Medicine and Health Sciences Commons^™

Rare Variants In Genes Encoding Subunits Of The Epithelial Na+ Channel Are Associated With Blood Pressure And Kidney Function, Brandon M Blobner, Annet Kirabo, Ossama B Kashlan, Shaohu Sheng, Donna K Arnett, Lewis C Becker, Eric Boerwinkle, Jenna C Carlson, Yan Gao, Richard A Gibbs, Jiang He, Marguerite R Irvin, Sharon L R Kardia, Tanika N Kelly, Charles Kooperberg, Stephen T Mcgarvey, Vipin K Menon, May E Montasser, Take Naseri, Susan Redline, Alexander P Reiner, Muagututi'a S Reupena, Jennifer A Smith, Xiao Sun, Dhananjay Vaidya, Karine A Viaud-Martinez, Daniel E Weeks, Lisa R Yanek, Xiaofeng Zhu, Ryan L Minster, Thomas R Kleyman

Faculty, Staff and Students Publications

Background: The epithelial Na+ channel (ENaC) is intrinsically linked to fluid volume homeostasis and blood pressure. Specific rare mutations in SCNN1A, SCNN1B, and SCNN1G, genes encoding the α, β, and γ subunits of ENaC, respectively, are associated with extreme blood pressure phenotypes. No associations between blood pressure and SCNN1D, which encodes the δ subunit of ENaC, have been reported. A small number of sequence variants in ENaC subunits have been reported to affect functional transport in vitro or blood pressure. The effects of the vast majority of rare and low-frequency ENaC variants on blood pressure are …

Choosing And Switching Biological Agents In Severe Asthma, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Trends, Predictors, And Outcomes Of Transcatheter Aortic Valve Implantation In Patients With Bicuspid Aortic Valve Related Disease: Insights From The Nationwide Inpatient Sample And Nationwide Readmission Database, Waqas Ullah, Salman Zahid, Hamza Muhammadzai, Fouad Khalil, Arnav Kumar, Abdul Mannan Khan Minhas, Muhammad Zia Khan, Salim S Virani, David L Fischman, Pinak Shah, Deepak L Bhatt

Faculty, Staff and Students Publications

Background: Transcatheter aortic valve implantation (TAVI) has increasingly been utilized in patients with bicuspid aortic valve (BAV) related aortic stenosis (AS) with insufficient large-scale data on its safety.

Methods: The Nationwide Inpatient Sample and Nationwide Readmission Database (2011-2018) were queried to identify patients undergoing TAVI for BAV versus trileaflet aortic valve (TAV) associated AS. The in-hospital, 30- and 180-day odds of outcomes were assessed using a propensity-matched analysis (PSM) to calculate adjusted odds ratios (aOR) with its 95% confidence interval (CI).

Results: A total of 216,723 TAVI (TAV: 214,050 and BAV: 2,673) crude and 5,347 matched population (TAV: 2,674 and …

Optimal Cardiometabolic Health And Risk Of Heart Failure In Type 2 Diabetes: An Analysis From The Look Ahead Trial, Kershaw V Patel, Muhammad Shahzeb Khan, Matthew W Segar, Judy L Bahnson, Katelyn R Garcia, Jeanne M Clark, Ashok Balasubramanyam, Alain G Bertoni, Muthiah Vaduganathan, Michael E Farkouh, James L Januzzi, Subodh Verma, Mark Espeland, Ambarish Pandey

Faculty, Staff and Students Publications

Aims: To evaluate the contribution of baseline and longitudinal changes in cardiometabolic health (CMH) towards heart failure (HF) risk among adults with type 2 diabetes (T2D).

Methods and results: Participants of the Look AHEAD trial with T2D and without prevalent HF were included. Adjusted Cox models were used to create a CMH score incorporating target levels of parameters weighted based on relative risk for HF. The associations of baseline and changes in the CMH score with risk of overall HF, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) were assessed using Cox models. Among the 5080 participants, 257 incident …

Predicting The Disease Severity In Male Individuals With Ornithine Transcarbamylase Deficiency, Svenja Scharre, Roland Posset, Sven F Garbade, Florian Gleich, Marie J Seidl, Ann-Catrin Druck, Jürgen G Okun, Andrea L Gropman, Sandesh C S Nagamani, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka, Urea Cycle Disorders Consortium (Ucdc) And The European Registry And Network For Intoxication Type Metabolic Diseases (E-Imd) Consortia Study Group

Faculty, Staff and Students Publications

Objective: Ornithine transcarbamylase deficiency (OTC-D) is an X-linked metabolic disease and the most common urea cycle disorder. Due to high phenotypic heterogeneity, ranging from lethal neonatal hyperammonemic events to moderate symptoms and even asymptomatic individuals, the prediction of the disease course at an early disease stage is very important to individually adjust therapies such as medical treatment or liver transplantation. In this translational study, we developed a severity-adjusted classification system based on in vitro residual enzymatic OTC activity.

Methods: Applying a cell-based expression system, residual enzymatic OTC activities of 71 pathogenic OTC variants were spectrophotometrically determined and subsequently correlated with …

Myocarditis Mimicking Stress-Induced (Takotsubo) Cardiomyopathy, Arzu Canan, Ryan C Van Woerkom, Prabhakar Shantha Rajiah

The Texas Heart Institute Journal

No abstract provided.

Relationship Between Preprocedural Lipid Levels And Periprocedural Myocardial Injury In Patients Undergoing Elective Percutaneous Coronary Intervention, Mohsen Maadani, Nima Sari Sarraf, Sanam Alilou, Kamran Aeinfar, Parham Sadeghipour, Ali Zahedmehr, Mahmood Sheikh Fathollahi, Seyyed Isa Hashemi Ghadi, Abbas Zavarehee, Maryam Zolfaghari, Reza Zolfaghari

The Texas Heart Institute Journal

BACKGROUND: Periprocedural myocardial injury is a predictor of cardiovascular morbidity and mortality after percutaneous coronary intervention.

METHODS: The authors examined the effects of preprocedural lipid levels (low-density lipoprotein, high-density lipoprotein, and triglycerides) in 977 patients with coronary artery disease who underwent elective percutaneous coronary intervention.

RESULTS: Elevated cardiac troponin I level (≥5× the upper limit of normal) was used to indicate periprocedural myocardial injury. Serum lipid samples were collected 12 hours preprocedurally. Cardiac troponin I was collected 1, 6, and 12 hours postprocedurally. Correlations between preprocedural lipid levels and postprocedural cardiac troponin I were studied. Low-density lipoprotein levels were less …

Dilated Cardiomyopathy With Multiple Left Ventricular Thrombi And Embolic Stroke After Mild Covid-19, Radhapriya Yalamanchi, Madhan Kumar Murugan, Krishnaswamy Chandrasekharan, Refai Showkathali

The Texas Heart Institute Journal

COVID-19 is a novel disease with multisystem involvement, but most patients have pulmonary and cardiovascular involvement in the acute stages. The cardiovascular impact of acute COVID-19 is well recognized and ranges from myocarditis, arrhythmias, and thrombotic occlusion of coronary arteries to spontaneous coronary artery dissection and microthrombi in small coronary vessels on autopsy. We report a case of a 37-year-old man who recovered from mild COVID-19 only to present a few weeks later with devastating cardiovascular involvement that included severe left ventricular impairment resulting from nonischemic cardiomyopathy, multiple left ventricular thrombi, and embolic stroke.

Clinical Characteristics And Associated Factors Of Colonic Polyps In Acromegaly, Guiliang Peng, Xing Li, Yuanyuan Zhou, Jianying Bai, Pian Hong, Weixing Li, Yuling Zhang, Lei Zhang, Qian Liao, Mingyu Liao, Ling Zhou, Zheng Sun, Rufei Shen, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

PURPOSE: To investigate the clinical characteristics and associated factors of colonic polyps in patients with acromegaly.

METHODS: Clinical characteristics and colonoscopy findings of 86 acromegaly patients who received treatment were retrospectively reviewed, and colonoscopy findings and the correlation with growth hormone (GH)-secreting pituitary adenoma (GHPA) volume and hormonal/metabolic levels were analyzed.

RESULTS: The prevalence of colonic polyps in acromegaly patients was 40.7% and increased significantly with advanced age, especially in those ≥50 years. Multiple polyps (62.8%) and colonic polyps in the left colon (54.2%) were detected more frequently. Compared to acromegaly patients without polyps, those with polyps displayed higher insulin-like …

Estimation Of Tumor Cell Total Mrna Expression In 15 Cancer Types Predicts Disease Progression, Shaolong Cao, Jennifer R Wang, Shuangxi Ji, Peng Yang, Yaoyi Dai, Shuai Guo, Matthew D Montierth, John Paul Shen, Xiao Zhao, Jingxiao Chen, Jaewon James Lee, Paola A Guerrero, Nicholas Spetsieris, Nikolai Engedal, Sinja Taavitsainen, Kaixian Yu, Julie Livingstone, Vinayak Bhandari, Shawna M Hubert, Najat C Daw, P Andrew Futreal, Eleni Efstathiou, Bora Lim, Andrea Viale, Jianjun Zhang, Matti Nykter, Bogdan A Czerniak, Powel H Brown, Charles Swanton, Pavlos Msaouel, Anirban Maitra, Scott Kopetz, Peter Campbell, Terence P Speed, Paul C Boutros, Hongtu Zhu, Alfonso Urbanucci, Jonas Demeulemeester, Peter Van Loo, Wenyi Wang

Faculty, Staff and Student Publications

Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patient tumors across 15 cancer types, identifying significant inter-tumor variability. Across cancers, high TmS is associated with increased risk of disease progression and death. TmS is influenced by cancer-specific patterns of gene …

Successful Use Of Continuous Erector Spinae Plane Blocks In A Patient With Variant Angina After Large Ventral Hernia Repair, Alexandra L Belfar, Yi Deng, Raymond C Yu, Annas Sabbagh

Faculty, Staff and Students Publications

Coronary artery spasm constitutes the primary underlying pathology of variant angina. Because provocation of coronary artery spasm may occur with both excess sympathetic and excess parasympathetic stimulation, patients with this disorder have extremely limited options for perioperative pain control. This is especially true for procedures involving extensive abdominal incision/manipulation. Whereas neuraxial analgesia might otherwise be appropriate in these cases, several studies have demonstrated that coronary artery spasm can occur as a result of epidural placement, and therefore, that this may not be an optimal choice for patients with variant angina. This report discusses the case of a patient with a …

Looking On The Horizon; Potential And Unique Approaches To Developing Radiation Countermeasures For Deep Space Travel, Rihana S Bokhari, Afshin Beheshti, Sarah E Blutt, Dawn E Bowles, David Brenner, Robert Britton, Lawrence Bronk, Xu Cao, Anushree Chatterjee, Delisa E Clay, Colleen Courtney, Donald T Fox, M Waleed Gaber, Sharon Gerecht, Peter Grabham, David Grosshans, Fada Guan, Erin A Jezuit, David G Kirsch, Zhandong Liu, Mirjana Maletic-Savatic, Kyle M Miller, Ruth A Montague, Prashant Nagpal, Sivan Osenberg, Luke Parkitny, Niles A Pierce, Christopher Porada, Susan M Rosenberg, Paul Sargunas, Sadhana Sharma, Jamie Spangler, Daniel Naveed Tavakol, Dilip Thomas, Gordana Vunjak-Novakovic, Chunbo Wang, Luke Whitcomb, Damian W Young, Dorit Donoviel

Faculty, Staff and Students Publications

Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human health and performance on future missions beyond low Earth orbit. This paper will describe three funded and complementary avenues for reducing the risk to humans from radiation exposure experienced in deep space. The first focus is on identifying new therapeutic targets to reduce the damaging effects of radiation by focusing on high throughput genetic screens in accessible, sometimes called lower, organism models. The second focus …

Longitudinal Associations Of Risk Factors And Hepatocellular Carcinoma In Patients With Cured Hepatitis C Virus Infection, Jennifer R Kramer, Yumei Cao, Liang Li, Donna Smith, Jagpreet Chhatwal, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Student Publications

Introduction: There are limited data on the effect and evolution of risk factors for hepatocellular carcinoma (HCC) in patients with virologically cured hepatitis C virus (HCV) infection.

Methods: We conducted a retrospective cohort study of patients with HCV who achieved sustained virological response with direct-acting antivirals from 130 Veterans Administration hospitals during 2014-2018, followed through 2021. Cox proportional hazards models were constructed at 3 landmark times (baseline and 12 and 24 months after sustained virological response) to examine associations between demographic, clinical, and behavioral factors and HCC risk, stratified by cirrhosis status.

Results: Among 92,567 patients (32% cirrhosis), 3,247 cases …

Clinical Exome Sequencing Uncovers A High Frequency Of Mendelian Disorders In Infants With Stroke: A Retrospective Analysis, Runjun D Kumar, Linyan Meng, Pengfei Liu, Christina Y Miyake, Kim C Worley, Weimin Bi, Seema R Lalani

Faculty, Staff and Students Publications

Background:

Stroke causes significant disability and is a common cause of death worldwide. Previous studies have estimated that 1-5% of stroke is attributable to monogenic etiologies. We set out to assess the utility of clinical exome sequencing (ES) in the evaluation of stroke.

Methods:

We retrospectively analyzed 124 individuals who received ES at the Baylor Genetics reference lab between 2012 and 2021 who had stroke as a major part of their reported phenotype.

Results:

Ages ranged from 10 days to 69 years. 8.9% of the cohort received a diagnosis, including 25% of infants less than 1 year old; an additional …

Analysis Of Insppire-2 Cohort: Risk Factors And Disease Burden In Children With Acute Recurrent Or Chronic Pancreatitis, Aliye Uc, Gretchen A Cress, Fuchenchu Wang, Maisam Abu-El-Haija, Kate M Ellery, Douglas S Fishman, Cheryl E Gariepy, Tanja Gonska, Tom K Lin, Quin Y Liu, Megha Mehta, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP).

METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP.

RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR …

Perceptions Of Various Treatment Approaches For Adults And Children With Misophonia, Eleanor E A Smith, Andrew G Guzick, Isabel A Draper, Jane Clinger, Sophie C Schneider, Wayne K Goodman, Jennifer J Brout, Marjin Lijffijt, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Objective: Misophonia is a complex disorder characterized by a heightened reaction to certain sounds and associated stimuli. While there is no uniformly accepted treatment to date, different intervention approaches are being investigated. Individual's perceptions of different misophonia treatment methods may affect compliance and satisfaction with treatment options. We sought to gather data on patient perceptions of currently available misophonia treatments.

Methods: Using an online survey, we collected data about treatment preferences, treatment usage, and diagnosis history from parents of children with misophonia (N = 141) and adults with misophonia (N = 252).

Results: Most respondents were not satisfied with misophonia …

Sars-Cov-2 Mrna Vaccination Causes Prolonged Increased Cortical Thickening And Vascularity In Ipsilateral Axillary Lymph Nodes, Sharlene A Teefey, William D Middleton, Jackson S Turner, Ali H Ellebedy, Teresa Suessen, Michael Wallendorf, Jane A O'Halloran, Rachel Presti

2020-Current year OA Pubs

OBJECTIVES: To describe the serial grey-scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer-BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) messenger RNA (mRNA) vaccine over 24 to 28 weeks.

METHODS: The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey-scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. …

Participation In A Longitudinal Seminar Series Increases Medical Student Engagement With The Covid-19 Pandemic, Katherine M Naeger, Kaelyn C Cummins, Prathit A Kulkarni

Faculty, Staff and Students Publications

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic required a multifaceted response by healthcare professionals. Medical students played only a limited role in the early response, resulting in feelings of disengagement. The authors developed a discussion-based elective course reviewing the COVID-19 response to address this gap in medical student education.

METHODS: Preclinical medical students enrolled in this elective participated in weekly virtual interactive seminars led by expert faculty members. Students completed a final survey quantifying their understanding of the overall COVID-19 response, knowledge of its individual facets, and their feelings of personal engagement on a Likert scale from 1 to 5, …

Magnetic Resonance Imaging Based Superficial Femoral Artery Velocity Measurements In Peripheral Artery Disease, Ankita Sinharoy, Neeti Reddy, John Kent Lin, Vijay Nambi, Eric Y Yang, Panagiotis Kougias, Addison A Taylor, Alan B Lumsden, Christie M Ballantyne, Joel D Morrisett, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. In this study, we analyzed how non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) measured velocity markers of the distal superficial femoral artery (SFA) are associated with clinical and functional characteristics of PAD. A total of 70 (27 diabetic and 43 non-diabetic) PAD patients were included in this secondary analysis of data collected from the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically (ECG)-gated 2D-PC-MRI was performed at a proximal and a distal imaging location of …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Meng Lin, Amy T Ku, Jie Dong, Fei Yue, Weiyu Jiang, Ahmed Atef Ibrahim, Fanglue Peng, Chad J Creighton, Chandandeep Nagi, Carolina Gutierrez, Jeffrey M Rosen, Xiang H-F Zhang, Susan G Hilsenbeck, Xi Chen, Yi-Chieh Nancy Du, Shixia Huang, Aiping Shi, Zhimin Fan, Yi Li

Faculty, Staff and Student Publications

Signal transducer and activator of transcription 5 (STAT5) promotes cell survival and instigates breast tumor formation, and in the normal breast it also drives alveolar differentiation and lactogenesis. However, whether STAT5 drives a differentiated phenotype in breast tumorigenesis and therefore impacts cancer spread and metastasis is unclear. We found in two genetically engineered mouse models of breast cancer that constitutively activated Stat5a (Stat5aca) caused precancerous mammary epithelial cells to become lactogenic and evolve into tumors with diminished potential to metastasize. We also showed that STAT5aca reduced the migratory and invasive ability of human breast cancer cell lines in …

Structural Brain Alterations Associated With Suicidal Thoughts And Behaviors In Young People: Results From 21 International Studies From The Enigma Suicidal Thoughts And Behaviours Consortium, Laura S Van Velzen, Maria R Dauvermann, Lejla Colic, Luca M Villa, Hannah S Savage, Yara J Toenders, Alyssa H Zhu, Joanna K Bright, Adrián I Campos, Lauren E Salminen, Sonia Ambrogi, Rosa Ayesa-Arriola, Nerisa Banaj, Zeynep Başgöze, Jochen Bauer, Karina Blair, Robert James Blair, Katharina Brosch, Yuqi Cheng, Romain Colle, Colm G Connolly, Emmanuelle Corruble, Baptiste Couvy-Duchesne, Benedicto Crespo-Facorro, Kathryn R Cullen, Udo Dannlowski, Christopher G Davey, Katharina Dohm, Janice M Fullerton, Ali Saffet Gonul, Ian H Gotlib, Dominik Grotegerd, Tim Hahn, Ben J Harrison, Mengxin He, Ian B Hickie, Tiffany C Ho, Frank Iorfino, Andreas Jansen, Fabrice Jollant, Tilo Kircher, Bonnie Klimes-Dougan, Melissa Klug, Elisabeth J Leehr, Elizabeth T C Lippard, Katie A Mclaughlin, Susanne Meinert, Adam Bryant Miller, Philip B Mitchell, Benson Mwangi, Igor Nenadić, Amar Ojha, Bronwyn J Overs, Julia-Katharina Pfarr, Fabrizio Piras, Kai G Ringwald, Gloria Roberts, Georg Romer, Marsal Sanches, Margaret A Sheridan, Jair C Soares, Gianfranco Spalletta, Frederike Stein, Giana I Teresi, Diana Tordesillas-Gutiérrez, Aslihan Uyar-Demir, Nic J A Van Der Wee, Steven J Van Der Werff, Robert R J M Vermeiren, Alexandra Winter, Mon-Ju Wu, Tony T Yang, Paul M Thompson, Miguel E Rentería, Neda Jahanshad, Hilary P Blumberg, Anne-Laura Van Harmelen, Enigma Suicidal Thoughts And Behaviours Consortium, Lianne Schmaal

Faculty, Staff and Student Publications

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample …

Aging-Associated Regγ Proteasome Decline Predisposes To Tauopathy, Jialu Tu, Haiyang Zhang, Ting Yang, Yun Liu, Solomon Kibreab, Yunpeng Zhang, Liangcai Gao, Robb E Moses, Bert W O'Malley, Jianru Xiao, Xiaotao Li

Faculty, Staff and Students Publications

The REGγ-20S proteasome is an ubiquitin- and ATP-independent degradation system, targeting selective substrates, possibly helping to regulate aging. The studies we report here demonstrate that aging-associated REGγ decline predisposes to decreasing tau turnover, as in a tauopathy. The REGγ proteasome promotes degradation of human and mouse tau, notably phosphorylated tau and toxic tau oligomers that shuttle between the cytoplasm and nuclei. REGγ-mediated proteasomal degradation of tau was validated in 3- to 12-month-old REGγ KO mice, REGγ KO;PS19 mice, and PS19 mice with forebrain conditional neuron-specific overexpression of REGγ (REGγ OE) and behavioral abnormalities. Coupled with tau accumulation, we found …

Brain-Wide Versus Genome-Wide Vulnerability Biomarkers For Severe Mental Illnesses, Peter Kochunov, Aris Sotiras, Et Al.

2020-Current year OA Pubs

Severe mental illnesses (SMI), including major depressive (MDD), bipolar (BD), and schizophrenia spectrum (SSD) disorders have multifactorial risk factors and capturing their complex etiopathophysiology in an individual remains challenging. Regional vulnerability index (RVI) was used to measure individual's brain-wide similarity to the expected SMI patterns derived from meta-analytical studies. It is analogous to polygenic risk scores (PRS) that measure individual's similarity to genome-wide patterns in SMI. We hypothesized that RVI is an intermediary phenotype between genome and symptoms and is sensitive to both genetic and environmental risks for SMI. UK Biobank sample of N = 17,053/19,265 M/F (age = 64.8 …

Manufacturing-Dependent Change In Biological Activity Of The Tlr4 Agonist Gsk1795091 And Implications For Lipid A Analog Development, Neeltje Steeghs, Haeseong Park, Et Al.

2020-Current year OA Pubs

A phase I trial (NCT03447314; 204686) evaluated the safety and efficacy of GSK1795091, a Toll-like receptor 4 (TLR4) agonist, in combination with immunotherapy (GSK3174998 [anti-OX40 monoclonal antibody], GSK3359609 [anti-ICOS monoclonal antibody], or pembrolizumab) in patients with solid tumors. The primary endpoint was safety; other endpoints included efficacy, pharmacokinetics, and pharmacodynamics (PD). Manufacturing of GSK1795091 formulation was modified during the trial to streamline production and administration, resulting in reduced PD (cytokine) activity. Fifty-four patients received GSK1795091 with a combination partner; 32 received only the modified GSK1795091 formulation, 15 received only the original formulation, and seven switched mid-study from the original to …

Herpes Simplex Virus And Rates Of Cognitive Decline Or Whole Brain Atrophy In The Dominantly Inherited Alzheimer Network, Charlotte Warren-Gash, Brian A Gordon, Eric Mcdade, Randall J Bateman, John C Morris, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN).

METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models …

Profilin-1 Regulates Dna Replication Forks In A Context-Dependent Fashion By Interacting With Snf2h And Bod1l, Cuige Zhu, Mari Iwase, Ziqian Li, Faliang Wang, Annabel Quinet, Alessandro Vindigni, Jieya Shao

2020-Current year OA Pubs

DNA replication forks are tightly controlled by a large protein network consisting of well-known core regulators and many accessory factors which remain functionally undefined. In this study, we report previously unknown nuclear functions of the actin-binding factor profilin-1 (PFN1) in DNA replication, which occur in a context-dependent fashion and require its binding to poly-L-proline (PLP)-containing proteins instead of actin. In unperturbed cells, PFN1 increases DNA replication initiation and accelerates fork progression by binding and stimulating the PLP-containing nucleosome remodeler SNF2H. Under replication stress, PFN1/SNF2H increases fork stalling and functionally collaborates with fork reversal enzymes to enable the over-resection of unprotected …

Real-World Evidence Supporting Tandem Control-Iq Hybrid Closed-Loop Success In The Medicare And Medicaid Type 1 And Type 2 Diabetes Populations, Gregory P Forlenza, Anders L Carlson, Rodolfo J Galindo, Davida F Kruger, Carol J Levy, Janet B Mcgill, Guillermo Umpierrez, Grazia Aleppo

2020-Current year OA Pubs

No abstract provided.

Real-World Utilization And Outcomes Of Systemic Therapy Among Patients With Advanced Or Recurrent Endometrial Cancer In The United States, Jinan Liu, Bruno Emond, Eric M Maiese, Marie-Hélène Lafeuille, Patrick Lefebvre, Isabelle Ghelerter, Caterina Wu, Jean A Hurteau, Premal H Thaker

2020-Current year OA Pubs

OBJECTIVE: Evaluate systemic therapy utilization patterns and outcomes by line of therapy among patients with advanced/recurrent endometrial cancer (EC) treated in the United States.

METHODS: This retrospective observational study used the Optum Clinformatics Extended Data Mart Date of Death database (1 January 2004-31 December 2019) and included de-identified data from adult patients with advanced/recurrent EC who were treated with first-line (1L) platinum-based chemotherapy and initiated second-line (2L) anti-neoplastic therapy. The index date was the date of 1L therapy initiation. The number and sequence of treatments received and the proportion of patients who received each type of treatment for each line …

Accounting For The Growth Of Observation Stays In The Assessment Of Medicare's Hospital Readmissions Reduction Program, Amber K Sabbatini, Karen E Joynt-Maddox, Joshua M Liao, Anirban Basu, Canada Parrish, William Kreuter, Brad Wright

2020-Current year OA Pubs

IMPORTANCE: Decreases in 30-day readmissions following the implementation of the Medicare Hospital Readmissions Reduction Program (HRRP) have occurred against the backdrop of increasing hospital observation stay use, yet observation stays are not captured in readmission measures.

OBJECTIVE: To examine whether the HRRP was associated with decreases in 30-day readmissions after accounting for observation stays.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a 20% sample of inpatient admissions and observation stays among Medicare fee-for-service beneficiaries from January 1, 2009, to December 31, 2015. Data analysis was performed from November 2021 to June 2022. A differences-in-differences analysis assessed changes in …

Upper Limb Nerve Transfer Surgery In Patients With Tetraplegia, Saad Javeed, Christopher F Dibble, Jacob K Greenberg, Justin K Zhang, Jawad M Khalifeh, Yikyung Park, Thomas J Wilson, Eric L Zager, Amir H Faraji, Mark A Mahan, Lynda J Yang, Rajiv Midha, Neringa Juknis, Wilson Z Ray

2020-Current year OA Pubs

IMPORTANCE: Cervical spinal cord injury (SCI) causes devastating loss of upper extremity function and independence. Nerve transfers are a promising approach to reanimate upper limbs; however, there remains a paucity of high-quality evidence supporting a clinical benefit for patients with tetraplegia.

OBJECTIVE: To evaluate the clinical utility of nerve transfers for reanimation of upper limb function in tetraplegia.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective case series, adults with cervical SCI and upper extremity paralysis whose recovery plateaued were enrolled between September 1, 2015, and January 31, 2019. Data analysis was performed from August 2021 to February 2022.

INTERVENTIONS: Nerve …