Digital Commons Network^™

Performance Of Multiple Multi-Cancer Detection Tests Using A Large Independent Reference Set (Alliance A212102), Marie E Wood, Mark Watson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Reference sets are needed to evaluate performance of multi-cancer detection (MCD) assays. The National Cancer Institute funded the Alliance reference set study to assess MCDs for use in future trials.

METHODS: Individuals with cancer and controls were recruited; blood specimens were collected prior to cancer treatment. A performance evaluation study was designed utilizing reference set samples. Companies (n = 6) were selected to participate based on review of performance data and ability to utilize the blood collection tube. Companies received samples from cancer types their assay was designed to detect ("targeted"), plus additional "non-targeted" and control samples. Companies reported …

Visual Recognition Of The Anteroposterior Female Body Axis Drives Spatial Elements Of Male Courtship In Drosophila, Ross M Mckinney, Christian Monroy Hernandez, Yehuda Ben-Shahar

2020-Current year OA Pubs

Drosophila males exhibit a highly stereotypic courtship ritual toward virgin females, which is comprised of a sequence of specific behavioral elements that depend on inputs from diverse sensory modalities. Particularly, the visual system of the male plays an important role in detecting salient patterns, colors, and motion cues from conspecifics, which can promote or inhibit specific aspects of male courtship such as chase and song production. Here, we use a computer vision and machine learning-based approach, with a simplified courtship paradigm, to show that males also depend on visual cues to determine the anterior-posterior body axis of females, which drives …

Hepatitis C Virus Testing In Perinatally Exposed Children, Rachel L Epstein, Sarah Munroe, Elizabeth A Erdman, Amy Bettano, Megan R Curtis, Laura White, Elisha M Wachman, Anthony Osinski, Alexander Y Walley, Benjamin P Linas

2020-Current year OA Pubs

IMPORTANCE: Despite rising hepatitis C virus (HCV) incidence in pregnant people, studies demonstrate that fewer than 50% of perinatally exposed infants receive HCV testing. Few studies report treatment of infected infants or factors affecting testing.

OBJECTIVE: To identify birthing parent and child factors associated with appropriate HCV testing for perinatally exposed infants and characterize HCV care for children with HCV.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included records on testing, care, and treatment for Massachusetts children perinatally exposed to HCV between 2014 and 2021 from a statewide health database linking statewide vital statistics, infectious disease surveillance data, substance use …

Mda5-Mavs And Interferon-Lambda Signaling In The Intestinal Epithelium Limit Murine Astrovirus Infection, Heyde Makimaa, Harshad Ingle, Leran Wang, Somya Aggarwal, Hongju Deng, Elizabeth A Kennedy, Lynne Foster, Yuhao Li, Megan T Baldridge

2020-Current year OA Pubs

Human astroviruses (HAstVs) are a global cause of pediatric gastroenteritis and can cause disseminated infection in immunocompromised hosts. Murine astrovirus (muAstV) causes acute asymptomatic infections in immunocompetent mice and chronic infection in immunodeficient models and has provided important insights into AstV pathogenesis in vivo. MuAstV can protect immunodeficient mice from other enteric viruses via robust induction of antiviral cytokine interferon-lambda (IFN-λ), with recent findings implicating goblet cells and enterocytes as both cell types infected by muAstV as well as potential sources of IFN-λ in vivo. However, the viral sensing pathways that regulate induction of IFN-λ, as well as the specific …

Glp-1 Receptor Agonists Or Sglt2 Inhibitors And Nonarteritic Anterior Ischemic Optic Neuropathy, Taeyoung Choi, Ziyad Al-Aly, Yan Xie

2020-Current year OA Pubs

No abstract provided.

Exploring Nurses' Documentation Prioritization Strategies To Alleviate Ehr Documentation Burden: A Phenomenological Study, Rosemary Mugoya, Jennifer Thate, Fan Hao, Sarah C Rossetti, Po-Yin Yen

2020-Current year OA Pubs

OBJECTIVE: This study aims to understand how inpatient nurses determine and prioritize necessary documentation within the context of the Excessive Documentation Burden (ExDocBurden) in Electronic Health Records (EHRs).

METHODOLOGY: A phenomenological approach was used to explore inpatient nurses' lived experiences of prioritizing EHR documentation. Interpretive phenomenology guided the study design, focusing on how nurses prioritize documentation. Purposive sampling recruited 14 registered nurses (RNs) from acute and critical care settings. Data was collected through semi-structured interviews and analyzed using Colaizzi's 7-step and Smith's Interpretive Phenomenology Analysis.

RESULTS: Five themes emerged: (1) Advocating for Quality Patient Care Environment and Patient Needs, (2) …

Multicenter Evaluation Of Ceftazidime/Avibactam In Pediatric Patients Across The United States: Real-World Insights Into The Management Of Drug-Resistant Gram-Negative Infections, Taylor Morrisette, Christine R Lockowitz, Valerie Yuenger, Evan E Facer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance among gram-negative pathogens is a global threat, with children particularly vulnerable due to limited treatment options and age-specific clinical outcomes data. Ceftazidime/avibactam (CZA) is effective against resistant gram-negative bacteria and demonstrates high success rates in adults; however, pediatric data remain limited. This study examined CZA use in children across United States medical centers.

METHODS: This multicenter, retrospective, observational cohort study included pediatric patients (< 18 years) who received ≥48 hours of CZA for suspected or confirmed gram-negative infections between February 2015 and October 2023. The primary outcome was clinical success, defined as occurrence of all 3 components: (1) absence of all-cause mortality within 30 days of CZA initiation, (2) absence of microbiologic and clinical recurrence within 30 days of CZA discontinuation, and (3) resolution or improvement of infection-related signs and symptoms during CZA therapy without modification of therapy due to clinical failure. Secondary outcomes included adverse events attributable to CZA and resistance development to CZA.

RESULTS: One-hundred patients were included, with most receiving CZA for targeted therapy (67%). The median (IQR) age and weight were 9.8 (1.9-15.9) years and 24.2 (12.2-49.9) kg, respectively. Nearly all patients (88%) had …

Automating Evaluation Of Llm-Generated Responses To Patient Questions About Rare Diseases, Min Zhao, Inez Y Oh, Aditi Gupta, Sally Cohen-Cutler, Kathryn M Harmoney, Albert M Lai, Bryan A Sisk

2020-Current year OA Pubs

OBJECTIVES: Patients with rare diseases often struggle to find accurate medical information, and large language model (LLM)-based chatbots may help meet this need. However, evaluating LLM-generated free-text answers typically requires physician review, which is time-consuming and difficult to scale. This study compared traditional natural language processing (NLP) metrics to emerging LLM-based evaluation approaches for assessing answer quality in the context of Complex Lymphatic Anomalies (CLAs).

MATERIALS AND METHODS: We compiled 25 common patients' questions about CLAs and generated 175 responses to these questions from seven LLMs. Three expert physicians scored these responses for accuracy. We compared these physician-assigned scores with …

Intracranial Mesenchymal Tumor, Fet::Creb Fusion-Positive: An Integrative Analysis Of 81 Cases, Sharika Rajan, Robert Schmidt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intracranial mesenchymal tumors, FET::CREB fusion-positive (ICMT), show fusions involving FET RNA-binding protein family genes (EWSR1 or FUS) and CREB family of transcription factors (ATF1, CREB1, or CREM). The methylation signature(s), gene expression characteristics, and clinical behavior of this important tumor type require further characterization.

METHODS: We study the methylation profiles of 81 ICMT cases (61 newly profiled cases and 20 cases from publicly available sources). Clinicopathologic and genomic data were recorded for each case when available.

RESULTS: ICMT showed a relatively distinct methylation signature compared to related tumors. Among the 65 cases where fusion types were documented, the identified …

Differential Regulation Of Cyclic Adenosine Monophosphate By Phosphodiesterase 3a Discriminates Thrombin-Induced Protease Activated Receptor 1- And 4-Dependent Platelet Activation, Izabella Andrianova, Abigail Ajanel, Jesse W Rowley, Darian C Murray, Yasuhiro Kosaka, Frederik Denorme, Paul F Bray, Robert A Campbell

2020-Current year OA Pubs

BACKGROUND: Human platelets express 2 thrombin-activated G protein-coupled receptors (GPCRs), protease activated receptor (PAR)1 and PAR4. Previous studies have demonstrated PAR1 activation to be fast on-fast off while PAR4 activation was slower but more sustained. However, how PARs regulate second messengers such as cyclic adenosine monophosphate (cAMP), a negative regulator of platelet activation, remain unknown.

OBJECTIVES: This study investigated how PAR1 and PAR4 activation by thrombin regulates cAMP levels and platelet activation.

METHODS: PAR1 and PAR4 on washed human platelets were inhibited with vorapaxar or BMS-986120, respectively, in the presence or absence of prostaglandin (PG)I

RESULTS: In the presence of …

Lyplal1 Rare Loss-Of-Function Variants In Humans And Deletion In Human Hepatoma Cells Protect Against Masld, Rawdat Hussain, Chinmay Raut, Ponnandy Prabhu, Akram Irshaid, Yash Hegde, Yue Chen, Asmita Pant, Antonino Oliveri, Xiaochao Wei, Lishi Yin, Tiffany L Russell, Brian Halligan, Clay F Semenkovich, Elizabeth K Speliotes

2020-Current year OA Pubs

Genetic variants near LYPLAL1 are associated with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) in humans, but their impact on LYPLAL1 function is unknown. We identified LYPLAL1 loss-of-function variants from UK BioBank (UKBB) whole-exome sequencing data that had AlphaMissense or GPN-MSA scores in the top 20% of LYPLAL1 variants for being disruptive. We aggregated these variants and carried out burden analysis for effects on MRI Proton Density-Fat Fraction (MRI-PDFF) and ICD-based MASLD in UKBB. Rare loss-of-function LYPLAL1 variants were associated with reduced MRI-PDFF and ICD diagnosed MASLD across sexes. We used CRISPR to knockout and overexpress LYPLAL1 in human hepatoma cells …

Alterations In Ascending Aortic Hemodynamics And Aortic Length Correlate With Sex-Specific Thoracic Aortic Aneurysm Dilation And Lifespan In A Mouse Model Of Severe Marfan Syndrome, Krashn Kr Dwivedi, Yufan Wu, Marisa S Bazzi, Hadi Wiputra, Jacob Rother, James D Quirk, Victor H Barocas, Jessica E Wagenseil

2020-Current year OA Pubs

Thoracic aortic aneurysm (TAA) is a dilation of the aorta that may eventually dissect and/or rupture. It is associated with genetic disorders such as Marfan syndrome (MFS) and is a life-threatening cardiovascular condition if left untreated. Current clinical guidelines for TAA management are primarily based on maximum diameter thresholds that are often inadequate, particularly in MFS patients. Moreover, the diameter thresholds are not sex-specific, despite growing evidence that TAA outcomes in MFS are influenced by sex. The aim of this study was to identify non-invasive biomarkers for better management of TAA using male and female mice that are a genetic …

Promoting Community And Social Participation In Chronic Stroke: A Pilot Study Of The Engage Intervention, Elizabeth Skidmore, Carolyn Baum, Jessica Kersey, Emily Kringle, Kelsey Voltz-Poremba, Sular Gordon, Tina Harris, Heidi Fischer, Maureen Gecht, Michelle Furman, Joy Hammel

2020-Current year OA Pubs

BACKGROUND: Survivors of stroke report low levels of community and social participation, even years after stroke. ENGAGE is a community-based intervention that merges social learning, guided problem solving, and supervised practice to collaboratively identify, generate, and apply solutions to challenges with community and social participation after stroke.

OBJECTIVE: We examined the feasibility, acceptability, and safety of ENGAGE and characterized within group changes in community and social participation outcomes.

METHODS: Community-dwelling survivors of stroke, occupational therapy providers, and occupational therapy scientists partnered to co-design the essential and structural elements of ENGAGE, as well as to evaluate ENGAGE using a multi-site single-arm …

Deep Learning In Fetal, Infant, And Toddler Neuroimaging Research, Jenna H Chin, Madeleine K Wyburd, Vladislav Ayzenberg, Laurie Bayet, Berkin Bilgic, Emily M Chen, Yuting Chen, Áine Dineen, Shohei Fujita, Janelle Liu, Yohan Jun, M Catalina Camacho, Lilla Zöllei

2020-Current year OA Pubs

Artificial intelligence (AI) is increasingly being integrated into everyday tasks and work environments. However, its adoption in medical image analysis has progressed more slowly due to high clinical stakes, limited availability of labeled data, and substantial variability in imaging protocols and population. These challenges are further pronounced in the field of fetal, infant, and toddler (FIT) neuroimaging, where datasets are especially scarce and subject to large amounts of anatomical variability. However, deep learning (DL), a specific method within machine learning, which is itself a subfield of AI, has emerged as a powerful framework to adapt to the challenges of medical …

Deviation From Ai-Predicted Implant Sizes In Total Hip Arthroplasty Is Associated With Increased Complication Risk, Michael P Murphy, Andrew M Schneider, Cameron J Killen, Daniel R Schmitt, Nicholas M Brown

2020-Current year OA Pubs

BACKGROUND: Patient characteristics may predict implant sizes in total hip arthroplasty (THA), but the clinical value and generalizability of such models remain uncertain. This study evaluated the accuracy and relevance of an artificial intelligence (AI)-driven prediction tool for THA sizing in a diverse population.

METHODS: We retrospectively reviewed 2410 primary THAs at 2 academic hospitals (2007-2021). Data included patient characteristics, surgical approach, surgeon fellowship training, and complications (periprosthetic femur fracture [PPF], aseptic loosening within 1 year). An AI model predicted femoral stem and acetabular cup sizes using age, sex, height, weight, and race/ethnicity, and these predictions were compared with implanted …

Two-Year Outcomes Following Delandistrogene Moxeparvovec Treatment In Ambulatory Patients With Duchenne Muscular Dystrophy: Phase 3 Embark Trial, Jerry R Mendell, Craig M Zaidman, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Delandistrogene moxeparvovec is a recombinant adeno-associated virus rhesus isolate serotype 74 vector-based gene therapy that addresses the absence of functional dystrophin in Duchenne muscular dystrophy (DMD). EMBARK is a phase 3, two-part, crossover, randomized, placebo-controlled trial assessing the safety and efficacy of delandistrogene moxeparvovec (single intravenous dose 1.33 × 10

METHODS: As a result of the crossover study design, 2-year functional outcomes of patients receiving delandistrogene moxeparvovec in part 1 of EMBARK were compared, by pre-specified analysis, with a matched propensity score-weighted external control (EC).

RESULTS: At 2 years, EMBARK patients showed statistically significant benefit versus the EC cohort …

De Novo Heterozygous Variants Of The Rsf1 Gene Are Responsible For A Syndromic Neurodevelopmental Disorder, Céline Jost, Daniel Wegner, Marwan Shinawi, Kathleen Sisco, Alexander J Paul, Et Al.

2020-Current year OA Pubs

Neurodevelopmental disorders (NDD) are a wide and heterogenous group of conditions due to impaired brain development, orchestrated by the crosstalk between genome and environment. Dynamic chromatin regulation during cortical development is fundamental, and chromatin remodelers are critical determinants of this process. Recently, numerous chromatin remodeling genes have been implicated in NDDs. By altering genes' epigenetic state, mutated chromatin remodelers disrupt the spatiotemporal regulation of gene expression during development, potentially leading to severe consequences. The Remodeling and Spacing Factor 1 (RSF1) gene encodes a ubiquitous nuclear protein involved in chromatin remodeling, crucial for processes such as DNA transcription, replication, and repair. …

Predictors Of Delayed Recovery In Ambulatory Advanced Endoscopic Procedures, Zoilo K Suarez, Alexandria Lenyo, Philip M Frasse, Derek J Platt, Thomas Hollander, Talwinder Nagi, Michael Dedonno, Vladimir Kushnir, Juan Reyes Genere

2020-Current year OA Pubs

BACKGROUND: There is a scarcity of data evaluating patient-related outcomes of advanced or complex endoscopy (ACE) through the post-anesthesia recovery course. Yet, gastrointestinal distress following ACE can occur commonly, and this may impact recovery length of stay and the approach to post-anesthesia care. This study aimed to describe post-procedural symptoms in patients undergoing ACE and identify factors that influence recovery time and course.

METHODS: We retrospectively reviewed a prospectively collected database of patients who underwent ambulatory ACE. Procedural-related symptoms, recovery time, dismissal rate, and adverse events (AE) were recorded. Factors associated with extended recovery time were analyzed using multiple regression …

An International Mega-Analysis Of Psychedelic Drug Effects On Brain Circuit Function, Manesh Girn, Nico Dosenbach, Et Al.

2020-Current year OA Pubs

Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and …

Metabolically Reprogrammed Eosinophils Impair T Cell Immunity And Cause Chronic Skin Infection, David Barinberg, Heidi Sebald, Tobias Gold, Baplu Rai, Daniel Radtke, Dominik Lerm, David Voehringer, Jonathan Jantsch, Stefan Wirtz, Alina Ulezko Antonova, Marco Colonna, Christian Bogdan, Ulrike Schleicher

2020-Current year OA Pubs

Eosinophils exhibit antimicrobial, cytotoxic and immunoregulatory effects, but our knowledge of their transcriptional and functional heterogeneity is still limited, especially in non-intestinal tissues. Here, we used a mouse model of chronic cutaneous inflammation elicited by the protozoan pathogen Leishmania mexicana to investigate the function and transcriptional dynamics of skin eosinophils. Infection of C57BL/6 mice triggered local and systemic eosinophilia that was driven by type 2 innate lymphoid cells and interleukin-5. Genetic and pharmacological eosinophil depletion led to an enhanced Th1 response, polarization towards M1-like macrophages and resolution of clinical disease, despite an unexpected simultaneous upregulation of IL-4. Single-cell transcriptomics revealed …

Sialidosis Type I: How To Alleviate Disabling Myoclonic Seizures? - A Multicenter Analysis Of Eight Cases And Review Of The Literature, Janina Gburek-Augustat, Shao Ching Tu, Marwan Shinawi, Isabel Alfradique-Dunham, Manouela Valtcheva, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sialidosis type I (ST-1) is an autosomal-recessive, very rare, progressive lysosomal storage disorder caused by pathogenic variants in NEU1. It is clinically characterized by progressive ataxia, myoclonic seizures (MS), bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological findings. Given the lack of curative options, in this study, we investigated symptomatic treatment strategies, with a particular focus on the efficacy of antiseizure medications (ASMs).

METHODS: We describe the clinical course of a patient followed from diagnosis to 18 years of age, and review seven additional cases from our cohort. In parallel, we conducted a narrative review of the literature (PubMed, January …

Neuropsychiatric Symptoms Mimicking Dementia In A Patient Treated With Imatinib, Ashley Jones, Samuele Bonomi, Keith E Stockerl-Goldstein, Randall J Bateman

2020-Current year OA Pubs

Tyrosine kinase inhibitors are the cornerstone of chronic myeloid leukemia treatment. Newer agents have more potency and a broader spectrum of action, but also a higher potential for neuropsychiatric side effects. We present a case of a patient on imatinib who developed progressive cognitive, mood, and behavioral alterations. He was investigated for dementia and psychiatric disorders but ultimately improved only after discontinuing imatinib. His decompensation years after therapy start, followed by complete and rapid remission, is atypical. We also review the most recent neurobiological findings on the role of tyrosine kinase alterations in dementia and their importance for mood regulation.

Knowledge, Attitudes, And Practices Among Sexually Active Individuals Toward Trichomoniasis In The Ashaiman Municipality, Ghana: A Cross-Sectional Study, Christopher Yaw Dumevi, Percival Delali Agordoh, Yaw Osei Owusu, Josephine Afi Nukpedu Banini, Roberta Araba Amoquandoh, George Boateng Kyei, Patience B Tetteh-Quarcoo, Irene Ayi, Patrick F Ayeh-Kumi

2020-Current year OA Pubs

BACKGROUND AND AIMS: Trichomoniasis is a significant public health concern due to its implications for reproductive health and HIV transmission. Despite its prevalence, there is limited understanding of community knowledge, attitudes, and practices (KAP) regarding trichomoniasis in Ghana. This study aimed to assess KAP toward trichomoniasis among sexually active individuals in the Ashaiman Municipality of the Greater Accra Region.

METHODS: A hospital-based cross-sectional study was conducted from February to April 2024 among 397 sexually active individuals aged 15-65 years. Participants were selected via simple random sampling. Data were analyzed using SPSS version 26 and Stata version 17. Descriptive statistics summarized …

Sensitivity And Concordance Study Of An Open Source Epid-Based Linear Accelerator Test Suite, Lana C Critchfield, Cory S Knill, Ellie Durussel, Justin K Mikell, Michael Barnes, Michael Pillainayagam, William P Donahue, Seng Boh Lim, John J Demarco, Mario Perez, Nilendu Gupta, Hania Al-Hallaq, Richard A Popple, Jim Irrer, Jean M Moran

2020-Current year OA Pubs

BACKGROUND: Electronic portal imaging devices (EPIDs) enhance linear accelerator (linac) quality assurance (QA) efficiency but are not universally used beyond patient-specific IMRT QA. A multi-institutional Consortium seeks to standardize linac QA utilizing an EPID-based test suite.

PURPOSE: This study evaluates the sensitivity of a test suite to intentional linac and plan errors and the concordance with linac fluctuations over time.

METHODS: Baseline and error-introduced tests were performed on a Varian TrueBeam and Clinac. Evaluated parameters included enhanced dynamic wedge factors (EDW) (6MV), central axis dose (6MV, 6MV FFF, 16MV), focal spot alignment and beam symmetry (6MV, 16MV), dose rate-gantry speed …

Apoe-Stratified Proteomic And Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation And Lipid Dysregulation In Alzheimer's Disease, Fuhai Li, Yike Chen, Daniel Western, Muhammad Ali, Menghan Liu, Katherine Gong, Ying Xu, Joseph Lowery, David M Holtzman, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Apolipoprotein E (APOE) ε4 is the strongest genetic risk factor for Alzheimer's disease (AD). However, it is known that other pathways independent of APOE also play a role in AD. Disentangling APOE-dependent and independent effects is instrumental for understanding the biology of AD. We conducted an APOE-stratified multi-omic analysis in multiple large datasets to identify AD-associated plasma proteins and metabolites. More than 64% of the identified proteins were not found in non-APOE stratified studies, and 17% of the proteins showed APOE-specific trends. Mitochondrial dysfunction was associated in AD independently of APOE and was accompanied by disruptions in glucose and lipid …

The Femoral Head Edema Zone: A Novel Classification Scheme To Better Predict Osteonecrosis Progression, Deniz C Ince, Vivek P Shah, Kenichi Kikuchi, Kyle P O'Connor, Elizabeth L Yanik, John C Clohisy, Cecilia Pascual-Garrido

2020-Current year OA Pubs

BACKGROUND: This study proposed a new classification, the Edema Zone classification, that uses magnetic resonance imaging images to grade the extent of edema in osteonecrosis of the femoral head. The purpose of the study was (1) to examine how the Edema Zone classification compared to the Japanese Investigation Committee (JIC) classification's prognostic ability for early conversion to total hip arthroplasty (THA), and (2) to determine how accurately and reliably the Edema Zone classification performed as a classification system.

METHODS: This was a retrospective study of hips that converted to THA from a core decompression within 26 months compared to hips …

Quality Of Antenatal And Delivery Care And Postnatal Care Use: A Multi-Country Observational Study Of 400,000 Births, Jan E. Cooper, Hwa-Young Lee, Katherine Wright, Prashant Jaryan, Margaret E. Kruk

2020-Current year OA Pubs

BACKGROUND: Postnatal care (PNC) plays a crucial role in averting newborn mortality, yet its use remains low, particularly in regions with the highest mortality. While demographic and social determinants of PNC use have been well studied and have informed current strategies focused on changing care-seeking behaviors, the stagnating decline in neonatal mortality highlights the need for upstream and system-wide approaches to increase PNC uptake. Limited evidence exists to guide system-level reforms; therefore, we investigated whether health systems that ensure high-quality perinatal care are associated with increased use of PNC.

METHODS AND FINDINGS: We performed a cross-sectional observational study using Demographic …

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, …