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Epcam (Cd326) Regulates Intestinal Epithelial Integrity And Stem Cells Via Rho-Associated Kinase, Takeshi Ouchi, Sohshi Morimura, Lukas E Dow, Hiroyuki Miyoshi, Mark C Udey

Open Access Publications

Humans with biallelic inactivating mutations in Epithelial Cell Adhesion Molecule (EpCAM) develop congenital tufting enteropathy (CTE). To gain mechanistic insights regarding EpCAM function in this disorder, we prepared intestinal epithelial cell (IEC) organoids and spheroids. IEC organoids and spheroids were generated from

Intracranial Delivery Of Aav9 Gene Therapy Partially Prevents Retinal Degeneration And Visual Deficits In Cln6-Batten Disease Mice, Katherine A. White, Hemanth R. Nelvagal, Timothy A. Poole, Bin Lu, Tyler B. Johnson, Samantha Davis, Melissa A. Pratt, Jon Brudvig, Ana B. Assis, Shibi Likhite, Kathrin Meyer, Brian K. Kaspar, Jonathan D. Cooper, Shaomei Wang, Jill M. Weimer

Open Access Publications

No abstract provided.

Effects Of Dietary Restriction On Neuroinflammation In Neurodegenerative Diseases, Luigi Fontana, Laura Ghezzi, Anne H. Cross, Laura Piccio

Open Access Publications

Recent and accumulating work in experimental animal models and humans shows that diet has a much more pervasive and prominent role than previously thought in modulating neuroinflammatory and neurodegenerative mechanisms leading to some of the most common chronic central nervous system (CNS) diseases. Chronic or intermittent food restriction has profound effects in shaping brain and peripheral metabolism, immunity, and gut microbiome biology. Interactions among calorie intake, meal frequency, diet quality, and the gut microbiome modulate specific metabolic and molecular pathways that regulate cellular, tissue, and organ homeostasis as well as inflammation during normal brain aging and CNS neurodegenerative diseases, including …

Preliminary, Real-World, Multicenter Experience With Omadacycline For Mycobacterium Abscessus Infections, Taylor Morrisette, Sara Alosaimy, Julie V. Philley, Carly Wadle, Catessa Howard, Andrew J. Webb, Michael P. Veve, Melissa L. Barger, Jeannette Bouchard, Tristan W. Gore, Abdalhamid M. Lagnf, Iman Ansari, Carlos Mejia-Chew, Keira A. Cohen, Michael J. Rybak

Open Access Publications

Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen for

How The Field Of Infectious Diseases Can Leverage Digital Strategy And Social Media Use During A Pandemic, Jasmine R. Marcelin, Nicolás Cortés-Penfield, Carlos Del Rio, Angel Desai, Ignacio Echenique, Bruno Granwehr, Folake Lawal, Kevin Kuriakose, Dong Heun Lee, Maricar Malinis, Diandra Ruidera, Javeed Siddiqui, Andrej Spec, Talia H. Swartz

Open Access Publications

Rapid information dissemination is critical in a world changing rapidly due to global threats. Ubiquitous internet access has created new methods of information dissemination that are rapid, far-reaching, and universally accessible. However, inaccuracies may accompany rapid information dissemination, and rigorous evaluation of primary data through various forms of peer review is crucial. In an era in which high-quality information can save lives, it is critical that infectious diseases specialists are well versed in digital strategy to effectively disseminate information to colleagues and the community and diminish voices spreading misinformation. In this study, we review how social media can be used …

Chemoprevention Agents To Reduce Mammographic Breast Density In Premenopausal Women: A Systematic Review Of Clinical Trials, Ana S. Salazar, Malika Rakhmankulova, Laura E. Simon, Adetunji T. Toriola

Open Access Publications

Background: Higher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts.

Methods: We searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were …

Ash Isth Nhf Wfh 2021 Guidelines On The Diagnosis Of Von Willebrand Disease, Paula D. James, Jorge Di Paola, Et Al.

Open Access Publications

No abstract provided.

Nav1.3 And Fgf14 Are Primary Determinants Of The Ttx-Sensitive Sodium Current In Mouse Adrenal Chromaffin Cells, Pedro L. Martinez-Espinosa, Chengtao Yang, Xiao-Ming Xia, Christopher J. Lingle

Open Access Publications

Adrenal chromaffin cells (CCs) in rodents express rapidly inactivating, tetrodotoxin (TTX)-sensitive sodium channels. The resulting current has generally been attributed to Nav1.7, although a possible role for Nav1.3 has also been suggested. Nav channels in rat CCs rapidly inactivate via two independent pathways which differ in their time course of recovery. One subpopulation recovers with time constants similar to traditional fast inactivation and the other ∼10-fold slower, but both pathways can act within a single homogenous population of channels. Here, we use Nav1.3 KO mice to probe the properties and molecular components of Nav current in CCs. We find that …

American Society Of Hematology 2021 Guidelines On The Use Of Anticoagulation For Thromboprophylaxis In Patients With Covid-19, Adam Cuker, Kristen M. Sanfilippo, Et Al.

Open Access Publications

No abstract provided.

Brain Network Motifs Are Markers Of Loss And Recovery Of Consciousness, Catherine Duclos, Danielle Nadin, Yacine Mahdid, Vijay Tarnal, Paul Picton, Giancarlo Vanini, Goodarz Golmirzaie, Ellen Janke, Michael S. Avidan, Max B. Kelz, George A. Mashour, Stefanie Blain-Moraes

Open Access Publications

No abstract provided.

The Ideological Divide In Confidence In Science And Participation In Medical Research, Matthew Gabel, Jonathan Gooblar, Catherine M. Roe, John C. Morris

Open Access Publications

No abstract provided.

Glucosamine And Chondroitin Use In Relation To C-Reactive Protein Concentration: Results By Supplement Form, Formulation, And Dose, Elizabeth D. Kantor, Kelli O'Connell, Mengmeng Du, Chao Cao, Xuehong Zhang, Dong Hoon Lee, Yin Cao, Edward L. Giovannucci

Open Access Publications

No abstract provided.

Dynamic Patterns Of Yap1 Expression And Cellular Localization In The Developing And Injured Utricle, Vikrant Borse, Matthew Barton, Harry Arndt, Tejbeer Kaur, Mark E. Warchol

Open Access Publications

No abstract provided.

Long Runs Of Homozygosity Are Associated With Alzheimer’S Disease, Sonia Moreno-Grau, Maria Victoria Fernández, Fabiana Farias, John P. Budde, Carlos Cruchaga, O. Maroñas, Et Al.

Open Access Publications

No abstract provided.

Pd‑L1 Expression In Angiomatoid Fbrous Histiocytoma, Joshua Byers, Hong Yin, Heather Rytting, Suzanna Logan, Mai He, Zhongxin Yu, Dehua Wang, Mikako Warren, Shamlal Mangray, Louis P. Dehner, Shengmei Zhou

Open Access Publications

No abstract provided.

Cardiovascular Assessment Tool For Breast Cancer Survivors And Oncology Providers: Usability Study, Kathryn E Weaver, Heidi D Klepin, Brian J Wells, Emily V Dressler, Karen M Winkfield, Zanetta S Lamar, Tiffany P Avery, Nicholas M Pajewski, W Gregory Hundley, Aimee Johnson, Eleanor C Davidson, Marcelo Lopetegui, Randi E Foraker

Open Access Publications

BACKGROUND: Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors' attainment or maintenance of cardiovascular health.

OBJECTIVE: We sought to evaluate survivors' awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers.

METHODS: Breast cancer survivors (n=49) recruited from a survivorship clinic interacted …

Disparities In Breastfeeding Among U.S. Black Mothers: Identification Of Mechanisms, Cara B. Safon, Timothy C. Heeren, Stephen M. Kerr, Daphney Clermont, Michael J. Corwin, Eve R. Colson, Rachel Y. Moon, Ann L. Kellams, Fern R. Hauck, Margaret G. Parker

Open Access Publications

No abstract provided.

Redox-Responsive Hyaluronic Acid-Based Nanogels For The Topical Delivery Of The Visual Chromophore To Retinal Photoreceptors, Amine M. Laradji, Alexander V. Kolesnikov, Bedia B. Karakoçak, Vladimir J. Kefalov, Nathan Ravi

Open Access Publications

No abstract provided.

A Priori Activation Of Apoptosis Pathways Of Tumor (Aaapt) Technology: Development Of Targeted Apoptosis Initiators For Cancer Treatment, Raghu S. Pandurangi, Marco Tomasetti, Sekar T. Verapazham, Ramasamy Paulmurugan, Cynthia Ma, Sandeep Rajput, Manjushree Anjanappa, Harikrishna Nakshatri

Open Access Publications

Cancer cells develop tactics to circumvent the interventions by desensitizing themselves to interventions. Amongst many, the principle routes of desensitization include a) activation of survival pathways (e.g. NF-kB, PARP) and b) downregulation of cell death pathways (e.g. CD95/CD95L). As a result, it requires high therapeutic dose to achieve tumor regression which, in turn damages normal cells through the collateral effects. Methods are needed to sensitize the low and non-responsive resistant tumor cells including cancer stem cells (CSCs) in order to evoke a better response from the current treatments. Current treatments including chemotherapy can induce cell death only in bulk cancer …

Proteomic And Functional Mapping Of Cardiac Nav1.5 Channel Phosphorylation Sites, Maxime Lorenzini, Emily Wagner, Kiersten M. Ruff, Rohit V. Pappu, Jeanne M. Nerbonne, Jonathan R. Silva, R. Reid Townsend, Et Al

Open Access Publications

Phosphorylation of the voltage-gated Na+ (NaV) channel NaV1.5 regulates cardiac excitability, yet the phosphorylation sites regulating its function and the underlying mechanisms remain largely unknown. Using a systematic, quantitative phosphoproteomic approach, we analyzed NaV1.5 channel complexes purified from nonfailing and failing mouse left ventricles, and we identified 42 phosphorylation sites on NaV1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic NaV1.5 mutants revealed the roles of three phosphosites in regulating NaV1.5 channel expression and gating. The phosphorylated serines S664 and S667 regulate the voltage dependence of channel activation in a cumulative …

Tumor-Associated Neutrophils (Tans) In Human Carcinoma-Draining Lymph Nodes: A Novel Tan Compartment, Silvia Lonardi, William Vermi, Et Al.

Open Access Publications

No abstract provided.

Measuring Activities Of Daily Living In Stroke Patients With Motion Machine Learning Algorithms: A Pilot Study, Pin-Wei Chen, Nathan A Baune, Igor Zwir, Jiayu Wang, Victoria Swamidass, Alex W K Wong

Open Access Publications

Measuring activities of daily living (ADLs) using wearable technologies may offer higher precision and granularity than the current clinical assessments for patients after stroke. This study aimed to develop and determine the accuracy of detecting different ADLs using machine-learning (ML) algorithms and wearable sensors. Eleven post-stroke patients participated in this pilot study at an ADL Simulation Lab across two study visits. We collected blocks of repeated activity ("atomic" activity) performance data to train our ML algorithms during one visit. We evaluated our ML algorithms using independent semi-naturalistic activity data collected at a separate session. We tested Decision Tree, Random Forest, …

Pore-Forming Transmembrane Domains Control Ion Selectivity And Selectivity Filter Conformation In The Kirbac1.1 Potassium Channel, Marcos Matamoros, Colin G. Nichols

Open Access Publications

Potassium (K+) channels are membrane proteins with the remarkable ability to very selectively conduct K+ ions across the membrane. High-resolution structures have revealed that dehydrated K+ ions permeate through the narrowest region of the pore, formed by the backbone carbonyls of the signature selectivity filter (SF) sequence TxGYG. However, the existence of nonselective channels with similar SF sequences, as well as effects of mutations in other regions on selectivity, suggest that the SF is not the sole determinant of selectivity. We changed the selectivity of the KirBac1.1 channel by introducing mutations at residue I131 in transmembrane helix 2 (TM2). These …

The Dark Side Of The Gut: Virome-Host Interactions In Intestinal Homeostasis And Disease, Yuhao Li, Scott A. Handley, Megan T. Baldridge

Open Access Publications

The diverse enteric viral communities that infect microbes and the animal host collectively constitute the gut virome. Although recent advances in sequencing and analysis of metaviromes have revealed the complexity of the virome and facilitated discovery of new viruses, our understanding of the enteric virome is still incomplete. Recent studies have uncovered how virome-host interactions can contribute to beneficial or detrimental outcomes for the host. Understanding the complex interactions between enteric viruses and the intestinal immune system is a prerequisite for elucidating their role in intestinal diseases. In this review, we provide an overview of the enteric virome composition and …

Integrating Imaging And Rna-Seq Improves Outcome Prediction In Cervical Cancer, Jin Zhang, Ramachandran Rashmi, Matthew Inkman, Kay Jayachandran, Fiona Ruiz, Michael R Waters, Perry W Grigsby, Stephanie Markovina, Julie K Schwarz

Open Access Publications

Approaches using a single type of data have been applied to classify human tumors. Here we integrate imaging features and transcriptomic data using a prospectively collected tumor bank. We demonstrate that increased maximum standardized uptake value on pretreatment 18F-fluorodeoxyglucose-positron emission tomography correlates with epithelial-to-mesenchymal transition (EMT) gene expression. We derived and validated 3 major molecular groups, namely squamous epithelial, squamous mesenchymal, and adenocarcinoma, using prospectively collected institutional (n = 67) and publicly available (n = 304) data sets. Patients with tumors of the squamous mesenchymal subtype showed inferior survival outcomes compared with the other 2 molecular groups. High mesenchymal gene …

Concordance Of Antibiotic Prescribing With The American Dental Association Acute Oral Infection Guidelines Within Veterans' Affairs (Va) Dentistry, Daniel B Carlsen, Michael J Durkin, Gretchen Gibson, M Marianne Jurasic, Ursula Patel, Linda Poggensee, Margaret A Fitzpatrick, Kelly Echevarria, Jessina Mcgregor, Charlesnika T Evans, Katie J Suda

Open Access Publications

OBJECTIVE: United States dentists prescribe 10% of all outpatient antibiotics. Assessing appropriateness of antibiotic prescribing has been challenging due to a lack of guidelines for oral infections. In 2019, the American Dental Association (ADA) published clinical practice guidelines (CPG) on the management of acute oral infections. Our objective was to describe baseline national antibiotic prescribing for acute oral infections prior to the release of the ADA CPG and to identify patient-level variables associated with an antibiotic prescription.

DESIGN: Cross-sectional analysis.

METHODS: We performed an analysis of national VA data from January 1, 2017, to December 31, 2017. We identified cases …

Rural-Urban Differences In Antibiotic Prescribing For Uncomplicated Urinary Tract Infection, Abbye W Clark, Michael J Durkin, Margaret A Olsen, Matthew Keller, Yinjiao Ma, Caroline A O'Neil, Anne M Butler

Open Access Publications

OBJECTIVE: To examine rural-urban differences in temporal trends and risk of inappropriate antibiotic use by agent and duration among women with uncomplicated urinary tract infection (UTI).

DESIGN: Observational cohort study.

METHODS: Using the IBM MarketScan Commercial Database (2010-2015), we identified US commercially insured women aged 18-44 years coded for uncomplicated UTI and prescribed an oral antibiotic agent. We classified antibiotic agents and durations as appropriate versus inappropriate based on clinical guidelines. Rural-urban status was defined by residence in a metropolitan statistical area. We used modified Poisson regression to determine the association between rural-urban status and inappropriate antibiotic receipt, accounting for …

Trem2 Sustains Macrophage-Hepatocyte Metabolic Coordination In Nonalcoholic Fatty Liver Disease And Sepsis, Jinchao Hou, Yingyue Zhou, Marco Colonna, Et Al

Open Access Publications

Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of …

A Pilot Study Examining The Prognostic Utility Of Tumor Shrinkage On Cone-Beam Computed Tomography (Cbct) For Stage Iii Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Definitive Chemoradiation, Kylie H Kang, Jimmy T Efird, Tarun K Podder, Yuxia Zhang, Afshin Dowlati, Mitchell Machtay, Charulata Jindal, Tithi Biswas

Open Access Publications

There has been growing interest in utilizing information from cone-beam computed tomography (CBCT) to help guide both treatment delivery and prognosis. In this assessment of locally advanced unresectable stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation, we aimed to determine the survival advantage associated with using CBCT to measure tumor regression. Patient, tumor, and treatment characteristics were collected. The serial tumor shrinkage for each patient was determined from tumor volume contours on weekly CBCTs. Survival analysis was performed using the Kaplan-Meier technique and a Cox proportional hazards model. At least two-thirds of patients had a tumor volume …

Atoh7-Independent Specification Of Retinal Ganglion Cell Identity, Justin Brodie-Kommit, Brian S Clark, Fion Shiau, Philip A Ruzycki, Et Al

Open Access Publications

Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor