tbuckley/cabot-search huggingface dataset:
Antibody-based therapies for COVID-19: Can Europe move faster?
Authors: Michel D. Kazatchkine, Michel Goldman, Jean-Louis Vincent
Journal: PLoS Medicine (2020)

Countries of the European Union (EU) are among the most seriously affected areas by COVID-19.Deaths have exceeded 75,000 across the EU within 2 months of the epidemic.The main cause of death is respiratory failure complicated, in a number of cases, by shock and multiple organ failure [1].There are no therapeutic options beyond symptomatic intensive care treatment for severely ill patients at this time.We call on European physicians and scientists to urgently evaluate the potential of antibody-based therapies in this context.Recovery from infection with SARS-CoV-2 is associated with the generation of neutralizing immunoglobulin G (IgG) antibodies to the virus within 6 to 10 days of symptomatic infection [2,3].Studies in rhesus macaques indicate that monkeys infected with the new coronavirus produce neutralizing antibodies and resist further infection [4].Although no data are available on the duration of acquired anti-COVID-19 immunity, studies of the SARS outbreak had shown that people infected with SARS coronavirus generated protective immunity that lasted for up to 10 years [5].Immune convalescent individuals might contribute to the treatment of critically ill infected patients through donation of their plasma.Preliminary uncontrolled studies in China indeed indicate that infusion of convalescent plasma might benefit patients on mechanical ventilation [6].On this basis, programs of convalescent plasma therapy ("passive immunotherapy") have been launched in several centers in the United States [7].Passive immunotherapy has been conceptualized over 100 years ago with the pioneering works of von Behring and Roux.Europe has played a major role in the development of passive immunotherapy with plasma and ensuing hyperimmune immunoglobulins, F(ab')2 or Fab fragments of immunoglobulins and monoclonal antibodies.Effective neutralizing antibodies for passive immunotherapy have been generated in recent outbreaks of H5N1 [8,9], SARS [10], and Ebola [11].Blood transfusion centers in Germany, France, Italy, the Netherlands, and Belgium are launching plasma collection campaigns focusing on donors screened for anti-COVID-19 antibodies.Anti-COVID-19-rich plasma will then be used in intensive care centers in the framework of controlled prospective clinical trials.Currently available assays will allow selection of plasma donors with high titers of neutralizing antibodies for plasma therapy and the preparation of hyperimmune intravenous immunoglobulin.Efforts are underway to harmonize protocols.However, further coordination is urgently needed to ensure that significant conclusions can be drawn to inform about the benefit or lack of benefit of this approach.We call on the medical and scientific European community to urgently coordinate research efforts on passive immunotherapy, share data and protocols in real-time, and pool efforts to decrease as much as possible the time for validating immunotherapy with donated plasma.
Part 10: Pediatric Basic and Advanced Life Support
Authors: Monica E. Kleinman, Allan R. de Caen, Leon Chameides, Dianne L. Atkins, Robert A. Berg, Marc D. Berg, Farhan Bhanji, Dominique Biarent, Robert Bingham, Ashraf H. Coovadia, Mary Fran Hazinski, Robert W. Hickey, Vinay M. Nadkarni, Amelia G. Reis, Antonio Rodriguez-Nunez, James Tibballs, Arno L. Zaritsky, David Zideman, Ian Adatia, Richard P. Aickin, John Berger, Jeffrey M. Berman, Desmond Bohn, Kate L. Brown, Mark G. Coulthard, Douglas S. Diekema, Aaron Donoghue, Jonathan Duff, Jonathan R. Egan, Christoph B. Eich, Diana G. Fendya, Ericka L. Fink, Loh Tsee Foong, Eugene B. Freid, Susan Fuchs, Anne-Marie Guerguerian, Bradford D. Harris, George M. Hoffman, James S. Hutchison, Sharon B. Kinney, Sasa Kurosawa, Jesús Lopez-Herce, Sharon E. Mace, Ian Maconochie, Duncan Macrae, Mioara D. Manole, Bradley S. Marino, Felipe Martinez, Reylon A. Meeks, Alfredo Misraji, Marilyn Morris, Akira Nishisaki, Masahiko Nitta, Gabrielle Nuthall, Sergio Pesutic Perez, Lester T. Proctor, Faiqa A. Qureshi, Sergio Rendich, Ricardo A. Samson, Kennith Sartorelli, Stephen M. Schexnayder, William Scott, Vijay Srinivasan, Robert M. Sutton, Mark Terry, Shane Tibby, Alexis Topjian, Elise W. van der Jagt, David Wessel
Journal: Circulation (2010)

Throughout this article, the reader will notice combinations of superscripted letters and numbers (eg, "Family Presence During Resuscitation Peds-003 ").These callouts are hyperlinked to evidence-based worksheets, which were used in the development of this article.An appendix of worksheets, applicable to this article, is located at the end of the text.The worksheets are available in PDF format and are open access.T he 2010 ILCOR Pediatric Task Force experts developed 55 questions related to pediatric resuscitation.Topics were selected based on the 2005 Consensus on Science and Treatment Recommendations (CoSTR) document, 1,2 emerging science, and newly identified issues.Not every topic reviewed for the 2005 International Consensus on Science was reviewed in the 2010 evidence evaluation process.In general, evidence-based worksheets were assigned to at least 2 authors for each topic.The literature search strategy was first reviewed by a "worksheet expert" for completeness.The expert also approved the final worksheet to ensure that the levels of evidence were correctly assigned according to the established criteria.
Reply to “MiR-205 and miR-375 microRNA Assays to Distinguish Squamous Cell Carcinoma From Adenocarcinoma in Lung Cancer Biopsies”
Authors: Santosh K. Patnaik, Sai Yendamuri, Reema Mallick, Samjot S. Dhillon
Journal: Journal of Thoracic Oncology (2015)
Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury
Authors: Lingling Zhu, Yujia Yuan, Longhui Yuan, Lan Li, Fei Liu, Jingping Liu, Younan Chen, Yanrong Lu, Jingqiu Cheng
Journal: Theranostics (2020)

Aims: Cisplatin, an anticancer drug, always leads to nephrotoxicity by causing mitochondrial dysfunction.As a major mechanism for cellular self-degradation, autophagy has been proven to protect against cisplatin-induced acute kidney injury (AKI).Based on the activation of autophagy induced by trehalose, we aimed to investigate the nephroprotective effects of trehalose on cisplatin-induced AKI and its underlying mechanisms.Results: Due to the activation of autophagy, mitochondrial dysfunction (mitochondrial fragmentation, depolarization, reactive oxygen species (ROS), and reduced ATP generation) and apoptosis induced by cisplatin were markedly inhibited in trehalose-treated HK2 cells in vitro.Based on the transcriptional regulation role of transcription factor EB (TFEB) in autophagy and lysosome, we characterized trehalose-induced nuclear translocation of TFEB.Furthermore, consistent with trehalose treatment, overexpression of TFEB inhibited cell injury induced by cisplatin.However, the protective effects of trehalose were largely abrogated in tfeb-knockdown cells.In vivo, cisplatin injection resulted in severe kidney dysfunction and histological damage in mice.Trehalose administration activated TFEB-mediated autophagy, alleviated mitochondrial dysfunction and kidney injury in AKI mice.Innovation and conclusion: Our data suggest that trehalose treatment preserves mitochondria function via activation of TFEB-mediated autophagy and attenuates cisplatin-induced kidney injury.
The endothelial basement membrane acts as a checkpoint for entry of pathogenic T cells into the brain
Authors: Xueli Zhang, Ying Wang, Jian Song, Hanna Gerwien, Omar Chuquisana, Anna Chashchina, Cornelia Denz, Lydia Sorokin
Journal: The Journal of Experimental Medicine (2020)

The endothelial cell basement membrane (BM) is a barrier to migrating leukocytes and a rich source of signaling molecules that can influence extravasating cells. Using mice lacking the major endothelial BM components, laminin 411 or 511, in murine experimental autoimmune encephalomyelitis (EAE), we show here that loss of endothelial laminin 511 results in enhanced disease severity due to increased T cell infiltration and altered polarization and pathogenicity of infiltrating T cells. In vitro adhesion and migration assays reveal higher binding to laminin 511 than laminin 411 but faster migration across laminin 411. In vivo and in vitro analyses suggest that integrin α6β1- and αvβ1-mediated binding to laminin 511–high sites not only holds T cells at such sites but also limits their differentiation to pathogenic Th17 cells. This highlights the importance of the interface between the endothelial monolayer and the underlying BM for modulation of immune cell phenotype.
Importance of the Intention-to-Treat Principle
Authors: Simon Nagel, Diogo C. Haussen, Raul G. Nogueira
Journal: JAMA Neurology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Systematic review examining changes over time and variation in the incidence and prevalence of psoriasis by age and gender*
Authors: I.Y.K. Iskandar, R. Parisi, C.E.M. Griffiths, D.M. Ashcroft
Journal: British Journal of Dermatology (2020)

There is a lack of any overview of changes over time and variation in the epidemiology of psoriasis with age and between genders. To perform a systematic review of published population‐based studies on variations in psoriasis incidence and prevalence with age and between genders, and to explore trends in psoriasis epidemiology over time. Eleven electronic and regional databases were searched from their inception dates to October 2019. No language restrictions were applied. Studies were eligible if they reported on changes in psoriasis incidence and/or prevalence over time and/or by age group and gender. In total 308 papers were critically appraised, from which 90 studies from 22 countries were included. Incidence data confirmed a clear bimodal age pattern in psoriasis onset, with the first and second peaks at around 30–39 and 60–69 years of age, respectively, and evidence suggesting that it presents slightly earlier in women than in men. Prevalence data showed an increasing trend with age until around 60 or 70 years, after which it decreases. Although there was lack of agreement on specific gender differences in psoriasis incidence and prevalence, a slight male predominance was reported in several studies. Studies worldwide suggested a stable or slightly decreasing trend in psoriasis incidence, while an increasing trend in psoriasis prevalence has been consistently reported. One particular challenge faced was the vastly different methodologies used in the included studies, which contributed to some of the heterogeneity of the results. Studies on changes over time in the occurrence of psoriasis have contributed to a greater appreciation of the increasing burden of the disease. However, further research is required to determine the reasons driving the increase in psoriasis prevalence over time.
Tomasello on “we” and the sense of obligation
Authors: Michael E. Bratman
Journal: Behavioral and Brain Sciences (2020)

Abstract Tomasello explores four interrelated phenomena: (1) joint intentional collaboration; (2) joint commitment; (3) “self-regulative pressure from ‘we’”; and (4) the sense of interpersonal obligation. He argues that the version of (1) that involves (2) is the “source” of (3) and so the source of (4). I note an issue that arises once we distinguish two versions of (3).
Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications
Authors: Claudio Luchini, Lodewijk A A Brosens, Laura D Wood, Deyali Chatterjee, Jae Il Shin, Concetta Sciammarella, Giulia Fiadone, Giuseppe Malleo, Roberto Salvia, Valentyna Kryklyva, Maria L Piredda, Liang Cheng, Rita T Lawlor, Volkan Adsay, Aldo Scarpa
Journal: Gut (2020)

Objective Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC). Design PubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project). Results Overall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%–2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p&lt;0.01) and with a KRAS / TP53 wild-type molecular background (p&lt;0.01), with more common JAK genes mutations. Data on survival are still unclear. Conclusion PDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.
Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2
Authors: Evan A. Farkash, Allecia M. Wilson, Jeffrey M. Jentzen
Journal: Journal of the American Society of Nephrology (2020)

A significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%-7% progressing to ARF, a marker of poor prognosis. The cause of the renal failure in COVID-19 is unknown, but one hypothesized mechanism is direct renal infection by the causative virus, SARS-CoV-2.We performed an autopsy on a single patient who died of COVID-19 after open repair of an aortic dissection, complicated by hypoxic respiratory failure and oliguric renal failure. We used light and electron microscopy to examine renal tissue for evidence of SARS-CoV-2 within renal cells.Light microscopy of proximal tubules showed geographic isometric vacuolization, corresponding to a focus of tubules with abundant intracellular viral arrays. Individual viruses averaged 76 µm in diameter and had an envelope studded with crown-like, electron-dense spikes. Vacuoles contained double-membrane vesicles suggestive of partially assembled virus.The presence of viral particles in the renal tubular epithelium that were morphologically identical to SARS-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-CoV-2. This finding offers confirmatory evidence that direct renal infection occurs in the setting of AKI in COVID-19. However, the frequency and clinical significance of direct infection in COVID-19 is unclear. Tubular isometric vacuolization observed with light microscopy, which correlates with double-membrane vesicles containing vacuoles observed with electronic microscopy, may be a useful histologic marker for active SARS-CoV-2 infection in kidney biopsy or autopsy specimens.
Identification of Susceptibility Loci for Spontaneous Coronary Artery Dissection
Authors: Tamiel N. Turley, Megan M. O’Byrne, Matthew L. Kosel, Mariza de Andrade, Rajiv Gulati, Sharonne N. Hayes, Marysia S. Tweet, Timothy M. Olson
Journal: JAMA Cardiology (2020)

Spontaneous coronary artery dissection (SCAD), an idiopathic disorder that predominantly affects young to middle-aged women, has emerged as an important cause of acute coronary syndrome, myocardial infarction, and sudden cardiac death.To identify common single-nucleotide variants (SNVs) associated with SCAD susceptibility.This single-center genome-wide association study examined approximately 5 million genotyped and imputed SNVs and subsequent SNV-targeted replication analysis results in individuals enrolled in the Mayo Clinic SCAD registry from August 30, 2011, to August 2, 2018. Data analysis was performed from June 21, 2017, to December 30, 2019.Genetic loci and positional candidate genes associated with SCAD.This study included 484 white women with SCAD (mean [SD] age, 46.6 [9.2] years) and 1477 white female controls in the discovery cohort (mean [SD] age, 64.0 [14.5] years) and 183 white women with SCAD (mean [SD] age, 47.1 [9.9] years) and 340 white female controls in the replication cohort (mean [SD] age, 51.0 [15.3] years). Associations with SCAD risk reached genome-wide significance at 3 loci (1q21.3 [OR, 1.78; 95% CI, 1.51-2.09; P = 2.63 × 10-12], 6p24.1 [OR, 1.77; 95% CI, 1.51-2.09; P = 7.09 × 10-12], and 12q13.3 [OR, 1.67; 95% CI, 1.42-1.97; P = 3.62 × 10-10]), and 7 loci had evidence suggestive of an association (1q24.2 [OR, 2.10; 95% CI, 1.58-2.79; P = 2.88 × 10-7], 3q22.3 [OR, 1.47; 95% CI, 1.26-1.71; P = 6.65 × 10-7], 4q34.3 [OR, 1.84; 95% CI, 1.44-2.35; P = 9.80 × 10-7], 8q24.3 [OR, 2.57; 95% CI, 1.76-3.75; P = 9.65 × 10-7], 15q21.1 [OR, 1.75; 95% CI, 1.40-2.18; P = 7.23 × 10-7], 16q24.1 [OR, 1.91; 95% CI, 1.49-2.44; P = 2.56 × 10-7], and 21q22.11 [OR, 2.11; 95% CI, 1.59-2.82; P = 3.12 × 10-7]) after adjusting for the top 5 principal components. Associations were validated for 5 of the 10 risk alleles in the replication cohort. In a meta-analysis of the discovery and replication cohorts, associations for the 5 SNVs were significant, with relatively large effect sizes (1q21.3 [OR, 1.77; 95% CI, 1.54-2.03; P = 3.26 × 10-16], 6p24.1 [OR, 1.71; 95% CI, 1.49-1.97; P = 4.59 × 10-14], 12q13.3 [OR, 1.69; 95% CI, 1.47-1.94; P = 1.42 × 10-13], 15q21.1 [OR, 1.79; 95% CI, 1.48-2.17; P = 2.12 × 10-9], and 21q22.11 [OR, 2.18; 95% CI, 1.70-2.81; P = 1.09 × 10-9]). Each index SNV was within or near a gene highly expressed in arterial tissue and previously linked to SCAD (PHACTR1) and/or other vascular disorders (LRP1, LINC00310, and FBN1).This study revealed 5 replicated risk loci and positional candidate genes for SCAD, most of which are associated with extracoronary arteriopathies. Moreover, the alternate alleles of 3 SNVs have been previously associated with atherosclerotic coronary artery disease, further implicating allelic susceptibility to coronary artery atherosclerosis vs dissection.
Psychometric validation of the living with pulmonary hypertension questionnaire in pulmonary arterial hypertension patients
Authors: Nicola Bonner, Linda Abetz, Juliette Meunier, Mirko Sikirica
Journal: European Respiratory Journal (2012)

Background: The Living with Pulmonary Hypertension questionnaire (LPH) was adapted from the Minnesota Living with Heart Failure Questionnaire for use in patients with pulmonary arterial hypertension (PAH).

Objectives: To confirm the structure, assess the psychometric properties and provide guidance for the interpretation of the LPH.

Methods: LPH was given at baseline and last visit (week 12) to patients with PAH as part of a double blind, Phase III, clinical trial; this data was used to perform the LPH validation analyses: description of items, scores and quality of completion, construct validity, reliability, clinical validity and responsiveness. Analyses to provide an estimation of the Minimal Important Difference (MID) for the LPH scores were performed.

Results: The LPH Emotional and Physical scores met the criteria for convergent and discriminant validity; for the total score all but two items met the test for item convergent validity. Internal consistency reliability of the LPH scores was demonstrated by Cronbach's alpha values of >0.70 for all LPH scores. The LPH Physical and Total scores discriminated between World Health Organisation (WHO) Functional classes and 6 Minute walking test scores, indicating clinical validity and were also responsive to change in clinical severity, as measured by change in WHO functional class and Borg CR 10 Scale. Further investigation is required to confirm the responsiveness of the Emotional score. Estimation of MID using distribution-based methods indicated a change of 3 points for the sub-scales and 7 for the total score to be clinically meaningful.

Conclusion: The LPH is a valid and reliable instrument.
COVID-19: PCR screening of asymptomatic health-care workers at London hospital
Authors: Thomas A Treibel, Charlotte Manisty, Maudrian Burton, Áine McKnight, Jonathan Lambourne, João B Augusto, Xosé Couto-Parada, Teresa Cutino-Moguel, Mahdad Noursadeghi, James C Moon
Journal: The Lancet (2020)
Effects of metformin on clinical outcome in advanced hcc patients receiving sorafenib
Authors: G. Marisi, M. Scartozzi, L. Faloppi, G. Marisi, G. Masi, C. Vivaldi, N. Silvestris, S. Tamberi, E. Tamburini, A. Casadei Gardini
Journal: Annals of Oncology (2015)
Abstract IA15: Role of human papillomaviruses in carcinogenesis
Authors: Massimo Tommasino
Journal: Cancer Research (2020)

Abstract Infectious agents represent a major group of risk factors for cancer development and contribute to about 15% of human cancers worldwide. Six viruses and one bacterium, i.e., human papillomavirus (HPV), hepatitis C virus (HCV), hepatitis B virus, human T-lymphotropic virus type I (HTLV-1), Epstein-Barr virus (EBV), Kaposi sarcoma-associated virus (KSHV), and Helicobacter pylori, have been clearly associated with human carcinogenesis. The mucosal high-risk (HR) HPV types are the etiologic factors of cervical cancers and subset of oropharyngeal cancers. In addition, ongoing studies concerning a subgroup of HPV types that infect the skin suggest their involvement, together with ultraviolet radiation (or solar exposure), in the development of nonmelanoma skin cancer (NMSC). Biologic studies have demonstrated that the products of two early genes from the HR HPV types, E6 and E7, play a key role in cancer development. Both viral oncoproteins are able to target several cellular pathways leading to the evasion of the immune surveillance and cellular transformation. These studies also substantially contributed to our understanding of key mechanisms involved in the normal life of the cell. In the last few years, we have performed additional studies on cutaneous and mucosal HPV types and have characterized novel oncogenic viral mechanisms involved in the evasion of the immune response and/or in cellular transformation. A few examples will be presented. Citation Format: Massimo Tommasino. Role of human papillomaviruses in carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA15.