Digital Commons Network^™

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, …

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 …

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 …

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. …

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 …

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.

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.

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. …

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 …

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 …

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 …

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

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 …

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 …