Digital Commons Network^™

Resistance, Rebound, And Recurrence Regrowth Patterns In Pediatric Low-Grade Glioma Treated By Mapk Inhibition: A Modified Delphi Approach To Build International Consensus-Based Definitions-International Pediatric Low-Grade Glioma Coalition, Patricia O'Hare, David H Gutmann, Et Al.

2020-Current year OA Pubs

Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morbidities. The majority of pLGGs have an underlying activation of the RAS/MAPK pathway due to mutational events, leading to the use of molecularly targeted therapies in clinical trials, with recent regulatory approval for the combination of BRAF and MEK inhibition for BRAFV600E mutated pLGG. Despite encouraging activity, tumor …

A Human Stat3 Gain-Of-Function Variant Drives Local Th17 Dysregulation And Skin Inflammation In Mice, Kelsey A Toth, Erica G Schmitt, Ana Kolicheski, Zev J Greenberg, Elizabeth Levendosky, Nermina Saucier, Kelsey Trammel, Vasileios Oikonomou, Michail S Lionakis, Eynav Klechevsky, Brian S Kim, Laura G Schuettpelz, Naresha Saligrama, Megan A Cooper

2020-Current year OA Pubs

Germline gain-of-function (GOF) variants in STAT3 cause an inborn error of immunity associated with early-onset poly-autoimmunity and immune dysregulation. To study tissue-specific immune dysregulation, we used a mouse model carrying a missense variant (p.G421R) that causes human disease. We observed spontaneous and imiquimod (IMQ)-induced skin inflammation associated with cell-intrinsic local Th17 responses in STAT3 GOF mice. CD4+ T cells were sufficient to drive skin inflammation and showed increased Il22 expression in expanded clones. Certain aspects of disease, including increased epidermal thickness, also required the presence of STAT3 GOF in epithelial cells. Treatment with a JAK inhibitor improved skin disease without …

Maturation Of Germinal Center B Cells After Influenza Virus Vaccination In Humans, Katherine M Mcintire, Wooseob Kim, Sameer Kumar Malladi, Bassem M Mohammed, Julian Q Zhou, Aaron J Schmitz, Teresa Suessen, William D Middleton, Sharlene A Teefey, Rachel M Presti, Jackson S Turner, Ali H. Ellebedy, Et Al.

2020-Current year OA Pubs

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity …

Mucosal Immunization With Chad-Sars-Cov-2-S Prevents Sequential Transmission Of Sars-Cov-2 To Unvaccinated Hamsters, Tamarand L Darling, Houda H Harastani, Astha Joshi, Traci L Bricker, Nadia Soudani, Kuljeet Seehra, Ahmed O Hassan, Michael S Diamond, Adrianus C M Boon

2020-Current year OA Pubs

COVID-19 vaccines have successfully reduced severe disease and death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nonetheless, COVID-19 vaccines are variably effective in preventing transmission and symptomatic SARS-CoV-2 infection. Here, we evaluated the impact of mucosal or intramuscular vaccine immunization on airborne infection and transmission of SARS-CoV-2 in Syrian hamsters. Immunization of the primary contact hamsters with a mucosal chimpanzee adenoviral-vectored vaccine (ChAd-CoV-2-S), but not intramuscular messenger RNA (mRNA) vaccine, reduced infectious virus titers ~100-fold and 100,000-fold in the upper and lower respiratory tract of the primary contact hamster following SARS-CoV-2 exposure. This reduction in virus titer in …

Dihydrothiazolo Ring-Fused 2-Pyridone Antimicrobial Compounds Streptococcus Pyogenes Skin And Soft Tissue Infection, Zongsen Zou, Pardeep Singh, Jerome S Pinkner, Chloe L P Obernuefemann, Wei Xu, Taylor M Nye, Karen W Dodson, Fredrik Almqvist, Scott J Hultgren, Michael G Caparon

2020-Current year OA Pubs

We have developed GmPcides from a peptidomimetic dihydrothiazolo ring-fused 2-pyridone scaffold that has antimicrobial activities against a broad spectrum of Gram-positive pathogens. Here, we examine the treatment efficacy of GmPcides using skin and soft tissue infection (SSTI) and biofilm formation models by

High-Dimensional Single-Cell Analysis Of Human Natural Killer Cell Heterogeneity, Lucas Rebuffet, Marco Colonna, Et Al.

2020-Current year OA Pubs

Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic …

Cell-Free Dna For The Detection Of Kidney Allograft Rejection, Olivier Aubert, Tarek Alhamad, Raja Dandamudi, Vikas R Dharnidharka, Et Al.

2020-Current year OA Pubs

Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P < 0.0001), T cell-mediated rejection (P < 0.0001) and mixed rejection (P < 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P < 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379 .

Lisocabtagene Maraleucel In Follicular Lymphoma: The Phase 2 Transcend Fl Study, Franck Morschhauser, Brad Kahl, Et Al.

2020-Current year OA Pubs

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. …

The Space Omics And Medical Atlas (Soma) And International Astronaut Biobank, Eliah G Overbey, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space

Neoantigen-Specific Cytotoxic Tr1 Cd4 T Cells Suppress Cancer Immunotherapy, Hussein Sultan, Yoshiko Takeuchi, Jeffrey P Ward, Tian-Tian Liu, Vladimir Sukhov, Yuang Song, Samuel Ameh, Simone Brioschi, Darya Khantakova, Cora D Arthur, J Michael White, Heather Kohlmiller, Kathleen C F Sheehan, Marco Colonna, Kenneth M Murphy, Maxim N Artyomov, Robert D Schreiber, Et Al.

2020-Current year OA Pubs

CD4

Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk, Duc Tran, J Scott Beeler, Jie Liu, Brian Wiley, Irenaeus C C Chan, Zilan Xin, Michael H Kramer, Armel L Batchi-Bouyou, Xiaoyu Zong, Matthew J Walter, Giulia E M Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T Oh, Daniel C Link, Ben Busby, Yin Cao, Kelly L Bolton

2020-Current year OA Pubs

PURPOSE: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet, our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our understanding of the mechanisms promoting MN development.

EXPERIMENTAL DESIGN: We jointly characterized CH and plasma proteomic profiles of 46,237 individuals in the UK Biobank at baseline study entry. During 500,036 person-years of follow-up, 115 individuals developed MN. Cox proportional hazard …

Expanding A Behavioral View On Digital Health Access: Drivers And Strategies To Promote Equity, Maura M Kepper, Lauren A Fowler, Isabelle S Kusters, Jean W Davis, Manal Baqer, Sara Sagui-Henson, Yunyu Xiao, Adati Tarfa, Jean C Yi, Bryan Gibson, Kristin E Heron, Nicole M Alberts, Marissa Burgermaster, Veronica Ps Njie-Carr, Lisa M Klesges

2020-Current year OA Pubs

The potential and threat of digital tools to achieve health equity has been highlighted for over a decade, but the success of achieving equitable access to health technologies remains challenging. Our paper addresses renewed concerns regarding equity in digital health access that were deepened during the COVID-19 pandemic. Our viewpoint is that (1) digital health tools have the potential to improve health equity if equitable access is achieved, and (2) improving access and equity in digital health can be strengthened by considering behavioral science-based strategies embedded in all phases of tool development. Using behavioral, equity, and access frameworks allowed for …

A Maternal Brain Hormone That Builds Bone, Muriel E Babey, Xiao Zhang, Erica L Scheller, Et Al.

2020-Current year OA Pubs

In lactating mothers, the high calcium (Ca

Psilocybin Desynchronizes The Human Brain, Joshua S Siegel, Demetrius Perry, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, T Rick Reneau, Nicholas V Metcalf, Samuel R Krimmel, Joshua S Shimony, Julie A Schweiger, Dean F Wong, David A Bender, Kristen M Scheidter, Forrest I Whiting, Jonah A Padawer-Curry, Eric J Lenze, Marcus E Raichle, Abraham Z Snyder, Ginger E Nicol, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials

Community-Based Participatory Research And System Dynamics Modeling For Improving Retention In Hypertension Care, Jiancheng Ye, Ikechukwu A Orji, Michelle A Birkett, Lisa R Hirschhorn, Theresa L Walunas, Justin D Smith, Namratha R Kandula, Gabriel L Shedul, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

IMPORTANCE: The high prevalence of hypertension calls for broad, multisector responses that foster prevention and care services, with the goal of leveraging high-quality treatment as a means of reducing hypertension incidence. Health care system improvements require stakeholder input from across the care continuum to identify gaps and inform interventions that improve hypertension care service, delivery, and retention; system dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and ways to model sustainable system-level improvements.

OBJECTIVE: To assess the association of simulated interventions with hypertension care retention rates in the Nigerian primary health care system using …

Potential Us Health Care Savings Based On Clinician Views Of Feasible Site-Of-Care Shifts, Nikhil R Sahni, Crosbie Marine, David M Cutler, Laura N Medford-Davis, Melvin Mezue, Omar Kattan, Ed Levine, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Shifting care to alternative sites when clinically appropriate may be associated with reduced US health care spending, improved access, and, in some cases, improved care outcomes.

OBJECTIVE: To fill 2 main gaps in the current literature on site-of-care shifts: (1) understanding the clinician perspective on appropriateness of alternative care sites, given the central role they play in referrals and patient trust and (2) considering all potential sites where care could shift and calculating net savings potential.

DESIGN, SETTING, AND PARTICIPANTS: In this survey study, physicians (MDs and DOs), nurse practitioners, physician assistants, nurse anesthetists, radiology and imaging technicians, and …

Posttraumatic Stress Disorder And Type 2 Diabetes Outcomes In Veterans, Jeffrey F Scherrer, Joanne Salas, Wenjin Wang, Kenneth E Freedland, Patrick J Lustman, Paula P Schnurr, Beth E Cohen, Allan S Jaffe, Matthew J Friedman

2020-Current year OA Pubs

IMPORTANCE: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown.

OBJECTIVE: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used deidentified data from US Veterans Health Administration (VHA) historical medical records (from October 1, 2011, to …

A Protocol For The Inclusion Of Minoritized Persons In Alzheimer Disease Research From The Adni3 Diversity Taskforce, Ozioma C Okonkwo, Beau M Ances, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.

OBJECTIVE: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from a longitudinal, multisite, …

Traumatic Brain Injury, Seizures, And Cognitive Impairment Among Older Adults, Yiqi Zhu, Jonathan Williams, Kebede Beyene, Jean-Francois Trani, Ganesh M Babulal

2020-Current year OA Pubs

IMPORTANCE: Traumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups.

OBJECTIVE: To investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer's Coordination …

Gemykibivirus Detection In Acute Encephalitis Patients From Nepal, Eans Tara Tuladhar, Smita Shrestha, Susan Vernon, Lindsay Droit, Kathie A Mihindukulasuriya, Mamta Tamang, Lata Karki, Annie Elong Ngono, Bimlesh Jha, Bal Krishna Awal, Bimal Sharma Chalise, Runa Jha, Sujan Shresta, David Wang, Krishna Das Manandhar

2020-Current year OA Pubs

UNLABELLED: Acute encephalitis syndrome (AES) causes significant morbidity and mortality worldwide. In Nepal, Japanese encephalitis virus (JEV) accounts for ~5-20% of AES cases, but ~75% of AES cases are of unknown etiology. We identified a gemykibivirus in CSF collected in 2020 from an 8-year-old male patient with AES using metagenomic next-generation sequencing. Gemykibiviruses are single stranded, circular DNA viruses in the family

IMPORTANCE: Viral encephalitis is a devastating disease, but unfortunately, worldwide, the causative virus in many cases is unknown. Therefore, it is important to identify viruses that could be responsible for cases of human encephalitis. Here, using metagenomic sequencing …

Phase Ii Basket Trial Of Dual Anti-Ctla-4 And Anti-Pd-1 Blockade In Rare Tumors (Dart) Swog S1609: Adrenocortical Carcinoma Cohort, Sandip P Patel, Megan Othus, Young Kwang Chae, Tridu Huynh, Benjamin Tan, Timothy Kuzel, Christine Mcleod, Gabby Lopez, Helen X Chen, Elad Sharon, Howard Streicher, Christopher W Ryan, Charles Blanke, Razelle Kurzrock

2020-Current year OA Pubs

OBJECTIVES: Multiple common cancers benefit from immunotherapy; however, less is known about efficacy in rare tumors. We report the results of the adrenocortical carcinoma cohort of NCI/SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors.

DESIGN/SETTING: A prospective, phase 2 clinical trial of ipilimumab plus nivolumab was conducted by the SWOG Early Therapeutics and Rare Cancers Committee for multiple rare tumor cohorts across >1,000 National Clinical Trial Network sites.

PARTICIPANTS: 21 eligible patients were registered. Median age was 53 years (range 26-69); 16 (76%) were women.

INTERVENTIONS: Ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously …

Nucleolytic Processing Of Abasic Sites Underlies Parp Inhibitor Hypersensitivity In Alc1-Deficient Brca Mutant Cancer Cells, Natasha Ramakrishnan, Tyler M Weaver, Lindsey N Aubuchon, Ayda Woldegerima, Taylor Just, Kevin Song, Alessandro Vindigni, Bret D Freudenthal, Priyanka Verma

2020-Current year OA Pubs

Clinical success with poly (ADP-ribose) polymerase inhibitors (PARPi) is impeded by inevitable resistance and associated cytotoxicity. Depletion of Amplified in Liver Cancer 1 (ALC1), a chromatin-remodeling enzyme, can overcome these limitations by hypersensitizing BReast CAncer genes 1/2 (BRCA1/2) mutant cells to PARPi. Here, we demonstrate that PARPi hypersensitivity upon ALC1 loss is reliant on its role in promoting the repair of chromatin buried abasic sites. We show that ALC1 enhances the ability of the abasic site processing enzyme, Apurinic/Apyrimidinic endonuclease 1 (APE1) to cleave nucleosome-occluded abasic sites. However, unrepaired abasic sites in ALC1-deficient cells are readily accessed by APE1 at …

Reconciling Shared Versus Context-Specific Information In A Neural Network Model Of Latent Causes, Qihong Lu, Tan T Nguyen, Qiong Zhang, Uri Hasson, Thomas L Griffiths, Jeffrey M Zacks, Samuel J Gershman, Kenneth A Norman

2020-Current year OA Pubs

It has been proposed that, when processing a stream of events, humans divide their experiences in terms of inferred latent causes (LCs) to support context-dependent learning. However, when shared structure is present across contexts, it is still unclear how the "splitting" of LCs and learning of shared structure can be simultaneously achieved. Here, we present the Latent Cause Network (LCNet), a neural network model of LC inference. Through learning, it naturally stores structure that is shared across tasks in the network weights. Additionally, it represents context-specific structure using a context module, controlled by a Bayesian nonparametric inference algorithm, which assigns …

Senescent Cancer-Associated Fibroblasts In Pancreatic Adenocarcinoma Restrict Cd8+ T Cell Activation And Limit Responsiveness To Immunotherapy In Mice, Benjamin Assouline, Sheila A Stewart, Et Al.

2020-Current year OA Pubs

Senescent cells within tumors and their stroma exert complex pro- and anti-tumorigenic functions. However, the identities and traits of these cells, and the potential for improving cancer therapy through their targeting, remain poorly characterized. Here, we identify a senescent subset within previously-defined cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinomas (PDAC) and in premalignant lesions in mice and humans. Senescent CAFs isolated from mouse and humans expressed elevated levels of immune-regulatory genes. Depletion of senescent CAFs, either genetically or using the Bcl-2 inhibitor ABT-199 (venetoclax), increased the proportion of activated CD8

Targeted Degradation Of Extracellular Mitochondrial Aspartyl-Trna Synthetase Modulates Immune Responses, Benjamin S Johnson, Janet S Lee, Et Al.

2020-Current year OA Pubs

The severity of bacterial pneumonia can be worsened by impaired innate immunity resulting in ineffective pathogen clearance. We describe a mitochondrial protein, aspartyl-tRNA synthetase (DARS2), which is released in circulation during bacterial pneumonia in humans and displays intrinsic innate immune properties and cellular repair properties. DARS2 interacts with a bacterial-induced ubiquitin E3 ligase subunit, FBXO24, which targets the synthetase for ubiquitylation and degradation, a process that is inhibited by DARS2 acetylation. During experimental pneumonia, Fbxo24 knockout mice exhibit elevated DARS2 levels with an increase in pulmonary cellular and cytokine levels. In silico modeling identified an FBXO24 inhibitory compound with immunostimulatory …

Whole Cervix Imaging Of Collagen, Muscle, And Cellularity In Term And Preterm Pregnancy, Wenjie Wu, Zhexian Sun, Hansong Gao, Yuan Nan, Stephanie Pizzella, Haonan Xu, Josephine Lau, Yiqi Lin, Hui Wang, Pamela K Woodard, Hannah R Krigman, Qing Wang, Yong Wang

2020-Current year OA Pubs

Cervical softening and dilation are critical for the successful term delivery of a fetus, with premature changes associated with preterm birth. Traditional clinical measures like transvaginal ultrasound and Bishop scores fall short in predicting preterm births and elucidating the cervix's complex microstructural changes. Here, we introduce a magnetic resonance diffusion basis spectrum imaging (DBSI) technique for non-invasive, comprehensive imaging of cervical cellularity, collagen, and muscle fibers. This method is validated through ex vivo DBSI and histological analyses of specimens from total hysterectomies. Subsequently, retrospective in vivo DBSI analysis at 32 weeks of gestation in ten term deliveries and seven preterm …

Targeted Co-Expression Networks For The Study Of Traits, A Gómez-Pascual, G Rocamora-Pérez, L Ibanez, J A Botía

2020-Current year OA Pubs

Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used approach for the generation of gene co-expression networks. However, networks generated with this tool usually create large modules with a large set of functional annotations hard to decipher. We have developed TGCN, a new method to create Targeted Gene Co-expression Networks. This method identifies the transcripts that best predict the trait of interest based on gene expression using a refinement of the LASSO regression. Then, it builds the co-expression modules around those transcripts. Algorithm properties were characterized using the expression of 13 brain regions from the Genotype-Tissue Expression project. When …

A Randomized Controlled Trial Testing The Effects Of A Social Needs Navigation Intervention On Health Outcomes And Healthcare Utilization Among Medicaid Members With Type 2 Diabetes, Amy Mcqueen, David Von Nordheim, Charlene Caburnay, Linda Li, Cynthia Herrick, Lauren Grimes, Darrell Broussard, Rachel E Smith, Dana Lawson, Yan Yan, Matthew Kreuter

2020-Current year OA Pubs

Health systems are increasingly assessing and addressing social needs with referrals to community resources. The objective of this randomized controlled trial was to randomize adult Medicaid members with type 2 diabetes to receive usual care (

Chromatin Conformation And Histone Modification Profiling Across Human Kidney Anatomic Regions, Haikuo Li, Dian Li, Benjamin D Humphreys

2020-Current year OA Pubs

The three major anatomic regions of the human kidney include the cortex, medulla and papilla, with different functions and vulnerabilities to kidney diseases. Epigenetic mechanisms underlying these anatomic structures are incompletely understood. Here, we performed chromatin conformation capture with Hi-C and histone modification H3K4me3/H3K27me3 Cleavage Under Targets and Release Using Nuclease (CUT&RUN) sequencing on the kidney cortex, medulla and papilla dissected from one individual donor. Nuclear suspensions were generated from each region and split subjected to paired Hi-C and CUT&RUN sequencing. We evaluated the quality of next-generation sequencing data, Hi-C chromatin contact matrices and CUT&RUN peak calling. H3K4me3 and H3K27me3 …

Cellular Endosomal Potassium Ion Flux Regulates Arenavirus Uncoating During Virus Entry, Amelia B Shaw, Hiu Nam Tse, Owen Byford, Grace Plahe, Alex Moon-Walker, Samantha E Hover, Erica Ollmann Saphire, Sean P J Whelan, Jamel Mankouri, Juan Fontana, John N Barr

2020-Current year OA Pubs

Lymphocytic choriomeningitis virus (LCMV) is an enveloped and segmented negative-sense RNA virus classified within the