tbuckley/cabot-search huggingface dataset:
Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice
Authors: Meghan E. Flanigan, Hossein Aleyasin, Long Li, C. Joseph Burnett, Kenny L. Chan, Katherine B. LeClair, Elizabeth K. Lucas, Bridget Matikainen-Ankney, Romain Durand-de Cuttoli, Aki Takahashi, Caroline Menard, Madeline L. Pfau, Sam A. Golden, Sylvain Bouchard, Erin S. Calipari, Eric J. Nestler, Ralph J. DiLeone, Akihiro Yamanaka, George W. Huntley, Roger L. Clem, Scott J. Russo
Journal: Nature Neuroscience (2020)
Incidental CT Findings Suspicious for COVID-19–Associated Pneumonia on Nuclear Medicine Examinations
Authors: Mark Tulchinsky, Joseph S. Fotos, Einat Slonimsky
Journal: Clinical Nuclear Medicine (2020)

Some patients undergoing routine SPECT/CT and PET/CT examinations during the COVID-19 pandemic may incidentally reveal findings of COVID-19-associated pneumonia (C-19AP) on localizing CT. It is critical for nuclear medicine physicians to develop diagnostic skills for timely recognition of typical findings of C-19AP on a localizing CT. Furthermore, it is our responsibility to know the optimal practices for safely isolating and managing such patients while protecting the staff, other patients at the facility, family and/or friend accompanying the patients, and the public in general from risky exposure to COVID-19 sources. We offer several steps following an encounter suspicious of C-19AP.
Association Between Nocturnist Supervision and Perceived Overnight Supervision Adequacy Among Internal Medicine Residents in the US
Authors: Jillian S. Catalanotti, Alec B. O’Connor, Michael Kisielewski, Davoren A. Chick, Kathlyn E. Fletcher
Journal: JAMA (2020)

This cross-sectional study uses data from a voluntary survey that was administered during the American College of Physicians Internal Medicine In-Training Examination to assess whether residents in programs with nocturnists perceived nighttime supervision differently than those in programs without nocturnists.
Three lessons for the COVID-19 response from pandemic HIV
Authors: James Hargreaves, Calum Davey, James Hargreaves, Calum Davey, Judith Auerbach, Jamie Blanchard, Virginia Bond, Chris Bonell, Rochelle Burgess, Joanna Busza, Tim Colbourn, Frances Cowan, Aoife Doyle, James Hakim, Bernadette Hensen, Mina Hosseinipour, Leesa Lin, Saul Johnson, Nyasha Masuka, Webster Mavhu, Owen Mugurungi, Solomon Mukungunugwa, Angela Mushavi, Andrew Phillips, Lucy Platt, Audrey Prost, Eugene Ruzagira, Janet Seeley, Isaac Taramusi, Raymond Yekeye
Journal: The Lancet HIV (2020)
Molecular subtype, biological sex and age shape melanoma tumour evolution
Authors: M. Lotz, T. Budden, S.J. Furney, A. Virós
Journal: British Journal of Dermatology (2020)

Many cancer types display sex and age disparity in incidence and outcome. The mutational load of tumours, including melanoma, varies according to sex and age. However, there are no tools to explore systematically whether clinical variables such as age and sex determine the genomic landscape of cancer.To establish a mathematical approach using melanoma mutational data to analyse how sex and age shape the tumour genome.We model how age-related (clock-like) somatic mutations that arise during cell division, and extrinsic (environmental ultraviolet radiation) mutations accumulate in cancer genomes.Melanoma is driven primarily by cell-intrinsic age-related mutations and extrinsic ultraviolet radiation-induced mutations, and we show that these mutation types differ in magnitude and chronology and by sex in the distinct molecular melanoma subtypes. Our model confirms that age and sex are determinants of cellular mutation rate, shaping the final mutation composition. We show mathematically for the first time how, similarly to noncancer tissues, melanoma genomes reflect a decline in cell division during ageing. We find that clock-like mutations strongly correlate with the acquisition of ultraviolet-induced mutations, but critically, men present a higher number and rate of cell-division-linked mutations.These data indicate that the contribution of environmental damage to melanoma likely extends beyond genetic damage to affect cell division. Sex and age determine the final mutational composition of melanoma.
A framework for identifying regional outbreak and spread of COVID-19 from one-minute population-wide surveys
Authors: Hagai Rossman, Ayya Keshet, Smadar Shilo, Amir Gavrieli, Tal Bauman, Ori Cohen, Esti Shelly, Ran Balicer, Benjamin Geiger, Yuval Dor, Eran Segal
Journal: Nature Medicine (2020)

A framework for identifying regional outbreak
Inflammatory Response Cells During Acute Respiratory Distress Syndrome in Patients With Coronavirus Disease 2019 (COVID-19)
Authors: Yulin Zhang, Yuxue Gao, Luxin Qiao, Wenjing Wang, Dexi Chen
Journal: Annals of Internal Medicine (2020)

CD8(+) CD45RA(+)/CD4(-) CD45RO(+)/CD4(-) CD16(-)/CD107A(+) CD3(+)/CD4(2+) CD3(+)/CD8(+) CD45RA(3+)/CD4(2+) CD45RO(+)/CD4(2+) CD16(2+)/CD107A(2+) CD3(+)/CD4(+) CD3(+)/CD8(+) CD45RA(4+)/CD4(+) CD45RO(+)/CD4(+) CD16(+)/
EIF3H Orchestrates Hippo Pathway–Mediated Oncogenesis via Catalytic Control of YAP Stability
Authors: Zhuan Zhou, Honghong Zhou, Luca Ponzoni, Aiping Luo, Rui Zhu, Mingjing He, Yi Huang, Kun-Liang Guan, Ivet Bahar, Zhihua Liu, Yong Wan
Journal: Cancer Research (2020)

EIF3H is presumed to be a critical translational initiation factor. Here, our unbiased screening for tumor invasion factors has identified an unexpected role for EIF3H as a deubiquitylating enzyme that dictates breast tumor invasion and metastasis by modulating the Hippo-YAP pathway. EIF3H catalyzed YAP for deubiquitylation, resulting in its stabilization. Structure-based molecular modeling and simulations coupled with biochemical characterization unveiled a unique catalytic mechanism for EIF3H in dissociating polyubiquitin chains from YAP through a catalytic triad consisting of Asp90, Asp91, and Gln121. Trp119 and Tyr 140 on EIF3H directly interacted with the N-terminal region of YAP1, facilitating complex formation of EIF3H and YAP1 for YAP1 deubiquitylation. Stabilization of YAP via elevated EIF3H promoted tumor invasion and metastasis. Interference of EIF3H-mediated YAP deubiquitylation blocked YAP-induced tumor progression and metastasis in breast cancer models. These findings point to a critical role for YAP regulation by EIF3H in tumor invasion and metastasis. SIGNIFICANCE: This work demonstrates that EIF3H is a novel
Circular RNA circFBXW4 suppresses hepatic fibrosis via targeting the miR-18b-3p/FBXW7 axis
Authors: Xin Chen, Hai-Di Li, Fang-Tian Bu, Xiao-Feng Li, Yu Chen, Sai Zhu, Jia-Nan Wang, Si-Yu Chen, Ying-Yin Sun, Xue-Yin Pan, Na-Na Yin, Jie-Jie Xu, Cheng Huang, Jun Li
Journal: Theranostics (2020)

Rationale: Circular RNAs (circRNAs) are a new form of noncoding RNAs that play crucial roles in various pathological processes. However, the expression profile and function of circRNAs in hepatic fibrosis (HF) remain largely unknown. In this study, we show a novel circFBXW4 mediates HF via targeting the miR-18b-3p/FBXW7 axis. Methods: We investigated the expression profile of circRNAs, microRNAs and mRNAs in hepatic stellate cells (HSCs) from HF progression and regression mice by circRNAs-seq and microarray analysis. We found a significantly dysregulated circFBXW4 in HF. Loss-of-function and gain-of-function analysis of circFBXW4 were performed to assess the role of circFBXW4 in HF. Furthermore, we confirmed that circFBXW4 directly binds to miR-18b-3p by luciferase reporter assay, RNA pull down and fluorescence in situ hybridization analysis. Results: We found that circFBXW4 downregulated in liver fibrogenesis. Enforcing the expression of circFBXW4 inhibited HSCs activation, proliferation and induced apoptosis, attenuated mouse liver fibrogenesis injury and showed anti-inflammation effect. Mechanistically, circFBXW4 directly targeted to miR-18b-3p to regulate the expression of FBXW7 in HF. Conclusions: circFBXW4 may act as a suppressor of HSCs activation and HF through the circFBXW4/miR-18b-3p/FBXW7 axis. Our findings identify that circFBXW4 serves as a potential biomarker for HF therapy.
Covid-19: UK government is urged to publish daily care home deaths as it promises more testing
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The UK government’s pledge to boost covid-19 testing for staff in care homes must be delivered as quickly as possible and be matched with greater transparency over the number of residents dying from the virus, healthcare leaders have urged.

The government announced on 15 April that it would expand testing in care homes to all residents and staff with covid-19 symptoms “as capacity is built up,” after its pledge to conduct 100 000 tests a day by the end of April. Currently, only the first five symptomatic residents in care homes are tested for the virus to determine an outbreak.

The government also promised that all potential care home residents would now be tested before being discharged from hospital, to help care providers implement isolation procedures for residents who test positive.

England’s health and …
The Aphid X Chromosome Is a Dangerous Place for Functionally Important Genes: Diverse Evolution of Hemipteran Genomes Based on Chromosome-Level Assemblies
Authors: Yiyuan Li, Bo Zhang, Nancy A Moran
Journal: Molecular Biology and Evolution (2020)

Abstract Different evolutionary forces shape gene content and sequence evolution on autosomes versus sex chromosomes. Location on a sex chromosome can favor male-beneficial or female-beneficial mutations depending on the sex determination system and selective pressure on different sexual morphs. An X0 sex determination can lead to autosomal enrichment of male-biased genes, as observed in some hemipteran insect species. Aphids share X0 sex determination; however, models predict the opposite pattern, due to their unusual life cycles, which alternate between all-female asexual generations and a single sexual generation. Predictions include enrichment of female-biased genes on autosomes and of male-biased genes on the X, in contrast to expectations for obligately sexual species. Robust tests of these models require chromosome-level genome assemblies for aphids and related hemipterans with X0 sex determination and obligate sexual reproduction. In this study, we built the first chromosome-level assembly of a psyllid, an aphid relative with X0 sex determination and obligate sexuality, and compared it with recently resolved chromosome-level assemblies of aphid genomes. Aphid and psyllid X chromosomes differ strikingly. In aphids, female-biased genes are strongly enriched on autosomes and male-biased genes are enriched on the X. In psyllids, male-biased genes are enriched on autosomes. Furthermore, functionally important gene categories of aphids are enriched on autosomes. Aphid X-linked genes and male-biased genes are under relaxed purifying selection, but gene content and order on the X is highly conserved, possibly reflecting constraints imposed by unique chromosomal mechanisms associated with the unusual aphid life cycle.
The Importance of Defining Shared Criteria for the Diagnosis of Nonverbal Learning Disability
Authors: Irene C. Mammarella
Journal: JAMA Network Open (2020)

Amy E. Margolis, PhD; Jessica Broitman, PhD; John M. Davis, PhD; Lindsay Alexander, MPH; Ava Hamilton, BA; Zhijie Liao, MA; Sarah Banker, BA; Lauren Thomas, EdM; Bruce Ramphal, BA; Giovanni A. Salum, MD, PhD; Kathleen Merikangas, PhD; Jeff Goldsmith, PhD; Tomas Paus, MD, PhD; Katherine Keyes, PhD; Michael P. Milham, MD, PhD
Abstract 162: A Novel Approach to Quality Improvement in a Hospital’s Targeted Temperatue Management Program for Post Arrest Patients
Authors: Delia R Russell
Journal: Circulation (2019)

Introduction: Studies indicate that initiating therapeutic hypothermia (THT) in a timely manner after return of spontaneous circulation (ROSC) decreases mortality. Our hospital has had an established protocol for THT since 2014; however, we believed that there were opportunities to improve our practice, particularly around time to initiation of therapy and time to target temperature. Goal: Initiate THT as soon as feasible to reach target temperature within 6 hours after ROSC. Methods: Data was downloaded from our Targeted Temperature Management (TTM) devices for post-arrest cases from January to December 2018. The data was used to calculate various metrics including time from ROSC to therapy initiation (time to initiation) and time to target temperature (time to target). These metrics were compared to our THT protocol to identify areas for practice improvement. Concurrently, a product training verification assessment designed to determine the level of knowledge of our TTM device was conducted with our Intensive Care Unit (ICU) staff. Results: Case data was collected, analyzed, and reviewed quarterly with ICU staff and leadership. The product training verification assessment reveled gaps in staff knowledge, including patient management while on TTM therapy, which was addressed with clinician education. Over the four quarters of 2018, there was a decrease in both in time to initiation and time to target. By quarter four, the combined measure of time to initiation and time to target had decreased from over 6 hours in quarter one to 5 hours. Our quarter 4 patient outcomes revealed a 43% survival to discharge rate with a Cerebral Performance Category of 1 or 2 (positive neurological outcomes). Conclusions: Review of the current process, analyzing and comparing data to current protocol, and assessment of staff knowledge revealed gaps in our hospital’s THT program. Implementation of new processes and education using a collaborative approach lead to positive patient outcomes with a measurable decrease in time to initiation and time to target temperature.
Global Reach 2018 Heightened α-Adrenergic Signaling Impairs Endothelial Function During Chronic Exposure to Hypobaric Hypoxia
Authors: Michael M. Tymko, Justin S. Lawley, Philip N. Ainslie, Alexander B. Hansen, Florian Hofstaetter, Simon Rainer, Sachin Amin, Gilbert Moralez, Christopher Gasho, Gustavo Vizcardo-Galindo, Daniela Bermudez, Francisco C. Villafuerte, Christopher M. Hearon
Journal: Circulation Research (2020)

Rationale: Chronic exposure to hypoxia is associated with elevated sympathetic nervous activity and reduced vascular function in lowlanders, and Andean highlanders suffering from excessive erythrocytosis (EE); however, the mechanistic link between chronically elevated sympathetic nervous activity and hypoxia-induced vascular dysfunction has not been determined. Objective: To determine the impact of heightened sympathetic nervous activity on resistance artery endothelial-dependent dilation (EDD), and endothelial-independent dilation, in lowlanders and Andean highlanders with and without EE. Methods and Results: We tested healthy lowlanders (n=9) at sea level (344 m) and following 14 to 21 days at high altitude (4300 m), and permanent Andean highlanders with (n=6) and without (n=9) EE at high altitude. Vascular function was assessed using intraarterial infusions (3 progressive doses) of acetylcholine (ACh; EDD) and sodium nitroprusside (endothelial-independent dilation) before and after local α+β adrenergic receptor blockade (phentolamine and propranolol). Intraarterial blood pressure, heart rate, and simultaneous brachial artery diameter and blood velocity were recorded at rest and during drug infusion. Changes in forearm vascular conductance were calculated. The main findings were (1) chronic hypoxia reduced EDD in lowlanders (changes in forearm vascular conductance from sea level: ACh1: −52.7±19.6%, ACh2: −25.4±38.7%, ACh3: −35.1±34.7%, all P ≤0.02); and in Andeans with EE compared with non-EE (changes in forearm vascular conductance at ACh3: −36.4%, P =0.007). Adrenergic blockade fully restored EDD in lowlanders at high altitude, and normalized EDD between EE and non-EE Andeans. (2) Chronic hypoxia had no effect on endothelial-independent dilation in lowlanders, and no differences were detected between EE and non-EE Andeans; however, EID was increased in the non-EE Andeans after adrenergic blockade ( P =0.012), but this effect was not observed in the EE Andeans. Conclusions: These data indicate that chronic hypoxia reduces EDD via heightened α-adrenergic signaling in lowlanders and in Andeans with EE. These vascular mechanisms have important implications for understanding the physiological consequences of acute and chronic high altitude adaptation.
Medicare Part D and Cost-Sharing for Antiretroviral Therapy and Preexposure Prophylaxis
Authors: Chien-Wen Tseng, R. Adams Dudley, Randi Chen, Rochelle P. Walensky
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The 2019 federal Ending the HIV Epidemic initiative requires a vast expansion of access to antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) for HIV treatment and prevention. However, high prices for ART and PrEP can reduce their affordability and use. Medicare covers 1 in 4 persons living with HIV, and the Medicare Part D drug benefit imposes complicated cost-sharing between patients and other stakeholders. <h3>Objective</h3> To determine how the Medicare Part D design distributes the cost burden for ART and PrEP between patients, insurance plans, manufacturers, and Medicare. <h3>Design and Setting</h3> Nationwide cross-sectional analyses of first quarter 2019 Medicare formulary and pricing files for 3326 Part D plans were performed. These files contain drug benefit data, including prices and cost-sharing requirements. <h3>Main Outcomes and Measures</h3> For 18 ART and 2 PrEP regimens, the out-of-pocket costs for patients and the cost borne by plans, manufacturers, and Medicare were projected for 1 year of treatment or prevention under a 2019 standard Medicare Part D insurance plan. Analyses assumed that patients used the ART or PrEP regimen and no other medications. <h3>Results</h3> In 2019, ART prices ranged from $24 010 to $46 770 annually (median price, $35 780), with patients projected to pay 9% to 14% of the cost ($3270-$4350), insurance plans 18% to 24% ($5340-$8450), manufacturers 6% to 11% ($2370-$2750), and Medicare 53% to 67% ($12 770-$31 270). The price of PrEP was $20 570 annually, with patients contributing 15% ($2990), insurance plans 22% ($4570), manufacturers 13% ($2750), and Medicare 50% ($10 260). For beneficiaries with low-income subsidies that cover all patient cost-sharing, Medicare would assume 67% to 76% of ART costs and 65% of PrEP costs. <h3>Conclusions and Relevance</h3> Medicare Part D mandates universal ART and PrEP coverage, but high prices (&gt;$35 000 annually for ART and&gt;$20 000 annually for PrEP) and the design of Part D can jeopardize affordability for patients and place most of the cost burden on taxpayers. Under a standard Medicare Part D benefit, patients pay $3000 to $4000 out-of-pocket yearly, unless they qualify for low-income subsidies, and half to two-thirds of the cost of ART and PrEP is borne by Medicare rather than insurance plans or manufacturers. To end the HIV epidemic by 2030, it appears that policies must address both high drug prices and revamp Medicare Part D cost-sharing.
Early life acetaminophen exposure, glutathione S-transferase genes, and development of adolescent asthma in a high-risk birth cohort
Authors: Xin Dai, Shyamali C. Dharmage, Michael J. Abramson, Bircan Erbas, Catherine M. Bennett, Cecilie Svanes, Jennie Hui, Christine Axelrad, Adrian J. Lowe, Caroline J. Lodge
Journal: Journal of Allergy and Clinical Immunology (2020)
Allergic contact dermatitis to nonmethacrylate nail allergens in the <scp>UK</scp>
Authors: V. Eleftheriadou, L. Roche, J.F. Bourke, D.A. Buckley, D.I. Orton, N.M. Stone, S.M. Wilkinson, D.A. Thompson, G.A. Johnston
Journal: British Journal of Dermatology (2020)
Irene Higginson: progress towards a better ending
Authors: Geoff Watts
Journal: The Lancet (2020)

Media coverage can drive change—so the note of exasperation in Irene Higginson's voice is understandable: "I wish there was as much attention paid to people who don't have proper access to palliative care as there has been to the assisted dying debate", she says. Higginson has a particular interest in the way we die; as Professor of Palliative Care and Policy at King's College London (KCL), London, UK, she is eager to advocate for her specialty. "UK hospices still rely for two-thirds of their funding on charitable donations", she explains.
Endothelial mTOR maintains hematopoiesis during aging
Authors: Pradeep Ramalingam, Michael G. Poulos, Michael C. Gutkin, Lizabeth Katsnelson, Ana G. Freire, Elisa Lazzari, Jason M. Butler
Journal: The Journal of Experimental Medicine (2020)

Aging leads to a decline in hematopoietic stem and progenitor cell (HSPC) function. We recently discovered that aging of bone marrow endothelial cells (BMECs) leads to an altered crosstalk between the BMEC niche and HSPCs, which instructs young HSPCs to behave as aged HSPCs. Here, we demonstrate aging leads to a decrease in mTOR signaling within BMECs that potentially underlies the age-related impairment of their niche activity. Our findings reveal that pharmacological inhibition of mTOR using Rapamycin has deleterious effects on hematopoiesis. To formally determine whether endothelial-specific inhibition of mTOR can influence hematopoietic aging, we conditionally deleted mTOR in ECs (mTOR(ECKO)) of young mice and observed that their HSPCs displayed attributes of an aged hematopoietic system. Transcriptional profiling of HSPCs from mTOR(ECKO) mice revealed that their transcriptome resembled aged HSPCs. Notably, during serial transplantations, exposure of wild-type HSPCs to an mTOR(ECKO) microenvironment was sufficient to recapitulate aging-associated phenotypes, confirming the instructive role of EC-derived signals in governing HSPC aging.
Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1
Authors: Andrea Mazzanti, Dmitri Guz, Alessandro Trancuccio, Eleonora Pagan, Deni Kukavica, Tekla Chargeishvili, Natalia Olivetti, Elżbieta Katarzyna Biernacka, Luciana Sacilotto, Georgia Sarquella-Brugada, Oscar Campuzano, Eyal Nof, Aristides Anastasakis, Valeria A. Sansone, Juan Jimenez-Jaimez, Fernando Cruz, Jessica Sánchez-Quiñones, Julio Hernandez-Afonso, Maria Eugenia Fuentes, Beata Średniawa, Anastasia Garoufi, Irena Andršová, Maite Izquierdo, Rumen Marinov, Asaf Danon, Victor Expósito-García, Amaya Garcia-Fernandez, Carmen Muñoz-Esparza, Martín Ortíz, Agnieszka Zienciuk-Krajka, Elisa Tavazzani, Nicola Monteforte, Raffaella Bloise, Maira Marino, Mirella Memmi, Carlo Napolitano, Esther Zorio, Lorenzo Monserrat, Vincenzo Bagnardi, Silvia G. Priori
Journal: Journal of the American College of Cardiology (2020)
Rapid drug desensitization for platinum‐based chemotherapy drugs significantly increases peripheral blood IL‐10 levels
Authors: Can Tüzer, Murat Sari, Esin Aktaş Çetin, Naziye Ak, Suna Büyüköztürk, Bahattin Çolakoğlu, Pınar Mualla Saip, Günnur Deniz, Aslı Gelincik
Journal: Allergy (2020)

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