Medicine and Health Sciences Commons^™

Screening For Problematic Opioid Use In The Emergency Department: Comparison Of Two Screening Measures, Brittany E Punches, Caroline E Freiermuth, Jon E Sprague, Jennifer L Brown, Elizabeth Hutzel-Dunham, Joshua Lambert, Robert Braun, Andrew Littlefield, Jennifer A Frey, Daniel J Bachmann, Jason J Bischof, Michael V Pantalon, Rachel M Ancona, David F Kisor, Michael S Lyons

2020-Current year OA Pubs

STUDY OBJECTIVE: Earlier intervention for opioid use disorder (OUD) may reduce long-term health implications. Emergency departments (EDs) in the United States treat millions with OUD annually who may not seek care elsewhere. Our objectives were (1) to compare two screening measures for OUD characterization in the ED and (2) to determine the proportion of ED patients screening positive for OUD and those who endorse other substance use to guide future screening programs.

METHODS: A cross-sectional study of randomly selected adult patients presenting to three Midwestern US EDs were enrolled, with duplicate patients excluded. Surveys were administered via research assistant and …

Caregiver Descriptions Of Dystonia In Cerebral Palsy, Fayza Jaleel, Alyssa Rust, Shirley Cheung, Toni S Pearson, Keisuke Ueda, Amy Robichaux-Viehoever, Katie Leger, Keerthana Chintalapati, Danielle Guez-Barber, Michele Shusterman, Bhooma Aravamuthan

2020-Current year OA Pubs

OBJECTIVE: To determine how caregivers describe dystonia in people with cerebral palsy (CP).

METHODS: In this prospective cohort study, paper surveys were administered to caregivers between September 7, 2021 and October 28, 2021 during CP Center visits at a large tertiary care center. Caregivers were asked to describe involuntary movements triggered by voluntary movement or triggered by tactile stimulation in the people with CP they cared for. Their CP Center medical provider separately assessed people with CP for dystonia. Movement features described exclusively by caregivers of people with CP and dystonia were determined using conventional content analysis.

RESULTS: 113 caregivers …

A Deep Learning Approach To Remove Contrast From Contrast-Enhanced Ct For Proton Dose Calculation, Xu Wang, Yao Hao, Ye Duan, Deshan Yang

2020-Current year OA Pubs

PURPOSE: Non-Contrast Enhanced CT (NCECT) is normally required for proton dose calculation while Contrast Enhanced CT (CECT) is often scanned for tumor and organ delineation. Possible tissue motion between these two CTs raises dosimetry uncertainties, especially for moving tumors in the thorax and abdomen. Here we report a deep-learning approach to generate NCECT directly from CECT. This method could be useful to avoid the NCECT scan, reduce CT simulation time and imaging dose, and decrease the uncertainties caused by tissue motion between otherwise two different CT scans.

METHODS: A deep network was developed to convert CECT to NCECT. The network …

Creation Of A National Emergency Medicine Medical Education Journal Club, Jessica Pelletier, James Ahn, Andrew Golden, Caroline Astemborski, Michelle D. Lall, Albert Kim, Sara Dimeo

2020-Current year OA Pubs

Background There are a relatively limited number of emergency medicine (EM) medical education (MedEd) fellowships with few trainees at each program, creating barriers to local collaboration and networking. While best practices for developing MedEd journal clubs exist, there has not been an established national EM MedEd journal club. To address this need, we created a national journal club, the Council of Residency Directors (CORD) MedEd Journal Club (MEJC), to facilitate collaboration and networking opportunities by providing a synchronous online journal club. Objectives Our primary objective was to create a network for collaboration across geographical barriers to form a virtual community …

Spatial And Amplitude Dynamics Of Neurostimulation: Insights From The Acute Intrahippocampal Kainate Seizure Mouse Model, Thomas J Foutz, Nicholas Rensing, Lirong Han, Dominique M Durand, Michael Wong

2020-Current year OA Pubs

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model.

METHODS: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes.

RESULTS: …

Serological Assays For Differentiating Natural Covid-19 Infection From Vaccine Induced Immunity, Samuel M S Cheng, Gaya K Amarasinghe, Et Al.

2020-Current year OA Pubs

BACKGROUND: Natural SARS-CoV-2 infection may elicit antibodies to a range of viral proteins including non-structural protein ORF8. RNA, adenovirus vectored and sub-unit vaccines expressing SARS-CoV-2 spike would be only expected to elicit S-antibodies and antibodies to distinct domains of nucleocapsid (N) protein may reliably differentiate infection from vaccine-elicited antibody. However, inactivated whole virus vaccines may potentially elicit antibody to wider range of viral proteins, including N protein. We hypothesized that antibody to ORF8 protein will discriminate natural infection from vaccination irrespective of vaccine type.

METHODS: We optimized and validated the anti-ORF8 and anti-N C-terminal domain (NCTD) ELISA assays using sera …

Patterns Of Self-Care Decision-Making And Associated Factors: A Cross-Sectional Observational Study, Christopher S Lee, Kenneth E Freedland, Tiny Jaarsma, Anna Strömberg, Ercole Vellone, Shayleigh Dickson Page, Heleen Westland, Sara Pettersson, Michelle Van Rijn, Subhash Aryal, Andrew Belfiglio, Douglas Wiebe, Barbara Riegel

2020-Current year OA Pubs

OBJECTIVE: The aim of this study was to identify for the first time patterns of self-care decision-making (i.e. the extent to which participants viewed contextual factors influencing decisions about symptoms) and associated factors among community-dwelling adults with chronic illness.

METHODS: This was a secondary analysis of data collected during the development and psychometric evaluation of the 27-item Self-Care Decisions Inventory that is based on Naturalistic Decision-Making (n = 430, average age = 54.9 ± 16.2 years, 70.2 % female, 87.0 % Caucasian, average number of chronic conditions = 3.6 ± 2.8). Latent class mixture modeling was used to identify patterns …

Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael D Chuong, Hyun Kim, Lauren E Henke, Alex T Price, Et Al.

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …

Stem Cell Modeling Of Nervous System Tumors, Frank B Furnari, Corina Anastasaki, Shan Bian, Howard A Fine, Tomoyuki Koga, Lu Q Le, Fausto J Rodriguez, David H Gutmann

2020-Current year OA Pubs

Nervous system tumors, particularly brain tumors, represent the most common tumors in children and one of the most lethal tumors in adults. Despite decades of research, there are few effective therapies for these cancers. Although human nervous system tumor cells and genetically engineered mouse models have served as excellent platforms for drug discovery and preclinical testing, they have limitations with respect to accurately recapitulating important aspects of the pathobiology of spontaneously arising human tumors. For this reason, attention has turned to the deployment of human stem cell engineering involving human embryonic or induced pluripotent stem cells, in which genetic alterations …

Functional Network Disorganization And Cognitive Decline Following Fractionated Whole-Brain Radiation In Mice, Benjamin A. Seitzman, Francisco J. Reynoso, Timothy J. Mitchell, Annie R. Bice, Anmol Jarang, Xiaodan Wang, Cedric Mpoy, Lori Strong, Buck E. Rogers, Carla M. Yuede, Joshua B. Rubin, Stephanie M. Perkins, Adam Q. Bauer

2020-Current year OA Pubs

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain's functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of …

Core Requirements Of Frailty Screening In The Emergency Department: An International Delphi Consensus Study, Elizabeth Moloney, Christopher R Carpenter, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Frailty is associated with adverse outcomes among patients attending emergency departments (EDs). While multiple frailty screens are available, little is known about which variables are important to incorporate and how best to facilitate accurate, yet prompt ED screening. To understand the core requirements of frailty screening in ED, we conducted an international, modified, electronic two-round Delphi consensus study.

METHODS: A two-round electronic Delphi involving 37 participants from 10 countries was undertaken. Statements were generated from a prior systematic review examining frailty screening instruments in ED (logistic, psychometric and clinimetric properties). Reflexive thematic analysis generated a list of 56 statements …

High-Dimensional Quantile Mediation Analysis With Application To A Birth Cohort Study Of Mother-Newborn Pairs, Haixiang Zhang, Xiumei Hong, Yinan Zheng, Lifang Hou, Cheng Zheng, Xiaobin Wang, Lei Liu

2020-Current year OA Pubs

MOTIVATION: There has been substantial recent interest in developing methodology for high-dimensional mediation analysis. Yet, the majority of mediation statistical methods lean heavily on mean regression, which limits their ability to fully capture the complex mediating effects across the outcome distribution. To bridge this gap, we propose a novel approach for selecting and testing mediators throughout the full range of the outcome distribution spectrum.

RESULTS: The proposed high-dimensional quantile mediation model provides a comprehensive insight into how potential mediators impact outcomes via their mediation pathways. This method's efficacy is demonstrated through extensive simulations. The study presents a real-world data application …

Legionella Pneumophila Usurps Host Cell Lipids For Vacuole Expansion And Bacterial Growth, Soma Ghosh, Saumya Bandyopadhyay, Danielle M. Smith, Sangeeta Adak, Clay F. Semenkovich, Laszlo Nagy, Michael J. Wolfgang, Tamara J. O'Connor

2020-Current year OA Pubs

Vacuolar pathogens reside in membrane-bound compartments within host cells. Maintaining the integrity of this compartment is paramount to bacterial survival and replication as it protects against certain host surveillance mechanisms that function to eradicate invading pathogens. Preserving this compartment during bacterial replication requires expansion of the vacuole membrane to accommodate the increasing number of bacteria, and yet, how this is accomplished remains largely unknown. Here, we show that the vacuolar pathogen Legionella pneumophila exploits multiple sources of host cell fatty acids, including inducing host cell fatty acid scavenging pathways, in order to promote expansion of the replication vacuole and bacteria …

Public Platform With 39,472 Exome Control Samples Enables Association Studies Without Genotype Sharing, Mykyta Artomov, Alexander A Loboda, Maxim N Artyomov, Mark J Daly

2020-Current year OA Pubs

Acquiring a sufficiently powered cohort of control samples matched to a case sample can be time-consuming or, in some cases, impossible. Accordingly, an ability to leverage genetic data from control samples that were already collected elsewhere could dramatically improve power in genetic association studies. Sharing of control samples can pose significant challenges, since most human genetic data are subject to strict sharing regulations. Here, using the properties of singular value decomposition and subsampling algorithm, we developed a method allowing selection of the best-matching controls in an external pool of samples compliant with personal data protection and eliminating the need for …

Longitudinal Predictors Of Health-Related Quality Of Life In Isolated Dystonia, Johanna Junker, Joel S Perlmutter, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To determine longitudinal predictors of health-related quality of life (HR-QoL) in an international multicenter cohort of patients with isolated dystonia.

METHODS: Out of 603 dystonia patients prospectively enrolled in the Natural History Dystonia Coalition study, 155 were assessed three times within 2 years for HR-QoL, symptoms of depression, generalized anxiety disorder (GAD), and social anxiety disorder (SAD), as well as dystonia severity and dystonic tremor. In addition, the impact of botulinum neurotoxin (BoNT) injections on HR-QoL was evaluated after 1 year.

RESULTS: Depressive symptoms at baseline predicted lower HR-QoL on all subscales after 2 years (all p ≤ 0.001). …

Structural Biases In Disordered Proteins Are Prevalent In The Cell, David Moses, Karina Guadalupe, Feng Yu, Eduardo Flores, Anthony R Perez, Ralph Mcanelly, Nora M Shamoon, Gagandeep Kaur, Estefania Cuevas-Zepeda, Andrea D Merg, Erik W Martin, Alex S Holehouse, Shahar Sukenik

2020-Current year OA Pubs

Intrinsically disordered proteins and protein regions (IDPs) are prevalent in all proteomes and are essential to cellular function. Unlike folded proteins, IDPs exist in an ensemble of dissimilar conformations. Despite this structural plasticity, intramolecular interactions create sequence-specific structural biases that determine an IDP ensemble's three-dimensional shape. Such structural biases can be key to IDP function and are often measured in vitro, but whether those biases are preserved inside the cell is unclear. Here we show that structural biases in IDP ensembles found in vitro are recapitulated inside human-derived cells. We further reveal that structural biases can change in a sequence-dependent …

Primary Non-Function Of Hepatic Allograft With Preexisting Microvesicular Steatosis/Foamy Degeneration And Mild Large-Droplet Macrovesicular Steatosis, Melissa E Limia, Xiu Li Liu, Jennifer Yu, Kathleen Byrnes

2020-Current year OA Pubs

It has been established that more than mild large-droplet macrovesicular steatosis (LD-MAS) is associated with increased risk of graft non-function. In contrast, even severe small-droplet macrovesicular steatosis (SD-MAS) has been found to be less prognostically significant. It remains unclear if a donor liver with diffuse microvesicular steatosis is associated with an increased risk of graft dysfunction. A 56-year-old male with alcoholic cirrhosis was transplanted with a liver from a 42-year-old overweight male donor after brain death. The frozen section of the donor liver biopsy taken at harvest showed diffusely enlarged clear/foamy hepatocytes and mild LD-MAS (about 5-10% of total tissue). …

Clinicopathologic Features Of Antibrush Border Antibody Disease, Joel D Murphy, Nidia Messias, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Antibrush border antibody disease (ABBA) is an autoimmune tubulointerstitial kidney disease that primarily affects older individuals and results in progressive kidney failure. It is rare with only 20 reported cases. Here, we describe a case series to further define the clinicopathologic spectrum and natural history, and to inform management.

METHODS: We identified 67 patients with ABBA who underwent kidney biopsy, including 65 native and 2 transplants. Demographics, clinical findings, and laboratory data were obtained. Histopathologic data included light microscopy, immunofluorescence, electron microscopy and immunostaining for LRP2, CUBN, and AMN. Follow-up data, including treatment(s), laboratory values, and outcomes, were available …

Quantification Of Enteric Dysfunction In Cystic Fibrosis: Inter- And Intraindividual Variability, Laura A Duckworth, Kimberly A Sutton, Nurmohammad Shaikh, Jinli Wang, Carla Hall-Moore, Lori R Holtz, Phillip I Tarr, Ronald C Rubenstein

2020-Current year OA Pubs

OBJECTIVES: To test the utility of various biomarkers as indicators of gut dysfunction in cystic fibrosis (CF) and determine whether intraindividual variations in these measures are repeatable over short intervals and whether interindividual variations correlate with clinical outcomes.

STUDY DESIGN: We performed a cross-sectional, limited longitudinal study of children with CF aged 1-21 years who provided blood and stool samples at 2 or 3 visits, 2 weeks and 3 months apart, which were assayed for markers of intestinal inflammation (fecal calprotectin [fCal], lipocalin-2 [fLcn2], neopterin), and permeability (plasma lipopolysaccharide [LPS] antibodies, LPS-binding protein) by enzyme immunoassays. Control specimens were obtained …

Assessment Of Bovine Cortical Bone Fracture Behavior Using Impact Microindentation As A Surrogate Of Fracture Toughness, Babak Jahani, Rachana Vaidya, James M Jin, Donald A Aboytes, Kaitlyn S Broz, Siva Krothapalli, Bhanuteja Pujari, Walee M Baig, Simon Y Tang

2020-Current year OA Pubs

The fracture behavior of bone is critically important for evaluating its mechanical competence and ability to resist fractures. Fracture toughness is an intrinsic material property that quantifies a material's ability to withstand crack propagation under controlled conditions. However, properly conducting fracture toughness testing requires the access to calibrated mechanical load frames and the destructive testing of bone samples, and therefore fracture toughness tests are clinically impractical. Impact microindentation mimicks certain aspects of fracture toughness measurements, but its relationship with fracture toughness remains unknown. In this study, we aimed to compare measurements of notched fracture toughness and impact microindentation in fresh …

Bintrafusp Alfa With Ccrt Followed By Bintrafusp Alfa Versus Placebo With Ccrt Followed By Durvalumab In Patients With Unresectable Stage Iii Nsclc: A Phase 2 Randomized Study, Everett E Vokes, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment.

METHODS: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 …

Current Understanding Of The Alzheimer's Disease-Associated Microbiome And Therapeutic Strategies, Dong-Oh Seo, David M Holtzman

2020-Current year OA Pubs

Alzheimer's disease (AD) is a fatal progressive neurodegenerative disease. Despite tremendous research efforts to understand this complex disease, the exact pathophysiology of the disease is not completely clear. Recently, anti-Aβ antibodies have been shown to remove amyloid from the brain and slow the clinical progression of mild dementia by ~30%. However, exploring alternative strategies is crucial to understanding and developing more effective therapeutic interventions. In recent years, the microbiota-gut-brain axis has received significant attention in the AD field. Numerous studies have suggested that alterations in the gut microbiota composition are associated with the progression of AD, and several underlying mechanisms …

The Impact Of Patterns In Linkage Disequilibrium And Sequencing Quality On The Imprint Of Balancing Selection, Tristan J Hayeck, Yang Li, Timothy L Mosbruger, Jonathan P Bradfield, Adam G Gleason, George Damianos, Grace Tzun-Wen Shaw, Jamie L Duke, Laura K Conlin, Tychele N Turner, Marcelo A Fernández-Viña, Mahdi Sarmady, Dimitri S Monos

2020-Current year OA Pubs

Regions under balancing selection are characterized by dense polymorphisms and multiple persistent haplotypes, along with other sequence complexities. Successful identification of these patterns depends on both the statistical approach and the quality of sequencing. To address this challenge, at first, a new statistical method called LD-ABF was developed, employing efficient Bayesian techniques to effectively test for balancing selection. LD-ABF demonstrated the most robust detection of selection in a variety of simulation scenarios, compared against a range of existing tests/tools (Tajima's D, HKA, Dng, BetaScan, and BalLerMix). Furthermore, the impact of the quality of sequencing on detection of balancing selection was …

Pycallingcards: An Integrated Environment For Visualizing, Analyzing, And Interpreting Calling Cards Data, Juanru Guo, Wenjin Zhang, Xuhua Chen, Allen Yen, Lucy Chen, Christian A Shively, Daofeng Li, Ting Wang, Joseph D Dougherty, Robi D Mitra

2020-Current year OA Pubs

MOTIVATION: Unraveling the transcriptional programs that control how cells divide, differentiate, and respond to their environments requires a precise understanding of transcription factors' (TFs) DNA-binding activities. Calling cards (CC) technology uses transposons to capture transient TF binding events at one instant in time and then read them out at a later time. This methodology can also be used to simultaneously measure TF binding and mRNA expression from single-cell CC and to record and integrate TF binding events across time in any cell type of interest without the need for purification. Despite these advantages, there has been a lack of dedicated …

Concurrent Administration Of Serotonergic Antidepressants And Ozanimod In Participants With Relapsing Multiple Sclerosis From The Open-Label Extension Daybreak Trial, Robert T Naismith, Jeffrey A Cohen, Amit Bar-Or, Giancarlo Comi, Krzysztof W Selmaj, Hans-Peter Hartung, James K Sheffield, Anthony Krakovich, Daniel Tatosian, Chun-Yen Cheng, Jennifer Reardon, Vadim Khaychuk, Jon V Riolo, Diego Silva, Bruce Ac Cree

2020-Current year OA Pubs

BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro.

OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717).

METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using …

Epidemiology And Preventability Of Hospital-Onset Bacteremia And Fungemia In 2 Hospitals In India, Sumanth Gandra, Dorothy Sinclair, Dustin Stwalley, Jacaranda Van Rheenen, David K Warren, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs).

DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to …

Evidence That Anemia Accelerates As Progression Via Shear-Induced Tgf-Β1 Activation: Heyde's Syndrome Comes Full Circle, Kumar Subramani, Jeffrey Bander, Sixia Chen, Mayte Suárez-Fariñas, Thamizhiniyan Venkatesan, Sandeep Subrahmanian, Rohan Varshney, Annapoorna Kini, Samin Sharma, Daniel B Rifkin, Jaehyung Cho, Barry S Coller, Jasimuddin Ahamed

2020-Current year OA Pubs

The severity of aortic stenosis (AS) is associated with acquired von Willebrand syndrome (AVWS) and gastrointestinal bleeding, leading to anemia (Heyde's syndrome). We investigated how anemia is linked with AS and AVWS using the LA100 mouse model and patients with AS. Induction of anemia in LA100 mice increased transforming growth factor (TGF)-β1 activation, AVWS, and AS progression. Patients age >75 years with severe AS had higher plasma TGF-β1 levels and more severe anemia than AS patients age <75 years, and there was a correlation between TGF-β1 and anemia. These data are compatible with the hypothesis that the blood loss anemia of Heyde's syndrome contributes to AS progression via WSS-induced activation of platelet TGF-β1 and additional gastrointestinal bleeding via WSS-induced AVWS.

Lobe-Specific Lymph Node Sampling Is Associated With Lower Risk Of Cancer Recurrence, Melanie P Subramanian, Daniel B Eaton Jr, Brendan T Heiden, Whitney S Brandt, Ulysses L Labilles, Su-Hsin Chang, Yan Yan, Martin W Schoen, Mayank R Patel, Daniel Kreisel, Ruben G Nava, Theodore Thomas, Bryan F Meyers, Benjamin D Kozower, Varun Puri

2020-Current year OA Pubs

OBJECTIVE: Adequate intraoperative lymph node (LN) assessment is a critical component of early-stage non-small cell lung cancer (NSCLC) resection. The National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer (CoC) recommend station-based sampling minimums agnostic to tumor location. Other institutions advocate for lobe-specific LN sampling strategies that consider the anatomic likelihood of LN metastases. We examined the relationship between lobe-specific LN assessment and long-term outcomes using a robust, highly curated cohort of stage I NSCLC patients.

METHODS: We performed a cohort study using a uniquely compiled dataset from the Veterans Health Administration and manually abstracted data …

Control Intervention Design For Preclinical And Clinical Trials: Consensus-Based Core Recommendations From The Third Stroke Recovery And Rehabilitation Roundtable, Kathryn S Hayward, Emily J Dalton, Jessica Barth, Marian Brady, Leora R Cherney, Leonid Churilov, Andrew N Clarkson, Jesse Dawson, Sean P Dukelow, Peter Feys, Maree Hackett, Steve R Zeiler, Catherine E Lang

2020-Current year OA Pubs

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was …

Integrative Analysis Of Pathogenic Variants In Glucose-6-Phosphatase Based On An Alphafold2 Model, Matt Sinclair, Richard A Stein, Jonathan H Sheehan, Emily M Hawes, Richard M O'Brien, Emad Tajkhorshid, Derek P Claxton

2020-Current year OA Pubs

Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. Consistent with its vital contribution to glucose homeostasis, inactivating mutations in G6PC1 causes glycogen storage disease (GSD) type 1a characterized by hepatomegaly and severe hypoglycemia. Despite its physiological importance, the structural basis of G6P binding to G6PC1 and the molecular disruptions induced by missense mutations within the active site that give rise to GSD type 1a are unknown. In this study, we determine the atomic interactions …