Student Publications

No abstract provided.

Microbiotyping The Sinonasal Microbiome, Ahmed Bassiouni, Sathish Paramasivan, Arron Shiffer, Matthew R Dillon, Emily K Cope, Clare Cooksley, Mahnaz Ramezanpour, Sophia Moraitis, Mohammad Javed Ali, Benjamin S Bleier, Claudio Callejas, Marjolein E Cornet, Richard G Douglas, Daniel Dutra, Christos Georgalas, Richard J Harvey, Peter H Hwang, Amber U Luong, Rodney J Schlosser, Pongsakorn Tantilipikorn, Marc A Tewfik, Sarah Vreugde, Peter-John Wormald, J Gregory Caporaso, Alkis J Psaltis

Faculty, Staff and Student Publications

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based …

Burden Of Rare Deleterious Variants In Wnt Signaling Genes Among 511 Myelomeningocele Patients, Luke Hebert, Paul Hillman, Craig Baker, Michael Brown, Allison Ashley-Koch, James E Hixson, Alanna C Morrison, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

Genes in the noncanonical WNT signaling pathway controlling planar cell polarity have been linked to the neural tube defect myelomeningocele. We hypothesized that some genes in the WNT signaling network have a higher mutational burden in myelomeningocele subjects than in reference subjects in gnomAD. Exome sequencing data from 511 myelomeningocele subjects was obtained in-house and data from 29,940 ethnically matched subjects was provided by version 2 of the publicly available Genome Aggregation Database. To compare mutational burden, we collapsed rare deleterious variants across each of 523 human WNT signaling genes in case and reference populations. Ten WNT signaling genes were …

Adenosine At The Interphase Of Hypoxia And Inflammation In Lung Injury, Xiangyun Li, Nathanial K Berg, Tingting Mills, Kaiying Zhang, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine …

The Fms21 (Pila)-Fms20 Locus Encoding One Of Four Distinct Pili Of Enterococcus Faecium Is Harboured On A Large Transferable Plasmid Associated With Gut Colonization And Virulence, Louis Maximilian Buja, Dwayne A Wolf, Bihong Zhao, Bindu Akkanti, Michelle Mcdonald, Laura Lelenwa, Noah Reilly, Giulia Ottaviani, M Tarek Elghetany, Daniel Ocazionez Trujillo, Gabriel M Aisenberg, Mohammad Madjid, Biswajit Kar

Faculty, Staff and Student Publications

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in …

Transcriptional Insights Into Pathogenesis Of Cutaneous Systemic Sclerosis Using Pathway Driven Meta-Analysis Assisted By Machine Learning Methods, Xiao Xu, Meera Ramanujam, Sudha Visvanathan, Shervin Assassi, Zheng Liu, Li Li

Faculty, Staff and Student Publications

Pathophysiology of systemic sclerosis (SSc, Scleroderma), an autoimmune rheumatic disease, comprises of mechanisms that drive vasculopathy, inflammation and fibrosis. Understanding of the disease and associated clinical heterogeneity has advanced considerably in the past decade, highlighting the necessity of more specific targeted therapy. While many of the recent trials in SSc failed to meet the primary end points that predominantly relied on changes in modified Rodnan skin scores (MRSS), sub-group analysis, especially those focused on the basal skin transcriptomic data have provided insights into patient subsets that respond to therapies. These findings suggest that deeper understanding of the molecular changes in …