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Brief Electrical Stimulation Accelerates Axon Regeneration And Promotes Recovery Following Nerve Transection And Repair In Mice, Junichi Sayanagi, Jesús A Acevedo-Cintrón, Deng Pan, Lauren Schellhardt, Daniel A Hunter, Alison K Snyder-Warwick, Susan E Mackinnon, Matthew D Wood

Open Access Publications

BACKGROUND: Clinical outcomes following nerve injury repair can be inadequate. Pulsed-current electrical stimulation (ES) is a therapeutic method that facilitates functional recovery by accelerating axon regeneration. However, current clinical ES protocols involve the application of ES for 60 minutes during surgery, which can increase operative complexity and time. Shorter ES protocols could be a strategy to facilitate broader clinical adoption. The purpose of the present study was to determine if a 10-minute ES protocol could improve outcomes.

METHODS: C57BL/6J mice were randomized to 3 groups: no ES, 10 minutes of ES, and 60 minutes of ES. In all groups, the …

Sirtuin 1 Mediates Protection Against Delayed Cerebral Ischemia In Subarachnoid Hemorrhage In Response To Hypoxic Postconditioning, Deepti Diwan, Ananth K Vellimana, Diane J Aum, Julian Clarke, James W Nelson, Molly Lawrence, Byung Hee Han, Jeffrey M Gidday, Gregory J Zipfel

Open Access Publications

Background Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in aneurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic preconditioning) provides powerful protection against DCI. Here, we expanded upon these findings to determine whether hypoxic conditioning delivered at clinically relevant time points after SAH (hypoxic postconditioning) provides similarly robust DCI protection. Methods and Results In this study, we found that hypoxic postconditioning (8% O

Syndrome Of Reversible Cardiogenic Shock And Left Ventricular Ballooning In Obstructive Hypertrophic Cardiomyopathy, Mark V Sherrid, Daniel G Swistel, Iacopo Olivotto, Maurizio Pieroni, Omar Wever-Pinzon, Katherine Riedy, Richard G Bach, Mustafa Husaini, Sharon Cresci, Alex Reyentovich, Daniele Massera, Martin S Maron, Barry J Maron, Bette Kim

Open Access Publications

Background Cardiogenic shock from most causes has unfavorable prognosis. Hypertrophic cardiomyopathy (HCM) can uncommonly present with apical ballooning and shock in association with sudden development of severe and unrelenting left ventricular (LV) outflow obstruction. Typical HCM phenotypic features of mild septal thickening, outflow gradients, and distinctive mitral abnormalities differentiate these patients from others with Takotsubo syndrome, who have normal mitral valves and no outflow obstruction. Methods and Results We analyzed 8 patients from our 4 HCM centers with obstructive HCM and abrupt presentation of cardiogenic shock with LV ballooning, and 6 cases reported in literature. Of 14 patients, 10 (71%) …

Relationship Between Quality Of Life Indicators And Cardiac Status Indicators In Chemotherapy Patients, Blaž Matija Geršak, Andreja Kukec, Henning Steen, Moritz Montenbruck, Maja Šoštarič, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Sorin Giusca, Grigorios Korosoglou, Pia Wülfing, Susan Dent, Daniel Lenihan

Open Access Publications

AIM: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients.

METHODS: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. …

Alternative Pre-Mrna Splicing Of The Mu Opioid Receptor Gene, Oprm1: Insight Into Complex Mu Opioid Actions, Shan Liu, Wen-Jia Kang, Anna Abrimian, Jin Xu, Luca Cartegni, Susruta Majumdar, Patrick Hesketh, Alex Bekker, Ying-Xian Pan

Open Access Publications

Most opioid analgesics used clinically, including morphine and fentanyl, as well as the recreational drug heroin, act primarily through the mu opioid receptor, a class A Rhodopsin-like G protein-coupled receptor (GPCR). The single-copy mu opioid receptor gene,

Aducanumab For Alzheimer Disease: The Amyloid Hypothesis Moves From Bench To Bedside, Erik S. Musiek, Teresa Gomez-Isla, David M Holtzman

Open Access Publications

No abstract provided.

Cullin4 E3 Ubiquitin Ligases Regulate Male Gonocyte Migration, Proliferation And Blood-Testis Barrier Homeostasis, Yan Yin, Liming Zhu, Qiufang Li, Pengbo Zhou, Liang Ma

Open Access Publications

Ubiquitination, an essential posttranslational modification, plays fundamental roles during mammalian spermatogenesis. We previously reported the requirement of two Cullin 4 ubiquitin ligase family genes, Cullin 4a (

Formylglycine-Generating Enzyme-Like Proteins Constitute A Novel Family Of Widespread Type Vi Secretion System Immunity Proteins, Juvenal Lopez, Nguyen-Hung Le, Ki Hwan Moon, Dor Salomon, Eran Bosis, Mario F Feldman

Open Access Publications

Competition is a critical aspect of bacterial life, as it enables niche establishment and facilitates the acquisition of essential nutrients. Warfare between Gram-negative bacteria is largely mediated by the type VI secretion system (T6SS), a dynamic nanoweapon that delivers toxic effector proteins from an attacking cell to adjacent bacteria in a contact-dependent manner. Effector-encoding bacteria prevent self-intoxication and kin cell killing by the expression of immunity proteins, which neutralize effector toxicity by specifically binding their cognate effector and either occluding its active site or preventing the structural rearrangements necessary for effector activation. In this study, we investigate Tsi3, a previously …

Plasmid-Encoded H-Ns Controls Extracellular Matrix Composition In A Modern Acinetobacter Baumannii Urinary Isolate, Saida Benomar, Gisela Di Venanzio, Mario F Feldman

Open Access Publications

Acinetobacter baumannii is emerging as a multidrug-resistant (MDR) nosocomial pathogen of increasing threat to human health worldwide. The recent MDR urinary isolate UPAB1 carries the plasmid pAB5, a member of a family of large conjugative plasmids (LCPs). LCPs encode several antibiotic resistance genes and repress the type VI secretion system (T6SS) to enable their dissemination, employing two TetR transcriptional regulators. Furthermore, pAB5 controls the expression of additional chromosomally encoded genes, impacting UPAB1 virulence. Here, we show that a pAB5-encoded H-NS transcriptional regulator represses the synthesis of the exopolysaccharide PNAG and the expression of a previously uncharacterized three-gene cluster that encodes …

Comparative Cellular Analysis Of Motor Cortex In Human, Marmoset And Mouse, Trygve E. Bakken, Xinxin Wang, Et Al

Open Access Publications

No abstract provided.

Disparities In Treatment Decisions For Abnormal Uterine Bleeding, Lulu Yu, Bhavana Janga, Rebecca Mcalister, Donna B Jeffe, Tammy Sonn

Open Access Publications

No abstract provided.

Coronary Artery Calcification And Plaque Characteristics In People Living With Hiv: A Systematic Review And Meta-Analysis, Cullen Soares, Amjad Samara, Matthew F Yuyun, Justin B Echouffo-Tcheugui, Ahmad Masri, Ahmad Samara, Alan R Morrison, Nina Lin, Wen-Chih Wu, Sebhat Erqou

Open Access Publications

Background Studies have reported that people living with HIV have higher burden of subclinical cardiovascular disease, but the data are not adequately synthesized. We performed meta-analyses of studies of coronary artery calcium and coronary plaque in people living with HIV. Methods and Results We performed systematic search in electronic databases, and data were abstracted in standardized forms. Study-specific estimates were pooled using meta-analysis. 43 reports representing 27 unique studies and involving 10 867 participants (6699 HIV positive, 4168 HIV negative, mean age 52 years, 86% men, 32% Black) were included. The HIV-positive participants were younger (mean age 49 versus 57 …

Role Of Enhancers In Development And Diseases, Shailendra S Maurya

Open Access Publications

Enhancers are cis-regulatory elements containing short DNA sequences that serve as binding sites for pioneer/regulatory transcription factors, thus orchestrating the regulation of genes critical for lineage determination. The activity of enhancer elements is believed to be determined by transcription factor binding, thus determining the cell state identity during development. Precise spatio-temporal control of the transcriptome during lineage specification requires the coordinated binding of lineage-specific transcription factors to enhancers. Thus, enhancers are the primary determinants of cell identity. Numerous studies have explored the role and mechanism of enhancers during development and disease, and various basic questions related to the functions and …

Data-Driven Clustering Identifies Features Distinguishing Multisystem Inflammatory Syndrome From Acute Covid-19 In Children And Adolescents, Alon Geva, Philip C Spinella, Et Al

Open Access Publications

Background: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia.

Methods: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients.

Findings: Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (

Interpretation: Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C …

X-Treme Loss Of Sequence Diversity Linked To Neo-X Chromosomes In Filarial Nematodes, John Mattick, Ramakrishna Rao, Et Al

Open Access Publications

The sequence diversity of natural and laboratory populations of Brugia pahangi and Brugia malayi was assessed with Illumina resequencing followed by mapping in order to identify single nucleotide variants and insertions/deletions. In natural and laboratory Brugia populations, there is a lack of sequence diversity on chromosome X relative to the autosomes (πX/πA = 0.2), which is lower than the expected (πX/πA = 0.75). A reduction in diversity is also observed in other filarial nematodes with neo-X chromosome fusions in the genera Onchocerca and Wuchereria, but not those without neo-X chromosome fusions in the genera Loa and Dirofilaria. In the species …

Deep Learning-Based Method To Accurately Estimate Breast Tissue Optical Properties In The Presence Of The Chest Wall, Menghao Zhang, Shuying Li, Yun Zou, Quing Zhu

Open Access Publications

SIGNIFICANCE: In general, image reconstruction methods used in diffuse optical tomography (DOT) are based on diffusion approximation, and they consider the breast tissue as a homogenous, semi-infinite medium. However, the semi-infinite medium assumption used in DOT reconstruction is not valid when the chest wall is underneath the breast tissue.

AIM: We aim to reduce the chest wall's effect on the estimated average optical properties of breast tissue and obtain accurate forward model for DOT reconstruction.

APPROACH: We propose a deep learning-based neural network approach where a convolution neural network (CNN) is trained to simultaneously obtain accurate optical property values for …

Investigation Of Effect Of Modulation Frequency On High-Density Diffuse Optical Tomography Image Quality, Weihao Fan, Hamid Dehghani, Adam Eggebrecht

Open Access Publications

No abstract provided.

Diffusion-Weighted Imaging Reveals Distinct Patterns Of Cytotoxic Edema In Patients With Subdural Hematomas, David Robinson, Natalie Kreitzer, Laura B Ngwenya, Opeolu Adeoye, Daniel Woo, Jed Hartings, Brandon Foreman

Open Access Publications

Subdural hematomas (SDHs) are increasingly common and can cause ischemic brain injury. Previous work has suggested that this is driven largely by vascular compression from herniation, although this work was done before the era of magnetic resonance imaging (MRI). We thus sought to study SDH-related ischemic brain injury by looking at patterns of cytotoxic edema on diffusion-weighted MRI. To do so, we identified all SDH patients at a single institution from 2015 to 2019 who received an MRI within 2 weeks of presentation. We reviewed all MRIs for evidence of restricted diffusion consistent with cytotoxic edema. Cases were excluded if …

Cd177 Modulates The Function And Homeostasis Of Tumor-Infiltrating Regulatory T Cells, Myung-Chul Kim, Nicholas Borcherding, Kawther K. Ahmed, Andrew P. Voigt, Gaurav Pandey, Et Al

Open Access Publications

No abstract provided.

Pretreatment Neutrophil-To-Lymphocyte Ratio As An Important Prognostic Marker In Stage Iii Locally Advanced Non-Small Cell Lung Cancer: Confirmatory Results From The Proclaim Phase Iii Clinical Trial, Tithi Biswas, Rohin Gawdi, Charulata Jindal, Sharanya Iyer, Kylie H. Kang, David Bajor, Mitchell Machtay, Yuk Ming Choi, Jimmy T. Efird

Open Access Publications

Background: Neutrophil-to-lymphocyte ratio (NLR) is an important pretreatment marker of systemic inflammation and tumor aggressiveness. Increased levels of this ratio have been associated with reduced survival in several observational studies of lung cancer. However, supporting analyses from large clinical trial data are lacking.

Methods: To validate the prognostic role of NLR, the current study evaluated data from a randomized phase III study (PROCLAIM; clinicaltrial.gov ID: NCT00686959) of patients with stage IIIA/B, unresectable, non-squamous, non-small cell lung cancer (NSCLC), originally comparing combination pemetrexed-cisplatin chemoradiotherapy with etoposide-cisplatin chemoradiotherapy. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for survival were estimated using …

A Transcriptomic And Epigenomic Cell Atlas Of The Mouse Primary Motor Cortex, Zizhen Yao, Hanqing Liu, Fangming Xie, Stephan Fischer, Xinxin Wang, Et Al

Open Access Publications

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain

Upstaging And Survival Outcomes For Non-Muscle Invasive Bladder Cancer After Radical Cystectomy: Results From The International Robotic Cystectomy Consortium, Umar Iqbal, Eric Kim, Et Al

Open Access Publications

No abstract provided.

Protocol For Draup: A Deimplementation Programme To Decrease Routine Chest Radiographs After Central Venous Catheter Insertion, Enyo Ablordeppey, Byron Powell, Virginia Mckay, Shannon Keating, Aimee James, Christopher Carpenter, Marin Kollef, Richard Griffey

Open Access Publications

INTRODUCTION: Avoiding low value medical practices is an important focus in current healthcare utilisation. Despite advantages of point-of-care ultrasound (POCUS) over chest X-ray including improved workflow and timeliness of results, POCUS-guided central venous catheter (CVC) position confirmation has slow rate of adoption. This demonstrates a gap that is ripe for the development of an intervention.

METHODS: The intervention is a deimplementation programme called DRAUP (

ETHICS AND DISSEMINATION: Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data …

Genetic Characterization, Current Model Systems And Prognostic Stratification In Pax Fusion-Negative Vs. Pax Fusion-Positive Rhabdomyosarcoma, Carina A Dehner, Amy E Armstrong, Marielle Yohe, Jack F Shern, Angela C Hirbe

Open Access Publications

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents and accounts for approximately 2% of soft tissue sarcomas in adults. It is subcategorized into distinct subtypes based on histological features and fusion status (

Inhibition Of Chylomicron Assembly Leads To Dissociation Of Hepatic Steatosis From Inflammation And Fibrosis, Yan Xie, Elizabeth P Newberry, Elizabeth M Brunt, Samuel J Ballentine, Saeed Soleymanjahi, Elizabeth A Molitor, Nicholas O Davidson

Open Access Publications

Regulating dietary fat absorption may impact progression of nonalcoholic fatty liver disease (NAFLD). Here we asked if inducible inhibition of chylomicron assembly, as observed in intestine-specific microsomal triglyceride transfer protein knockout mice (Mttp-IKO), could retard NAFLD progression and/or reverse established fibrosis in two dietary models. Mttp-IKO mice fed a methionine/choline deficient (MCD) diet exhibited reduced hepatic triglycerides (TG), inflammation and fibrosis, associated with reduced oxidative stress and downstream activation of JNK and NFκB signaling pathways. However, when Mttp

Effectiveness Of Mrna Covid-19 Vaccine Among U.S. Health Care Personnel, Tamara Pilishvili, Jennie H. Kwon, Et Al

Open Access Publications

No abstract provided.

Methodological Rigor And Temporal Trends Of Cardiovascular Medicine Meta-Analyses In Highest-Impact Journals, Dhruv Mahtta, Ahmed Altibi, Mohamed M Gad, Amjad Samara, Amr F Barakat, Rodrigo Bagur, Hend Mansoor, Hani Jneid, Salim S Virani, Mamas A Mamas, Ahmad Masri, Islam Y Elgendy

Open Access Publications

Background Well-conducted meta-analyses are considered to be at the top of the evidence-based hierarchy pyramid, with an expansion of these publications within the cardiovascular research arena. There are limited data evaluating the trends and quality of such publications. The objective of this study was to evaluate the methodological rigor and temporal trends of cardiovascular medicine-related meta-analyses published in the highest impact journals. Methods and Results Using the Medline database, we retrieved cardiovascular medicine-related systematic reviews and meta-analyses published in

Increased Blood Pressure Variability And The Risk Of Probable Dementia Or Mild Cognitive Impairment: A Post Hoc Analysis Of The Sprint Mind Trial, Adam De Havenon, Mohammad Anadani, Shyam Prabhakaran, Ka-Ho Wong, Shadi Yaghi, Natalia Rost

Open Access Publications

Background Increased systolic blood pressure variability (BPV) is associated with stroke, cardiovascular disease, and dementia and mild cognitive impairment. However, prior studies assessing the relationship between BPV and dementia or mild cognitive impairment had infrequent measurement of blood pressure or suboptimal blood pressure control. Methods and Results We performed a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial) MIND (Memory and Cognition in Decreased Hypertension) trial. The primary outcome was probable dementia during follow-up. We defined our exposure period, during which blood pressures were collected, as the first 600 days of the trial, and outcomes were ascertained …

Exploring Contextual Factors Influencing The Implementation Of Evidence-Based Care For Hypertension In Rwanda: A Cross-Sectional Study Using The Coach Questionnaire, Ana Baumann, Cole Hooley, Charles Goss, Vincent Mutabazi, Angela Brown, Kenneth Schechtman, Marc Twagirumukiza, Lisa De Las Fuentes, Dominic Reeds, Makeda Williams, Eugene Mutimura, Anna Bergström, Aurore Nishimwe, Cecile Ingabire, Victor Davila-Roman

Open Access Publications

IMPORTANCE: Hypertension is the largest contributor to the Global Burden of Disease. In Rwanda, as in most low-income and middle-income countries, an increasing prevalence of hypertension and its associated morbidity and mortality is causing major healthcare and economic impact. Understanding healthcare systems context in hypertension care is necessary.

OBJECTIVE: To study the hypertension healthcare context as perceived by healthcare providers using the Context Assessment for Community Health (COACH) tool.

DESIGN: A cross-sectional cohort responded to the COACH questionnaire and a survey about hypertension training.

SETTING: Three tertiary care hospitals in Rwanda.

PARTICIPANTS: Healthcare professionals (n=223).

PRIMARY OUTCOMES AND MEASURES: The …

Clinicians' Perspectives On The Functions Of Communication In Pediatric Oncology, Bryan A. Sisk, Ginny L. Schulz, Erica C. Kaye, Justin N. Baker, Jennifer W. Mack, James M. Dubois

Open Access Publications

No abstract provided.