Medicine and Health Sciences Commons^™

Corticosteroid Burst Therapy In Patients With Acute Heart Failure: Design Of The Cortahf Pilot Study, Gad Cotter, Douglas L Mann, Et Al.

2020-Current year OA Pubs

AIMS: Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID-19. Our hypothesis is that in patients with AHF and elevated C-reactive protein (CRP) levels without symptoms or signs of infection, a 7-day course of steroid therapy will lead to reduced inflammation and short-term improvement in quality …

Agreement Between Three Noninvasive Temperature Monitoring Devices During Spinal Anaesthesia For Caesarean Delivery: A Prospective Observational Study, D O Vawda, Christopher King, L Du Toit, R A Dyer, N J Masuku, D G Bishop

2020-Current year OA Pubs

Hypothermia during obstetric spinal anaesthesia is a common and important problem, yet temperature monitoring is often not performed due to the lack of a suitable, cost-effective monitor. This study aimed to compare a noninvasive core temperature monitor with two readily available peripheral temperature monitors during obstetric spinal anaesthesia. We undertook a prospective observational study including elective and emergency caesarean deliveries, to determine the agreement between affordable reusable surface temperature monitors (Welch Allyn SureTemp® Plus oral thermometer and the Braun 3-in-1 No Touch infrared thermometer) and the Dräger T-core© (using dual-sensor heat flux technology), in detecting thermoregulatory changes during obstetric spinal …

Generation Of An Induced Pluripotent Stem Cell Line (Biortci001-A) From A Healthy Adult Indigenous Nigerian Participant, Zaid Muhammad, Phoebe W Brown, Larema Babazau, Abdulrahman I Alkhamis, Baba W Goni, Haruna A Nggada, Kefas M Mbaya, Selina Wray, Isa H Marte, Celeste M Karch, Louise C Serpell, Mahmoud B Maina

2020-Current year OA Pubs

Genetic backgrounds influence cellular phenotypes, drug responses, and health outcomes, yet most human iPSC lines are derived from individuals of European descent, with lines from indigenous Africans particularly scarce. Addressing this gap, we generated iPSCs from dermal fibroblasts of a healthy 60-year-old indigenous Nigerian male of the Babur ethnic group using Sendai virus. The iPSC line displayed a normal karyotype, was characterized for pluripotency markers and differentiated into neural progenitor cells and astrocytes. To enhance African representation in research, this iPSC line will be available to the scientific community, with ongoing efforts focused on creating an open-access African iPSC biobank. …

Metabolically Active Neutrophils Represent A Permissive Niche For Mycobacterium Tuberculosis, J Tucker Andrews, G V R Krishna Prasad, Jennifer A Philips, Et Al.

2020-Current year OA Pubs

Mycobacterium tuberculosis (Mtb)-infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils …

Western Diet Reduces Small Intestinal Intraepithelial Lymphocytes Via Fxr-Interferon Pathway, Chen-Ting Hung, Changqing Ma, Santosh K Panda, Tihana Trsan, Miki Hodel, Jennifer Frein, Amanda Foster, Shengxiang Sun, Hung-Ting Wu, Justin Kern, Richa Mishra, Umang Jain, Marco Colonna, Ta-Chiang Liu, Et Al.

2020-Current year OA Pubs

The prevalence of obesity in the United States has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar "Western" diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed gut adaptive immunity. Using small intestinal intraepithelial lymphocytes (IEL) as a readout, we found that in non-inflammatory bowel disease (IBD) subjects, high body mass index correlated with reduced IEL …

Discovery Of Genomic And Transcriptomic Pleiotropy Between Kidney Function And Soluble Receptor For Advanced Glycation End Products Using Correlated Meta-Analyses: The Long Life Family Study, Mary F Feitosa, Shiow J Lin, Sandeep Acharya, Bharat Thyagarajan, Mary K Wojczynski, Allison L Kuipers, Alexander Kulminski, Kaare Christensen, Joseph M Zmuda, Michael R Brent, Michael A Province

2020-Current year OA Pubs

Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genome-wide association study (GWAS) p-values in 4182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of …

Immune Checkpoint Markers And Tumour Mutation Burden In Wilms Tumour: A Study Of 59 Cases, Aidas J Mattis, Jie-Fu Chen, Ivan A Gonzalez, Rehan Rais, Louis P Dehner, John Pfeifer, Mai He

2020-Current year OA Pubs

Wilms tumour (WT) is the most common renal tumour in children, and studies of immune checkpoint inhibitors (ICIs) treatment and markers are limited in number. In this study we investigated the ICIs' related immune landscape by examining the expression of PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) proteins by immunohistochemistry (IHC), tumour mutation burden (TMB), and correlations with histology and clinical outcome. Positive PD-L1 (SP263) expression was defined as modified combined positive score (CPS) ≥1. A total of 59 WTs (from 2000 to 2017), including eight (14.0%) with anaplasia, from 46 patients were analysed (45 primary and 14 metastatic). …

A Retrospective Assessment Of Guideline Adherence And Treatment Outcomes From Clostridioides Difficile Infection Following The Idsa 2021 Clinical Guideline Update: Clostridioides Difficile Infection, Erik R Dubberke, Qinghua Li, Engels N Obi, Vladimir Turzhitsky, Fakhar Siddiqui, Brian H Nathanson

2020-Current year OA Pubs

BACKGROUND: The 2021 update to the Infectious Diseases Society of America

METHODS: This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections.

RESULTS: A total of …

Sequential Early-Life Viral Infections Modulate The Microbiota And Adaptive Immune Responses To Systemic And Mucosal Vaccination, Yuhao Li, Jerome M. Molleston, Crystal Lovato, Jasmine Wright, Isabel Erickson, Duyen Bui, Andrew H. Kim, Harshad Ingle, Somya Aggarwal, Lila S Nolan, Ahmed O. Hassan, Lynne Foster, Michael S. Diamond, Megan T. Baldridge

2020-Current year OA Pubs

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, …

Impacts Of Employment Status, Partnership, Cancer Type, And Surgical Treatment On Health-Related Quality Of Life In Irradiated Head And Neck Cancer Survivors, Ching-Rong Lin, Tsung-Min Hung, Eric Yi-Liang Shen, Ann-Joy Cheng, Po-Hung Chang, Shiang-Fu Huang, Chung-Jan Kang, Tuan-Jen Fang, Li-Ang Lee, Chih-Hung Chang, Joseph Tung-Chieh Chang

2020-Current year OA Pubs

No abstract provided.

Endosomal Fusion Of Ph-Dependent Enveloped Viruses Requires Ion Channel Trpm7, Catherine A Doyle, Marta E Stremska, Louis-Marie Bloyet, Cassandra E Thompson, Paul W Rothlauf, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

The majority of viruses classified as pandemic threats are enveloped viruses which enter the cell through receptor-mediated endocytosis and take advantage of endosomal acidification to activate their fusion machinery. Here we report that the endosomal fusion of low pH-requiring viruses is highly dependent on TRPM7, a widely expressed TRP channel that is located on the plasma membrane and in intracellular vesicles. Using several viral infection systems expressing the envelope glycoproteins of various viruses, we find that loss of TRPM7 protects cells from infection by Lassa, LCMV, Ebola, Influenza, MERS, SARS-CoV-1, and SARS-CoV-2. TRPM7 ion channel activity is intrinsically necessary to …

15-Gene Expression Profile And Prame As Integrated Prognostic Test For Uveal Melanoma: First Report Of Collaborative Ocular Oncology Group Study No. 2 (Coog2.1), J William Harbour, Kisha D Piggott, Et Al.

2020-Current year OA Pubs

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity In Outcomes Between Use Of Matched Or Mismatched Unrelated Donors, Brian C Shaffer, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.RESULTSIncluded were 10,025 …

Accessibility Of And Barriers To Long-Term Follow-Up Care For Childhood Cancer Survivors, Jiaoyang Cai, Sara Malone, Nickhill Bhakta, Ching-Hon Pui, Jing Chen, Shaoyan Hu, Hui Jiang, Xiuli Ju, Fen Zhou, Melissa M Hudson, Yin Ting Cheung

2020-Current year OA Pubs

IMPORTANCE: Childhood cancer survivorship programs and long-term follow-up (LTFU) practices are inadequate in most regions of China.

OBJECTIVE: To understand the clinician and caregiver perceptions of LTFU care and to identify barriers to adherence to LTFU care in mainland China.

DESIGN, SETTING, AND PARTICIPANTS: This survey study had a 2-phase sequential mixed-methods approach, consisting of a cross-sectional survey followed by semistructured interviews. Participants included oncology clinicians recruited through an educational seminar on LTFU and caregivers recruited through convenience sampling. Data were collected from November 2022 to September 2023.

MAIN OUTCOMES AND MEASURES: The clinician survey and interview focused on the …

Perioperative Antibiotic Prophylaxis Duration In Patients Undergoing Cystectomy With Urinary Diversion: A Randomized Clinical Trial, Maria C Thurnheer, Astrid Schürmann, Markus Huber, Jonas Marschall, Patrick Y Wuethrich, Fiona C Burkhard

2020-Current year OA Pubs

IMPORTANCE: Perioperative antibiotic prophylaxis (PAP) reduces the incidence of surgical site infections (SSIs). Guidelines recommend 24 hours or less of PAP for cystectomy with urinary diversion; however, evidence specifying optimal PAP duration for this surgery is lacking, and prolonged administration of PAP is common practice.

OBJECTIVE: To establish noninferiority of 24-hour PAP vs extended-duration PAP in preventing SSIs within 90 days after cystectomy with urinary diversion.

DESIGN, SETTING, AND PARTICIPANTS: This single-center, noninferiority randomized clinical trial was performed from April 18, 2018, to August 18, 2022, in patients aged older than 18 years undergoing elective open cystectomy with urinary diversion. …

Rehabilitation Transition Program To Improve Community Participation Among Stroke Survivors: A Randomized Clinical Trial, Rebecca M Bollinger, Melissa J Krauss, Emily K Somerville, Brianna M Holden, Gabrielle Blenden, Holly Hollingsworth, Audrey A Keleman, Alexandre Carter, Timothy D Mcbride, Abigail R Barker, Yan Yan, Susan L Stark

2020-Current year OA Pubs

IMPORTANCE: Interventions are needed to support the long-term needs of stroke survivors when they transition from inpatient rehabilitation to home, where they face new home and community environmental barriers.

OBJECTIVE: To compare the efficacy of a novel, enhanced rehabilitation transition program with attentional control to improve community participation and activity of daily living (ADL) performance and to reduce environmental barriers in the home and community after stroke.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2b, parallel randomized clinical trial assessed patients 50 years or older who had experienced an acute ischemic stroke or intracerebral hemorrhage, were independent in ADLs before stroke, …

Infectious Diseases Fellowship Training In Caring For People Who Use Drugs: A National Assessment Of An Emerging Training Need, Shilpa Vasishta, Raagini Jawa, Sarah Kurz, Nathanial S Nolan

2020-Current year OA Pubs

BACKGROUND: Infectious complications of substance use are increasingly encountered in infectious diseases (ID) clinical care. In this study, we surveyed ID fellows in the United States to assess training experiences, clinical practices, and perspectives in caring for people who use drugs (PWUD).

METHODS: An 18-item survey was distributed to ID fellows via email and social media platforms. Four focus groups were conducted with a subset of participants to elucidate themes in fellowship experiences and training needs.

RESULTS: Among 196 survey respondents (estimated 24% response rate), all reported caring for PWUD in ID fellowship. Forty-nine percent received some formal fellowship-based didactics …

Dominantly Inherited Muscle Disorders: Understanding Their Complexity And Exploring Therapeutic Approaches, Andrew R Findlay

2020-Current year OA Pubs

Treatments for disabling and life-threatening hereditary muscle disorders are finally close to becoming a reality. Research has thus far focused primarily on recessive forms of muscle disease. The gene replacement strategies that are commonly employed for recessive, loss-of-function disorders are not readily translatable to most dominant myopathies owing to the presence of a normal chromosome in each nucleus, hindering the development of novel treatments for these dominant disorders. This is largely due to their complex, heterogeneous disease mechanisms that require unique therapeutic approaches. However, as viral and RNA interference-based therapies enter clinical use, key tools are now in place to …

Network-Level Enrichment Provides A Framework For Biological Interpretation Of Machine Learning Results, Jiaqi Li, Ari Segel, Xinyang Feng, Jiaxin Cindy Tu, Andy Eck, Kelsey T King, Babatunde Adeyemo, Nicole R Karcher, Likai Chen, Adam T Eggebrecht, Muriah D Wheelock

2020-Current year OA Pubs

Machine learning algorithms are increasingly being utilized to identify brain connectivity biomarkers linked to behavioral and clinical outcomes. However, research often prioritizes prediction accuracy at the expense of biological interpretability, and inconsistent implementation of ML methods may hinder model accuracy. To address this, our paper introduces a network-level enrichment approach, which integrates brain system organization in the context of connectome-wide statistical analysis to reveal network-level links between brain connectivity and behavior. To demonstrate the efficacy of this approach, we used linear support vector regression (LSVR) models to examine the relationship between resting-state functional connectivity networks and chronological age. We compared …

Cranioencephalic Functional Lymphoid Units In Glioblastoma, Celia Dobersalske, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition to treatment-naive glioblastoma tumors, harbors active lymphoid populations at the time of initial diagnosis. Clinical and anatomical imaging, single-cell molecular and immune cell profiling and quantification of tumor reactivity identified CD8

Hospital Strain During The Covid-19 Pandemic And Outcomes In Older Racial And Ethnic Minority Adults, Laurent G Glance, Karen E Joynt Maddox, Patricia W Stone, E Yoko Furuya, Jingjing Shang, Mark J Sorbero, Ashley Chastain, Stewart J Lustik, Andrew W Dick

2020-Current year OA Pubs

IMPORTANCE: Marginalized populations have been disproportionately affected by the COVID-19 pandemic. Critically ill patients belonging to racial and ethnic minority populations treated in hospitals operating under crisis or near-crisis conditions may have experienced worse outcomes than White individuals.

OBJECTIVE: To examine whether hospital strain was associated with worse outcomes for older patients hospitalized with sepsis and whether these increases in poor outcomes were greater for members of racial and ethnic minority groups compared with White individuals.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, multivariable regression analysis was conducted to assess differential changes in all-cause 30-day mortality and major morbidity …

Postprostatectomy Radiotherapy Timing And Long-Term Health-Related Quality Of Life, Sagar A Patel, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The association between radiotherapy (RT) timing after radical prostatectomy and long-term patient-reported health-related quality of life (HRQOL) in men with prostate cancer is unknown.

OBJECTIVE: To measure long-term HRQOL in men with prostate cancer up to 15 years after prostatectomy with or without RT and examine whether early vs late postprostatectomy RT is associated with differences in sexual, urinary, and bowel HRQOL.

DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, longitudinal cohort analysis using HRQOL data from the PROST-QA (2003-2006) and RP2 consortium (2010-2013) studies was conducted. Men with localized prostate cancer undergoing radical prostatectomy were included. Data were analyzed …

Three- And Seven-Month Prostate-Specific Antigen Levels As Prognostic Markers For Overall Survival In Metastatic Hormone-Sensitive Prostate Cancer: Results From Swog S1216, A Phase 3 Randomized Trial Of Androgen Deprivation Plus Orteronel Or Bicalutamide, Mamta Parikh, Russell K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: A robust decrease in prostate-specific antigen (PSA) in response to androgen deprivation therapy (ADT) has been evaluated as a prognostic factor in patients with metastatic hormone-sensitive prostate cancer (mHSPC) since 2006, but the treatment of mHSPC has since evolved to include intensified therapy.

OBJECTIVE: We assessed the association of PSA levels at 3 (PSA-3mo) and 7 (PSA-7mo) mo with overall survival (OS) in patients with mHSPC treated with ADT combined with either bicalutamide or orteronel in the S1216 phase 3 clinical trial.

DESIGN, SETTING, AND PARTICIPANTS: PSA responses to treatment of patients in the S1216 trial were categorized as: …

Cardiovascular Outcomes, Health-Promoting Behaviors, And Social Determinants: Structural Racism And The Behavioral Risk Factor Surveillance System, Jaclyn K. Schwartz, Emily A. Kringle, Suzanne Perea Burns, Catherine R. Hoyt, Kelly M. Harris, Sami Tayeb

2020-Current year OA Pubs

No abstract provided.

Effect Of Universal Masking On Non-Severe Acute Respiratory Syndrome Coronavirus 2 Healthcare-Associated Respiratory Viral Infections, Satish Munigala, Patrick R Ching, Helen Wood, R J Waken, Josephine Fox, Heather Gasama, Robert Russell, Melanie L Yarbrough, David K Warren

2020-Current year OA Pubs

BACKGROUND: Respiratory viral infections are common and are a major cause of morbidity and mortality. We evaluated the impact of universal masking implemented during the coronavirus disease 2019 (COVID-19) pandemic on other healthcare-associated respiratory viral infections (HA-RIs) in an academic medical center.

METHODS: A retrospective cohort study was performed among all inpatients aged ≥18 years admitted between 1 May 2019 and 30 June 2022. Universal masking was implemented in May 2020 at our hospital and state-level mask mandates had been lifted by May 2021. We evaluated and compared the HA-RI rates, adjusted for monthly community-onset viral infections, during the premasking …

Himal: Multimodal Hierarchical Multi-Task Auxiliary Learning Framework For Predicting Alzheimer's Disease Progression, Sayantan Kumar, Sean C Yu, Andrew Michelson, Thomas Kannampallil, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVE: We aimed to develop and validate a novel multimodal framework

MATERIALS AND METHODS: HiMAL utilized multimodal longitudinal visit data including imaging features, cognitive assessment scores, and clinical variables from MCI patients in the Alzheimer's Disease Neuroimaging Initiative dataset, to predict at each visit if an MCI patient will progress to AD within the next 6 months. Performance of HiMAL was compared with state-of-the-art single-task and multitask baselines using area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. An ablation study was performed to assess the impact of each input modality on model performance. Additionally, longitudinal …

Structural Basis For Adhesin Secretion By The Outer-Membrane Usher In Type 1 Pili, Ryan M Bitter, Maxwell I Zimmerman, Brock T Summers, Jerome S Pinkner, Karen W Dodson, Scott J Hultgren, Peng Yuan

2020-Current year OA Pubs

Gram-negative bacteria produce chaperone-usher pathway pili, which are extracellular protein fibers tipped with an adhesive protein that binds to a receptor with stereochemical specificity to determine host and tissue tropism. The outer-membrane usher protein, together with a periplasmic chaperone, assembles thousands of pilin subunits into a highly ordered pilus fiber. The tip adhesin in complex with its cognate chaperone activates the usher to allow extrusion across the outer membrane. The structural requirements to translocate the adhesin through the usher pore from the periplasm to the extracellular space remains incompletely understood. Here, we present a cryoelectron microscopy structure of a quaternary …

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Cross-Ancestry Genetic Investigation Of Schizophrenia, Cannabis Use Disorder, And Tobacco Smoking, Emma C Johnson, Isabelle Austin-Zimmerman, Hayley H A Thorpe, Daniel F Levey, David A A Baranger, Sarah M C Colbert, Ditte Demontis, Jibran Y Khokhar, Lea K Davis, Howard J Edenberg, Marta Di Forti, Sandra Sanchez-Roige, Joel Gelernter, Arpana Agrawal

2020-Current year OA Pubs

Individuals with schizophrenia frequently experience co-occurring substance use, including tobacco smoking and heavy cannabis use, and substance use disorders. There is interest in understanding the extent to which these relationships are causal, and to what extent shared genetic factors play a role. We explored the relationships between schizophrenia (Scz; European ancestry N = 161,405; African ancestry N = 15,846), cannabis use disorder (CanUD; European ancestry N = 886,025; African ancestry N = 120,208), and ever-regular tobacco smoking (Smk; European ancestry N = 805,431; African ancestry N = 24,278) using the largest available genome-wide studies of these phenotypes in individuals of …

Mucosal Adenovirus Vaccine Boosting Elicits Iga And Durably Prevents Xbb.1.16 Infection In Nonhuman Primates, Matthew Gagne, James Brett Case, Igor P Dmitriev, Elena A Kashentseva, Baoling Ying, David T Curiel, Michael S Diamond, Et Al.

2020-Current year OA Pubs

A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1-BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG …