tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 pandemic and research gaps: Understanding SARS-CoV-2 interaction with the ACE2 receptor and implications for therapy
Authors: Prasun K. Datta, Fengming Liu, Tracy Fischer, Jay Rappaport, Xuebin Qin
Journal: Theranostics (2020)

The COVID-19 pandemic is an emerging threat to global public health. While our current understanding of COVID-19 pathogenesis is limited, a better understanding will help us develop efficacious treatment and prevention strategies for COVID-19. One potential therapeutic target is angiotensin converting enzyme 2 (ACE2). ACE2 primarily catalyzes the conversion of angiotensin I (Ang I) to a nonapeptide angiotensin or the conversion of angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) and has direct effects on cardiac function and multiple organs via counter-regulation of the renin-angiotensin system (RAS). Significant to COVID-19, ACE2 is postulated to serve as a major entry receptor for SARS-CoV-2 in human cells, as it does for SARS-CoV. Many infected individuals develop COVID-19 with fever, cough, and shortness of breath that can progress to pneumonia. Disease progression promotes the activation of immune cells, platelets, and coagulation pathways that can lead to multiple organ failure and death. ACE2 is expressed by epithelial cells of the lungs at high level, a major target of the disease, as seen in post-mortem lung tissue of patients who died with COVID-19, which reveals diffuse alveolar damage with cellular fibromyxoid exudates bilaterally. Comparatively, ACE2 is expressed at low level by vascular endothelial cells of the heart and kidney but may also be targeted by the virus in severe COVID-19 cases. Interestingly, SARS-CoV-2 infection downregulates ACE2 expression, which may also play a critical pathogenic role in COVID-19. Importantly, targeting ACE2/Ang 1-7 axis and blocking ACE2 interaction with the S protein of SARS-CoV-2 to curtail SARS-CoV-2 infection are becoming very attractive therapeutics potential for treatment and prevention of COVID-19. Here, we will discuss the following subtopics: 1) ACE2 as a receptor of SARS-CoV-2; 2) clinical and pathological features of COVID-19; 3) role of ACE2 in the infection and pathogenesis of SARS; 4) potential pathogenic role of ACE2 in COVID-19; 5) animal models for pathological studies and therapeutics; and 6) therapeutics development for COVID-19.
Impact of compliance to chemoradiation on long-term outcomes in squamous cell carcinoma of the anus: results of a post hoc analysis from the randomised phase III ACT II trial
Authors: R. Glynne-Jones, H.M. Meadows, A. Lopes, R. Muirhead, D. Sebag-Montefiore, R. Adams
Journal: Annals of Oncology (2020)
RNA-binding protein NONO contributes to cancer cell growth and confers drug resistance as a theranostic target in TNBC
Authors: Seong-Jin Kim, Jin-Sung Ju, Myoung-Hee Kang, Ji Eun Won, Young Ha Kim, Prahlad V Raninga, Kum Kum Khanna, Balázs Győrffy, Chan-Gi Pack, Hee-Dong Han, Hee Jin Lee, Gyungyub Gong, Yong Shin, Gordon B. Mills, Seong-il Eyun, Yun-Yong Park
Journal: Theranostics (2020)

Breast cancer (BC) is one of the most common cancers in women. TNBC (Triple-negative breast cancer) has limited treatment options and still lacks viable molecular targets, leading to poor outcomes. Recently, RNA-binding proteins (RBPs) have been shown to play crucial roles in human cancers, including BC, by modulating a number of oncogenic phenotypes. This suggests that RBPs represent potential molecular targets for BC therapy. Methods: We employed genomic data to identify RBPs specifically expressed in TNBC. NONO was silenced in TNBC cell lines to examine cell growth, colony formation, invasion, and migration. Gene expression profiles in NONO-silenced cells were generated and analyzed. A high-throughput screening for NONO-targeted drugs was performed using an FDA-approved library. Results: We found that the NONO RBP is highly expressed in TNBC and is associated with poor patient outcomes. NONO binds to STAT3 mRNA, increasing STAT3 mRNA levels in TNBC. Surprisingly, NONO directly interacts with STAT3 protein increasing its stability and transcriptional activity, thus contributing to its oncogenic function. Importantly, high-throughput drug screening revealed that auranofin is a potential NONO inhibitor and inhibits cell growth in TNBC. Conclusions: NONO is an RBP upstream regulator of both STAT3 RNA and protein levels and function. It represents an important and clinically relevant promoter of growth and resistance of TNBCs. NONO is also therefore a potential therapeutic target in TNBC.
Response to ‘Classification of the cutaneous manifestations of COVID‐19: a rapid prospective nationwide consensus study in Spain with 375 cases’: vesicular eruption in COVID‐19 – to exclude varicella
Authors: S.Y.D. Lim, H.L. Tey
Journal: British Journal of Dermatology (2020)

Linked Article: Galván Casas et al. Br J Dermatol 2020; 183:71–77. Dear Editor, We read with interest the classification of cutaneous manifestations in COVID-19 by Galván Casas et al.1 In particular, vesicular eruptions are characterized as monomorphic vesicles, involving the trunk, happening early in the course of the disease, and occasionally preceding other symptoms.1-3 However, investigations to exclude other causes of widespread vesicular eruption, in particular varicella, were absent. In our clinical experience to date, we have had four patients with SARS-CoV-2 infection presenting with vesicular eruptions, which were subsequently confirmed to be true varicella with microbiological and serological investigations (Table 1). All four patients were young to middle-aged men with no previous history of varicella infection, vaccination or exposure, presenting with vesicular eruptions of variable durations. Each patient had some features not completely typical of varicella – two described no or mild pruritus, two did not report any prodromal symptoms, and two presented with monomorphic vesicular eruptions early in the course of varicella infection. They were all given systemic antiviral therapy with aciclovir or valaciclovir, with resolution. In a patient presenting with a widespread vesicular eruption, differential diagnoses include infections, a drug-induced blistering process, and an autoimmune blistering disease. Among the infections, varicella, disseminated zoster, disseminated herpes, smallpox and rickettsialpox are possible causes. Our experience with concomitant SARS-CoV-2 and varicella infection highlights the importance of excluding true varicella before ascribing vesicular eruptions to COVID-19. Atypical features may be present, especially in early or recurrent varicella. Moreover, we have also previously reported coinfection of varicella with another viral infection (herpes simplex virus) in an immunocompetent host.4 Hence, it is possible that cases of vesicular eruptions in COVID-19 may be arising from varicella infection. As an accurate diagnosis of varicella has far-reaching clinical implications on the treatment, patient disposition and postexposure prophylaxis for contacts, varicella infection should be excluded in patients with COVID-19 presenting with vesicular eruptions.
Acute Kidney Injury in Decompensated Cirrhosis Is Associated With Both Hypo‐coagulable and Hyper‐coagulable Features
Authors: Alberto Zanetto, Henry M. Rinder, Elena Campello, Graziella Saggiorato, Yanhong Deng, Maria Ciarleglio, Francis P. Wilson, Marco Senzolo, Sabrina Gavasso, Cristiana Bulato, Paolo Simioni, Guadalupe Garcia‐Tsao
Journal: Hepatology (2020)

Recent evidence suggests that acute kidney injury (AKI) is the main predictor of postparacentesis bleeding in patients with cirrhosis. To assess the factors responsible for bleeding tendency in AKI, we performed a prospective study comparing all three aspects of hemostasis (platelets, coagulation, and fibrinolysis) in patients with decompensated cirrhosis with and without AKI.Primary hemostasis assessment included platelet aggregation and secretion (platelet function markers) and von Willebrand factor. Secondary hemostasis assessment included pro-coagulant (factor VIII and factor XIII) and anti-coagulant (protein C, protein S, and antithrombin) factors and thrombin generation. Tertiary hemostasis assessment included fibrinolytic factors and plasmin-antiplasmin complex. Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Severity of cirrhosis and platelet count were comparable between groups. Median serum creatinine was 1.8 mg/dL and 0.8 mg/dL in patients with and without AKI, respectively. At baseline, patients with cirrhosis and AKI had lower platelet aggregation and secretion, indicative of impaired platelet function (increased bleeding tendency), without differences in von Willebrand factor. Regarding coagulation factors, factor VIII was higher, whereas protein C, protein S, and antithrombin were all lower, which, together with increased thrombin generation, indicate hypercoagulability. In contrast, factor XIII was lower in AKI (increased bleeding tendency). Finally, while both hypofibrinolytic and hyperfibrinolytic changes were present in AKI, a higher plasmin-antiplasmin complex indicated a hyperfibrinolytic state. After AKI resolution (n = 23 of 40), platelet function and coagulation improved to levels observed in patients with cirrhosis patients without AKI; however, fibrinolysis remained hyperactivated.In patients with decompensated cirrhosis, AKI is associated with both hypocoagulable and hypercoagulable features that can potentially increase the risk of both bleeding and thrombosis.
Police launch investigation into maternity services at scandal hit Midlands trust
Authors: Clare Dyer
Journal: BMJ (2020)

Police have opened a criminal investigation into maternity services at the scandal hit Shrewsbury and Telford NHS Hospital Trust after an independent review found serious concerns over avoidable deaths of babies and mothers.

The interim report of a government commissioned review of 250 cases concluded that at least 42 babies and three mothers might have died avoidably and more than 50 newborns might have sustained avoidable brain damage at the trust from 1979 to 2018. By last April the number of cases of concern had risen to 1170 over a 40 year period, making …
Recent advances in polymeric biomaterials-based gene delivery for cartilage repair
Authors: Ran Yang, Fei Chen, Jinshan Guo, Dongfang Zhou, Shifang Luan
Journal: Bioactive Materials (2020)

Untreated articular cartilage damage normally results in osteoarthritis and even disability that affects millions of people. However, both the existing surgical treatment and tissue engineering approaches are unable to regenerate the original structures of articular cartilage durably, and new strategies for integrative cartilage repair are needed. Gene therapy provides local production of therapeutic factors, especially guided by biomaterials can minimize the diffusion and loss of the genes or gene complexes, achieve accurate spatiotemporally release of gene products, thus provideing long-term treatment for cartilage repair. The widespread application of gene therapy requires the development of safe and effective gene delivery vectors and supportive gene-activated matrices. Among them, polymeric biomaterials are particularly attractive due to their tunable physiochemical properties, as well as excellent adaptive performance. This paper reviews the recent advances in polymeric biomaterial-guided gene delivery for cartilage repair, with an emphasis on the important role of polymeric biomaterials in delivery systems.
Government unveils roadmap for making UK a “science superpower”
Authors: Ingrid Torjesen
Journal: BMJ (2020)

The government has published a plan for strengthening science, research, and innovation to help the economy and society recover from covid-19 and to "build a greener, healthier and more resilient UK." 1 Before covid-19 the science community had warned of the damage that Brexit would do to the UK's science base in terms of lost research funding and collaborative opportunities, as well as difficulties in recruiting top scientists. 2 Robert Lechler, president of the Academy of Medical Sciences, said that the roadmap provided welcome recognition of the critical role that research and innovation played in the UK's future and the global recovery from covid-19."The UK's track record of innovation has never been more important," he said."What's more, investing in medical research will improve society beyond covid-19 by addressing health inequalities, helping patients, and creating highly skilled jobs across the country."The plan reiterates the government's commitment in March to increase UK investment in research and development (R&D) to 2.4% of GDP by 2027 and to increase public funding for R&D to £22bn (€24.4bn;$27.4bn) a year by 2024-25. 1
In vivo gene delivery mediated by non-viral vectors for cancer therapy
Authors: Reza Mohammadinejad, Ali Dehshahri, Vijay Sagar Madamsetty, Masoumeh Zahmatkeshan, Shima Tavakol, Pooyan Makvandi, Danial Khorsandi, Abbas Pardakhty, Milad Ashrafizadeh, Elham Ghasemipour Afshar, Ali Zarrabi
Journal: Journal of Controlled Release (2020)
Nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant Plasmodium falciparum
Authors: Kun Zhang, Yu Zhao, Zheng Zhang, Mengyao Zhang, Xiaodong Wu, Huijie Bian, Ping Zhu, Zhinan Chen
Journal: Acta Pharmaceutica Sinica B (2020)

Meplazumab is an anti-CD147 humanized IgG2 antibody. The purpose of this study was to characterize the nonclinical safety, tolerance and efficacy evaluation of meplazumab treating chloroquine resistant Plasmodium falciparum. Meplazumab was well tolerated in repeat-dose toxicology studies in cynomolgus monkeys. No observed adverse effect level was 12 mg/kg. No difference between genders in the primary toxicokinetic parameters after repeat intravenous injection of meplazumab. No increased levels of drug exposure and drug accumulation were observed in different gender and dose groups. Meplazumab had a low cross-reactivity rate in various tissues and did not cause hemolysis or aggregation of red blood cells. The biodistribution and excretion results indicated that meplazumab was mainly distributed in the plasma, whole blood, and hemocytes, and excreted in the urine. Moreover, meplazumab effectively inhibited the parasites from invading erythrocytes in humanized mice in a time-dependent manner and the efficacy is superior to that of chloroquine. All these studies suggested that meplazumab is safe and well tolerated in cynomolgus monkeys, and effectively inhibits P. falciparum from invading into human red blood cells. These nonclinical data facilitated the initiation of an ongoing clinical trial of meplazumab for antimalarial therapy.
Re: Prostate Cancer Incidence 5 Years After US Preventive Services Task Force Recommendations Against Screening
Authors: Steven Lehrer, Peter H Rheinstein
Journal: JNCI Journal of the National Cancer Institute (2020)

Jemal et al. (1) analyzed prostate cancer incidence between 1998 and 2016.Their analysis included the 5 years after the US Preventive Services Task Force (USPSTF) 2012 recommended against routine prostate-specific antigen (PSA) screening.In a recent article in the Journal, using the Surveillance, Epidemiology, and End Results (SEER) database, Jemal et al. ( 1). reported that regional-and distant-stage prostate cancer incidence continued to increase in the United States in men aged 50 years and older.Rising obesity may play a role, because obesity predisposes to aggressive prostate cancer (2).However, Jemal et al. did not examine associated survival data.Using SEER, we have examined survival data to augment the results of the study by Jemal et al. (1).SEER data from population-based cancer registries include 28% of the US population (3).We analyzed 5-year relative survival data from 18 251 pros-
Excess Deaths From COVID-19 and Other Causes, March-April 2020
Authors: Steven H. Woolf, Derek A. Chapman, Roy T. Sabo, Daniel M. Weinberger, Latoya Hill
Journal: JAMA (2020)

This study uses data from the National Center for Health Statistics to estimate excess deaths (ie, the difference between observed and expected deaths) in the US and the District of Columbia in the early weeks of the COVID-19 pandemic.
COVID-19 and Disruptive Modifications to Cardiac Critical Care Delivery
Authors: Jason N. Katz, Shashank S. Sinha, Carlos L. Alviar, David M. Dudzinski, Ann Gage, Samuel B. Brusca, M. Casey Flanagan, Timothy Welch, Bram J. Geller, P. Elliott Miller, Sergio Leonardi, Erin A. Bohula, Susanna Price, Sunit-Preet Chaudhry, Thomas S. Metkus, Connor G. O’Brien, Alessandro Sionis, Christopher F. Barnett, Jacob C. Jentzer, Michael A. Solomon, David A. Morrow, Sean van Diepen
Journal: Journal of the American College of Cardiology (2020)
Perspectives on Urinary Tract Infection and Race
Authors: Sara H. Goza
Journal: JAMA Pediatrics (2020)

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Inferior Cancer Survival for Men with Localized High-grade Prostate Cancer but Low Prostate-specific Antigen
Authors: Christian D. Fankhauser, Kathryn L. Penney, Amparo G. Gonzalez-Feliciano, Noel W. Clarke, Thomas Hermanns, Konrad H. Stopsack, Michelangelo Fiorentino, Massimo Loda, Brandon Mahal, Travis A. Gerke, Mark A. Preston, Lorelei A. Mucci
Journal: European Urology (2020)
Excess all-cause mortality during the COVID-19 pandemic in Europe – preliminary pooled estimates from the EuroMOMO network, March to April 2020
Authors: Lasse S Vestergaard, Jens Nielsen, Lukas Richter, Daniela Schmid, Natalia Bustos, Toon Braeye, Gleb Denissov, Tatjana Veideman, Oskari Luomala, Teemu Möttönen, Anne Fouillet, Céline Caserio-Schönemann, Matthias an der Heiden, Helmut Uphoff, Theodore Lytras, Kassiani Gkolfinopoulou, Anna Paldy, Lisa Domegan, Joan O'Donnell, Francesca de’ Donato, Fiammetta Noccioli, Patrick Hoffmann, Telma Velez, Kathleen England, Liselotte van Asten, Richard A White, Ragnhild Tønnessen, Susana P da Silva, Ana P Rodrigues, Amparo Larrauri, Concepción Delgado-Sanz, Ahmed Farah, Ilias Galanis, Christoph Junker, Damir Perisa, Mary Sinnathamby, Nick Andrews, Mark O'Doherty, Diogo FP Marquess, Sharon Kennedy, Sonja J Olsen, Richard Pebody, Tyra G Krause, Kåre Mølbak
Journal: Eurosurveillance (2020)

A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March–April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45–64 (8%) and 15–44 year olds (1%). No excess mortality was observed in 0–14 year olds.
The usefulness of quantitative interferon-gamma releasing assay response for predicting active tuberculosis in kidney transplant recipients: A quasi-experimental study
Authors: Haein Kim, Sung-Han Kim, Joo Hee Jung, Min Jae Kim, Hyosang Kim, Sung Shin, Yong Pil Chong, Young-Hoon Kim, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Su-Kil Park, Duck Jong Han
Journal: Journal of Infection (2020)
Who will guard the guards? Covid-19 research may be incomplete, but experts are vital during this pandemic
Authors: Shyan Goh
Journal: BMJ (2020)

I share Armstrong’s concerns about research integrity and the peer review process.1 The inconsistencies surrounding hydroxychloroquine (HCQ) and its potential role in treating covid-19 is a case in point.

Many covid-19 HCQ studies are published as preprints without peer review on websites like medRxiv. Despite headings stating that preprints are “not certified by peer review,” many readers, including clinicians, do not place enough significance on these warnings.

Comments from world leaders …
Response to: ‘Changing the outcome measures, changing the results? The urgent need of a specific Disease Activity Score to adult-onset Still’s disease’ by Ruscitti <i>et al</i>
Authors: Claudia Kedor, Joachim Listing, Jan Zernicke, Eugen Feist
Journal: Annals of the Rheumatic Diseases (2020)

We would like to thank Ruscitti et al 1 for their interest in our recent publication, in which we presented the results of the Canakinumab for treatment of adult onset Still‘s disease to achieve reduction ofarthritic manifestation (CONSIDER) trial. In this study, we investigated the efficacy of canakinumab for the treatment of patients with adult-onset Still’s disease (AOSD) with articular involvement (tender and swollen joint counts≥4 each) by means of a multicentre, double-blind, randomised, placebo-controlled trial.2 Patients were randomised to receive either canakinumab 4 mg/kg body weight (maximum 300 mg) every 4 weeks or placebo. According to the study goal, the primary endpoint was defined as the proportion of patients with a clinically relevant reduction in Disease Activity Score (DAS 28 >1.2) at week 12.

Since no controlled studies existed in this indication at that time of the study initiation, we were not able to base our statistical considerations on known facts of response rates to placebo or any immunosuppressive regimen. After careful consideration, our sample size calculation indicated that it requires a total of n=68 randomised patients to show a significant difference between the groups. …
Abstract 13727: Effects of Ziltivekimab (ZILTI), a Novel Anti-Interleukin-6 Monoclonal Antibody, on Markers of Inflammation and Cardiovascular Risk in Patients With Chronic Kidney Disease on Hemodialysis
Authors: Rahul Kakkar, Larry Lo, Douglas Kling, Matt Devalaraja, Michael H Davidson
Journal: Circulation (2019)

Introduction: Levels of the inflammatory cytokine IL-6 and its associated biomarker CRP, the production of which is predominantly stimulated by IL-6, are strongly correlated with CV outcomes in CKD...
A “new normal” after covid-19 for NHS healthcare workers who are also carers?
Authors: Raka Maitra
Journal: BMJ (2020)

Nelson discusses the positive effects of this pandemic.1 Covid-19 has opened up the vulnerabilities in society. Many healthcare workers are identified by the NHS as either being “clinically vulnerable” or taking care of someone who is clinically vulnerable. Health education boards and the NHS have allowed for remote arrangements for those who are shielding. The Royal Colleges of Psychiatrists and General Practitioners are engaging remotely and developing alternative arrangements for exams such as clinical skills assessment. …
A retrospective multicenter study of fatal pediatric melanoma
Authors: Elena B. Hawryluk, Danna Moustafa, Diana Bartenstein, Meera Brahmbhatt, Kelly Cordoro, Laura Gardner, Abigail Gauthier, Douglas Grossman, Deepti Gupta, Raegan D. Hunt, Melinda Jen, Pei-Chi Kao, Lacey L. Kruse, Leslie P. Lawley, Wendy B. London, Danny Mansour, Judith A. O'Haver, Thuy Phung, Elena Pope, Harper N. Price, Tova Rogers, Sonal D. Shah, Zachary Wolner, Jennifer Huang, Ashfaq A. Marghoob
Journal: Journal of the American Academy of Dermatology (2020)