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Neuroskeletal Effects Of Chronic Bioelectric Nerve Stimulation In Health And Diabetes, Alec T Beeve, Ivana Shen, Xiao Zhang, Kristann Magee, Ying Yan, Matthew R Macewan, Erica L Scheller

Open Access Publications

Background/Aims: Bioelectric nerve stimulation (eStim) is an emerging clinical paradigm that can promote nerve regeneration after trauma, including within the context of diabetes. However, its ability to prevent the onset of diabetic peripheral neuropathy (DPN) has not yet been evaluated. Beyond the nerve itself, DPN has emerged as a potential contributor to sarcopenia and bone disease; thus, we hypothesized that eStim could serve as a strategy to simultaneously promote neural and musculoskeletal health in diabetes.

Methods: To address this question, an eStim paradigm pre-optimized to promote nerve regeneration was applied to the sciatic nerve, which directly innervates the tibia and …

Cohort Study Protocol To Characterize The Incidence And Severity Of Neuropathic Pain In Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Chioma U. Odozor, Kristen Roles, Carrie Burk, Thomas Kannampallil, David B. Clifford, Jay F. Piccirillo, Simon Haroutounian

Open Access Publications

No abstract provided.

Quantitative Evaluation Of Frequency Domain Measurements In High Density Diffuse Optical Tomography, Guy A. Perkins, Adam T. Eggebrecht, Hamid Dehghani

Open Access Publications

No abstract provided.

Bromodomain Protein Brd4 Directs And Sustains Cd8 T Cell Differentiation During Infection, J. Justin Milner, Takeshi Egawa, Et Al

Open Access Publications

In response to infection, pathogen-specific CD8 T cells differentiate into functionally diverse effector and memory T cell populations critical for resolving disease and providing durable immunity. Through small-molecule inhibition, RNAi studies, and induced genetic deletion, we reveal an essential role for the chromatin modifier and BET family member BRD4 in supporting the differentiation and maintenance of terminally fated effector CD8 T cells during infection. BRD4 bound diverse regulatory regions critical to effector T cell differentiation and controlled transcriptional activity of terminal effector-specific super-enhancers in vivo. Consequentially, induced deletion of Brd4 or small molecule-mediated BET inhibition impaired maintenance of a terminal …

Survival Predictors Of Heart Rate Variability After Myocardial Infarction With And Without Low Left Ventricular Ejection Fraction, Junichiro Hayano, Norihiro Ueda, Masaya Kisohara, Emi Yuda, Robert M Carney, James A Blumenthal

Open Access Publications

Background: Heart rate variability (HRV) and heart rate (HR) dynamics are used to predict the survival probability of patients after acute myocardial infarction (AMI), but the association has been established in patients with mixed levels of left ventricular ejection fraction (LVEF).

Objective: We investigated whether the survival predictors of HRV and HR dynamics depend on LVEF after AMI.

Methods: We studied 687 post-AMI patients including 147 with LVEF ≤35% and 540 with LVEF >35%, of which 23 (16%) and 22 (4%) died during the 25 month follow-up period, respectively. None had an implanted cardioverter-defibrillator. From baseline 24 h ECG, the …

Tms-Eeg Biomarkers Of Amnestic Mild Cognitive Impairment Due To Alzheimer's Disease: A Proof-Of-Concept Six Years Prospective Study, Florinda Ferreri, Andrea Guerra, Luca Vollero, David Ponzo, Sara Määtta, Mervi Könönen, Fabrizio Vecchio, Patrizio Pasqualetti, Francesca Miraglia, Ilaria Simonelli, Maurizio Corbetta, Paolo Maria Rossini

Open Access Publications

No abstract provided.

Perlecan In Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation And Mechanoregulation Of Load-Bearing Connective Tissues, Farshid Guilak, Anthony J Hayes, James Melrose

Open Access Publications

In this study, we review mechanoregulatory roles for perlecan in load-bearing connective tissues. Perlecan facilitates the co-acervation of tropoelastin and assembly of elastic microfibrils in translamellar cross-bridges which, together with fibrillin and elastin stabilise the extracellular matrix of the intervertebral disc annulus fibrosus. Pericellular perlecan interacts with collagen VI and XI to define and stabilize this matrix compartment which has a strategic position facilitating two-way cell-matrix communication between the cell and its wider extracellular matrix. Cues from the extracellular matrix are fed through this pericellular matrix back to the chondrocyte, allowing it to perceive and respond to subtle microenvironmental changes …

Aapm Medical Physics Practice Guideline 3.B.: Levels Of Supervision For Medical Physicists In Clinical Training, Douglas Pfeiffer, Hania Al-Hallaq, Per Halvorsen, Kristi Hendrickson, Zheng Feng Lu, Melissa Carol Martin, Beth Schueler, Jillian Shuman, Jacqueline E Zoberi

Open Access Publications

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth …

Current And Prospective Methods For Assessing Anti-Tumor Immunity In Colorectal Cancer, Yulia I Nussbaum, Yariswamy Manjunath, Kanve N Suvilesh, Wesley C Warren, Chi-Ren Shyu, Jussuf T Kaifi, Matthew A Ciorba, Jonathan B Mitchem

Open Access Publications

Colorectal cancer (CRC) remains one of the deadliest malignancies worldwide despite recent progress in treatment strategies. Though immune checkpoint inhibition has proven effective for a number of other tumors, it offers benefits in only a small group of CRC patients with high microsatellite instability. In general, heterogenous cell groups in the tumor microenvironment are considered as the major barrier for unveiling the causes of low immune response. Therefore, deconvolution of cellular components in highly heterogeneous microenvironments is crucial for understanding the immune contexture of cancer. In this review, we assimilate current knowledge and recent studies examining anti-tumor immunity in CRC. …

Overlapping But Disparate Inflammatory And Immunosuppressive Responses To Sars-Cov-2 And Bacterial Sepsis: An Immunological Time Course Analysis, Tyler J Loftus, Ricardo Ungaro, Marvin Dirain, Philip A Efron, Monty B Mazer, Kenneth E Remy, Richard S Hotchkiss, Luer Zhong, Rhonda Bacher, Petr Starostik, Lyle L Moldawer, Scott C Brakenridge

Open Access Publications

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis

Approaches For Ending Ineffective Programs: Strategies From State Public Health Practitioners, Emily Rodriguez Weno, Peg Allen, Stephanie Mazzucca, Louise Farah Saliba, Margaret Padek, Sarah Moreland-Russell, Ross C Brownson

Open Access Publications

No abstract provided.

Identifying The Impact Of Intimate Partner Violence In Humanitarian Settings: Using An Ecological Framework To Review 15 Years Of Evidence, Melissa Meinhart, Ilana Seff, Katrina Troy, Samantha Mcnelly, Luissa Vahedi, Catherine Poulton, Lindsay Stark

Open Access Publications

Intimate partner violence (IPV) is a pervasive form of gender-based violence that exacerbates in humanitarian settings. This systematic review examined the myriad IPV impacts and the quality of existing evidence of IPV in humanitarian settings. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedures, a total of 51 articles were included from the 3924 screened. We identified the impact of IPV across two levels of the ecological framework: individual and microsystem. Our findings corroborated previous evidence that indicated IPV to be associated with adverse physical and mental health for survivors. Our findings also uniquely synthesized the intergenerational …

Pattern And Degree Of Individual Brain Atrophy Predicts Dementia Onset In Dominantly Inherited Alzheimer's Disease, Ophir Keret, Randal J Bateman, Tammie L S Benzinger, John C Morris, Beau M Ances, Nelly Joseph-Mathurin, Richard J Perrin, Brian A Gordon, Dominantly Inherited Alzheimer Network, Et Al

Open Access Publications

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment.

Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally.

Results: Our risk score separated asymptomatic versus demented …

Bispecific T Cell Engagers For The Treatment Of Multiple Myeloma: Achievements And Challenges, Kinan Alhallak, Jennifer Sun, Amanda Jeske, Chaelee Park, Jessica Yavner, Hannah Bash, Berit Lubben, Ola Adebayo, Ayah Khaskiah, Abdel Kareem Azab

Open Access Publications

MM is the second most common hematological malignancy and represents approximately 20% of deaths from hematopoietic cancers. The advent of novel agents has changed the therapeutic landscape of MM treatment; however, MM remains incurable. T cell-based immunotherapy such as BTCEs is a promising modality for the treatment of MM. This review article discusses the advancements and future directions of BTCE treatments for MM.

Dnmt3a Deficiency In The Skin Causes Focal, Canonical Dna Hypomethylation And A Cellular Proliferation Phenotype, David Y. Chen, Ian M. Ferguson, Krista A. Braun, Leslie A. Sutton, Nichole M. Helton, Sai Mukund Ramakrishnan, Amanda M. Smith, Christopher A. Miller, Timothy J. Ley

Open Access Publications

No abstract provided.

Tailoring Of Arteriovenous Graft‑To‑Vein Anastomosis Angle To Attenuate Pathological Flow Fields, Dillon Williams, Eric C. Leuthardt, Guy M. Genin, Mohamed Zayed

Open Access Publications

No abstract provided.

Endothelial Ether Lipids Link The Vasculature To Blood Pressure, Behavior, And Neurodegeneration, Larry D. Spears, Sangeeta Adak, Guifang Dong, Xiaochao Wei, George Spyropoulos, Qiang Zhang, Li Yin, Chu Feng, Donghua Hu, Irfan J. Lodhi, Fong-Fu Hsu, Rithwick Rajagopal, Kevin K. Noguchi, Carmen M. Halabi, Lindsey Brier, Annie R. Bice, Brian V. Lananna, Erik S. Musiek, Oshri Avraham, Valeria Cavalli, Jerrah K. Holth, David M. Holtzman, David F. Wozniak, Joseph P. Culver, Clay F. Semenkovich

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 …

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

Apobec1 Complementation Factor Overexpression Promotes Hepatic Steatosis, Fibrosis, And Hepatocellular Cancer, Valerie Blanc, Jesse D Riordan, Saeed Soleymanjahi, Joseph H Nadeau, Ilke Nalbantoglu, Yan Xie, Elizabeth A Molitor, Blair B Madison, Elizabeth M Brunt, Jason C Mills, Deborah C Rubin, Irene O Ng, Yeonjung Ha, Lewis R Roberts, Nicholas O Davidson

Open Access Publications

The RNA-binding protein Apobec1 complementation factor (A1CF) regulates posttranscriptional ApoB mRNA editing, but the range of RNA targets and the long-term effect of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf-transgenic (A1cf+/Tg), A1cf+/Tg Apobec1-/-, and A1cf-/- mice fed chow or high-fat/high-fructose diets using RNA-Seq, RNA CLIP-Seq, and tissue microarrays from human hepatocellular cancer (HCC). A1cf+/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution. Aged A1cf+/Tg mice developed spontaneous fibrosis, dysplasia, and HCC, and this development was accelerated on a high-fat/high-fructose …

Evaluation Of Diffusion-Weighted Mri And Geometric Distortion On A 0.35t Mr-Linac At Multiple Gantry Angles, Benjamin Lewis, Anamaria Guta, Stacie Mackey, H Michael Gach, Sasa Mutic, Olga Green, Taeho Kim

Open Access Publications

Diffusion-weighted imaging (DWI) provides a valuable diagnostic tool for tumor evaluation. Yet, it is difficult to acquire daily MRI data sets in the traditional radiotherapy clinical setting due to patient burden and limited resources. However, integrated MRI radiotherapy treatment systems facilitate daily functional MRI acquisitions like DWI during treatment exams. Before ADC values from MR-RT systems can be used clinically their reproducibility and accuracy must be quantified. This study used a NIST traceable DWI phantom to verify ADC values acquired on a 0.35 T MR-LINAC system at multiple gantry angles. A diffusion-weighted echo planar imaging sequence was used for all …

Adherence Of Internet-Based Cancer Risk Assessment Tools To Best Practices In Risk Communication: Content Analysis, Erika A Waters, Jeremy L Foust, Laura D Scherer, Amy Mcqueen, Jennifer M Taber

Open Access Publications

BACKGROUND: Internet-based risk assessment tools offer a potential avenue for people to learn about their cancer risk and adopt risk-reducing behaviors. However, little is known about whether internet-based risk assessment tools adhere to scientific evidence for what constitutes good risk communication strategies. Furthermore, their quality may vary from a user experience perspective.

OBJECTIVE: This study aims to understand the extent to which current best practices in risk communication have been applied to internet-based cancer risk assessment tools.

METHODS: We conducted a search on August 6, 2019, to identify websites that provided personalized assessments of cancer risk or the likelihood of …

Comparison Of Upper Respiratory Viral Load Distributions In Asymptomatic And Symptomatic Children Diagnosed With Sars-Cov-2 Infection In Pediatric Hospital Testing Programs, Larry K Kociolek, Bijal A Parikh, Ariel Hernandez-Leyva, Et Al

Open Access Publications

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL …

Evaluation Of Surrogate Tests For The Presence Of Meca-Mediated Methicillin Resistance In Staphylococcus Capitis, Staphylococcus Haemolyticus, Staphylococcus Hominis, And Staphylococcus Warneri, Romney M Humphries, Paul Magnano, C A Burnham, Jennifer Dien Bard, Tanis C Dingle, Katrina Callan, Lars F Westblade

Open Access Publications

Testing of staphylococci other than

A Clinical Epidemiology And Molecular Attribution Evaluation Of Adenoviruses In Pediatric Acute Gastroenteritis: A Case-Control Study, Kanti Pabbaraju, Raymond Tellier, Xiao-Li Pang, Jianling Xie, Bonita E Lee, Linda Chui, Ran Zhuo, Otto G Vanderkooi, Samina Ali, Phillip I Tarr, Anna Funk, Stephen B Freedman

Open Access Publications

The objective of this study was to characterize the etiological role of human adenovirus (HAdV) serotypes in pediatric gastroenteritis. Using a case-control design, we compared the frequencies of HAdV serotypes between children with ≥3 episodes of vomiting or diarrhea within 24 h and <7 days of symptoms (i.e., cases) and those with no infectious symptoms (i.e., controls). Stool samples and/or rectal swabs underwent molecular serotyping with cycle threshold (Ct) values provided by multiplex real-time reverse transcription-PCR testing. Cases without respiratory symptoms were analyzed to calculate the proportion of disease attributed to individual HAdV serotypes (i.e., attributable fraction). Between December 2014 and August 2018, adenoviruses were detected in 18.8% (629/3,347) of cases and 7.2% (97/1,355) of controls, a difference of 11.6% (95% confidence interval [CI], 9.6%, 13.5%). In 96% (95% CI, 92 to 98%) of HAdV F40/41 detections, the symptoms could be attributed to the identified serotype; when serotypes C1, C2, C5, and C6 were detected, they were responsible for symptoms in 52% (95% CI, 12 to 73%). Ct values were lower among cases than among controls (

A Study Protocol For A Multicentre, Prospective, Before-And-After Trial Evaluating The Feasibility Of Implementing Targeted Sedation After Initiation Of Mechanical Ventilation In The Emergency Department (The Ed-Sed Pilot Trial), Brian M Fuller, Brian W Roberts, Nicholas M Mohr, Ryan D Pappal, Robert J Stephens, Yan Yan, Chris Carpenter, Marin H Kollef, Michael Simon Avidan

Open Access Publications

INTRODUCTION: Sedation is a cornerstone therapy in the management of patients receiving mechanical ventilation and is highly influential on outcome. Early sedation depth appears especially influential, as early deep sedation is associated with worse outcome when compared with light sedation. Our research group has shown that patients receiving mechanical ventilation in the emergency department (ED) are exposed to deep sedation commonly, and ED sedation depth is impactful on intensive care unit (ICU) care and clinical outcomes. While extensive investigation has occurred for patients in the ICU, comparatively little data exist from the ED. Given the influence that ED sedation seems …

Associations Between Atrial Cardiopathy And Cerebral Amyloid: The Aric-Pet Study, Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman

Open Access Publications

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m

Comparative Evaluation Of Clinical Manifestations And Risk Of Death In Patients Admitted To Hospital With Covid-19 And Seasonal Influenza: Cohort Study, Yan Xie, Benjamin Bowe, Geetha Maddukuri, Ziyad Al-Aly

Open Access Publications

No abstract provided.

Coronary Computed Tomography Angiography Compared With Single Photon Emission Computed Tomography Myocardial Perfusion Imaging As A Guide To Optimal Medical Therapy In Patients Presenting With Stable Angina: The Rescue Trial, Arthur E Stillman, Constantine Gatsonis, Joao A C Lima, Tao Liu, Bradley S Snyder, Jean Cormack, Vinay Malholtra, Mitchell D Schnall, James E Udelson, Udo Hoffmann, Pamela K Woodard, Rescue Investigators

Open Access Publications

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of …

Protocol For The Prognosticating Delirium Recovery Outcomes Using Wakefulness And Sleep Electroencephalography (P-Drows-E) Study: A Prospective Observational Study Of Delirium In Elderly Cardiac Surgical Patients, S Kendall Smith, Thomas Nguyen, Alyssa K Labonte, Mohammadmehdi Kafashan, Orlandrea Hyche, Christian S Guay, Elizabeth Wilson, Courtney W Chan, Anhthi Luong, L Brian Hickman, Bradley A Fritz, Daniel Emmert, Thomas J Graetz, Spencer J Melby, Brendan P Lucey, Yo-El S Ju, Troy S Wildes, Michael S Avidan, Ben J A Palanca

Open Access Publications

INTRODUCTION: Delirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in the early detection, mitigation and assessment of response to interventions. Because sleep disruption has been posited as a contributor to the development of this syndrome, expression of abnormal electroencephalography (EEG) patterns during sleep and wakefulness may be informative. Here we hypothesise that abnormal EEG patterns of sleep and wakefulness may serve as predictive and diagnostic …