tbuckley/cabot-search huggingface dataset:
Covid 19: death certification in England and Wales
Authors: Tom Luce
Journal: BMJ (2020)

<h3>Objectives</h3> In a qualitative substudy, we sought to elicit participants’ perspectives of their behavioural change and maintenance of new behaviours towards intervention optimisation. <h3>Setting</h3> The intervention was delivered in leisure and community settings in a local authority, which according to the UK government statistics ranks as 1 of the 10 most socioeconomically deprived areas in England. <h3>Participants</h3> We recruited 218 adults aged 40–65 years at elevated risk of type 2 diabetes (Finnish Diabetes Risk Score≥11) to the intervention. Follow-up at 12 months was completed by 134 (62%). We recruited 15 participants, purposively sampled for physical activity increase, to the qualitative substudy. <h3>Intervention</h3> Lifestyle intervention can prevent type 2 diabetes, but translation to service provision remains challenging. The ‘New life, New you’ intervention aimed to promote physical activity, healthy eating and weight loss, and included supervised group physical activity sessions. Behavioural change and weight loss at 12-month follow-up were encouraging. <h3>Design</h3> We conducted 15 individual semistructured interviews. The Framework approach, with a comparison of emerging themes, was used in analysis of the transcribed data and complemented by the Theory Domains Framework. <h3>Results</h3> Themes emerging from the data were grouped as perceptions that promoted initiating, enacting and maintaining behavioural change. The data were then categorised in accordance with the Theory Domains Framework: intentions and goals; reinforcement; knowledge; social role and identity; social influences; skills and beliefs about capabilities; behavioural regulation, memory, emotion, attention and decision processes and environmental context and resources. Participant perceptions of intervention features that facilitated behavioural change processes were then similarly analysed. <h3>Conclusions</h3> Social influences, reference to social role and identity (eg, peer support), and intentions and goals (eg, to lose weight) were dominant themes across the three phases of behavioural change. Reinforcement, regulation and decision processes were more evident in the maintenance phase. The socioeconomic status of participants was reflected in the environmental context and resource theme. Analysis of phases and theoretical domains of behavioural change added depth and utility to inform intervention optimisation. We will develop the intervention with improved peer support and explicit monitoring of the behavioural change techniques used, prior to a definitive trial.
Harnessing Machine Intelligence in Automatic Echocardiogram Analysis: Current Status, Limitations, and Future Directions
Authors: Ghada Zamzmi, Li-Yueh Hsu, Wen Li, Vandana Sachdev, Sameer Antani
Journal: IEEE Reviews in Biomedical Engineering (2020)

Echocardiography (echo) is a critical tool in diagnosing various cardiovascular diseases. Despite its diagnostic and prognostic value, interpretation and analysis of echo images are still widely performed manually by echocardiographers. A plethora of algorithms has been proposed to analyze medical ultrasound data using signal processing and machine learning techniques. These algorithms provided opportunities for developing automated echo analysis and interpretation systems. The automated approach can significantly assist in decreasing the variability and burden associated with manual image measurements. In this paper, we review the state-of-the-art automatic methods for analyzing echocardiography data. Particularly, we comprehensively and systematically review existing methods of four major tasks: echo quality assessment, view classification, boundary segmentation, and disease diagnosis. Our review covers three echo imaging modes, which are B-mode, M-mode, and Doppler. We also discuss the challenges and limitations of current methods and outline the most pressing directions for future research. In summary, this review presents the current status of automatic echo analysis and discusses the challenges that need to be addressed to obtain robust systems suitable for efficient use in clinical settings or point-of-care testing.
Hepatitis B Virus DNA Polymerase Restrains Viral Replication Through the CREB1/HOXA Distal Transcript Antisense RNA Homeobox A13 Axis
Authors: Xiaopei Zhao, Hongxia Fan, Xi Chen, Xiaoqing Zhao, Xu Wang, Yujie Feng, Min Liu, Shengping Li, Hua Tang
Journal: Hepatology (2020)

Background and Aims Long noncoding RNAs (lncRNAs) have been associated with infection and hepatitis B virus (HBV)‐related diseases, though the underlying mechanisms remain unclear. Approach and Results We obtained HBV‐HCC lncRNA profiles by deep sequencing and found HOXA distal transcript antisense RNA (HOTTIP) to be significantly up‐regulated. RT‐qPCR indicated that HOTTIP is highly expressed in HBV‐positive hepatoma tissue and induced by HBV in vitro . Virological experiments showed that HOTTIP significantly suppresses the generation of hepatitis B viral surface antigen, hepatitis B viral e antigen and HBV replication. Homeobox A13 (HOXA13), a downstream factor of HOTTIP, was found to bind to HBV enhancer I and X promotor to repress the production of HBV pregenome RNA (pgRNA) and total RNA as well as HBV replication, suggesting that HOXA13 mediates HOTTIP‐induced suppression of HBV replication. More interestingly, HBV DNA polymerase (DNA pol) binds to and stabilizes cAMP‐responsive element‐binding protein 1 (CREB1) mRNA to facilitate translation of the protein, which, in turn, binds to the regulatory element of HOTTIP to promote its expression. Conclusions Our findings demonstrate that HBV DNA pol attenuates HBV replication through activation of the CREB1‐HOTTIP‐HOXA13 axis. These findings shed light on the mechanism by which HBV restrains replication to contribute to persistent infection.
Fatigue in breast cancer patients during and after radiotherapy
Authors: M. Rucinska, S. T. Langkjer
Journal: Journal of Clinical Oncology (2006)

18537 Background: Fatigue—an unpleasant sensation of tiredness, weakness or lack of energy—is one of the most prevalent and profound symptoms caused by malignancy itself and anti-neoplastic treatment. The aim of the study was to assess the level of fatigue during and after adjuvant postoperative radiotherapy of breast cancer patients. Methods: 125 patients with breast cancer were recruited between May 2004 and September 2005 (85 after breast-conserving surgery and 40 after mastectomy). Subjective feeling of fatigue intensity was measured according to 10-score visual analog scale (VAS) before the start and once a week during radiotherapy, 14 days and 3 months after radiotherapy (48 Gy/24 fractions/5 weeks; 25 patients received boost 10 Gy/5 fractions/1 week with tumor-bed). Results: 46% of patients demonstrated non-fatigue before the start of radiotherapy. Patients after breast-conserving surgery and chemotherapy manifested higher lever of fatigue in comparison with patients after lumpectomy but without chemotherapy and patients after mastectomy with and without chemotherapy (p = 0.01). Fatigue intensity increased gradually during radiotherapy (mean fatigue-VAS before and in the last week of treatment was 1.8, 2.75 after lumpectomy and 1.25, 2.95 after mastectomy, respectively). 14 days after the end of radiotherapy fatigue intensity was still higher than before treatment (p = 0.04), but 3 months later it was lower than the pretreatment level. However, 25% of the patients defined their fatigue as 2 or more in VAS three months after radiotherapy. 15% of patients reported non-fatigue during radiotherapy. Older patients (&gt;60 years) estimated their fatigue in the last week of treatment on lower level than younger patients (2.22 vs 2.90, p = 0.065). Patients with boost manifested only a little higher fatigue level in comparison with other patients (2.97 vs 2.52). Conclusions: Increasing fatigue was found in 85% of breast cancer patients during adjuvant radiotherapy. Three months after the end of therapy fatigue was reduced to lover then the preliminary level. There were no significant differences between patients after breast-conserving surgery and mastectomy. No significant financial relationships to disclose.
Outcomes of Patients With Discordant High-Gradient Aortic Valve Stenosis
Authors: Branka Vulesevic, Ian G. Burwash, Luc M. Beauchesne, Claire Cimadevilla, Leila Siouti, Sarah Tubiana, Xavier Duval, Virginia Nguyen, Dimitri Arangalage, Kwan L. Chan, Erin E. Mulvihill, David Messika-Zeitoun
Journal: JACC. Cardiovascular imaging (2020)
FDA Approval Summary: Pembrolizumab plus Lenvatinib for Endometrial Carcinoma, a Collaborative International Review under Project Orbis
Authors: Shaily Arora, Sanjeeve Balasubramaniam, Wei Zhang, Lijun Zhang, Rajeshwari Sridhara, Dianne Spillman, Jaigi P. Mathai, Bradley Scott, Sarah J. Golding, Michael Coory, Richard Pazdur, Julia A. Beaver
Journal: Clinical Cancer Research (2020)

Abstract On September 17, 2019, FDA granted accelerated approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. The submission and review of this application was conducted through an FDA Oncology Center of Excellence initiative named Project Orbis whereby the FDA, the Australian Therapeutic Goods Administration, and Health Canada were able to simultaneously review and collaborate, rendering simultaneous approval decisions in all countries. Accelerated approval of the pembrolizumab plus lenvatinib combination was based on a single-arm trial of 94 patients, with previously treated metastatic endometrial cancer whose tumors were not MSI-H/dMMR. Efficacy was demonstrated on the basis of an objective response rate of 38.3% (95% confidence interval, 28.5%–48.9%) with 10 complete responses (10.6%) accompanied by supportive durations of response. Trials to confirm clinical benefit of this combination are ongoing. Here, we summarize the benefit–risk analysis supporting accelerated approval of the pembrolizumab plus lenvatinib combination and describe the methodology for the first Project Orbis review.
Pooled RCTs: In patients with HF in sinus rhythm, β-blockers reduced mortality at GFR ≥ 30 mL/min/1.73 m<sup>2</sup>
Authors: Bishoy Deif, Harriette G.C. Van Spall
Journal: Annals of Internal Medicine (2020)

ACP Journal Club21 April 2020Pooled RCTs: In patients with HF in sinus rhythm, β-blockers reduced mortality at GFR ≥ 30 mL/min/1.73 m2Bishoy Deif, MD, Harriette G.C. Van Spall, MD, MPHBishoy Deif, MDMcMaster University, Hamilton, Ontario, Canada (B.D., H.G.V.)Search for more papers by this author, Harriette G.C. Van Spall, MD, MPHMcMaster University, Hamilton, Ontario, Canada (B.D., H.G.V.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202004210-038 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationKotecha D, Gill SK, Flather MD, et al. Impact of renal impairment on beta-blocker efficacy in patients with heart failure. J Am Coll Cardiol. 2019;74:2893-904. https://pubmed.ncbi.nlm.nih.gov/31806133Clinical Impact RatingsGIM/FP/GP: Hospitalists: Cardiology: References1 Cice G, Ferrara L, D’Andrea A, et al. Carvedilol increases two-year survival in dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol. 2003;41:1438-44. [PMID: 12742278] Google Scholar2 Rienstra M, Damman K, Mulder BA, et al. Beta-blockers and outcome in heart failure and atrial fibrillation: a meta-analysis. JACC Heart Fail. 2013;1:21-8. [PMID: 24621795] Google Scholar3 Heywood JT, Fonarow GC, Yancy CW, et al. Influence of renal function on the use of guideline-recommended therapies for patients with heart failure. Am J Cardiol. 2010;105:1140-6. [PMID: 20381667] Google Scholar Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, Canada (B.D., H.G.V.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-3041.This article was published at Annals.org on 7 April 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 April 2020Volume 172, Issue 8Page: JC38KeywordsAtrial fibrillationEstimated glomerular filtration rateHeart failureHeart rateLeft ventricular ejection fractionMortalityPatientsSafetySystolic pressure ePublished: 21 April 2020 Issue Published: 21 April 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cellular community detection for tissue phenotyping in colorectal cancer histology images
Authors: Sajid Javed, Arif Mahmood, Muhammad Moazam Fraz, Navid Alemi Koohbanani, Ksenija Benes, Yee-Wah Tsang, Katherine Hewitt, David Epstein, David Snead, Nasir Rajpoot
Journal: Medical Image Analysis (2020)
Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites
Authors: Sisi Kang, Mei Yang, Zhongsi Hong, Liping Zhang, Zhaoxia Huang, Xiaoxue Chen, Suhua He, Ziliang Zhou, Zhechong Zhou, Qiuyue Chen, Yan Yan, Changsheng Zhang, Hong Shan, Shoudeng Chen
Journal: Acta Pharmaceutica Sinica B (2020)

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
Covid-19, prison crowding, and release policies
Authors: Paul L Simpson, Tony G Butler
Journal: BMJ (2020)

<h3>SUMMARY</h3> <h3>Background</h3> Smell and taste disorders are reported very frequently and at an early stage in the evolution of the infectious disease caused by the SARS-CoV-2. These symptoms could be sensitive and specific to establish the condition of the infection, and may suggest the flow of decisions as to further therapy. We asked whether smell and taste impairment are earlier and more sensitive symptoms than the RT-PCR molecular assays for SARS-CoV-2 detection. <h3>Methodology</h3> Subjects (N=275) with a probable COVID19 diagnosis were classified as follows: Symptomatic with chemosensory dysfunction, symptomatic without chemosensory dysfunction, and asymptomatic. Subjects received a general clinical and otorhinolaryngology examination. Evaluation of the chemosensory dysfunction was performed by means of the Venezuelan Olfactory Test and taste test. Nasal swabs and blood samples were analyzed by real-time polymerase chain reaction analysis (RT-PCR) and a rapid diagnostic test to detect the SARS-CoV-2 virus and antiviral antibodies, respectively. Patients had access to molecular tests and smell and taste evaluations every 3 to 5 days until they recovered. <h3>Results</h3> Out of 44 patients that were positive for RT-PCR SARS-CoV-2: 45.83% had smell and taste disorders and COVID19 symptoms, 23.61% did not have smell or taste disorders, but had COVID19 symptoms, and 30.55% were asymptomatic. Mild hyposmia and hypogeusia account for the most frequent chemosensory disorders accompanying common SARS-CoV-2 symptoms. Time to recover from the chemosensory dysfunction ranges from 3 to 14 days, up to a maximum of 5 weeks, while RT-PCR becomes negative after 21 days and up to 35 days in some cases. The Venezuelan Olfactory Test and taste test has a 61.68% positive predictive value, 45.83% sensitivity, and 68.7% specificity for SARS-CoV-2 infection. <h3>Conclusions</h3> Smell and taste disorders are frequent symptoms of SARS-CoV-2 infection, but not a significant predictor of the disease, as compared to the molecular RT-PCR test.
Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016
Authors: Andrew Rhodes, Laura E. Evans, Waleed Alhazzani, Mitchell M. Levy, Massimo Antonelli, Ricard Ferrer, Anand Kumar, Jonathan E. Sevransky, Charles L. Sprung, Mark E. Nunnally, Bram Rochwerg, Gordon D. Rubenfeld, Derek C. Angus, Djillali Annane, Richard J. Beale, Geoffrey J. Bellinghan, Gordon R. Bernard, Jean-Daniel Chiche, Craig Coopersmith, Daniel P. De Backer, Craig J. French, Seitaro Fujishima, Herwig Gerlach, Jorge Luis Hidalgo, Steven M. Hollenberg, Alan E. Jones, Dilip R. Karnad, Ruth M. Kleinpell, Younsuk Koh, Thiago Costa Lisboa, Flavia R. Machado, John J. Marini, John C. Marshall, John E. Mazuski, Lauralyn A. McIntyre, Anthony S. McLean, Sangeeta Mehta, Rui P. Moreno, John Myburgh, Paolo Navalesi, Osamu Nishida, Tiffany M. Osborn, Anders Perner, Colleen M. Plunkett, Marco Ranieri, Christa A. Schorr, Maureen A. Seckel, Christopher W. Seymour, Lisa Shieh, Khalid A. Shukri, Steven Q. Simpson, Mervyn Singer, B. Taylor Thompson, Sean R. Townsend, Thomas Van der Poll, Jean-Louis Vincent, W. Joost Wiersinga, Janice L. Zimmerman, R. Phillip Dellinger
Journal: Intensive Care Medicine (2017)
Results of the 2nd Planned Interim Analysis of the RAPID Trial (involved field radiotherapy versus no further treatment) in Patients with Clinical Stages 1A and 2A Hodgkin Lymphoma and a ‘negative’ FDG-PET Scan after 3 Cycles ABVD
Authors: John Radford, Michael O’Doherty, Sally Barrington, Wendi Qian, Philippa Patrick, Stewart Coltart, Dominic Culligan, Jennie Wimperis, Eric Bessell, David Linch, Peter Johnson, David Cunningham, T. Andrew Lister, Peter Hoskin, Ruth Pettengell, Barry Hancock, Timothy Illidge
Journal: Blood (2008)
PPARγ Coactivator‐1α Suppresses Metastasis of Hepatocellular Carcinoma by Inhibiting Warburg Effect by PPARγ–Dependent WNT/β‐Catenin/Pyruvate Dehydrogenase Kinase Isozyme 1 Axis
Authors: Qiaozhu Zuo, Jia He, Shu Zhang, Hui Wang, Guangzhi Jin, Haojie Jin, Zhuoan Cheng, Xuemei Tao, Chengtao Yu, Botai Li, Chen Yang, Siying Wang, Yuanyuan Lv, Fangyu Zhao, Ming Yao, Wenming Cong, Cun Wang, Wenxin Qin
Journal: Hepatology (2020)

Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1α (PGC1α) is a key regulator of mitochondrial biogenesis and respiration. PGC1α is involved in the carcinogenesis, progression, and metabolic state of cancer. However, its role in the progression of hepatocellular carcinoma (HCC) remains unclear.In this study, we observed that PGC1α was down-regulated in human HCC. A clinical study showed that low levels of PGC1α expression were correlated with poor survival, vascular invasion, and larger tumor size. PGC1α inhibited the migration and invasion of HCC cells with both in vitro experiments and in vivo mouse models. Mechanistically, PGC1α suppressed the Warburg effect through down-regulation of pyruvate dehydrogenase kinase isozyme 1 (PDK1) mediated by the WNT/β-catenin pathway, and inhibition of the WNT/β-catenin pathway was induced by activation of PPARγ.Low levels of PGC1α expression indicate a poor prognosis for HCC patients. PGC1α suppresses HCC metastasis by inhibiting aerobic glycolysis through regulating the WNT/β-catenin/PDK1 axis, which depends on PPARγ. PGC1α is a potential factor for predicting prognosis and a therapeutic target for HCC patients.
Multifunctional Glyco‐Nanosheets to Eradicate Drug‐Resistant Bacteria on Wounds
Authors: Zhong Guo, Jing‐Xi He, Surendra H. Mahadevegowda, Shu Hui Kho, Mary B. Chan‐Park, Xue‐Wei Liu
Journal: Advanced Healthcare Materials (2020)

Abstract Bacterial infection is becoming increasingly lethal with the emergence of antimicrobial resistance, and wounds plagued by such infection are notoriously difficult to heal. Here, the first use of galactose‐black phosphorus nanosheets, (Gal‐BP NSs) as a delivery platform for synergistic antibiotic (kanamycin, Kana) and photothermal treatments against the Gram‐negative microbial strain, Pseudomonas aeruginosa PAO1 (PAO1) is reported. Gal‐BP NSs@Kana can actively target PAO1 and release kanamycin into the bacterial cytoplasm upon near‐infrared laser irradiation. This strategy kills most of the PAO1 through a simultaneous burst of intracellular kanamycin release and photothermal treatment. Comparable antibacterial activities of Gal‐BP NSs@Kana are observed within in vivo mouse models at their wound sites. In addition, this platform accelerates wound healing from PAO1 infection via promotion of neoangiogenesis and collagen production at the wound sites. This work demonstrates the material properties of Gal‐BP NS in fighting bacterial infections and in the treatment of wound healing.
Proteasome Stress Causes Apoptotic Sensitivity of Multiple Myeloma Cells to Proteasome Inhibition
Authors: Giada Bianchi, Laura Oliva, Paolo Cascio, Niccolo’ Pengo, Andrea Orsi, Francesca Fontana, Elena Pasqualetto, Alexandre Mezghrani, Fulvia Cerruti, Valeria Calbi, Giovanni Palladini, Nicola Giuliani, Dharminder Chauhan, Kenneth C. Anderson, Roberto Sitia, Simone Cenci
Journal: Blood (2008)