Digital Commons Network^™

Detailed Single-Cell Mapping Of The Transcriptional Response To A Virus Infection Driven By Copy-Back Viral Genomes, Yanling Yang, Emna Achouri, Munyaradzi Tambo, Carolina B. López

2020-Current year OA Pubs

The antiviral response to several clinically significant viruses, including respiratory syncytial virus and parainfluenza virus, is driven by copy-back viral genomes (cbVGs) generated during virus replication. However, the broader impact of cbVGs on the functional states of host cells remains undefined. Here, we developed a single-cell RNA-sequencing and computational framework to map cbVG-driven host responses during Sendai virus infection. Unsupervised profiling identified distinct transcriptional states throughout the course of infection, highlighting a shift from early antiviral signaling to later inflammatory and remodeling programs. Stratifying infected cells by cbVG status demonstrated that cbVG-positive cells initiate interferon and chemokine programs, which later …

Developing A Novel Index For Neighborhood Social Determinants Of Cardiovascular Diseases In The Cardia Study, Tao Gao, Yinan Zheng, Brian T Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Penny Gordon-Larsen, Chunyu Liu, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

2020-Current year OA Pubs

Neighborhood social determinants of health have been shown to influence cardiovascular risk and the development of cardiovascular disease, but few studies have been done about early-life exposure as well as the combined effect of multiple neighborhood social determinants of health measures. Each 1-standard-deviation increase in the neighborhood social determinants of health index is associated with increased risk of coronary artery calcification at the year 7, year 15, and year 20 visits (Odds Ratios range from 1.15 to 1.17). The area under the Receiver Operating Characteristics curve ranges between 0.718 (year 7) and 0.719 (year 20). Compared to White participants, Black …

Feasibility Of High-Intensity Interval Training In Older Adults With Hiv And Co-Occurring Hypertension, Michael J Hankes, Taylor L Taylor, Emily L Zumbro, Ene M Enogela, Fitzgerald Dodds, Mckenna Tharpe, Silvienne C Sint Jago, Burel R Goodin, Amanda L Willig, Thomas W Buford, Raymond Jones

2020-Current year OA Pubs

BACKGROUND: As life expectancy for people living with HIV (PWH) has increased, there has been a rise in age-related comorbidities such as hypertension. Exercise is an important nonpharmacological strategy to counter such adverse effects of chronic HIV infection. High-intensity interval training (HIIT) has been demonstrated to be safe and efficacious in improving health outcomes in individuals with chronic illness, but data are limited in older PWH and co-morbid conditions. The primary objective of this pilot feasibility study was to assess the feasibility, efficacy, and safety of a 6-week HIIT intervention among older PWH and co-occurring hypertension.

METHODS: PWH were recruited …

A Pathogenic Tau Mutation Drives Autophagy-Lysosome Dysfunction That Limits Tau Degradation In A Model Of Frontotemporal Dementia, Farzaneh S Mirfakhar, Jacob A Marsh, Chihiro Sato, Kylie J Schache, Miguel A Minaya, Roland E Dolle, Stephen C Pak, Gary A Silverman, David H Perlmutter, Shannon L Macauley, Celeste M Karch

2020-Current year OA Pubs

Tau accumulates in a group of neurodegenerative diseases known as tauopathies. A prevailing hypothesis has been that Tau degradation is impaired due to an age-related imbalance in the autophagy-lysosome pathway, but whether these defects are a cause or consequence of Tau accumulation remains unclear. Here we show that a disease-causing mutation in the MAPT gene, which encodes Tau, p.R406W, is sufficient to disrupt multiple steps of the autophagy-lysosome pathway in human neurons. Using Airyscan super-resolution imaging, we find that mutant Tau neurons accumulate Tau and phosphorylated Tau in dysfunctional lysosomes, exhibit reduced lysosome motility, impaired fusion of autophagosomes and lysosomes, …

Ketone Body Supplementation Exerts Renoprotective Effects Against Adenine-Induced Kidney Injury Via Oxct1-Mediated Ketolysis In Mice, Shoji Omachi, Sho Sugahara, Junya Horiguchi, Mako Yasuda-Yamahara, Shogo Kuwagata, Kosuke Yamahara, Yuki Tanaka-Sasaki, Shogo Ida, Tetsuro Kusaba, Benjamin D Humphreys, Kenji Kufukihara, Jin Nakahara, Masami Chin-Kanasaki, Shinji Kume

2020-Current year OA Pubs

Ketone bodies have traditionally been recognized as glucose-sparing energy sources, with hepatic ketogenesis and peripheral ketolysis serving pivotal functions in maintaining energy homeostasis during fasting. Although they are commonly seen as harmful due to their link with ketoacidosis, recent studies emphasize their roles in organ protection. This has sparked interest in their possible use as a treatment for chronic kidney disease (CKD). In this study, we examined both exogenous and endogenous ketone body supplementation in adenine-induced kidney injury in mice. Supplementation with the ketone body precursor 1,3-butanediol significantly improved adenine-induced renal fibrosis, inflammation, and apoptotic cell death. However, genetically deleting …

Post-Hemorrhagic Hydrocephalus Of Prematurity Is Associated With Disruption Of Tight Junctions And Increased Macrophage Activity In The Choroid Plexus, Maria Garcia-Bonilla, Rajiv Swarup, Owen W Limbrick, Habeebah Z Vohra, Ayodamola Otun, Konrad Mckalip, William Bernhardt, Kirill Shumilov, Marie Michenkova, Jayne Crouthamel, Mackenzie Newman, Krikor Dikranian, James P Mcallister Ii, David D Limbrick

2020-Current year OA Pubs

BACKGROUND: Previous studies on intraventricular hemorrhage (IVH), a common and severe complication of preterm birth, and subsequent post-hemorrhagic hydrocephalus (PHH), have predominantly concentrated on the secretory function of the choroid plexus (ChP), with considerably less emphasis on its barrier function. We hypothesized that PHH is associated with immune-related alterations in the junction biology of ChP. METHODS: We examined differences in tight junctions and macrophages using a neonatal mouse model of PHH (n = 40) and in vitro ChP explants (n = 22), as well as human post-mortem samples (n = 6). To test our hypothesis, we employed histology, immunofluorescence, magnetic …

Provider And Caregiver Perspectives On Vision Services For Childhood Cancer Survivors: A Qualitative Study, Asha Parvathaneni, Luke Zabotka, Jacob Strelnikov, Allison J L'Hotta, Matthew J Ehrhardt, Maria Montoya, Kyathi Thallapureddy, Robert J Hayashi, Margaret Reynolds, Sara Malone

2020-Current year OA Pubs

PURPOSE: This study qualitatively explored barriers and facilitators to accessing supportive vision services for childhood cancer survivors with vision deficits and identified current service-delivery contexts from the perspectives of community professionals and caregivers. METHODS: Participants included caregivers and professionals who completed semi-structured interviews. Provider questions focused on patient identification and assessment, follow-up protocols, and available resources, while caregiver questions addressed navigating survivorship care, academic needs, and goals for their children. Transcripts were thematically analyzed following inductive and deductive coding. RESULTS: Six caregivers and 10 professionals completed interviews. Thematic analysis resulted in three contexts for barriers and facilitators: school settings, community …

High Prevalence Of Criminal Legal Involvement Among Non-Fatally Injured Ed Patients - An Exploratory Retrospective Observational Cohort Analysis, Vidya Eswaran, Raphael Cohen, Taylor Kaser, Alysse G Wurcel, Michael Mancini, Kateri Chapman-Kramer, Nicholas Szoko, Keyria Page, Melik Coffey, Kristen Mueller

2020-Current year OA Pubs

BACKGROUND: Individuals who have been incarcerated are at high risk of death by homicide after release from carceral settings. Our study aimed to assess the prevalence of criminal legal system involvement (CLSI) among non-fatal violently injured patients enrolled in a hospital-based violence intervention (HVIP) program and describe demographic and clinical characteristics specific to this population.

METHODS: This is an exploratory retrospective cohort study of all patients enrolled in the St. Louis, Missouri based HVIP, Life Outside of Violence (LOV), between 08/15/2018 and 12/31/2024. LOV enrolls patients aged 8-30 who receive violent injury care at a partner hospital. We collected data …

Energetic Diversity In Retinal Ganglion Cells Is Modulated By Neuronal Activity And Correlates With Resilience To Degeneration, Zelun Wang, Christopher Zhao, Shelly Xu, Minglei Zhao, Sean Mccracken, Rajendra S Apte, Philip R Williams

2020-Current year OA Pubs

Neuronal function requires high energy expenditure that is likely customized to meet specific signaling demands. However, little is known about diversity of metabolic homeostasis among divergently-functioning types of neurons. To this end, we examined retinal ganglion cells (RGCs), a population of closely related, yet electrophysiologically distinct excitatory projection neurons. Using in vivo 2-photon imaging to measure ATP with single cell resolution, we identified differential homeostatic energy maintenance in the RGC population that correspond to distinct RGC types. In the presence of circuit activity, the most active RGC type (Alpha RGCs), had lower homeostatic ATP levels than other types and exhibited …

Impact Of Who Aware Antibiotic Handbook Training On Antibiotics Prescribing Knowledge Among Private Primary Care Providers: A Vignette-Based, Prep-Post Pilot Study In Patna, India, Poshan Thapa, Prachi Shukla, Chandrashekhar Joshi, Sena Sayood, Pradeep Kumar Sinha, Diwash Timilsina, Mili Dutta, Madhukar Pai, Samira Abbasgholizadeh Rahimi, Sumanth Gandra

2020-Current year OA Pubs

INTRODUCTION: Inappropriate antibiotic prescribing is a major concern in low- and middle-income countries (LMICs), particularly at the primary care level. The WHO AWaRe Antibiotic Handbook was introduced to promote rational antibiotic use, yet its real-world feasibility and potential impact remain underexplored. Our study evaluated the impact and usefulness of the WHO AWaRe Handbook training among private primary care providers (PCPs) in Patna, India.

METHODS: We conducted a pre-post pilot study among 145 private PCPs (40 formal PCPs (FPs) and 105 informal PCPs (IPs) in Patna, India. Participants received training from an infectious disease physician on the WHO AWaRe Antibiotic Handbook. …

Effective Spectrum-Based Antibiotic Resistance Index For Monitoring Resistance In Gram-Negative Bacilli, M Cristina Vazquez Guillamet, Alice Bewley, Nicole J Tarlton, Reid Goodman, Michael J Durkin, Michael Bernauer, Meghan Brett, Kevin Hsueh, Cristian Bologa, George Turabelidze, Andrew Atkinson, Victoria J Fraser

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance (AMR) is a growing public health threat, and we currently lack accurate measures to track and trend this resistance. We developed the antibiotic resistance index (ARI) that aggregates resistance of Gram-negative bacilli (GNB) into a single metric which can be tracked across healthcare settings and over time.

METHODS: Culture data were collected from adult patients who met the CDC adult sepsis event criteria across 10 Barnes-Jewish HealthCare (BJC) hospitals between January 2018 and December 2023. An antibiotic's effective spectrum (AES) was calculated as the ratio of susceptible GNB to all identified GNB. The ARI was calculated as …

Multimerin1 And Not Galectin-8 Tempers Wnt Signaling To Promote Gastric Chief Cell Differentiation, Xiaobo Lin, Gabriel Nicolazzi, Xuemei Liu, Chinye Nwokolo, Yehiel Zick, José B Sáenz, Jeffrey W Brown

2020-Current year OA Pubs

Galectins are a family of proteins that bind galactose-containing glycans. One member, galectin-8, preferentially binds galactose that contains a terminal sulfate. Aberrant expression and secretion of sulfated glycosylation epitopes, such as 3'-Sulfo-Le

Association Of Chronic Kidney Disease With In-Hospital Mortality Of Cardiogenic Shock Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation, Mounika Reddy Vadiyala, Jeffy Varghese, Giorgi Chilingarashvili, Vibhor Ahluwalia, Sakshi Sharma, Syed Mohammad Moosi Raza, Harsh Sura, Adhvithi Pingili, Rupak Desai

2020-Current year OA Pubs

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) improves survival in patients with cardiogenic shock (CS), but data on chronic kidney disease (CKD) as a predictor of mortality in these patients is limited.

AIM: To assess the association between CKD and in-hospital mortality in CS patients undergoing VA-ECMO through a systematic review and meta-analysis.

METHODS: We reviewed studies up to February 2024 that evaluated CKD's impact on in-hospital mortality in CS patients treated with extracorporeal membrane oxygenation. Databases included PubMed, Google Scholar, EMBASE, and Scopus. A random-effects model was used to calculate the pooled unadjusted odds ratio,

RESULTS: Thirteen studies, involving 12185 …

Association Between Charcoal Cooking Fuel And Cardiovascular Disease Prevalence In Haiti: A Cross-Sectional Analysis, Lily D Yan, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is little evidence on the association between cooking with polluting fuels, particularly charcoal, and heart disease from low- and middle-income countries, which have the highest burdens of polluting fuels and cardiovascular disease (CVD). We sought to assess the relationship between self-reported primary home cooking with charcoal and prevalent cardiovascular disease in the low-income country Haiti. METHODS: Demographic and clinical data were collected from 3,005 adults in the Haiti Cardiovascular Disease Cohort, recruited from Port-au-Prince using multistage random sampling from 2019 to 2021. Primary cooking fuel was self-reported in the household: charcoal orliquified petroleum gas (LPG). Prevalent CVD (heart …

Molecular Characterization Of Humanized Apoe Mouse Models Reveals Source And Genotype Dependent Differences, Na Wang, David M Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Humanized APOE targeted-replacement (TR) mice are essential tools for studying apoE isoform effects in Alzheimer’s disease (AD) and other apoE-related disorders. Despite their widespread use, existing APOE mouse models, generated with different gene targeting strategies, have not been directly compared in terms of apoE isoform expression, lipid profiles, and transcriptomic signatures. Such differences could impact how we interpret APOE genotype-related outcomes, as well as related underlying molecular mechanisms. METHODS: We conducted a comprehensive molecular comparison of humanized APOE mouse models from three sources: Taconic Biosciences (TAC), the Cure Alzheimer’s Fund (CAF), and The Jackson Laboratory (JAX). We assessed apoE …

Lipocalin 2 Orchestrates Resistance To Ferroptosis Via Axl, Sabrina Z Wang, J Payton Timken, Ellen S Hong, Sehaj Kaur, Eli Newby, Kristen E Kay, Erin E Mulkearns-Hubert, Daniel J Silver, Juyeun Lee, Joshua B Rubin, James R Connor, Loic P Deleyrolle, Deanna Tiek, Andrew Dhawan, Justin D Lathia

2020-Current year OA Pubs

Glioblastoma (GBM) remains a lethal tumor, largely due to robust mechanisms that prevent effective induction of cell death. Ferroptosis, a form of iron-dependent cell death, is a promising vulnerability in GBM. Here, we demonstrate that lipocalin-2 (LCN2) suppresses ferroptosis in GBM cells via the receptor tyrosine kinase AXL. LCN2 was elevated in GBM cells compared to lower-grade tumor and non-transformed cells, and Lcn2 knockdown impaired GBM cell fitness and growth in vitro and in vivo. Mechanistically, Lcn2 knockdown triggered ferroptosis, which was specifically rescued with ferroptosis inhibitors but not apoptosis or necroptosis inhibitors. Lcn2 knockdown reduced AXL phosphorylation, which was …

Perceived Partner Substance Use, Genetic Predispositions, And Their Associations With Problematic Alcohol Use, Emotional Well-Being, And Relationship Quality, Megan E Cooke, Kathleen K Bucholz, Vivia V. Mccutcheon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Romantic relationships are important contexts for substance use and emotional well-being. We tested the hypotheses that (i) genetic predispositions for alcohol consumption would be positively associated with partner substance use, (ii) partner substance use would moderate genetic influences on one's own alcohol outcomes, and (iii) partner discordance in substance use would be associated with lower emotional well-being and relationship quality.

METHODS: Analyses included 2,357 participants (M

RESULTS: Participant PGS

CONCLUSIONS: The results highlight the importance of partner substance use in etiological models of alcohol use, emotional health outcomes, and relationship quality.

Impact Of Prior Bendamustine Exposure On Bispecific Antibody Outcomes In Relapsed/Refractory Follicular Lymphoma, Gloria Iacoboni, David A Russler-Germain, Jing Luan, Et Al.

2020-Current year OA Pubs

No abstract provided.

Glomerular Basement Membrane Structural Integrity Dictates Trans-Tissue Deposition Of Laminin In The Kidney, Kohei Omachi, Meei-Hua Lin, Pongpratch Puapatanakul, Joshua F Begin, Karen K Mckee, Hironobu Fujiwara, Peter D Yurchenco, Jeffrey H Miner

2020-Current year OA Pubs

Basement membranes (BMs) are specialized extracellular matrices (ECMs) essential for tissue structure and function. In non-vertebrates, ECM components can be produced both locally and by distant tissues. In contrast, mammalian ECM has traditionally been considered to originate predominantly from adjacent or tissue-resident cells. The kidney glomerular basement membrane (GBM), composed of laminin-α5β2γ1 and collagen-α3α4α5(IV), is produced by neighboring cells and functions as a filtration barrier. Alport syndrome, a genetic kidney disease, is characterized by GBM structural defects and ectopic laminin-α2 deposition, but the source of this laminin remains unknown. Here, using CRISPR-Cas9 transgenic models, we demonstrated that ectopic laminin-α2 in …

Clinical Characteristics, Management, And Hematopoietic Cell Transplantation Of Patients With Tlr8 Gain-Of-Function, Danielle E Arnold, Jahnavi Aluri, Sarah S Mehta, Joshua M Tobin, Laura G Schuettpelz, Nermina Saucier, Elizabeth G Schmitz, Jeffrey J Bednarski, Megan A Cooper, Et Al.

2020-Current year OA Pubs

Toll-like receptor 8 (TLR8) gain-of-function (GOF) somatic variants were recently identified as causing severe neutropenia, lymphoproliferation, and immune dysregulation. We report the expanded clinical and laboratory phenotype and management of 10 patients, including the original cohort of 6 male patients. We identify the first female patient with TLR8 GOF who presented during infancy with pure red cell aplasia due to a germ line TLR8 variant, and 2 new disease-causing somatic variants in male patients. Eight patients had somatic mosaicism with peripheral blood variant allele fractions of 7% to 26%, and age of disease onset of 9 months to 28 years. …

Whole-Genome Crispr Screening Identifies Genetic Modifiers Of Stem Cell-Derived Islet Transplantation, Marlie M Maestas, Kameron Bradley, Mira Shunkarova, Noyonika Mukherjee, Matthew Ishahak, James Lu, Jeffrey R Millman

2020-Current year OA Pubs

INTRODUCTION: Genetically engineering human pluripotent stem cell (hPSC)-derived islets is a promising strategy for improving transplantation for diabetes cell therapy; however, genetic perturbations that modulate transplantation outcomes have yet to be systematically explored.

METHODS: To identify potential targets, we performed an unbiased whole-genome CRISPR-activation screen in transplanted stem cell-derived islets (SC-islets). Specifically, we created a stem cell line with CRISPR-activation components (HUES8-VPR) and then transduced these stem cells with a lentiviral guide RNA library targeting the whole human genome. Following transduction, the stem cells were differentiated into SC-islets, which were subsequently transplanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) immunodeficient mice. After transplantation, SC-islets …

4-Aminoquinolines Block Heme Iron Reactivity And Interfere With Artemisinin Action, Melissa Rosenthal, Daniel E Goldberg

2020-Current year OA Pubs

Artemisinin-based combination therapies (ACTs) remain the mainstay of treatment for

Mastr-Seq Enables Multiplexed Analysis Of Short Tandem Repeats With Sequencing, Chuanbin Su, Han-Seul Ryu, Keerthivasan Raanin Chandradoss, Thomas Malachowski, Ravi Boya, Linda Zhou, Hoa Emma Nguyen, Esteban O Mazzoni, Kristen J Brennand, Jennifer E Phillips-Cremins

2020-Current year OA Pubs

More than 60 human disorders are caused by unstable expansion of short tandem repeat (STR) tracts. These can exhibit cell-type-specific mosaicism in several repeat expansion disorders and remain difficult to characterize due to technical challenges intrinsic to highly repetitive sequences. Long-read approaches can measure STR length and DNA methylation on the same single molecule but are low-throughput and cost-prohibitive across multiple experimental conditions or patient samples. Here, we present MASTR-seq, multiplexed analysis of short tandem repeats with sequencing, for cost-effective, high-throughput, accurate measurement of STR genotype and DNA methylation at single-allele resolution. MASTR-seq couples long-read sequencing, Cas9-mediated target enrichment, size …

Eligibility For Amyloid Targeting Therapies Among Primary Care Patients With Cognitive Symptoms, Beata Borgström Bolmsjö, Josef Barbosa Djärf, Danielle Van Westen, Suzanne E Schindler, Ayesha Fawad, Lyduine Collij, Ruben Smith, Niklas Mattsson-Carlgren, Erik Stomrud, Pontus Tideman, Oskar Hansson, Sebastian Palmqvist

2020-Current year OA Pubs

BACKGROUND: Alzheimer’s disease (AD) is the most common cause of dementia and a growing healthcare challenge. Amyloid-targeting therapies (ATT) may slow progression, but implementation is limited by logistical and economic barriers. As primary care is the first contact for most patients with cognitive concerns, quantifying treatment eligibility in this setting is essential. The purpose of this study was to estimate the proportion of primary care patients presenting with cognitive symptoms who are eligible for ATT. METHODS: This cohort study included patients presenting with cognitive symptoms in primary care across the region Skåne, in southern Sweden, recruited between January 2020 and …

Progress Of Hiv Care Cascade And Transition Dynamics Along The Continuum Of Care Among Persons Living With Hiv In Ifakara, Tanzania: A Prospective Study, Aneth Vedastus Kalinjuma, Aaloke Mody, Tracy Renée Glass, Maja Weisser, Ezekiel Luoga, Honorati Masanja, Fiona Vanobberghen, Kennedy Otwombe

2020-Current year OA Pubs

BACKGROUND: While cross-sectional assessments offer snapshots of care cascade progress, longitudinal analyses are essential to capture the dynamic engagement in care of people living with HIV (PLHIV). We assessed the advancement of the HIV cascade, engagement in care and factors associated with different transitions among PLHIV at the Chronic Disease Clinic of Ifakara, Ifakara, Tanzania, using both cross-sectional and longitudinal analyses. METHODS: In this prospective study, we included PLHIV enrolled in care from 04/2005 to 09/2022 and consented to participate in the Kilombero and Ulanga Antiretroviral Cohort. A cross-sectional care cascade was assessed descriptively. In longitudinal analysis, we used continuous-time, …

Efficient Multi-Kilobase Knock-Ins In Mice And Cell Lines Using Crispr/Cas9 And Raav Donors With Unbiased Whole-Genome Characterization By Lock-Seq, Monica F Sentmanat, Zi Teng Wang, Evguenia Kouranova, Samuel T Peters, Wan Ching Chan, Jed Lin, Yong Miao, J Michael White, Mia Wallace, Xiaoxia Cui

2020-Current year OA Pubs

Multi-kilobase knock-ins (KIs) are a necessary, yet challenging type of genome editing to create and characterize in cell lines and animals. The combination of rAAV donor transduction and electroporation of single-cell mouse embryos with Cas9/gRNA ribonucleoprotein complex enables highly efficient KI, but the insert size is limited by the viral packaging capacity. Here, we report the creation of up to 6.7 kb precise KI achieved in one step by using three rAAVs designed to insert one after the other. To fully characterize the edited genome with large KIs, we developed LOCK-seq (LOng-read sequencing of Captured Kilo-base targets), where relevant genomic …

Glucagon-Like Peptide 1 Receptor Agonist Discontinuation And Risks Of Major Adverse Cardiovascular Events In Adults With Type 2 Diabetes: Target Trial Emulation, Yan Xie, Taeyoung Choi, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVES: To characterise patterns of use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) and assess the associations between various GLP-1RA treatment scenarios and the risk of major adverse cardiovascular events.

DESIGN: Target trial emulation.

SETTING: Electronic healthcare databases of US Department of Veterans Affairs, 1 January 2017 to 31 December 2023. Data obtained from domains in the Veterans Affairs Corporate Data Warehouse.

PARTICIPANTS: Veterans Affairs users with type 2 diabetes who started treatment with GLP-1RAs (n=132 551) or sulfonylureas (n=201 136), followed up for three years. Veterans Affairs users were defined as having at least two visits to Veterans Affairs …

On-Resin Diamsar-Conjugated Cd38-Targeted Peptides And Their Inverso And Dimeric-Inverso Analogs For Pet Imaging Of Multiple Myeloma, Amit Kumar Sharma, Rui Tang, Alexander Zheleznyak, Brad Manion, Erin Teubner, Julie L Prior, Tommy Bauer, Michael Riley Dyer, Stephen Lees, Kimberly Kelly, Monica Shokeen

2020-Current year OA Pubs

CD38 is an established biomarker of multiple myeloma (MM), and peptide-based radiopharmaceuticals targeted to this receptor offer a route to molecularly specific imaging. In this work, we identified a novel CD38-targeted peptide sequence (HAPWFRGGGGS) through phage display and synthesized it using automated solid-phase peptide synthesis. The peptide was modified by introducing a PEG

Dexmedetomidine On Supraventricular Tachycardia In Critical Illness: A Time-Dependent Propensity Score Matching Study, Qiaonan Zhong, Marin H Kollef, Patrick G Lyons, Andrew P Michelson

2020-Current year OA Pubs

BACKGROUND: Supraventricular tachycardia affects many critically ill patients. Dexmedetomidine, a commonly used sedative, has sympatholytic and vagotonic effects that may alter atrioventricular nodal conduction and contribute to SVT. We aim to determine the association between dexmedetomidine exposure and clinically significant supraventricular tachycardia in a heterogeneous cohort of mechanically ventilated, critically ill adults. METHODS: This retrospective cohort study included critically ill patients from 11 hospitals admitted between July 2018 and October 2022, who were intubated within 48 h of admission. The primary exposure was intravenous dexmedetomidine. The primary outcome was occurrence of clinically significant supraventricular tachycardia, defined as heart rate > 100 …

Avian Influenza Preparedness In Ghana: A Cross-Sectional Assessment Of Knowledge, Attitudes, And Practices Among Residents Of Nsawam-Adoagyiri Municipality, Eastern Region, Christopher Yaw Dumevi, George Boateng Kyei, Et Al.

2020-Current year OA Pubs

BACKGROUND: Avian influenza (AI) represents a persistent threat to public health, food security, and livelihoods in Ghana, where outbreaks of H5N1 and H9N2 have occurred. This cross-sectional study evaluated the knowledge, attitudes, and practices (KAP) related to avian influenza among residents of the Nsawam-Adoagyiri Municipality; an area characterized by intensive poultry production with the aim of delineating deficits in community-level preparedness and guiding evidence-based public health interventions. METHODS: A community-based cross-sectional study was conducted from May to July 2025 using a four-stage sampling technique. We surveyed 321 adults via structured questionnaires, evaluating socio-demographics and KAP related to AI. Scale reliability …