Medicine and Health Sciences Commons^™

Peptidoglycan Deacetylation Controls Type Iv Secretion And The Intracellular Survival Of The Bacterial Pathogen Legionella Pneumophila, David Boamah, Michael C Gilmore, Sarah Bourget, Anushka Ghosh, Mohammad J Hossain, Joseph P Vogel, Felipe Cava, Tamara J O'Connor

2020-Current year OA Pubs

Peptidoglycan is a critical component of the bacteria cell envelope. Remodeling of the peptidoglycan is required for numerous essential cellular processes and has been linked to bacterial pathogenesis. Peptidoglycan deacetylases that remove the acetyl group of the

Brain Abscess And Stroke In Children And Adults With Hereditary Hemorrhagic Telangiectasia: Analysis Of A Large National Claims Database, Andrew J. White, Itay Marmor, Kate M. Peacock, Katelin B. Nickel, Jessica Zavadil, Margaret A. Olsen

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in transforming growth factor-β signaling pathway-related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adults and children with HHT.

METHODS: We conducted a case-control study among participants aged 1-64 years in the MarketScan Commercial (2006-2019) and Multistate Medicaid Databases (2011-2019). We identified cases with HHT using

RESULTS: …

Novel Vaccine Against Pathological Pyroglutamate-Modified Amyloid Beta For Prevention Of Alzheimer's Disease, Karen Zagorski, Olga King, Armine Hovakimyan, Irina Petrushina, Tatevik Antonyan, Gor Chailyan, Manush Ghazaryan, Krzysztof L Hyrc, Jean Paul Chadarevian, Hayk Davtyan, Mathew Blurton-Jones, David H Cribbs, Michael G Agadjanyan, Anahit Ghochikyan

2020-Current year OA Pubs

Post-translationally modified N-terminally truncated amyloid beta peptide with a cyclized form of glutamate at position 3 (pE

Sustained Alternate-Day Fasting Potentiates Doxorubicin Cardiotoxicity, Mualla Ozcan, Zhen Guo, Carla Valenzuela Ripoll, Ahmed Diab, Antonino Picataggi, David Rawnsley, Aynaz Lotfinaghsh, Carmen Bergom, Jeff Szymanski, Daniel Hwang, Jie Zheng, Robert J Hayashi, Pamela K Woodard, Attila Kovacs, Joel Schilling, Babak Razani, Abhinav Diwan, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Fasting strategies are under active clinical investigation in patients receiving chemotherapy. Prior murine studies suggest that alternate-day fasting may attenuate doxorubicin cardiotoxicity and stimulate nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis. In this study, human heart tissue from patients with doxorubicin-induced heart failure demonstrated increased nuclear TFEB protein. In mice treated with doxorubicin, alternate-day fasting or viral TFEB transduction increased mortality and impaired cardiac function. Mice randomized to alternate-day fasting plus doxorubicin exhibited increased TFEB nuclear translocation in the myocardium. When combined with doxorubicin, cardiomyocyte-specific TFEB overexpression provoked cardiac remodeling, while systemic …

Inequities In Treatments And Outcomes Among Patients Hospitalized With Hypertrophic Cardiomyopathy In The United States, Daniel Y Johnson, R J Waken, Daniel K Fox, Gmerice Hammond, Karen E Joynt Maddox, Sharon Cresci

2020-Current year OA Pubs

Background Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies, sociodemographic factors have been associated with disparities in septal reduction therapy, but little is known about the association of sociodemographic factors with HCM treatments and outcomes more broadly. Methods and Results Using the National Inpatient Survey from 2012 to 2018, HCM diagnoses and procedures were identified by

Connective Tissue Presentation In Two Families Expands The Phenotypic Spectrum Of Pyroxd1 Disorders, Frances J Evesson, Gregory Dziaduch, Samantha J Bryen, Francesca Moore, Sara Pittman, Beena Devanapalli, Leigh B Waddell, Monique M Ryan, Manoj P Menezes, Conrad C Weihl, Adviye Ayper Tolun, Craig Zaidman, Helen Young, Lesley C Adès, Sandra T Cooper

2020-Current year OA Pubs

Recessive variants in the oxidoreductase PYROXD1 are reported to cause a myopathy in 22 affected individuals from 15 families. Here, we describe two female probands from unrelated families presenting with features of a congenital connective tissue disorder including osteopenia, blue sclera, soft skin, joint hypermobility and neuromuscular junction dysfunction in addition to known features of PYROXD1 myopathy including respiratory difficulties, weakness, hypotonia and oromotor dysfunction. Proband AII:1 is compound heterozygous for the recurrent PYROXD1 variant Chr12(GRCh38):g.21452130A>G;NM_024854.5:c.464A>G;p.(N155S) and Chr12(GRCh38):g.21462019_21462022del;NM_024854.5:c.892_895del;p.(V298Mfs*4) and proband BII:1 is compound heterozygous for Chr12(GRCh38):g.21468739-21468741del;NM_024854.5:c.1488_1490del;p.(E496del) and Chr12(GRCh38):g.21467619del;NM_024854.5:c.1254+1del. RNA studies demonstrate c.892_895del;p.(V298Mfs*4) is targeted by nonsense mediated decay …

Stromal And Therapy-Induced Macrophage Proliferation Promotes Pdac Progression And Susceptibility To Innate Immunotherapy, Chong Zuo, John M Baer, Brett L Knolhoff, Jad I Belle, Xiuting Liu, Angela Alarcon De La Lastra, Graham D Hogg, Natalie L Kingston, Marcus A Breden, Paarth B Dodhiawala, Daniel Cui Zhou, Varintra E Lander, C Alston James, Li Ding, Kian-Huat Lim, Ryan C Fields, William G Hawkins, Jason D Weber, Guoyan Zhao, David G Denardo, Et Al.

2020-Current year OA Pubs

Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling …

Clinical Characteristics And Treatment Patterns Of Pregnant Women With Hypertension In Primary Care In The Federal Capital Territory Of Nigeria: Cross-Sectional Results From The Hypertension Treatment In Nigeria Program, Zainab Mahmoud, Ikechukwu A Orji, Gabriel L Shedul, Kasarachi Aluka-Omitiran, Nanna Ripiye, Blessing Akor, Helen Eze, Tunde Ojo, Guhan Iyer, Abigail S Baldridge, Lisa R Hirschhorn, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

BACKGROUND: Hypertensive disorders of pregnancy, including hypertension, are a leading cause of maternal mortality in Nigeria. However, there is a paucity of data on pregnant women with hypertension who receive care in primary health care facilities. This study presents the results from a cross-sectional analysis of pregnant women enrolled in the Hypertension Treatment in Nigeria Program which is aimed at integrating and strengthening hypertension care in primary health care centres.

METHODS: A descriptive analysis of the baseline results from the Hypertension Treatment in Nigeria Program was performed. Baseline blood pressures, treatment and control rates of pregnant women were analysed and …

Intrinsic Tgf-Β Signaling Attenuates Proximal Tubule Mitochondrial Injury And Inflammation In Chronic Kidney Disease, Merve Kayhan, Judith Vouillamoz, Daymé Gonzalez Rodriguez, Milica Bugarski, Yasutaka Mitamura, Julia Gschwend, Christoph Schneider, Andrew Hall, David Legouis, Cezmi A Akdis, Leary Peter, Hubert Rehrauer, Leslie Gewin, Roland H Wenger, Stellor Nlandu Khodo

2020-Current year OA Pubs

Excessive TGF-β signaling and mitochondrial dysfunction fuel chronic kidney disease (CKD) progression. However, inhibiting TGF-β failed to impede CKD in humans. The proximal tubule (PT), the most vulnerable renal segment, is packed with giant mitochondria and injured PT is pivotal in CKD progression. How TGF-β signaling affects PT mitochondria in CKD remained unknown. Here, we combine spatial transcriptomics and bulk RNAseq with biochemical analyses to depict the role of TGF-β signaling on PT mitochondrial homeostasis and tubulo-interstitial interactions in CKD. Male mice carrying specific deletion of Tgfbr2 in the PT have increased mitochondrial injury and exacerbated Th1 immune response in …

Combinatorial Bcl2 Family Expression In Acute Myeloid Leukemia Stem Cells Predicts Clinical Response To Azacitidine/Venetoclax, Alexander Waclawiczek, Darja Karpova, Et Al.

2020-Current year OA Pubs

UNLABELLED: The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based "Mediators of …

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, C Charles Gu, Et Al.

2020-Current year OA Pubs

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …

Altered Signaling And Desensitization Responses In Pth1r Mutants Associated With Eiken Syndrome, Ignacio Portales-Castillo, Thomas Dean, Ross W Cheloha, Brendan A Creemer, Jean-Pierre Vilardaga, Sofya Savransky, Ashok Khatri, Harald Jüppner, Thomas J Gardella

2020-Current year OA Pubs

The parathyroid hormone receptor type 1 (PTH1R) is a G protein-coupled receptor that plays key roles in regulating calcium homeostasis and skeletal development via binding the ligands, PTH and PTH-related protein (PTHrP), respectively. Eiken syndrome is a rare disease of delayed bone mineralization caused by homozygous PTH1R mutations. Of the three mutations identified so far, R485X, truncates the PTH1R C-terminal tail, while E35K and Y134S alter residues in the receptor's amino-terminal extracellular domain. Here, using a variety of cell-based assays, we show that R485X increases the receptor's basal rate of cAMP signaling and decreases its capacity to recruit β-arrestin2 upon …

Nonoperative Management Of Tibial Stress Fractures Result In Higher Return To Sport Rates Despite Increased Failure Versus Operative Management: A Systematic Review, Sabrina F Schundler, Garrett R Jackson, Johnathon R Mccormick, Trevor Tuthill, Jonathan S Lee, Anjay Batra, Harkirat Jawanda, Daniel J Kaplan, Jimmy Chan, Derrick M Knapik, Nikhil N Verma, Jorge Chahla

2020-Current year OA Pubs

PURPOSE: To compare return to sport (RTS) rates and complications after nonoperative versus operative management of tibial stress fractures.

METHODS: A literature search was conducted per the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using EMBASE, PubMed, and Scopus computerized data from database inception to February 2023. Studies evaluating RTS sport rates and complications after nonoperative or operative management of tibial stress fractures were included. Failure was defined as defined by persistent stress fracture line seen on radiographic imaging. Study quality was assessed using the Modified Coleman Methodology Score.

RESULTS: Twenty-two studies consisting of 341 patients …

Language Exposure During Infancy Is Negatively Associated With White Matter Microstructure In The Arcuate Fasciculus, Katiana A Estrada, Sharnya Govindaraj, Hervé Abdi, Luke E Moraglia, Jason J Wolff, Shoba Sreenath Meera, Stephen R Dager, Robert C Mckinstry, Martin A Styner, Lonnie Zwaigenbaum, Joseph Piven, Meghan R Swanson, Ibis Network

2020-Current year OA Pubs

Decades of research have established that the home language environment, especially quality of caregiver speech, supports language acquisition during infancy. However, the neural mechanisms behind this phenomenon remain under studied. In the current study, we examined associations between the home language environment and structural coherence of white matter tracts in 52 typically developing infants from English speaking homes in a western society. Infants participated in at least one MRI brain scan when they were 3, 6, 12, and/or 24 months old. Home language recordings were collected when infants were 9 and/or 15 months old. General linear regression models indicated that …

Central Carbon Flux Controls Growth/Damage Balance For Streptococcus Pyogenes, Joseph A. Merriman, Wei Xu, Michael G. Caparon

2020-Current year OA Pubs

Microbial pathogens balance growth against tissue damage to achieve maximum fitness. Central carbon metabolism is connected to growth, but how it influences growth/damage balance is largely unknown. Here we examined how carbon flux through the exclusively fermentative metabolism of the pathogenic lactic acid bacterium Streptococcus pyogenes impacts patterns of growth and tissue damage. Using a murine model of soft tissue infection, we systematically examined single and pair-wise mutants that constrained carbon flux through the three major pathways that S. pyogenes employs for reduction of the glycolytic intermediate pyruvate, revealing distinct disease outcomes. Its canonical lactic acid pathway (via lactate dehydrogenase) …

Molecular Imaging Of Bone Metastasis, Eliana Khojasteh, Farrokh Dehdashti, Monica Shokeen

2020-Current year OA Pubs

Recent advances in molecularly targeted modular designs for in vivo imaging applications has thrusted open possibilities of investigating deep molecular interactions non-invasively and dynamically. The shifting landscape of biomarker concentration and cellular interactions throughout pathological progression requires quick adaptation of imaging agents and detection modalities for accurate readouts. The synergy of state of art instrumentation with molecularly targeted molecules is resulting in more precise, accurate and reproducible data sets, which is facilitating investigation of several novel questions. Small molecules, peptides, antibodies and nanoparticles are some of the commonly used molecular targeting vectors that can be applied for imaging as well …

Characterization Of Cell-Type Specific Circular Rnas Associated With Colorectal Cancer Metastasis, Sidi Zhao, Amy Ly, Jacqueline L Mudd, Emily B Rozycki, Jace Webster, Emily Coonrod, Ghofran Othoum, Jingqin Luo, Ha X Dang, Ryan C Fields, Christopher A Maher

2020-Current year OA Pubs

Colorectal cancer (CRC) is the most common gastrointestinal malignancy and a leading cause of cancer deaths in the United States. More than half of CRC patients develop metastatic disease (mCRC) with an average 5-year survival rate of 13%. Circular RNAs (circRNAs) have recently emerged as important tumorigenesis regulators; however, their role in mCRC progression remains poorly characterized. Further, little is known about their cell-type specificity to elucidate their functions in the tumor microenvironment (TME). To address this, we performed total RNA sequencing (RNA-seq) on 30 matched normal, primary and metastatic samples from 14 mCRC patients. Additionally, five CRC cell lines …

A Functional Genomics Pipeline To Identify High-Value Asthma And Allergy Cpgs In The Human Methylome, Andréanne Morin, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

BACKGROUND: DNA methylation of cytosines at cytosine-phosphate-guanine (CpG) dinucleotides (CpGs) is a widespread epigenetic mark, but genome-wide variation has been relatively unexplored due to the limited representation of variable CpGs on commercial high-throughput arrays.

OBJECTIVES: To explore this hidden portion of the epigenome, this study combined whole-genome bisulfite sequencing with in silico evidence of gene regulatory regions to design a custom array of high-value CpGs. This study focused on airway epithelial cells from children with and without allergic asthma because these cells mediate the effects of inhaled microbes, pollution, and allergens on asthma and allergic disease risk.

METHODS: This study …

Mri Findings Associated With Anterior Cruciate Ligament Tears In National Football League Athletes, Robert H. Brophy, Jon C. Baker, Jana M. Crain, Mackenzie M. Herzog, Ben Stollberg, Edward M. Wojtys, Christina D. Mack

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament (ACL) tears are a high-frequency injury requiring a lengthy recovery in professional American football players. Concomitant pathology associated with ACL tears as identified on magnetic resonance imaging (MRI) is not well understood in these athletes.

PURPOSE: To describe the MRI findings of concomitant injuries associated with ACL tears among athletes in the National Football League (NFL).

STUDY DESIGN: Cross-sectional study; Level of evidence, 3.

METHODS: Of 314 ACL injuries in NFL athletes from 2015 through 2019, 191 complete MRI scans from the time of primary ACL injury were identified and reviewed by 2 fellowship-trained musculoskeletal radiologists. …

Finding Motifs Using Dna Images Derived From Sparse Representations, Shane K Chu, Gary D Stormo

2020-Current year OA Pubs

MOTIVATION: Motifs play a crucial role in computational biology, as they provide valuable information about the binding specificity of proteins. However, conventional motif discovery methods typically rely on simple combinatoric or probabilistic approaches, which can be biased by heuristics such as substring-masking for multiple motif discovery. In recent years, deep neural networks have become increasingly popular for motif discovery, as they are capable of capturing complex patterns in data. Nonetheless, inferring motifs from neural networks remains a challenging problem, both from a modeling and computational standpoint, despite the success of these networks in supervised learning tasks.

RESULTS: We present a …

Cat Lca-Crx Model, Homozygous For An Antimorphic Mutation Has A Unique Phenotype, Laurence M Occelli, Nicholas M Tran, Shiming Chen, Simon M Petersen-Jones

2020-Current year OA Pubs

PURPOSE: Mutations in the CRX transcription factor are associated with dominant retinopathies often with more severe macular changes. The CRX-mutant cat (Rdy-A182d2) is the only animal model with the equivalent of the critical retinal region for high-acuity vision, the macula. Heterozygous cats (CRXRdy/+) have a severe phenotype modeling Leber congenital amaurosis. This study reports the distinct ocular phenotype of homozygous cats (CRXRdy/Rdy).

METHODS: Gene expression changes were assessed at both mRNA and protein levels. Changes in globe morphology and retinal structure were analyzed.

RESULTS: CRXRdy/Rdy cats had high levels of mutant CRX mRNA and protein. The expression of photoreceptor target …

Acinetobacter Baumannii Atcc 17978 Encodes A Microcin System With Antimicrobial Properties For Contact-Independent Competition, Fabiana Bisaro, Howard A Shuman, Mario F Feldman, Michael J Gebhardt, Stefan Pukatzki

2020-Current year OA Pubs

No abstract provided.

Interleukin-18 Signaling Promotes Activation Of Hepatic Stellate Cells In Mouse Liver Fibrosis, Jana Knorr, Joel D. Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Nucleotide-binding oligomerization domain-like receptor-family pyrin domain-containing 3 (NLRP3) inflammasome activation has been shown to result in liver fibrosis. Mechanisms and downstream signaling remain incompletely understood. Here, we studied the role of IL-18 in hepatic stellate cells (HSCs), and its impact on liver fibrosis.

APPROACH AND RESULTS: We observed significantly increased serum levels of IL-18 (128.4 pg/ml vs. 74.9 pg/ml) and IL-18 binding protein (BP; 46.50 ng/ml vs. 15.35 ng/ml) in patients with liver cirrhosis compared with healthy controls. Single cell RNA sequencing data showed that an immunoregulatory subset of murine HSCs highly expresses Il18 and Il18r1 . …

Defects In Lysosomal Function And Lipid Metabolism In Human Microglia Harboring A Trem2 Loss Of Function Mutation, Fabia Filipello, Shih-Feng You, Farzaneh S Mirfakhar, Sidhartha Mahali, Bryan Bollman, Mariana Acquarone, Jacob A Marsh, Anirudh Sivaraman, Rita Martinez, Claudia Cantoni, Luca De Feo, Laura Ghezzi, Miguel A Minaya, Arun Renganathan, Anil G Cashikar, Wandy Beatty, Abhirami K Iyer, Marina Cella, Laura Piccio, Celeste M Karch, Et Al.

2020-Current year OA Pubs

TREM2 is an innate immune receptor expressed by microglia in the adult brain. Genetic variation in the TREM2 gene has been implicated in risk for Alzheimer's disease and frontotemporal dementia, while homozygous TREM2 mutations cause a rare leukodystrophy, Nasu-Hakola disease (NHD). Despite extensive investigation, the role of TREM2 in NHD pathogenesis remains poorly understood. Here, we investigate the mechanisms by which a homozygous stop-gain TREM2 mutation (p.Q33X) contributes to NHD. Induced pluripotent stem cell (iPSC)-derived microglia (iMGLs) were generated from two NHD families: three homozygous TREM2 p.Q33X mutation carriers (termed NHD), two heterozygous mutation carriers, one related non-carrier, and two …

Patients With Stricturing Or Penetrating Crohn's Disease Phenotypes Report High Disease Burden And Treatment Needs, Yanni Fan, Ling Zhang, Negar Omidakhsh, Rhonda L Bohn, Jennifer S Thompson, Kimberly G Brodovicz, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Crohn's disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited.

METHODS: We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference.

RESULTS: A total of 1557 patients were identified: CD-I (n = 674, 43.3%), …

Biological Rhythms In Covid-19 Vaccine Effectiveness In An Observational Cohort Study Of 1.5 Million Patients, Guy Hazan, Or A. Duek, Hillel Alapi, Huram Mok, Alex Ganninger, Elaine Ostendorf, Carrie Gierasch, Gabriel Chodick, David Greenberg, Jeffrey A. Haspel

2020-Current year OA Pubs

BACKGROUNDCircadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.METHODSWe retrospectively analyzed a large Israeli cohort with timestamped COVID-19 vaccinations (n = 1,515,754 patients over 12 years old, 99.2% receiving BNT162b2). Endpoints included COVID-19 breakthrough infection and COVID-19-associated emergency department visits and hospitalizations. Our main comparison was among patients vaccinated during morning (800-1159 hours), afternoon (1200-1559 hours), or evening hours (1600-1959 hours). We employed Cox regression to adjust for differences in age, sex, and comorbidities.RESULTSBreakthrough infections differed based on …

American Academy Of Orthopaedic Surgeons Clinical Practice Guideline Summary: Management Of Anterior Cruciate Ligament Injuries, Robert H. Brophy, Kent Jason Lowry

2020-Current year OA Pubs

Management of Anterior Cruciate Ligament Injuries : Evidence-based Clinical Practice Guideline is based on a systematic review of published studies for the treatment of anterior cruciate ligament injurie in both skeletally mature and immature patients. This guideline contains eight recommendations and seven options to assist orthopaedic surgeons and all qualified physicians managing patients with ACL injuries based on the best current available evidence. It is also intended to serve as an information resource for professional healthcare practitioners and developers of practice guidelines and recommendations. In addition to providing pragmatic practice recommendations, this guideline also highlights gaps in the literature and …

Terrorist Attacks Against Sports Venues: Emerging Trends And Characteristics Spanning 50 Years, Grace R Rahman, Gregory N Jasani, Stephen Y Liang

2020-Current year OA Pubs

INTRODUCTION: Sports venues foster community and support local economies. Due to their capacity to host hundreds to thousands of spectators, sports venues are vulnerable to becoming targets of terrorism. Types of venues targeted, regional trends, and methods of attack employed world-wide have not been well-described.

METHODS: A search of the Global Terrorism Database (GTD) was conducted from 1970 through the end of 2019. Pre-coded variables for target type "business" and target subtype "entertainment/cultural/stadium/casino" were used to identify attacks involving venues where sports events might be viewed by spectators as part of an audience. Sports venues were specifically identified using the …

Genomic Approaches To Cancer And Minimal Residual Disease Detection Using Circulating Tumor Dna, Nicholas P. Semenkovich, Jeffrey J. Szymanski, Noah Earland, Pradeep S. Chauhan, Bruna Pellini, Aadel A. Chaudhuri

2020-Current year OA Pubs

Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma. However, ctDNA detection remains challenging in early-stage and post-treatment MRD settings where ctDNA levels are minuscule giving a high risk for false negative results, which is balanced with the risk of …

Deficiency In Galectin-3, -8, And -9 Impairs Immunity To Chronic Mycobacterium Tuberculosis Infection But Not Acute Infection With Multiple Intracellular Pathogens, Huntly M. Morrison, Wandy L. Beatty, Et Al.

2020-Current year OA Pubs

Macrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear. We found that Gal-9 binds directly to Mycobacterium tuberculosis (Mtb) and Salmonella enterica serovar Typhimurium (Stm) and localizes to Mtb in macrophages. To determine the combined contribution of membrane damage-sensing galectins to immunity, we generated …