Digital Commons Network^™

Short-Term Effects Of Appropriate Empirical Antimicrobial Treatment With Ceftolozane/Tazobactam In A Swine Model Of Nosocomial Pneumonia, Ana Motos, Marin Kollef, Et Al

Open Access Publications

The rising frequency of multidrug-resistant and extensively drug-resistant (MDR/XDR) pathogens is making more frequent the inappropriate empirical antimicrobial therapy (IEAT) in nosocomial pneumonia, which is associated with increased mortality. We aim to determine the short-term benefits of appropriate empirical antimicrobial treatment (AEAT) with ceftolozane/tazobactam (C/T) compared with IEAT with piperacillin/tazobactam (TZP) in MDR

Naturalistic Language Input Is Associated With Resting-State Functional Connectivity In Infancy, Lucy S. King, M. Catalina Camacho, David F. Montez, Kathryn L. Humphreys, Ian H. Gotlib

Open Access Publications

The quantity and quality of the language input that infants receive from their caregivers affects their future language abilities; however, it is unclear how variation in this input relates to preverbal brain circuitry. The current study investigated the relation between naturalistic language input and the functional connectivity (FC) of language networks in human infancy using resting-state functional magnetic resonance imaging (rsfMRI). We recorded the naturalistic language environments of five- to eight-month-old male and female infants using the Linguistic ENvironment Analysis (LENA) system and measured the quantity and consistency of their exposure to adult words (AWs) and adult-infant conversational turns (CTs). …

Coxsackievirus B3 Infection Early In Pregnancy Induces Congenital Heart Defects Through Suppression Of Fetal Cardiomyocyte Proliferation, Vipul Sharma, Lisa S Goessling, Anoop K Brar, Chetanchandra S Joshi, Indira U Mysorekar, Pirooz Eghtesady

Open Access Publications

Background Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation. Methods and Results We infected C57Bl/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose-response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of …

Death And Myocardial Infarction Following Initial Revascularization Versus Optimal Medical Therapy In Chronic Coronary Syndromes With Myocardial Ischemia: A Systematic Review And Meta-Analysis Of Contemporary Randomized Controlled Trials, Andrea Soares, William E Boden, Whady Hueb, Maria M Brooks, Helen E A Vlachos, Kevin O'Fee, Angela Hardi, David L Brown

Open Access Publications

Background In chronic coronary syndromes, myocardial ischemia is associated with a greater risk of death and nonfatal myocardial infarction (MI). We sought to compare the effect of initial revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) plus optimal medical therapy (OMT) with OMT alone in patients with chronic coronary syndrome and myocardial ischemia on long-term death and nonfatal MI. Methods and Results Ovid Medline, Embase, Scopus, and Cochrane Library databases were searched for randomized controlled trials of PCI or CABG plus OMT versus OMT alone for patients with chronic coronary syndromes. Studies were screened and data …

Designing And Undertaking Randomised Implementation Trials: Guide For Researchers, Luke Wolfenden, Robbie Foy, Justin Presseau, Jeremy Grimshaw, Noah Ivers, Byron Powell, Monica Taljaard, John Wiggers, Rachel Sutherland, Nicole Nathan, Christopher Williams, Melanie Kingsland, Andrew Milat, Rebecca Hodder, Sze Lin Yoong

Open Access Publications

No abstract provided.

The Dark Kinase Knowledgebase: An Online Compendium Of Knowledge And Experimental Results Of Understudied Kinases, Matthew E. Berginski, Nienke Moret, Changchang Liu, Dennis Goldfarb, Peter K. Sorger, Shawn M. Gomez

Open Access Publications

Kinases form the backbone of numerous cell signaling pathways, with their dysfunction similarly implicated in multiple pathologies. Further facilitated by their druggability, kinases are a major focus of therapeutic development efforts in diseases such as cancer, infectious disease and autoimmune disorders. While their importance is clear, the role or biological function of nearly one-third of kinases is largely unknown. Here, we describe a data resource, the Dark Kinase Knowledgebase (DKK; https://darkkinome.org), that is specifically focused on providing data and reagents for these understudied kinases to the broader research community. Supported through NIH's Illuminating the Druggable Genome (IDG) Program, the DKK …

Function Of Mammalian M-Cones Depends On The Level Of Cralbp In Müller Cells, Alexander V. Kolesnikov, Philip D. Kiser, Krzysztof Palczewski, Vladimir J. Kefalov

Open Access Publications

Cone photoreceptors mediate daytime vision in vertebrates. The rapid and efficient regeneration of their visual pigments following photoactivation is critical for the cones to remain photoresponsive in bright and rapidly changing light conditions. Cone pigment regeneration depends on the recycling of visual chromophore, which takes place via the canonical visual cycle in the retinal pigment epithelium (RPE) and the Müller cell-driven intraretinal visual cycle. The molecular mechanisms that enable the neural retina to regenerate visual chromophore for cones have not been fully elucidated. However, one known component of the two visual cycles is the cellular retinaldehyde-binding protein (CRALBP), which is …

Type 2 Diabetes Prevention Focused On Normalization Of Glycemia: A Two-Year Pilot Study, Amy L Mckenzie, Shaminie J Athinarayanan, Jackson J Mccue, Rebecca N Adams, Monica Keyes, James P Mccarter, Jeff S Volek, Stephen D Phinney, Sarah J Hallberg

Open Access Publications

The purpose of this study is to assess the effects of an alternative approach to type 2 diabetes prevention. Ninety-six patients with prediabetes (age 52 (10) years; 80% female; BMI 39.2 (7.1) kg/m

Optimal Method For Fetal Brain Age Prediction Using Multiplanar Slices From Structural Magnetic Resonance Imaging, Jinwoo Hong, Hyuk Jin Yun, Gilsoon Park, Seonggyu Kim, Yangming Ou, Lana Vasung, Caitlin K Rollins, Cynthia M Ortinau, Emiko Takeoka, Shizuko Akiyama, Tomo Tarui, Judy A Estroff, Patricia Ellen Grant, Jong-Min Lee, Kiho Im

Open Access Publications

The accurate prediction of fetal brain age using magnetic resonance imaging (MRI) may contribute to the identification of brain abnormalities and the risk of adverse developmental outcomes. This study aimed to propose a method for predicting fetal brain age using MRIs from 220 healthy fetuses between 15.9 and 38.7 weeks of gestational age (GA). We built a 2D single-channel convolutional neural network (CNN) with multiplanar MRI slices in different orthogonal planes without correction for interslice motion. In each fetus, multiple age predictions from different slices were generated, and the brain age was obtained using the mode that determined the most …

Association Of Pet-Based Estradiol-Challenge Test For Breast Cancer Progesterone Receptors With Response To Endocrine Therapy, Farrokh Dehdashti, Ningying Wu, Cynthia X. Ma, Michael J. Naughton, John A. Katzenellenbogen, Barry A. Siegel

Open Access Publications

No abstract provided.

Parental Factors Associated With The Decision To Participate In A Neonatal Clinical Trial, Elliott Mark Weiss, Rakesh Rao, Et Al

Open Access Publications

Importance: It remains poorly understood how parents decide whether to enroll a child in a neonatal clinical trial. This is particularly true for parents from racial or ethnic minority populations. Understanding factors associated with enrollment decisions may improve recruitment processes for families, increase enrollment rates, and decrease disparities in research participation.

Objective: To assess differences in parental factors between parents who enrolled their infant and those who declined enrollment for a neonatal randomized clinical trial.

Design, Setting, and Participants: This survey study conducted from July 2017 to October 2019 in 12 US level 3 and 4 neonatal intensive care units …

An Open Label, Randomized Clinical Trial To Compare The Tolerability And Efficacy Of Ivermectin Plus Diethylcarbamazine And Albendazole Vs. Diethylcarbamazine Plus Albendazole For Treatment Of Brugian Filariasis In Indonesia, Taniawati Supali, Yenny Djuardi, Michael Christian, Elisa Iskandar, Rahmat Alfian, Roospita Maylasari, Yossi Destani, Adriani Lomiga, Dominikus Minggu, Daphne Lew, Joshua Bogus, Gary J Weil, Peter U. Fischer

Open Access Publications

No abstract provided.

Temporal Trends In Incidence Rates Of Lower Extremity Amputation And Associated Risk Factors Among Patients Using Veterans Health Administration Services From 2008 To 2018, Miao Cai, Yan Xie, Benjamin Bowe, Andrew K. Gibson, Mohamed A. Zayed, Tingting Li, Ziyad Al-Aly

Open Access Publications

Importance: Lower extremity amputation (LEA) is associated with significant morbidity and mortality. However, national temporal trends of LEA incidence rates among US veterans and associated factors have not been well characterized.

Objective: To describe the temporal trends of LEA, characterize associated risk factors, and decompose the associations of these risk factors with changes in temporal trends of LEA among US veterans using Department of Veteran Affairs (VA) services between 2008 and 2018.

Design, Setting, and Participants: This cohort study used VA data from 2008 to 2018 to estimate incidence rates of LEA among veterans using VA services. Cox regression models …

Von Willebrand Disease: Proposing Definitions For Future Research, Nathan T. Connell, Jorge Di Paola, Et Al.

Open Access Publications

No abstract provided.

A Cross-Sectional Comparison Of Physical Activity During Covid-19 In A Sample Of Rural And Non-Rural Participants In The Us, Alan M Beck, Amanda S Gilbert, Dixie D Duncan, Eric M Wiedenman

Open Access Publications

Physical activity (PA) pre-COVID-19 was lower in rural areas compared to non-rural areas. The purpose of this study was to determine COVID-19's impact on PA in rural and non-rural residents. A cross-sectional study consisting of a convenience sample of 278 participants (50% rural, 50% non-rural) from 25 states completed an online survey describing their PA behaviors and perceptions during COVID-19. The global physical activity questionnaire was used to determine PA in various domains and summed to determine if the participant met the PA guidelines. Rural participants had a significantly higher body mass index, lower income, and a lower educational attainment. …

Mechanical Overstimulation Causes Acute Injury And Synapse Loss Followed By Fast Recovery In Lateral-Line Neuromasts Of Larval Zebrafish, Melanie Holmgren, Michael E. Ravicz, Kenneth E. Hancock, Olga Strelkova, Dorina Kallogjeri, Artur A. Indzhykulian, Mark E. Warchol, Lavinia Sheets

Open Access Publications

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced …

Concussion-Reporting Behavior In Rugby: A National Survey Of Rugby Union Players In The United States, J. Chance Miller, Kenneth Shubin Stein, Tyler Moon, David Trofa, Hamish Kerr, Thomas Bottiglieri, C. S. Ahmad

Open Access Publications

Background: Rugby is the fastest growing team sport in the United States for male and female athletes. It is a contact/collision sport with an injury risk profile that includes concussions.

Purpose: To examine the prevalence of concussions in male and female rugby players in the United States and to characterize behaviors around reporting concussions that could be a target for prevention and treatment efforts.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: An online survey distributed to active members on the USA Rugby membership list was used to examine self-reported concussions in male and female athletes. Concussion-reporting behaviors and …

Tissue Biodistribution And Tumor Targeting Of Near-Infrared Labelled Anti-Cd38 Antibody-Drug Conjugate In Preclinical Multiple Myeloma, Nicholas Cho, Sooah Ko, Monica Shokeen

Open Access Publications

Daratumumab (DARA) is an FDA-approved high-affinity monoclonal antibody targeting CD38 that has shown promising therapeutic efficacy in double refractory multiple myeloma (MM) patients. Despite the well-established clinical efficacy of DARA, not all heavily pretreated patients respond to single-agent DARA, and the majority of patients who initially respond eventually progress. Antibody-drug conjugates (ADCs) combine the highly targeted tumor antigen recognition of antibodies with the cell killing properties of chemotherapy for effective internalization and processing of the drug. In this study, we evaluated the anti-tumor efficacy of DARA conjugated to the maytansine derivative, mertansine (DM1), linked via a non-cleavable bifunctional linker. The …

Metformin Ameliorates The Severity Of Experimental Alport Syndrome, Kohei Omachi, Jeffrey H. Miner, Et Al.

Open Access Publications

No abstract provided.

The Valproate Mediates Radio-Bidirectional Regulation Through Rfwd3-Dependent Ubiquitination On Rad51, Guochao Liu, David Lim, Zuchao Cai, Wenwen Ding, Zhujun Tian, Chao Dong, Fengmei Zhang, Gongshe Guo, Xiaowei Wang, Pingkun Zhou, Zhihui Feng

Open Access Publications

Ionizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0.5 mM). We further demonstrated the decrease of homologous recombination (HR)-associated Rad51 in the transformed cells was related …

Corynebacterium Species Inhibit Streptococcus Pneumoniae Colonization And Infection Of The Mouse Airway, Kadi J Horn, Alexander C Jaberi Vivar, Vera Arenas, Sameer Andani, Edward N Janoff, Sarah E Clark

Open Access Publications

The stability and composition of the airway microbiome is an important determinant of respiratory health. Some airway bacteria are considered to be beneficial due to their potential to impede the acquisition and persistence of opportunistic bacterial pathogens such as

Assessing The Clinical Requirement Of 2.5% Phenylephrine For Diagnostic Pupil Examination, Junsang Cho, Brent Bruck, James C. Liu, Susan M. Culican

Open Access Publications

No abstract provided.

Green Nanotechnology Of Mgf‑Aunps For Immunomodulatory Intervention In Prostate Cancer Therapy, Menka Khoobchandani, Aslam Khan, Kavita K. Katti, Velaphi C. Thipe, Amal Y. Al-Yasiri, Darsha K. D. Mohandoss, Michael B. Nicholl, Ademar B. Lugão, Chetan P. Hans, Kattesh V. Katti

Open Access Publications

No abstract provided.

Disordered Eating, Food Insecurity, And Weight Status Among Transgender And Gender Nonbinary Youth And Young Adults: A Cross-Sectional Study Using A Nutrition Screening Protocol, Whitney R. Linsenmeyer, Ian M. Katz, Jamie L. Reed, Andrea M. Giedinghagen, Christopher B. Lewis, Sarah K. Garwood

Open Access Publications

No abstract provided.

The Utility Of Body Composition Assessment In Nutrition And Clinical Practice: An Overview Of Current Methodology, Clifton J Holmes, Susan B Racette

Open Access Publications

Body composition is a key component for maintaining good general health and longevity. It can be influenced by a variety of factors, including genetics, environment, and lifestyle choices. The assessment of body composition is an essential tool for nutrition specialists to effectively evaluate nutritional status and monitor progression during dietary interventions. As humans age, there is a natural increase in fat mass coupled with a gradual decline in lean mass, specifically in bone and muscle mass. Individuals with a high body fat percentage are at a greater risk of cardiovascular diseases, type 2 diabetes, several types of cancer, and early …

Cancer-Associated Mesothelial Cells Promote Ovarian Cancer Chemoresistance Through Paracrine Osteopontin Signaling, Jin Qian, Bauer L Lesavage, Kelsea M Hubka, Chenkai Ma, Suchitra Natarajan, Joshua T Eggold, Yiren Xiao, Katherine C Fuh, Venkatesh Krishnan, Annika Enejder, Sarah C Heilshorn, Oliver Dorigo, Erinn B Rankin

Open Access Publications

Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression …

The Sarm1 Tir Nadase: Mechanistic Similarities To Bacterial Phage Defense And Toxin-Antitoxin Systems, Aaron Diantonio, Jeffrey Milbrandt, Matthew D Figley

Open Access Publications

The Toll/interleukin-1 receptor (TIR) domain is the signature signalling motif of innate immunity, with essential roles in innate immune signalling in bacteria, plants, and animals. TIR domains canonically function as scaffolds, with stimulus-dependent multimerization generating binding sites for signalling molecules such as kinases and ligases that activate downstream immune mechanisms. Recent studies have dramatically expanded our understanding of the TIR domain, demonstrating that the primordial function of the TIR domain is to metabolize NAD

An International Virtual Hackathon To Build Tools For The Analysis Of Structural Variants Within Species Ranging From Coronaviruses To Vertebrates [Version 2; Peer Review: 1 Approved, 3 Approved With Reservations], Ann M. Mccartney, Daniel Paiva Agustinho, Et Al

Open Access Publications

No abstract provided.

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology And Demyelination Caused By Hypoperfusion, Mikko T Huuskonen, Qinghai Liu, Krista Lamorie-Foote, Kristina Shkirkova, Michelle Connor, Arati Patel, Axel Montagne, Hans Baertsch, Constantinos Sioutas, Todd E Morgan, Caleb E Finch, Berislav V Zlokovic, William J Mack

Open Access Publications

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white …

Metformin Downregulates Pd-L1 Expression In Esophageal Squamous Cell Catrcinoma By Inhibiting Il-6 Signaling Pathway, Yao Lu, Dao Xin, Lulu Guan, Mengli Xu, Yalan Yang, Yu Chen, Yuanyuan Yang, Andrea Wang-Gillam, Li Wang, Shanggang Zong, Feng Wang

Open Access Publications

Purpose: To characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response.

Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin …