Medicine and Health Sciences Commons^™

Integrative Analysis Of The 3d Genome And Epigenome In Mouse Embryonic Tissues, Miao Yu, Yang E Li, Et Al.

2020-Current year OA Pubs

While a rich set of putative cis-regulatory sequences involved in mouse fetal development have been annotated recently on the basis of chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, here we mapped chromatin contacts between gene promoters and distal sequences across the genome in seven mouse fetal tissues and across six developmental stages of the forebrain. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations and developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets …

Genomics Of Pediatric Cardiomyopathy, Teresa M Lee, Stephanie M Ware, Alicia M Kamsheh, Surbhi Bhatnagar, Mohammed Absi, Elyse Miller, Enkhsaikhan Purevjav, Kaitlin A Ryan, Jeffrey A Towbin, Steven E Lipshultz

2020-Current year OA Pubs

Cardiomyopathy in children is a leading cause of heart failure and cardiac transplantation. Disease-associated genetic variants play a significant role in the development of the different subtypes of disease. Genetic testing is increasingly being recognized as the standard of care for diagnosing this heterogeneous group of disorders, guiding management, providing prognostic information, and facilitating family-based risk stratification. The increase in clinical and research genetic testing within the field has led to new insights into this group of disorders. Mutations in genes encoding sarcomere, cytoskeletal, Z-disk, and sarcolemma proteins appear to play a major role in causing the overlapping clinical phenotypes …

Comparison Of 2 Thromboelastography Methods Using Patient And Control Samples, Robert Frick, Brittany Washburn, Dennis Plocher, Jonathan K Zoller, Jason Gillihan, Michael Dombrowski, Charles Eby, Christopher W Farnsworth

2020-Current year OA Pubs

BACKGROUND: Viscoelastic testing at point-of-care is associated with reduced blood loss and blood product transfusions. The ROTEM (Werfen) sigma is a cartridge-based system that may facilitate point-of-care use, but limited studies exist comparing the sigma with the predicated ROTEM delta.

OBJECTIVES: We compared the performance of the ROTEM delta with that of the sigma.

METHODS: Citrated blood was collected from 20 healthy donors and patients during liver transplants (

RESULTS: The coefficient of variation was < 10% for all assays/parameters except for the thromboelastometry with extrinsic activation (EXTEM) clotting time (10.3%) and EXTEM amplitude (A)5 (10.2%). Reference intervals for the delta and sigma were comparable to manufacturer claims. The Pearson r comparing the delta and sigma exceeded .85 for all parameters/assays except for thromboelastometry with cytochalasin D-mediated platelet inhibition (FIBTEM) A10 (.77; 95% CI, .66-.86), FIBTEM A20 (.78; 95% CI, .65-.87), and thromboelastometry with heparinase clotting time (.77; 95% CI, .61-.87). No difference was observed in extrapolated thresholds from the delta-guided algorithm. However, extrapolated sigma A5 parameters for EXTEM were 5 mm lower, and for FIBTEM were 1 mm lower than delta A10 parameters.

CONCLUSION: The ROTEM delta and sigma devices had comparable performance. A negative bias was observed in the FIBTEM assay with lower extrapolated clinical decision points …

Patient-Reported Social Risk Factor Screening Among Rheumatology Outpatients, Alissa Chandler, Mohammed Hamid, Ziqiao Jiao, Kelsey Hulcher, Isha Sharma, Patrice Odom, Andrew Robinson, Sara Kellahan, Maura Kepper, Colleen Dostal, Senada Fenelon, Seth Eisen, Daphne Lew, Alfred H J Kim

2020-Current year OA Pubs

OBJECTIVE: The purpose of this study was to pilot test a patient-reported social risk factor (SRF) screening tool among rheumatology outpatients and to examine the distribution of SRFs in this population.

METHODS: A SRF screening tool was completed electronically by patients. Patients were screened for four core SRF domains (financial strain, housing instability, food insecurity, and transportation needs) and four supplemental SRF domains (physical inactivity, social isolation, stress, and depression). Data from the electronic health record were extracted for patients with at least one domain screened who were seen by participating rheumatology providers between January 1 and October 31, 2023. …

Rapid Development Of An Online Tracker To Communicate The Human Impact Of Abruptly Halting Pepfar Support, Brooke E Nichols, Elvin H Geng, Eric Moakley, Andrew N Phillips, Jeffrey W Imai-Eaton, John Stover, Edinah Mudimu, Anna Grimsrud

2020-Current year OA Pubs

No abstract provided.

Vitamin K Deficiency Bleeding In Children With Cholestatic Liver Disease: A Systematic Review And Meta-Analysis, Anusak Sakwit, Pongpak Pongphitcha, Patcharee Komvilaisak, Masayuki Ochiai, Daijiro Takahashi, Shutaro Suga, Ampaiwan Chuansumrit, Marisol Betensky, Stephen P Pereira, Amber Afzal, C Heleen Van Ommen, Neil Goldenberg, Sasivimol Rattanasiri, Nongnuch Sirachainan

2020-Current year OA Pubs

Vitamin K deficiency (VKD) in cholestatic liver disease affects up to 23% of pediatric patients. While several vitamin K (VK) prophylaxis regimens have been proposed, optimal therapeutic strategies remain undefined. The study aimed to identify the most effective VK prophylaxis for children with cholestatic liver disease. We conducted a systematic review of articles focusing on studies of children aged < 18 years with cholestatic liver disease who reported outcomes of either VKD or vitamin K deficiency bleeding (VKDB) after VK prophylaxis. The articles were sourced from PubMed, Scopus, and Embase. A meta-analysis was performed to determine the prevalence of VKD and the efficacy of each prophylactic protocol in preventing VKD/VKDB. The study was registered on PROSPERO (CRD 42021270048). Of the 889 articles, 37 were selected (2 comparative studies, 6 noncomparative studies, and 29 case reports/series). The results from the comparative studies indicated a lower incidence of VKD in the parenteral than that in the oral VK. The meta-analysis of the noncomparative studies showed the prevalence of VKD in high prothrombin induced by vitamin K absence-II group was 56% (95% CI, 45%-68%;

Decreased Voluntary Alcohol Intake And Ventral Striatal Epigenetic And Transcriptional Remodeling In Male Acss2 Ko Mice, Gabor Egervari, Greg Donahue, Natalia A Quijano Cardé, Desi C Alexander, Connor Hogan, Jessica K Shaw, Erica M Periandri, Vanessa Fleites, Mariella De Biasi, Shelley L Berger

2020-Current year OA Pubs

Metabolic-epigenetic interactions are emerging as key pathways in regulating alcohol-related transcriptional changes in the brain. Recently, we have shown that this is mediated by the metabolic enzyme Acetyl-CoA synthetase 2 (Acss2), which is nuclear and chromatin-bound in neurons. Mice lacking ACSS2 fail to deposit alcohol-derived acetate onto histones in the brain and show no conditioned place preference for ethanol reward. Here, we further explored the role of this pathway during voluntary alcohol intake. We found that Acss2 KO mice consume significantly less alcohol in a model of binge drinking, an effect primarily driven by males. Genome-wide transcriptional profiling of 7 …

Local Genetic Covariance Analysis With Lipid Traits Identifies Novel Loci For Early-Onset Alzheimer's Disease, Nicholas R. Ray, Joseph Bradley, Elanur Yilmaz, Caghan Kizil, Jiji T. Kurup, Eden R. Martin, Hans-Ulrich Klein, Brian W Kunkle, David A. Bennett, Philip L. De Jager, Alzheimer’S Disease Genetics Consortium, Gary W. Beecham, Carlos Cruchaga, Christiane Reitz

2020-Current year OA Pubs

The genetic component of early-onset Alzheimer disease (EOAD), accounting for ~10% of all Alzheimer's disease (AD) cases, is largely unexplained. Recent studies suggest that EOAD may be enriched for variants acting in the lipid pathway. The current study examines the shared genetic heritability between EOAD and the lipid pathway using genome-wide multi-trait genetic covariance analyses. Summary statistics were obtained from the GWAS meta-analyses of EOAD by the Alzheimer's Disease Genetics Consortium (n=19,668) and five blood lipid traits by the Global Lipids Genetics Consortium (n=1,320,016). The significant results were compared between the EOAD and lipids GWAS and genetic covariance analyses were …

Loncastuximab In High-Risk And Heavily Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Real-World Analysis From 21 Us Centers, Viktoriya Zelikson, Behzad Amoozgar, Brad Kahl, Et Al.

2020-Current year OA Pubs

Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab- teserine (Lonca) is an antibody-drug conjugate which was approved by the Food and Drug Administration for the treatment of patients with R/R DLBCL who have received at least two prior lines of therapy, based on the results of the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting. This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis comprises 187 patients with notably higher-risk baseline features compared to those of the …

Reward Neurocircuitry Predicts Longitudinal Changes In Alcohol Use Following Trauma Exposure, Cecilia A Hinojosa, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry posttrauma in humans. Neuroimaging markers may be particularly useful because they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. In this study, we aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure.

METHODS: Participants were recruited from U.S. emergency departments for the AURORA study (n = 286; …

Bi-Allelic Lamp3 Variants In Childhood Interstitial Lung Disease: A Surfactant-Related Disease, Camille Louvrier, F Sessions Cole, Jennifer A Wambach, Daniel J Wegner, Et Al.

2020-Current year OA Pubs

BACKGROUND: LAMP3 encodes a lysosomal membrane protein associated with lamellar bodies and has recently been proposed as a candidate gene for childhood interstitial lung diseases (chILD). Here, we identified two LAMP3 variants in a proband with chILD and performed functional validation of these variants as well as the previously reported variants to demonstrate the role of LAMP3 in pathology.

METHODS: LAMP3 variants were identified by exome sequencing. Ex vivo studies included mRNA analysis from nasal brushing and lung tissue and immunohistochemistry from lung biopsy. In vitro functional analyses in the A549 cell line included immunofluorescence staining and expression analysis of …

Effect Of Midwife-Led Pelvic Floor Muscle Training On Prolapse Symptoms And Quality Of Life In Women With Pelvic Organ Prolapse In Ethiopia: A Cluster-Randomized Controlled Trial, Melese Siyoum, Rahel Nardos, Biniyam Sirak, Theresa Spitznagle, Wondwosen Teklesilasie, Ayalew Astatkie

2020-Current year OA Pubs

BACKGROUND: Pelvic organ prolapse (POP) is a common condition that can significantly impact a woman's quality of life. Pelvic floor muscle training (PFMT) is recommended as a first-line conservative treatment for prolapse, but evidence on its effectiveness from low-resource settings is limited. This study aimed to assess the effect of midwife-led PFMT on prolapse symptoms and health-related quality of life (HRQoL) among women with mild-to-moderate POP in Ethiopia.

METHODS AND FINDINGS: A community-based, parallel-groups, two-arm cluster-randomized controlled trial was conducted in Dale and Wonsho districts of Sidama Region, Ethiopia. Women with symptomatic POP stages I-III were randomized by cluster to …

Treatment Of Non-Hodgkin Lymphoma With Point-Of-Care Manufactured Car T Cells: A Dual Institution, Phase 1 Trial, Armin Ghobadi, Linda Eissenberg, John Dipersio, Et Al.

2020-Current year OA Pubs

BACKGROUND: Point-of-care manufacture of chimeric antigen receptor (CAR)-T cells can significantly reduce the time from apheresis to infusion. We conducted a dual-institution phase I trial aimed evaluating the safety and feasibility of this manufacturing model.

METHODS: CASE 2417 was a phase I clinical trial. Adults with relapsed or refractory CD19 positive non-Hodgkin lymphoma (R/R NHL) treated with ≥2 prior systemic therapies were eligible. MB-CART-19 is an anti-CD19 CAR T-cell product manufactured using the CliniMACS Prodigy device with 4-1BB and CD3ζ costimulatory domains. Lymphodepletion included fludarabine 25 mg/m

FINDINGS: Thirty-one patients were enrolled between July 2018 and January 2021. Twenty-four (77%) …

Prehospital Cricothyrotomy: A Narrative Review Of Technical, Educational, And Operational Considerations For Procedure Optimization, Aaron J Lacy, Michael J Kim, James L Li, Alexander Croft, Erin E Kane, Jason C Wagner, Philip W Walker, Christine M Brent, Jeremy J Brywczynski, Amanda C Mathews, Brit Long, Alex Koyfman, Bridgette Svancarek

2020-Current year OA Pubs

BACKGROUND: Definitive airway management is a requisite skill in the prehospital setting, most often accomplished with either an endotracheal tube or supraglottic airway. When clinicians encounter a cannot oxygenate and cannot ventilate scenario, a patient's airway still must be secured. Prehospital cricothyrotomy is a high acuity, low frequency procedure used to secure the airway through the anterior neck. Patients who require cricothyrotomy often have significant comorbid conditions and mortality, and there can be a high rate of procedural complications. The ability to perform a cricothyrotomy is within the scope of practice for many prehospital clinicians and mastery of the procedure …

Sleep Disorders Five Years After Acute Provoked Neonatal Seizures, Renée A Shellhaas, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To evaluate whether abnormal sleep is associated with adverse outcomes for children who survived acute provoked neonatal seizures, and their parents.

STUDY DESIGN: This 9-center study prospectively followed newborns with acute provoked seizures. When children reached age 5 years, parents completed the Children's Sleep Habits Questionnaire (CSHQ), the Pediatric Sleep Questionnaire-Sleep Related Breathing Disorders (PSQ-SRBD) subscale, the Vineland Adaptive Behavior Scales-3, and the Hospital Anxiety Depression Scale. Children were also assessed with the Wechsler Preschool and Primary Scale of Intelligence-IV (WPPSI-IV). Spearman correlations and multivariable analyses were used to evaluate risk factors for sleep problems.

RESULTS: The mean CSHQ …

Sacubitril/Valsartan Attenuates Inflammation And Myocardial Fibrosis In Takotsubo-Like Cardiomyopathy, Jiangying Kuang, Zhiyi Jia, Tou Kun Chong, Jian Chen, Kan Liu, Xin Wang, Zhaohua Li, Jing Zhang, Yanru Kong, Lin Deng, Martin Cadieras, Yuanyuan Sun, Rong Sun, Qinghua Lu, Yusheng Liu

2020-Current year OA Pubs

BACKGROUND: Takotsubo syndrome (TTS) primarily manifests as a cardiomyopathy induced by physical or emotional stress, remains a poorly understood condition with no established treatments. In this study, we investigated the potential of sacubitril/valsartan (sac/val) to increase the survival of TTS patients and reduce inflammation and myocardial fibrosis in experimental models.

AIM: This study aimed to evaluate whether sac/val could improve survival rates in TTS patients, mitigate cardiac remodeling in vivo, and explore its anti-inflammatory and antifibrotic mechanisms in vitro.

METHODS: Clinical cases from the Chinese Takotsubo syndrome (ChiTTS) registry were analyzed to assess patient survival rates. In addition, we used …

Exploring The Differences Between Brca Mutated And Hrwild-Type High Grade Serous Ovarian Cancer: A Multiomic Analysis, Ayesha B Alvero, Sharon Wu, Alex Farrell, Seongho Kim, John J Wallbillich, Ira Winer, Robert Morris, David Spetzler, Matthew L Anderson, Alberto Puccini, Nathaniel L Jones, Thomas J Herzog, Premal H Thaker, Gil Mor, Radhika P Gogoi

2020-Current year OA Pubs

OBJECTIVE: The purpose of this study was to evaluate the transcriptomic profile of BRCA1 mutant (BRCA1mut) and BRCA2 mutant (BRCA2mut) HGSOC compared to homologous recombination wild-type (HRwt) tumors utilizing the CARIS database.

METHODS: Next-generation and Whole Transcriptome Sequencing (WTS; Caris Life Sciences, Phoenix, AZ) was performed on a total of 2745 HGSOC tumor samples. BRCA mutations were defined as variants resulting in loss-of-function of the protein and HRwt was defined as samples wildtype for aberrations in both BRCA1 and BRCA2, as well as for 28 other HR genes. HRwt group was further classified into HRwt/LOH-low (< 16 %) and HRwt/LOH-high (≥16 %). Genomic analysis consists of mutation analysis and measurements of TMB and MSI. Transcriptomic analysis included identification of Differentially expressed genes (DEGs), GSEA and immune deconvolution.

RESULTS: We identified 519 …

Detection Of Alternative Lengthening Of Telomeres Via Chromogenic In Situ Hybridization For The Prognostication Of Pannets And Other Neoplasms, Christopher M Heaphy, Ta-Chiang Liu, Dengfeng Cao, Et Al.

2020-Current year OA Pubs

Molecular studies have shown alternative lengthening to telomeres (ALT) to be an important prognostic biomarker of shorter relapse-free survival (RFS) for patients with pancreatic neuroendocrine tumors (PanNETs) and other neoplasms. However, the preferred method of detecting ALT in tissue is by fluorescence in situ hybridization (FISH), which has several clinical limitations. These issues necessitate the creation of a chromogenic ALT assay that can be easily implemented into routine practice. A chromogenic in situ hybridization (CISH) assay was developed using genetically modified osteosarcoma cell lines, 20 normal pancreata, 20 ALT-positive PanNETs, and 20 ALT-negative PanNETs. Thereafter, it was validated on a …

Cropland Associated With Risk Of Parkinson's Disease In The Northern Great Plains, Brittany Krzyzanowski, Kassu M Beyene, Susan Searles Nielsen, Jordan A Killion, Brad A Racette

2020-Current year OA Pubs

INTRODUCTION: We sought to identify regional associations between cropland density and crop types and PD in the U.S.

METHODS: We conducted a population-based study of 21,639,190 Medicare beneficiaries, 89,790 with incident PD in 2009. We used county-level geographic weighted regression (GWR) to identify region(s) of the U.S. where the association between PD RR and cropland density was strongest. In a broad region identified by GWR in which cropland density was associated with PD, we performed logistic regression using individual-level beneficiary data (2733 cases and 805,984 non-cases) with high-resolution cropland density data. We adjusted for age, sex, race, smoking, healthcare utilization, …

Combining Radioembolization And Immune Checkpoint Inhibitors For The Treatment Of Hepatocellular Carcinoma: The Quest For Synergy, Christopher D Malone, Suryansh Bajaj, Aiwu He, Kabir Mody, Ryan M Hickey, Ammar Sarwar, Sunil Krishnan, Tushar C Patel, Beau B Toskich

2020-Current year OA Pubs

Hepatocellular carcinoma is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of yttrium-90 (

Identification Of A New Coq4 Spliceogenic Variant Causing Severe Primary Coenzyme Q Deficiency, María Alcázar-Fabra, Abigail K Bartlett, David J Pagliarini, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Primary Coenzyme Q (CoQ) deficiency caused by

MATERIALS AND METHODS: Both fibroblasts from a proband with

RESULTS: Here, we report the case of a subject harboring a new variant of the

CONCLUSION: Our results highlight the importance of expanding the genetic analysis beyond the coding sequence to reduce the misdiagnosis of primary CoQ deficiency patients.

Rest And Rinse: Sleeping Rhythms Drive Brain Detox, Leon C D Smyth, Benjamin A Plog, Jonathan Kipnis

2020-Current year OA Pubs

Sleep is a major driver of waste clearance from the brain, but the mechanisms underpinning brain cleansing during sleep, which are also important for immunological functions, are poorly understood. Recent mouse work by Hauglund et al. shows how oscillatory surges in norepinephrine (NE) during sleep drive vascular pulsation and cerebrospinal fluid (CSF) movement to cleanse the brain.

The Current State Of Outcome Measurements After Peripheral Nerve Injury: A Systematic Review, Abigail G Carey-Ewend, Jake H Goldfarb, Zachary D Randall, David M Brogan, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: The manner in which outcomes are reported after peripheral nerve injury (PNI) varies tremendously and often centers on surgeon-manual muscle testing. The purpose of our systematic review was to quantify the use of outcome measures after PNI in the contemporary literature (published in 2008 and beyond) and to evaluate which domains of recovery are assessed most frequently.

METHODS: With the assistance of a medical librarian, we performed a systematic review of the literature published in or after 2008 (to represent the last 15 years) for patients with upper-extremity PNI. We excluded articles with < 5 participants, minors, brachial plexus or digital nerve injuries, compressive neuropathies, or < 6 months of follow-up. Data were extracted to identify which outcome measures were used in each study, categorizing the outcome measures under the domains of motor, sensory, function, and pain.

RESULTS: Of the 4 outcome domains …

The Single-Cell Immune Profile Throughout Gestation And Its Potential Value For Identifying Women At Risk For Spontaneous Preterm Birth, Dorien Feyaerts, Maïgane Diop, Jose Galaz, Jakob F Einhaus, Petra C Arck, Anke Diemert, Virginia D Winn, Mana Parast, Cynthia Gyamfi-Bannerman, Jelmer R Prins, Nardhy Gomez-Lopez, Ina A Stelzer

2020-Current year OA Pubs

Precisely timed immune adaptations, observed in the maternal circulation, underpin the notion of an immune clock of human pregnancy that supports its successful progression and completion at delivery. This immune clock is divided into three immunological phases, with the first phase starting at the time of conception and implantation, shifting into the second phase that supports homeostasis and tolerance throughout pregnancy, and culminating in the last phase of labor and parturition. Disruptions of this immune clock are reported in pregnancy complications such as spontaneous preterm birth. However, our understanding of the immune clock preceding spontaneous preterm birth remains scattered. In …

Cardiotoxicity Following Thoracic Radiotherapy For Lung Cancer, Gerard M Walls, Carmen Bergom, Joshua D Mitchell, Stacey L Rentschler, Geoffrey D Hugo, Pamela P Samson, Clifford G Robinson

2020-Current year OA Pubs

Radiotherapy is the standard of care treatment for unresectable NSCLC, combined with concurrent chemotherapy and adjuvant immunotherapy. Despite technological advances in radiotherapy planning and delivery, the risk of damage to surrounding thoracic tissues remains high. Cardiac problems, including arrhythmia, heart failure and ischaemic events, occur in 20% of patients with lung cancer who undergo radiotherapy. As survival rates improve incrementally for this cohort, minimising the cardiovascular morbidity of RT is increasingly important. Problematically, the reporting of cardiac endpoints has been poor in thoracic radiotherapy clinical trials, and retrospective studies have been limited by the lack of standardisation of nomenclature and …

Emergence Of Infective Endocarditis Due To Serratia Spp.: Results Of A Multicenter Cohort, Leah Madeline Mccrary, Douglas Slain, Sunish Shah, Bobbi Jo Stoner, Ashley H Marx, Asher J Schranz

2020-Current year OA Pubs

BACKGROUND: Infective endocarditis due to

METHODS: This was a retrospective analysis of adults treated for S-IE at 4 academic health systems in different US states from 2015 to 2021. Multivariable logistic regression analyzed the association of inpatient mortality with procedural management and combination antibiotic treatment.

RESULTS: A total of 159 cases of S-IE were identified with a qualitative overall increase across the period, and a peak in 2019, although trends varied by site. Seventy-five were due to IDU, 57% involved a single left-sided valve, and inpatient mortality was 21%. In adjusted analyses, including 117 cases from 3 sites, lower inpatient …

Zanubrutinib Versus Bendamustine And Rituximab In Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up Of Sequoia, Mazyar Shadman, Brad S Kahl, Et Al.

2020-Current year OA Pubs

No abstract provided.

"Inpatient Pharmacological Thromboprophylaxis In The Antepartum Period: An Argument For Universal Thromboprophylaxis", Julia Burd, Amanda Zofkie

2020-Current year OA Pubs

Venous thromboembolism (VTE), a largely preventable condition, accounts for almost 15% of maternal mortalities. The physiologic changes of pregnancy, including quantitative changes in coagulation factors and compression of vasculature by the gravid uterus, cause an increase in risk of VTE, including deep vein thromboembolism (DVT), pulmonary embolism, and stroke (CVA). Long term antepartum admission for preeclampsia, preterm prelabor rupture of membranes (PPROM) or other high-risk pregnancy needs present additional risk factors for VTE due to the patient's medical condition and their inpatient status. Given the near-universal support for anticoagulation in patients with a history of venous thromboembolism or high-risk thrombophilia, …

Myelin-Reactive Cd8+ T Cells Influence Conventional Dendritic Cell Subsets Towards A Mature And Regulatory Phenotype In Experimental Autoimmune Encephalomyelitis, Mohit Upadhye, Connor R Wilhelm, Kai J Rogers, Chakrapani Vemulawada, Nicholas Borcherding, Alexander W Boyden, Kevin L Legge, Nitin J Karandikar

2020-Current year OA Pubs

Multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system, is modeled in mice as experimental autoimmune encephalomyelitis (EAE). While CD4

Norovirus Co-Opts Ninj1 For Selective Protein Secretion, Jaewon Song, Wandy L Beatty, Anthony Orvedahl, Et Al.

2020-Current year OA Pubs

Plasma membrane rupture by Ninjurin-1 (NINJ1) executes programmed cell death, releasing large cellular damage-associated molecular patterns (DAMPs). However, the regulation and selectivity of NINJ1-mediated DAMP release remain unexplored. Here, we uncover that murine norovirus (MNoV) strategically co-opts NINJ1 to selectively release the intracellular viral protein NS1, while NINJ1-mediated plasma membrane rupture simultaneously bulk-releases various cellular DAMPs. Host caspase-3 cleaves the precursor NS1/2, leading to NS1 secretion via an unconventional pathway. An unbiased CRISPR screen identifies NINJ1 as an essential factor for NS1 secretion. During infection, NINJ1 is recruited to the viral replication site, where it oligomerizes and forms speckled bodies, …