Medicine and Health Sciences Commons^™

Hsf1 Is A Driver Of Leukemia Stem Cell Self-Renewal In Acute Myeloid Leukemia, Qianze Dong, Nick Borcherding, Et Al.

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is maintained by self-renewing leukemic stem cells (LSCs). A fundamental problem in treating AML is that conventional therapy fails to eliminate LSCs, which can reinitiate leukemia. Heat shock transcription factor 1 (HSF1), a central regulator of the stress response, has emerged as an important target in cancer therapy. Using genetic Hsf1 deletion and a direct HSF1 small molecule inhibitor, we show that HSF1 is specifically required for the maintenance of AML, while sparing steady-state and stressed hematopoiesis. Mechanistically, deletion of Hsf1 dysregulates multifaceted genes involved in LSC stemness and suppresses mitochondrial oxidative phosphorylation through downregulation of …

Bold Cofluctuation 'Events' Are Predicted From Static Functional Connectivity, Zach Ladwig, Benjamin A. Seitzman, Ally Dworetsky, Yuhua Yu, Babatunde Adeyemo, Derek M. Smith, Steven E. Petersen, Caterina Gratton

2020-Current year OA Pubs

Recent work identified single time points ("events") of high regional cofluctuation in functional Magnetic Resonance Imaging (fMRI) which contain more large-scale brain network information than other, low cofluctuation time points. This suggested that events might be a discrete, temporally sparse signal which drives functional connectivity (FC) over the timeseries. However, a different, not yet explored possibility is that network information differences between time points are driven by sampling variability on a constant, static, noisy signal. Using a combination of real and simulated data, we examined the relationship between cofluctuation and network structure and asked if this relationship was unique, or …

Trial Of Ultrasound Guided Carpal Tunnel Release Versus Traditional Open Release (Tutor), Kyle R. Eberlin, Christopher J. Dy, Mark D. Fischer, James L. Gluck, F. Thomas D. Kaplan, Thomas J. Mcdonald, Larry E. Miller, Alexander Palmer, Marc E. Walker, James F. Watt

2020-Current year OA Pubs

BACKGROUND: Carpal tunnel release (CTR) is a surgical treatment option for patients with carpal tunnel syndrome (CTS) symptoms that are unresponsive to conservative treatment. Most patients experience symptomatic relief after CTR regardless of the surgical technique. However, direct comparisons of the safety and effectiveness between CTR surgical techniques are limited. The purpose of this randomized controlled trial is to compare the safety and effectiveness of CTR with ultrasound guidance (CTR-US) versus mini-open CTR (mOCTR) in subjects with symptomatic CTS.

DESIGN AND METHODS: TUTOR (Trial of Ultrasound guided CTR versus Traditional Open Release) is a randomized controlled trial in which 120 …

Predicting Postoperative Troponin In Patients Undergoing Elective Hip Or Knee Arthroplasty: A Comparison Of Five Cardiac Risk Prediction Tools, Merih T Tesfazghi, Anne R Bass, Noor Al-Hammadi, Scott C Woller, Scott M Stevens, Charles S Eby, Mitchell G Scott, Lindsey Snyder, Troy S Wildes, Brian F Gage

2020-Current year OA Pubs

BACKGROUND: Elderly patients undergoing hip or knee arthroplasty are at a risk for myocardial injury after noncardiac surgery (MINS). We evaluated the ability of five common cardiac risk scores, alone or combined with baseline high-sensitivity cardiac troponin I (hs-cTnI), in predicting MINS and postoperative day 2 (POD2) hs-cTnI levels in patients undergoing elective total hip or knee arthroplasty.

METHODS: This study is ancillary to the Genetics-InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, which enrolled patients 65 years and older undergoing elective total hip or knee arthroplasty. The five cardiac risk scores evaluated were the atherosclerotic cardiovascular …

Impact Of The Covid-19 Pandemic On The Implementation Of Mobile Health To Improve The Uptake Of Hydroxyurea In Patients With Sickle Cell Disease: Mixed Methods Study, Sherif M Badawy, Lisa Dimartino, Donald Brambilla, Lisa Klesges, Ana Baumann, Ebony Burns, Terri Demartino, Sara Jacobs, Hamda Khan, Chinonyelum Nwosu, Nirmish Shah, Jane S Hankins, Sickle Cell Disease Implementation Consortium

2020-Current year OA Pubs

BACKGROUND: Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care.

OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on the implementation of …

Clinical And Molecular Response To Tebentafusp In Previously Treated Patients With Metastatic Uveal Melanoma: A Phase 2 Trial, Richard D Carvajal, Leonel Hernandez-Aya, Et Al.

2020-Current year OA Pubs

In patients with previously treated metastatic uveal melanoma, the historical 1 year overall survival rate is 37% with a median overall survival of 7.8 months. We conducted a multicenter, single-arm, open-label phase 2 study of tebentafusp, a soluble T cell receptor bispecific (gp100×CD3), in 127 patients with treatment-refractory metastatic uveal melanoma (NCT02570308). The primary endpoint was the estimation of objective response rate based on RECIST (Response Evaluation Criteria in Solid Tumours) v1.1. Secondary objectives included safety, overall survival, progression-free survival and disease control rate. All patients had at least one treatment-related adverse event, with rash (87%), pyrexia (80%) and pruritus …

Personalized Structural Biology Reveals The Molecular Mechanisms Underlying Heterogeneous Epileptic Phenotypes Caused By De Novo Kcnc2 Variants, Souhrid Mukherjee, Jonathan H Sheehan, Et Al.

2020-Current year OA Pubs

Whole-exome sequencing (WES) in the clinic has identified several rare monogenic developmental and epileptic encephalopathies (DEE) caused by ion channel variants. However, WES often fails to provide actionable insight for rare diseases, such as DEEs, due to the challenges of interpreting variants of unknown significance (VUS). Here, we describe a "personalized structural biology" (PSB) approach that leverages recent innovations in the analysis of protein 3D structures to address this challenge. We illustrate this approach in an Undiagnosed Diseases Network (UDN) individual with DEE symptoms and a

Ho'ouna Pono Implementation: Applying Concept Mapping To A Culturally Grounded Substance Use Prevention Curriculum In Rural Hawai'i Schools, Kelsie H Okamura, Scott K Okamoto, Sarah Momilani Marshall, Steven Keone Chin, Pamela M Garcia, Byron J Powell, Kelly A Stern, Sara J Becker, David S Mandell

2020-Current year OA Pubs

BACKGROUND: Despite their potential to ameliorate health disparities and address youth substance use, prevention programs have been poorly disseminated and implemented across Hawai'i, which begs the question: Why are effective prevention programs not being used in communities most in need of them? Implementing and sustaining culturally grounded prevention programs is critical to address equitable healthcare and minimize health disparities in communities. The field of implementation science provides frameworks, theories, and methods to examine factors associated with community adoption of these programs.

METHOD: Our project applies concept mapping methods to a culturally grounded youth drug prevention program with state level educational …

Amyloid Β, Lipid Metabolism, Basal Cholinergic System, And Therapeutics In Alzheimer's Disease, Victoria Campos-Peña, Pavel Pichardo-Rojas, Talía Sánchez-Barbosa, Emma Ortíz-Islas, Citlali Ekaterina Rodríguez-Pérez, Pedro Montes, Gerardo Ramos-Palacios, Daniela Silva-Adaya, Rafael Valencia-Quintana, Jorge Francisco Cerna-Cortes, Danira Toral-Rios

2020-Current year OA Pubs

The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each …

Collaborative Quality Improvement Strategy In Secondary Prevention Of Cardiovascular Disease In India: Findings From A Multi-Stakeholder, Qualitative Study Using Consolidated Framework For Implementation Research (Cfir), Kavita Singh, Mark D. Huffman, Leslie C M Johnson, Nikhil Tandon, Dorairaj Prabhakaran, Emily Mendenhall

2020-Current year OA Pubs

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent in India, and little is known about the perception of patients and providers about a package of collaborative quality improvement (C-QIP) strategies consisting of provider-focused electronic health records-decision support system (EHR-DSS), non-physician health workers (NPHW), and patient-facing text messages to enhance the CVD care.

OBJECTIVE: To explore the barriers and enablers of the C-QIP strategy from the perspective of providers, health administrators, patients, and care givers in India.

METHODS: We conducted a qualitative study using the consolidated framework for implementation research (CFIR) to understand the challenges and facilitators of implementing C-QIP strategy to …

Whole Genome Sequence Analysis Of Blood Lipid Levels In >66,000 Individuals, Margaret Sunitha Selvaraj, Lisa De Las Fuentes, Susan K. Dutcher, Et Al.

2020-Current year OA Pubs

No abstract provided.

Association Of Α-Klotho With Subclinical Carotid Atherosclerosis In Subjects With Type 1 Diabetes Mellitus, Esmeralda Castelblanco, Marta Hernández, Nuria Alonso, Aina Ribes-Betriu, Jordi Real, Minerva Granado-Casas, Joana Rossell, Marina Idalia Rojo-López, Adriana Silvia Dusso, Josep Julve, Didac Mauricio

2020-Current year OA Pubs

BACKGROUND: Compelling evidence suggests that the fibroblast growth factor 23 (FGF23) / α-klotho axis is impaired in subjects with diabetes mellitus. We examined the relationship between parameters related to calcium/phosphate homeostasis, including FGF23 and α-klotho, and subclinical carotid atherosclerosis burden in type 1 diabetes mellitus (T1D) subjects.

METHODS: This cross-sectional study involved 226 subjects with T1D and 147 age-, sex- and plaque-matched, non-diabetic (non-T1D) subjects, both with normal renal function. Carotid ultrasound was performed to determine the presence and burden of atheromatous plaques. Concentrations of the intact form of FGF23 and α-klotho were assessed by ELISA. Calcium, phosphate, parathyroid hormone, …

Mesoscale Structure-Function Relationships In Mitochondrial Transcriptional Condensates, Marina Feric, Azadeh Sarfallah, Furqan Dar, Dmitry Temiakov, Rohit V Pappu, Tom Misteli

2020-Current year OA Pubs

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure-function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters …

Blood Culture Utilization Practices Among Febrile And/Or Hypothermic Inpatients, Kap Sum Foong, Satish Munigala, Stephanie Kern-Allely, David K Warren

2020-Current year OA Pubs

BACKGROUND: Predictors associated with the decision of blood culture ordering among hospitalized patients with abnormal body temperature are still underexplored, particularly non-clinical factors. In this study, we evaluated the factors affecting blood culture ordering in febrile and hypothermic inpatients.

METHODS: We performed a retrospective study of 15,788 adult inpatients with fever (≥ 38.3℃) or hypothermia (< 36.0℃) from January 2016 to December 2017. We evaluated the proportion of febrile and hypothermic episodes with an associated blood culture performed within 24h. Generalized Estimating Equations were used to determine independent predictors associated with blood culture ordering among febrile and hypothermic inpatients.

RESULTS: We identified 21,383 abnormal body temperature episodes among 15,788 inpatients (13,093 febrile and 8,290 hypothermic episodes). Blood cultures were performed in 36.7% (7,850/ 21,383) of these episodes. Predictors for blood culture ordering among inpatients with abnormal body temperature included fever ≥ 39℃ (adjusted …

Occupational Characteristics Associated With Sars-Cov-2 Infection In The Uk Biobank During August-November 2020: A Cohort Study, Elizabeth L Yanik, Bradley A Evanoff, Ann Marie Dale, Yinjiao Ma, Karen E Walker-Bone

2020-Current year OA Pubs

BACKGROUND: Occupational exposures may play a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk. We used a job-exposure matrix linked to the UK Biobank to measure occupational characteristics and estimate associations with a positive SARS-CoV-2 test.

METHODS: People reporting job titles at their baseline interview in England who were < 65 years of age in 2020 were included. Healthcare workers were excluded because of differential access to testing. Jobs were linked to the US Occupational Information Network (O*NET) job exposure matrix. O*NET-based scores were examined for occupational physical proximity, exposure to diseases/infection, working outdoors exposed to weather, and working outdoors under cover (score range = 1-5). Jobs were classified as remote work using two algorithms. SARS-CoV-2 test results were evaluated between August 5th-November 10th, 2020, when the UK was released from lockdown. Cox regression was used to calculate adjusted hazard ratios (aHRs), accounting for age, sex, race, education, neighborhood deprivation, assessment center, household size, and income.

RESULTS: We included 115,451 people with job titles, of whom 1746 tested positive for SARS-CoV-2. A one-point increase in physical proximity score was associated with 1.14 times higher risk of SARS-CoV-2 (95%CI = 1.05-1.24). A one-point increase in the exposure to diseases/infections score was associated with 1.09 …

Global Variation In Isolated Posterior Cruciate Ligament Reconstruction, Derrick M Knapik, Varun Gopinatth, Garrett R Jackson, Jorge Chahla, Matthew V Smith, Matthew J Matava, Robert H Brophy

2020-Current year OA Pubs

PURPOSE: In the setting of persistent instability or failed non-operative management, surgical reconstruction is commonly recommended for isolated posterior cruciate ligament (PCL) tears. The purpose of this study was to systematically review published studies to evaluate regional variation in the epidemiology of and surgical approaches to primary, isolated PCL reconstruction.

METHODS: A systematic review was performed in June 2022 to identify studies examining operative techniques during primary, isolated PCL reconstruction. Collected variables consisted of reconstruction technique, graft type, graft source, tibial reconstruction technique, femoral and tibial drilling and fixation methods, and whether the remnant PCL was preserved or debrided. Studies …

Cellular Sources And Neuroprotective Roles Of Interleukin-10 In The Facial Motor Nucleus After Axotomy, Elizabeth M Runge, Deborah O Setter, Abhirami K Iyer, Eric J Regele, Felicia M Kennedy, Virginia M Sanders, Kathryn J Jones

2020-Current year OA Pubs

Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA.

Why Tic Severity Changes From Then To Now And From Here To There, Ann M Iverson, Kevin J. Black

2020-Current year OA Pubs

Much of the research regarding Tourette's syndrome (TS) has focused on why certain individuals develop tics while others do not. However, a separate line of research focuses on the momentary influences that cause tics to increase or decrease in patients who are already known to have TS or another chronic tic disorder (CTD). Environmental and internal variables such as fatigue, anxiety, and certain types of thoughts all have been shown to worsen tic severity and may even overcome the positive effects of treatment. Other influences such as stress, distraction, and being observed have had mixed effects in the various studies …

Integrating A Patient Decision Aid Into The Electronic Health Record: A Case Report On The Implementation Of Breastchoice At 2 Sites, Clara N Lee, Janessa Sullivan, Randi Foraker, Terence M Myckatyn, Margaret A Olsen, Crystal Phommasathit, Jessica Boateng, Katelyn L Parrish, Milisa Rizer, Tim Huerta, Mary C Politi

2020-Current year OA Pubs

UNLABELLED: Patient decision aids can support shared decision making and improve decision quality. However, decision aids are not widely used in clinical practice due to multiple barriers. Integrating patient decision aids into the electronic health record (EHR) can increase their use by making them more clinically relevant, personalized, and actionable. In this article, we describe the procedures and considerations for integrating a patient decision aid into the EHR, based on the example of BREASTChoice, a decision aid for breast reconstruction after mastectomy. BREASTChoice's unique features include 1) personalized risk prediction using clinical data from the EHR, 2) clinician- and patient-facing …

Multi-Trait Genome-Wide Association Study Of Opioid Addiction: Oprm1 And Beyond, Nathan Gaddis, Arpana Agrawal, Paul W Jeffries, Kathleen Bucholz, Elliot C Nelson, Laura Bierut, Et Al.

2020-Current year OA Pubs

Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (r

A Bioresorbable Peripheral Nerve Stimulator For Electronic Pain Block, Geumbee Lee, Emily Ray, Sabrina Genovese, Ying Yan, Arman Odabas, Umang Khandpur, Wilson Z Ray, Matthew R Macewan, Et Al.

2020-Current year OA Pubs

Local electrical stimulation of peripheral nerves can block the propagation of action potentials, as an attractive alternative to pharmacological agents for the treatment of acute pain. Traditional hardware for such purposes, however, involves interfaces that can damage nerve tissue and, when used for temporary pain relief, that impose costs and risks due to requirements for surgical extraction after a period of need. Here, we introduce a bioresorbable nerve stimulator that enables electrical nerve block and associated pain mitigation without these drawbacks. This platform combines a collection of bioresorbable materials in architectures that support stable blocking with minimal adverse mechanical, electrical, …

Spontaneous Activity Patterns In Human Motor Cortex Replay Evoked Activity Patterns For Hand Movements, Tomer Livne, Dohyun Kim, Nicholas V Metcalf, Lu Zhang, Lorenzo Pini, Gordon L Shulman, Maurizio Corbetta

2020-Current year OA Pubs

Spontaneous brain activity, measured with resting state fMRI (R-fMRI), is correlated among regions that are co-activated by behavioral tasks. It is unclear, however, whether spatial patterns of spontaneous activity within a cortical region correspond to spatial patterns of activity evoked by specific stimuli, actions, or mental states. The current study investigated the hypothesis that spontaneous activity in motor cortex represents motor patterns commonly occurring in daily life. To test this hypothesis 15 healthy participants were scanned while performing four different hand movements. Three movements (Grip, Extend, Pinch) were ecological involving grip and grasp hand movements; one control movement involving the …

Integrating Transcriptomics, Metabolomics, And Gwas Helps Reveal Molecular Mechanisms For Metabolite Levels And Disease Risk, Xianyong Yin, Adam E Locke, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

Transcriptomics data have been integrated with genome-wide association studies (GWASs) to help understand disease/trait molecular mechanisms. The utility of metabolomics, integrated with transcriptomics and disease GWASs, to understand molecular mechanisms for metabolite levels or diseases has not been thoroughly evaluated. We performed probabilistic transcriptome-wide association and locus-level colocalization analyses to integrate transcriptomics results for 49 tissues in 706 individuals from the GTEx project, metabolomics results for 1,391 plasma metabolites in 6,136 Finnish men from the METSIM study, and GWAS results for 2,861 disease traits in 260,405 Finnish individuals from the FinnGen study. We found that genetic variants that regulate metabolite …

Continuous Npwt Regulates Fibrosis In Murine Diabetic Wound Healing, Mengfan Wu, Dany Y Matar, Zhen Yu, Ziyu Chen, Samuel Knoedler, Brian Ng, Oliver A Darwish, Sadaf Sohrabi, Leigh Friedman, Valentin Haug, George F Murphy, Yuval Rinkevich, Dennis P Orgill, Adriana C Panayi

2020-Current year OA Pubs

Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, -125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP (

Unravelling The Reservoirs For Colonisation Of Infants With Campylobacter Spp. In Rural Ethiopia: Protocol For A Longitudinal Study During A Global Pandemic And Political Tensions, Arie H Havelaar, Mark J Manary, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Undernutrition is an underlying cause of mortality in children under five (CU5) years of age. Animal-source foods have been shown to decrease malnutrition in CU5. Livestock are important reservoirs for

METHODS AND ANALYSIS: This longitudinal study involves 115 infants who are followed from birth to 12 months of age and are selected randomly from 10 kebeles of Haramaya woreda, East Hararghe zone, Oromia region, Ethiopia. Questionnaire-based information is obtained on demographics, livelihoods, wealth, health, nutrition and women empowerment; animal ownership/management and diseases; and water, sanitation and hygiene. Faecal samples are collected from infants, mothers, siblings and livestock, drinking water …

Antidepressant Use And Its Association With 28-Day Mortality In Inpatients With Sars-Cov-2: Support For The Fiasma Model Against Covid-19, Nicolas Hoertel, Angela M Reiersen, Eric J Lenze, Bradley A Fritz, Et Al.

2020-Current year OA Pubs

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant …

A Living Database Of Hiv Implementation Research (Live Project): Protocol For Rapid Living Reviews, Ingrid Eshun-Wilson, Nathan Ford, Noelle Le Tourneau, Stefan Baral, Sheree Schwartz, Christopher Kemp, Elvin Geng

2020-Current year OA Pubs

BACKGROUND: HIV implementation research evolves rapidly and is often complex and poorly characterized, which makes the synthesis of data on HIV implementation strategies inherently difficult. This is further compromised by prolonged data abstraction processes due to variable interventions, outcomes, and context, and delays in the publication of review findings; this can all result in outdated and irrelevant systematic reviews.

OBJECTIVE: The LIVE project (A Living Database of HIV Implementation Research) aims to overcome these challenges by applying an implementation science lens to the conduct of rapid living systematic reviews and meta-analyses to inform HIV service delivery priorities and guideline development. …

Global Longitudinal Strain And Biomarkers Of Cardiac Damage And Stress As Predictors Of Outcomes After Transcatheter Aortic Valve Implantation, Andrew S Perry, Nishath Quader, Alan Zajarias, Et Al.

2020-Current year OA Pubs

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (

Pan-Cancer Analysis Reveals Recurrent Bcar4 Gene Fusions Across Solid Tumors, Andrew Nickless, Jin Zhang, Ghofran Othoum, Jace Webster, Matthew J Inkman, Emily Coonrod, Sherron Fontes, Emily B Rozycki, Christopher A Maher, Nicole M White

2020-Current year OA Pubs

UNLABELLED: Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner-with differing upstream regions across a patient cohort-suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient …

A Non-Canonical Retina-Iprgcs-Scn-Pvt Visual Pathway For Mediating Contagious Itch Behavior, Fang Gao, Jun Ma, Yao-Qing Yu, Xiao-Fei Gao, Yang Bai, Yi Sun, Juan Liu, Xianyu Liu, Devin M Barry, Steven Wilhelm, Tyler Piccinni-Ash, Na Wang, Dongyang Liu, Yan Hao, Jin-Jing Jia, Qianyi Yang, Johan Van Nispen, Zhou-Feng Chen, Et Al.

2020-Current year OA Pubs

Contagious itch behavior informs conspecifics of adverse environment and is crucial for the survival of social animals. Gastrin-releasing peptide (GRP) and its receptor (GRPR) in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates contagious itch behavior in mice. Here, we show that intrinsically photosensitive retina ganglion cells (ipRGCs) convey visual itch information, independently of melanopsin, from the retina to GRP neurons via PACAP-PAC1R signaling. Moreover, GRPR neurons relay itch information to the paraventricular nucleus of the thalamus (PVT). Surprisingly, neither the visual cortex nor superior colliculus is involved in contagious itch. In vivo calcium imaging and extracellular recordings reveal contagious …