tbuckley/cabot-search huggingface dataset:
Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health
Authors: Satu Strausz, Sanni Ruotsalainen, Hanna M. Ollila, Juha Karjalainen, Tuomo Kiiskinen, Mary Reeve, Mitja Kurki, Nina Mars, Aki S. Havulinna, Elina Luonsi, Dina Mansour Aly, Emma Ahlqvist, Maris Teder-Laving, Priit Palta, Leif Groop, Reedik Mägi, Antti Mäkitie, Veikko Salomaa, Adel Bachour, Tiinamaija Tuomi, Aarno Palotie, Tuula Palotie, Samuli Ripatti
Journal: European Respiratory Journal (2020)

There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed to identify genetic loci associated with OSA risk, and to test if OSA and its comorbidities share a common genetic background. We conducted the first large-scale genome-wide association study of OSA using the FinnGen study (217 955 individuals) with 16 761 OSA patients identified using nationwide health registries. We estimated 0.08 (95% CI 0.06–0.11) heritability and identified five loci associated with OSA (p&lt;5.0×10 −8 ): rs4837016 near GAPVD1 (GTPase activating protein and VPS9 domains 1), rs10928560 near CXCR4 (C-X-C motif chemokine receptor type 4), rs185932673 near CAMK1D (calcium/calmodulin-dependent protein kinase ID) and rs9937053 near FTO (fat mass and obesity-associated protein; a variant previously associated with body mass index (BMI)). In a BMI-adjusted analysis, an association was observed for rs10507084 near RMST / NEDD1 (rhabdomyosarcoma 2 associated transcript/NEDD1 γ-tubulin ring complex targeting factor). We found high genetic correlations between OSA and BMI (r g =0.72 (95% CI 0.62–0.83)), and with comorbidities including hypertension, type 2 diabetes, coronary heart disease, stroke, depression, hypothyroidism, asthma and inflammatory rheumatic disease (r g &gt;0.30). The polygenic risk score for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile, and Mendelian randomisation supported a causal relationship between BMI and OSA. Our findings support the causal link between obesity and OSA, and the joint genetic basis between OSA and comorbidities.
Abstract IA17: Ethics, cancer, and COVID
Authors: Arthur Caplan
Journal: Clinical Cancer Research (2020)

Abstract This talk will review (1) the impact of the covid-19 outbreak on treating cancer patients who were infected with the virus with unapproved and off-label agents under a philosophy of compassionate use including disclosure of conflicts of interest; (2) the ethics of withholding diagnosis and treatment from patients with cancer or who might have acquired cancer in the USA once social isolation, quarantines, and restriction of “nonessential” services began; (3) decisions about how to define “essential” services during the onset of the pandemic in severely impacted areas of the U.S.; (4) the management of those who died during the pandemic as lessons for future clinical care of cancer patients; (5) decisions about how to decide how much risk to permit those involved in clinical care for cancer or for reassigned duties to assume during an ongoing pandemic; and (6) how to prioritize future cancer research as the viral outbreak continues and resources remain restricted. Citation Format: Arthur Caplan. Ethics, cancer, and COVID [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr IA17.
The effect of the magnitude of weight loss on non-alcoholic fatty liver disease: A systematic review and meta-analysis
Authors: Dimitrios A. Koutoukidis, Constantinos Koshiaris, John A. Henry, Michaela Noreik, Elizabeth Morris, Indrani Manoharan, Kate Tudor, Emma Bodenham, Anna Dunnigan, Susan A. Jebb, Paul Aveyard
Journal: Metabolism (2020)
18708 Comparative pharmacokinetic evaluation of delivery of three different vitamin C molecules in target tissues: Ascorbyl glucoside, nanoencapsulated vitamin C, and acid ascorbic
Authors: Ana Coutinho, Fernanda Chaves Beltrao, Nathalie Borotra, Sandrine Bessou Touya, Helene Duplan, Anne Laure Gaudry, Carine Jacques Jamin, Camille Genies, Andreia Feital
Journal: Journal of the American Academy of Dermatology (2020)
18494 Reflectance confocal microscopy features in cutaneous leishmaniasis
Authors: Virginia Velasco-Tamariz, Cristina Vico-Alonso, Alba Calleja Algarra, Belén Pinilla-Martín, Mario Puerta-Peña, Alba Sanchez-Velazquez, Reyes Gamo, Pablo L. Ortiz Romero
Journal: Journal of the American Academy of Dermatology (2020)
Network Analysis of Psychopathology: Controversies and Challenges
Authors: Richard J. McNally
Journal: Annual Review of Clinical Psychology (2020)

Empirical publications inspired by the network approach to psychopathology have increased exponentially in the twenty-first century. The central idea that an episode of mental disorder arises from causal interactions among its symptomatic elements has especially resonated with those clinical scientists whose disenchantment with traditional categorical and dimensional approaches to mental illness has become all too apparent. As the field has matured, conceptual and statistical concerns about the limitations of network approaches to psychopathology have emerged, inspiring the development of novel methods to address these concerns. Rather than reviewing the vast empirical literature, I focus instead on the issues and controversies regarding this approach and sketch directions where the field might go next.
Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions
Authors: Han Yu, Shaoxing Yu, Hua Qiu, Peng Gao, Yingzhong Chen, Xin Zhao, Qiufen Tu, Minggang Zhou, Lin Cai, Nan Huang, Kaiqin Xiong, Zhilu Yang
Journal: Bioactive Materials (2020)

Application of extracorporeal circuits and indwelling medical devices has saved many lives. However, it is accompanied with two major complications: thrombosis and infection. To address this issue, we apply therapeutic nitric oxide gas (NO) and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions. Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions (Cu-DOTA) and dibenzylcyclooctyne- (DBCO-) modified antimicrobial peptide based on carbodiimide and click chemistry respectively. The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth, but also catalytically generate NO from endogenous s-nitrosothiols (RSNO) to reduce adhesion and activation of platelets, preventing the formation of thrombus. We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices, with reduced clinical complications associated with thrombosis and infection.
5MO Evaluation of pathological complete response (pCR) after neoadjuvant chemo-radiation therapy for primary breast cancer (JCOG0306A1)
Authors: T. Shien, H. Tsuda, K. Sasaki, J. Mizusawa, F. Akiyama, M. Kurosumi, M. Sawaki, N. Tamura, K. Tanaka, M. Takahashi, N. Hayashi, H. Mukai, N. Masuda, H. Iwata
Journal: Annals of Oncology (2020)
Abstract 14151: Role of Mechanical Circulatory Support Devices in Patient With Pulmonary Hypertension and STEMI
Authors: Ahmad A Awan, Muhammad Rizwan, Richard Ogunti, Mohammad M Munawwar, Manila Jindal, Isaac Opoku-Asare
Journal: Circulation (2019)

Introduction: Pulmonary hypertension is associated with worse outcomes in patients following STEMI. The use of mechanical circulatory support (MCS) in this patient population is not well studied. I...
Diabetes and Coronary Disease: A Need for New Therapies for an Expanding Disease Burden⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Wilbur Y.W. Lew, Anthony N. DeMaria
Journal: Journal of the American College of Cardiology (2013)
316P Implementation of Vela Analytics to accelerate comprehensive interpretation and reporting of next-generation sequencing-based oncology testing in clinical diagnostic laboratories
Authors: Y. Yu, O. Scully, T. Zhang, Z.H. Kyaw, V.Y. Chung, D. Tay, P. Ariyaratne, M.K.K. Aye, M.Q. Yee, Y.L. Kok, E. Wee, L. Lacroix, C. Lee
Journal: Annals of Oncology (2020)
THU0088 Prevention of a novel and newly discovered anti-arthritic compound sx-5452 on development of collagen-induced arthritis in dba/1 mice and autoimmune responses in mrl/lpr mice
Authors: MN Itoh, M Tanaka, S Mishina, T Murata, K Ohno
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In trying to elucidate the value of new drug regimens in rheumatoid arthritis (RA), it is of critical importance to use animal models which share as many features as possible with the human disease. Collagen 0 induced arthritis) CIA) is characterised by development of both cellular and humoral immune responses directed against heterologous and autologous CII. Newly discovered diphenylpyrimidine amino acetamide derivatives pretreatment has been shown <i>in vitro</i> to reduce anti-CII antibody formation. Against this background, we wanted to investigate the clinical effects of SX-5452 on CIA and MRL/lpr. <h3>Objectives</h3> To investigate the effectiveness of SX-5452 in preventing the development of arthritis/autoimmune diseases and to compare the potency/mechanisms with Leflunomide, a novel anti-rheumatic drug. <h3>Methods</h3> Male DBA/1 mice and female MRL/lpr/lpr mice were used. The degrees of swelling, redness were evaluated macroscopically and intensity of inflammation was evaluated by histologically. At the same time the antibody formation was evaluated <i>in vivo</i> and <i>in vitro</i>. <h3>Results</h3> Oral administration of SX-5452(0.03 mg/kg/day-10 mg/kg/day) from the day of immunisation with CII strongly and dose-dependently suppressed the development of arthritis. SX-5452 at the dose of 10 mg/kg prevented completely the development of arthritis in both arthritic score and histological changes. Furthermore administration of SX-5452 at the dose of 10 mg/kg one a week also suppressed almost completely the development of CIA. It also showed inhibitory effect on the production of anti-CII antibody in CIA mice as well as anti-DNA antibody in MRL/lpr mice. These effects were at least three-fold more potent than those of leflunomide. MAPK-pathway and tyrosine phosphorylation are raised as the possible molecular mechanisms. <h3>Conclusion</h3> The development of CIA and autoimmune responses in MRL/lpr mice were markedly suppressed by SX-5452 via inhibition of anti-CII/anti-DNA antibodies formation. Since SX-5452 exerts no overt toxicity after repeated administration in mice, it is an interesting candidate for therapeutic use in rheumatoid arthritis.
13605 Burden of atopic dermatitis: Real-world data from a large nationwide health care provider
Authors: Clara Weil, Philip Sugerman, Gabriel Chodick, Huifang Liang, Hongwei Wang, Brian Calimlim, Tal Giterman-Galam, Dan Ben-Amitai, Yael Anne Leshem
Journal: Journal of the American Academy of Dermatology (2020)
MEK inhibition reprograms CD8+ T lymphocytes into memory stem cells with potent antitumor effects
Authors: Vivek Verma, Nazli Jafarzadeh, Shannon Boi, Subhadip Kundu, Zhinuo Jiang, Yiping Fan, Jose Lopez, Rahul Nandre, Peng Zeng, Fatmah Alolaqi, Shamim Ahmad, Pankaj Gaur, Simon T. Barry, Viia E. Valge-Archer, Paul D. Smith, Jacques Banchereau, Mikayel Mkrtichyan, Benjamin Youngblood, Paulo C. Rodriguez, Seema Gupta, Samir N. Khleif
Journal: Nature Immunology (2020)
Low LDL-C Levels and Cancer: Reassuring But Still Not Definitive⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Ori Ben-Yehuda, Anthony N. DeMaria
Journal: Journal of the American College of Cardiology (2008)
From Economic Recovery to Health Resilience
Authors: Dave A. Chokshi
Journal: JAMA (2021)

Chokski discusses economic recovery to health resilience  For decades, scholars have debated not whether the economy and public health are interlinked, but how  Several recent studies indicate a strong and persistent correlation between lower incomes and excess mortality, though this link sometimes manifests over years or even generations  As it has with so much else, the coronavirus disease 2019 (COVID-19) pandemic has compressed time in a way that reveals the interconnection between the economy and public health  With the change in the federal administration, there is a renewed chance to challenge the false dichotomy of economic growth vs public health and adopt policies that advance both together
Development and initial psychometric validation of a patient-reported outcome measure for Crohn’s perianal fistula: the Crohn’s Anal Fistula Quality of Life (CAF-QoL) scale
Authors: Samuel O Adegbola, Lesley Dibley, Kapil Sahnan, Tiffany Wade, Azmina Verjee, Rachel Sawyer, Sameer Mannick, Damian McCluskey, Paul Bassett, Nuha Yassin, Janindra Warusavitarne, Omar Faiz, Robin Phillips, Phil J Tozer, Christine Norton, Ailsa L Hart
Journal: Gut (2020)

Introduction Crohn’s perianal fistulas are challenging for patients and clinicians. Many do not respond to available treatments and despite recommendations by a global consensus, there are currently no specific patient-derived quality of life tools to measure response to treatment. We present a new validated patient-reported outcome measure (PROM) for this complicated disease phenotype. Methods A draft questionnaire was generated using unstructured qualitative patient interviews on the experience of living with Crohn’s perianal fistula, a nationwide multidisciplinary consensus exercise, a systematic review of outcomes assessing medical/surgical/combined treatment and a patient and public involvement day. Psychometric properties were assessed including construct validity (by comparison with the Hospital Anxiety and Depression Scale (HADS) and the UK Inflammatory Bowel Disease Questionnaire (UK-IBDQ)), and reliability and responsiveness was assessed by test–retest analysis. Results Data from 211 patients contributed to development of a final 28-item questionnaire. The Crohn’s Anal Fistula Quality of Life (CAF-QoL) demonstrated good internal consistency (Cronbach’s alpha 0.88), excellent stability (intraclass correlation 0.98) and good responsiveness and construct validity, with positive correlation with the UK-IBDQ and HADS. Conclusion The CAF-QoL scale is ready for use as a PROM in research and clinical practice. It complements objective clinical evaluation of fistula by capturing impact on the patient.
Outbreak of Mycoplasma pneumoniae at a military academy
Authors: Xin Zhang, Min-Na Han, Jing-Hui Dong, Xiao-Xi Li, Xian-Yun Hu, Zhi Wang, En-Qiang Qin, Jing Li, Jun-Yuan Tan, Fu-Sheng Wang, Lei Huang
Journal: Military Medical Research (2020)

Abstract In 2019, an outbreak of Mycoplasma pneumoniae occurred at a military academy in China. The attack rate (10.08%,60/595) was significantly different among the units. High-intensity training and crowded environments to which cadets are exposed are the high risk factors for the outbreak of M. pneumoniae . In-time prevention and control measures effectively controlled the spread of the epidemic.
Impact of low blood culture usage on rates of antimicrobial resistance
Authors: Cherry Lim, Viriya Hantrakun, Nittaya Teerawattanasook, Pramot Srisamang, Prapit Teparrukkul, Nithima Sumpradit, Paul Turner, Nicholas PJ Day, Ben S Cooper, Sharon J Peacock, Direk Limmathurotsakul
Journal: Journal of Infection (2020)

ObjectivesThe magnitude of impact caused by low blood culture utilization on estimates of the proportions and incidence rates of antimicrobial-resistant (AMR) bacterial infections is largely unknown.MethodsWe used routine electronic databases of microbiology, hospital admission and drug prescription at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand, from 2011 to 2015, and bootstrap simulations.ResultsThe proportions of Escherichia coli and Klebsiella pneumoniae bacteraemias caused by 3rd generation cephalosporin resistant isolates (3GCREC and 3GCRKP) were estimated to increase by 13 and 24 percentage points (from 44% to 57% and from 51% to 75%), respectively, if blood culture utilization rate was reduced from 82 to 26 blood culture specimens per 1,000 patient-days. Among patients with hospital-origin bloodstream infections, the proportion of 3GCREC and 3GCRKP whose first positive blood culture was taken within ±1 calendar day of the start of a parenteral antibiotic at the study hospital was substantially lower than those whose first positive blood culture was taken later into parenteral antibiotic treatment (30% versus 79%, p<0.001; and 37% versus 86%, p<0.001). Similar effects were observed for methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter spp. and carbapenem-resistant Pseudomonas aeruginosa.ConclusionImpacts of low blood culture utilization rate on the estimated proportions and incidence rates of AMR infections could be high. We recommend that AMR surveillance reports should additionally include blood culture utilization rate and stratification by exposure to a parenteral antibiotic at the hospital.
374TiP LAURA: Osimertinib maintenance following definitive chemoradiation therapy (CRT) in patients (pts) with unresectable stage III epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC)
Authors: S. Lu, I. Casarini, T. Kato, M. Cobo Dols, M. Özgüroğlu, L. Zeng, T. van der Gronde, M. Saggese, S. Ramalingam
Journal: Annals of Oncology (2020)
N6-methyladenosine-modified CircRNA-SORE sustains sorafenib resistance in hepatocellular carcinoma by regulating β-catenin signaling
Authors: Junjie Xu, Zhe Wan, Minyue Tang, Zhongjie Lin, Shi Jiang, Lin Ji, Kirill Gorshkov, Qijiang Mao, Shunjie Xia, Dong Cen, Junhao Zheng, Xiao Liang, Xiujun Cai
Journal: Molecular Cancer (2020)

Abstract Background and aims Accumulating evidence suggests that the primary and acquired resistance of hepatocellular carcinoma (HCC) to sorafenib is mediated by multiple molecular, cellular, and microenvironmental mechanisms. Understanding these mechanisms will enhance the likelihood of effective sorafenib therapy. Methods In vitro and in vivo experiments were performed and clinical samples and online databases were acquired for clinical investigation. Results In this study, we found that a circular RNA, circRNA-SORE, which is up-regulated in so rafenib-resistant HCC cells, was necessary for the maintenance of sorafenib resistance, and that silencing circRNA-SORE substantially increased the efficacy of sorafenib-induced apoptosis. Mechanistic studies determined that circRNA-SORE sequestered miR-103a-2-5p and miR-660-3p by acting as a microRNA sponge, thereby competitively activating the Wnt/β-catenin pathway and inducing sorafenib resistance. The increased level of circRNA-SORE in sorafenib-resistant cells resulted from increased RNA stability. This was caused by an increased level of N 6 -methyladenosine (m 6 A) at a specific adenosine in circRNA-SORE. In vivo delivery of circRNA-SORE interfering RNA by local short hairpin RNA lentivirus injection substantially enhanced sorafenib efficacy in animal models. Conclusions This work indicates a novel mechanism for maintaining sorafenib resistance and is a proof-of-concept study for targeting circRNA-SORE in sorafenib-treated HCC patients as a novel pharmaceutical intervention for advanced HCC.
Axl and Mertk Receptors Cooperate to Promote Breast Cancer Progression by Combined Oncogenic Signaling and Evasion of Host Antitumor Immunity
Authors: Viralkumar Davra, Sushil Kumar, Ke Geng, David Calianese, Dhriti Mehta, Varsha Gadiyar, Canan Kasikara, Kevin C. Lahey, Yun-juan Chang, Michael Wichroski, Chan Gao, Mariana S. De Lorenzo, Sergei V. Kotenko, Tessa Bergsbaken, Pankaj K. Mishra, William C. Gause, Michael Quigley, Thomas E. Spires, Raymond B. Birge
Journal: Cancer Research (2020)

Despite the promising clinical benefit of targeted and immune checkpoint blocking therapeutics, current strategies have limited success in breast cancer, indicating that additional inhibitory pathways are required to complement existing therapeutics. TAM receptors (Tyro-3, Axl, and Mertk) are often correlated with poor prognosis because of their capacities to sustain an immunosuppressive environment. Here, we ablate Axl on tumor cells using CRISPR/Cas9 gene editing, and by targeting Mertk in the tumor microenvironment (TME), we observed distinct functions of TAM as oncogenic kinases, as well as inhibitory immune receptors. Depletion of Axl suppressed cell intrinsic oncogenic properties, decreased tumor growth, reduced the incidence of lung metastasis and increased overall survival of mice when injected into mammary fat pad of syngeneic mice, and demonstrated synergy when combined with anti-PD-1 therapy. Blockade of Mertk function on macrophages decreased efferocytosis, altered the cytokine milieu, and resulted in suppressed macrophage gene expression patterns. Mertk-knockout mice or treatment with anti-Mertk-neutralizing mAb also altered the cellular immune profile, resulting in a more inflamed tumor environment with enhanced T-cell infiltration into tumors and T-cell-mediated cytotoxicity. The antitumor activity from Mertk inhibition was abrogated by depletion of cytotoxic CD8α T cells by using anti-CD8α mAb or by transplantation of tumor cells into B6.CB17-Prkdc SCID mice. Our data indicate that targeting Axl expressed on tumor cells and Mertk in the TME is predicted to have a combinatorial benefit to enhance current immunotherapies and that Axl and Mertk have distinct functional activities that impair host antitumor response. SIGNIFICANCE: This study demonstrates how TAM receptors act both as oncogenic tyrosine kinases and as receptors that mediate immune evasion in cancer progression.
Overdose-Related Cardiac Arrests Observed by Emergency Medical Services During the US COVID-19 Epidemic
Authors: Joseph Friedman, Leo Beletsky, David L. Schriger
Journal: JAMA Psychiatry (2020)

This cohort study characterizes emergent trends in overdose-related cardiac arrests in the US during the coronavirus disease 2019 (COVID-19) pandemic using a large, national emergency medical services database.