tbuckley/cabot-search huggingface dataset:
Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome
Authors: Elisabet Stener-Victorin, Vasantha Padmanabhan, Kirsty A Walters, Rebecca E Campbell, Anna Benrick, Paolo Giacobini, Daniel A Dumesic, David H Abbott
Journal: Endocrine Reviews (2020)

Abstract More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite its high prevalence, PCOS and its accompanying morbidities are likely underdiagnosed, averaging &amp;gt; 2 years and 3 physicians before women are diagnosed. Although it has been intensively researched, the underlying cause(s) of PCOS have yet to be defined. In order to understand PCOS pathophysiology, its developmental origins, and how to predict and prevent PCOS onset, there is an urgent need for safe and effective markers and treatments. In this review, we detail which animal models are more suitable for contributing to our understanding of the etiology and pathophysiology of PCOS. We summarize and highlight advantages and limitations of hormonal or genetic manipulation of animal models, as well as of naturally occurring PCOS-like females.
Current epidemiological and clinical features of COVID-19; a global perspective from China
Authors: Huilan Tu, Sheng Tu, Shiqi Gao, Anwen Shao, Jifang Sheng
Journal: Journal of Infection (2020)

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a potentially fatal disease of great global public health importance. As of March 26, 2020, the outbreak of COVID-19 has resulted in 462,801 confirmed cases and 20,839 deaths globally, which is more than those caused by SARS and Middle East respiratory syndrome (MERS) in 2003 and 2013, respectively. The epidemic has posed considerable challenges worldwide. Under a strict mechanism of massive prevention and control, China has seen a rapid decrease in new cases of coronavirus; however, the global situation remains serious. Additionally, the origin of COVID-19 has not been determined and no specific antiviral treatment or vaccine is currently available. Based on the published data, this review systematically discusses the etiology, epidemiology, clinical characteristics, and current intervention measures related to COVID-19 in the hope that it may provide a reference for future studies and aid in the prevention and control of the COVID-19 epidemic.
Knowledge use in the development of sugar-sweetened beverage tax policy in Mexico and Chile: a qualitative analysis
Authors: Gordon C Shen, Benjamin McCarthy, Melissa Fuster, Sarah Lewis, Sahai Burrowes
Journal: The Lancet Global Health (2020)

BackgroundKnowledge use is an integral theme of public policy studies. National obesity policy merits attention given its technical and social complexity. Scientific evidence about the obesity epidemic has been contested and obesity prevention is political in nature because it raises tensions between population health promotion and the principle of non-interference in citizens' lives. Countries that are early adopters of obesity policy are enmeshed in this two-fold complexity. In this study, we examine the knowledge that was used in the development of sugar-sweetened beverage (SSB) tax policy in Mexico and Chile.MethodsWe conducted semi-structured interviews with key informants from the epistemic community, civil society, and food and beverage industry. We also collected documents about SSB tax policy in Mexico, Chile, and elsewhere in Latin America. Interviews were professionally transcribed and translated verbatim. We analysed the transcripts and published material using the same coding scheme. We also conducted a bibliometric analysis of the documents collected.FindingsBetween February and August, 2018, we interviewed 24 key informants: 16 researchers, five civil society representatives, and three food and beverage industry representatives; nine from Mexico, seven from Chile, and eight international respondents. We included 215 total documents dated from Jan 17, 2002, to Feb 11, 2020, including 175 journal articles, 25 newspaper articles, eight books, five conference papers, one report, and one master's thesis. Three themes emerged from our dataset. First, interviewees focused on the evidence that showed an immediate relation between tax and reduced consumption of SSB rather than SSB's long-term impact on population health. Second, interviewees endorsed the concept of "policy-based evidence making", defined as an increase in the production of scientific evidence after SSB tax policy was enacted in the two countries. Lastly, the document analysis showed that each type of respondent cited literature published by their peers.InterpretationThe study of public policy should include the evaluation of evidence in the national response to population health problems. Our findings on causality, knowledge gaps, and citation homophily have implications for the adoption of controversial health policy.FundingPSC-CUNY Award (#60806-00), jointly funded by The Professional Staff Congress and The City University of New York.
Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration
Authors: Kai Kaarniranta, Hannu Uusitalo, Janusz Blasiak, Szabolcs Felszeghy, Ram Kannan, Anu Kauppinen, Antero Salminen, Debasish Sinha, Deborah Ferrington
Journal: Progress in Retinal and Eye Research (2020)

Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is considered to be a key factor in age-related macular degeneration (AMD) pathology. RPE cells are constantly exposed to oxidative stress that may lead to the accumulation of damaged cellular proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. The ubiquitin-proteasome and the lysosomal/autophagy pathways are the two major proteolytic systems to remove damaged proteins and organelles. There is increasing evidence that proteostasis is disturbed in RPE as evidenced by lysosomal lipofuscin and extracellular drusen accumulation in AMD. Nuclear factor-erythroid 2-related factor-2 (NFE2L2) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) are master transcription factors in the regulation of antioxidant enzymes, clearance systems, and biogenesis of mitochondria. The precise cause of RPE degeneration and the onset and progression of AMD are not fully understood. However, mitochondria dysfunction, increased reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) damage are observed together with increased protein aggregation and inflammation in AMD. In contrast, functional mitochondria prevent RPE cells damage and suppress inflammation. Here, we will discuss the role of mitochondria in RPE degeneration and AMD pathology focused on mtDNA damage and repair, autophagy/mitophagy signaling, and regulation of inflammation. Mitochondria are putative therapeutic targets to prevent or treat AMD.
Low-dose colchicine after MI reduced a composite ischemic cardiovascular outcome vs placebo
Authors: Richard G. Bach
Journal: Annals of Internal Medicine (2020)

ACP Journal Club21 April 2020Low-dose colchicine after MI reduced a composite ischemic cardiovascular outcome vs placeboRichard G. Bach, MDRichard G. Bach, MDWashington University School of Medicine, St. Louis, Missouri, USA (R.G.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202004210-039 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationTardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381:2497-2505. https://pubmed.ncbi.nlm.nih.gov/31733140Clinical Impact RatingsGIM/FP/GP: Cardiology: References1 Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-97. [PMID: 26039521] Google Scholar2 Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61:404-10. [PMID: 23265346] Google Scholar3 Deftereos S, Giannopoulos G, Angelidis C, et al. Anti-Inflammatory treatment with colchicine in acute myocardial infarction: a pilot study. Circulation. 2015;132:1395-403. [PMID: 26265659] Google Scholar4 Vaidya K, Arnott C, Martínez GJ, et al. Colchicine therapy and plaque stabilization in patients with acute coronary syndrome: a CT coronary angiography study. JACC Cardiovasc Imaging. 2018;11:305-16. [PMID: 29055633] Google Scholar5 Verma S, Eikelboom JW, Nidorf SM, et al. Colchicine in cardiac disease: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2015;15:96. [PMID: 26318871] Google Scholar Author, Article, and Disclosure InformationAffiliations: Washington University School of Medicine, St. Louis, Missouri, USA (R.G.B.)Disclosures: The commentator has disclosed no conflicts of interest. The form 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: JC39KeywordsAcute coronary syndromeAnginaColchicineCoronary arteriesCoronary revascularizationHospitalizationsMyocardial infarctionStable coronary artery diseaseStrokeTreatment guidelines ePublished: 21 April 2020 Issue Published: 21 April 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Nanoparticles modified by polydopamine: Working as “drug” carriers
Authors: Anting Jin, Yitong Wang, Kaili Lin, Lingyong Jiang
Journal: Bioactive Materials (2020)

Inspired by the mechanism of mussel adhesion, polydopamine (PDA), a versatile polymer for surface modification has been discovered. Owing to its unique properties like extraordinary adhesiveness, excellent biocompatibility, mild synthesis requirements, as well as distinctive drug loading approach, strong photothermal conversion capacity and reactive oxygen species (ROS) scavenging facility, various PDA-modified nanoparticles have been desired as drug carriers. These nanoparticles with diverse nanostructures are exploited in multifunctions, consisting of targeting, imaging, chemical treatment (CT), photodynamic therapy (PDT), photothermal therapy (PTT), tissue regeneration ability, therefore have attracted great attentions in plenty biomedical applications. Herein, recent progress of PDA-modified nanoparticle drug carriers in cancer therapy, antibiosis, prevention of inflammation, theranostics, vaccine delivery and adjuvant, tissue repair and implant materials are reviewed, including preparation of PDA-modified nanoparticle drug carriers with various nanostructures and their drug loading strategies, basic roles of PDA surface modification, etc. The advantages of PDA modification in overcoming the existing limitations of cancer therapy, antibiosis, tissue repair and the developing trends in the future of PDA-modified nanoparticle drug carriers are also discussed.
Abstract IA22: The role of the intestinal microbiome in allogeneic hematopoietic cell transplantation
Authors: Marcel van den Brink
Journal: Cancer Research (2020)

Abstract Relationships between microbiota composition and clinical outcomes of patients following allogeneic hematopoietic cell transplantation (allo-HCT) have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. Therefore, we studied 8,767 fecal samples from 1,362 allo-HCT patients at four centers on three continents by 16S ribosomal sequencing. In an observational study, we examined associations between microbiota diversity and overall survival during two years of follow-up after allo-HCT with proportional-hazards analysis. We observed reproducible patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Low diversity in the peri-neutrophil engraftment period was reproducibly associated with increased risk of death (multivariate-adjusted HR 0.48, 95% CI 0.30-0.77, p = 0.002 in the largest cohort). Subset analysis suggested that these reductions in overall survival were in part due to an increased risk of transplant-related mortality and graft-versus-host disease. Baseline pre-HCT samples already bore evidence of microbiome disruption, and low diversity prior to transplantation was associated with poor survival. In addition, we found that Enterococcus faecium dominates the intestinal microbiota of up to 65% allo-HCT patients early after transplant at all four transplant centers. Enterococcus domination was associated with an increased incidence of acute graft-versus-host disease (GVHD), increased GVHD-related mortality, and reduced overall survival. Post-transplant expansion of Enterococci was also observed in mouse models of GVHD in the absence of antibiotic treatment. Spiking a minimal flora with Enterococci in gnotobiotic mice exacerbated lethal GVHD. Metagenomic sequencing of human and murine Enterococcus-dominated fecal samples revealed an enrichment of lactose and galactose degradation genes, a pathway necessary for Enterococcus growth in vitro. A lactose-free chow attenuated the intestinal outgrowth of Enterococcus and reduced the severity of lethal GVHD in mice. In patients, a lactose-nonabsorber genotype was associated with an increased Enterococcus abundance after cessation of antibiotic treatment after allo-HCT. In conclusion, the concordance of microbiota disruption patterns and their associations with clinical outcomes suggest that approaches to manipulate the intestinal microbiota with the aim of improving allo-HCT clinical outcomes may be generalizable. Citation Format: Marcel van den Brink. The role of the intestinal microbiome in allogeneic hematopoietic cell transplantation [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 IA22.
A case of complete colorectal anastomotic obstruction treated by fully covered metal stents of gradually increasing diameter
Authors: Benedetto Mangiavillano, Francesco Auriemma, Mario Bianchetti, Francesca Scaltrini, Andrea Porta, Alessandro Repici
Journal: Endoscopy (2020)

Benign colorectal postoperative stricture occurs in 5 % – 20 % of cases of sigmoid resection or rectal anterior resection and often involves the distal extraperitoneal rectum. Anastomotic ischemia seems to play an important role. Surgical management with a “re-do” anastomosis was considered the standard treatment in previous years. Nowadays, balloon dilation is considered the gold standard for the treatment of anastomotic strictures, but the treatment often results in a re-stenosis [1]. A limited amount of data have been published in the literature about the use of fully covered metal stents (FCSEMSs) for the treatment of anastomotic refractory fibrotic strictures, but no data showing the effectiveness of gradually increasing the diameter of the FCSEMSs in the treatment of these patients has ever been published.
Ronald Wellesley Pigott: plastic surgeon who specialised in cleft lip and palate repairs
Authors: Rebecca Wallersteiner
Journal: BMJ (2020)

Ronald Wellesley Pigott was born in Isfahan, Persia (now Iran), the son of a general practitioner who settled in Kettering, Northamptonshire. He attended Oakham School.

His friend and colleague, Brian Sommerlad, recalled, “In adulthood, Ron and his sister visited Isfahan to try to find the hospital where their father had worked as a doctor and surgeon, but could not find it. I go there regularly, found the hospital, and sent Ron pictures—of a very run down hospital and locked-up church. He was very pleased.”

Pigott read medicine in Dublin. While a student, he excelled at sport and made many friends. As well as qualifying as a doctor in 1954, he was an Irish international hockey player and played both hockey and tennis for the University of Dublin.

Pigott’s general surgery rotation was at the Hammersmith Hospital, London, and he was awarded the fellowship of the Royal College of Surgeons of Ireland in 1960 and of the Royal College of Surgeons of England in 1962. He took a short service commission with the British Army Parachute Field Ambulance from 1960 to 1962 and then started plastic surgery training. He worked at Odstock Hospital, Salisbury, under John Baron and then went to Stoke Mandeville Hospital, where he was senior registrar under JP Reidy until 1968.

In 1958 Pigott married Sheila, a state registered nurse and midwife; they had four sons. His friend and colleague, Nigel Mercer, recalled: “Ron and Sheila were consummate hosts, and at one party it became clear who was the ‘boss’ at home. When asked where a new brand of peanut came from, Ron replied, ‘I don’t know. I just come home and they are here!’ Ron continued to play tennis for many …
Do pain, depression and fatigue cluster in advanced cancer?
Authors: K. Hauser, L. Rybicki, D. Walsh
Journal: Journal of Clinical Oncology (2006)

8522 Background: A cancer symptom cluster of pain, depression and fatigue has been proposed. We evaluated the frequency and strength of association between these symptoms in advanced cancer, and the risk factors for experiencing all three. Methods: Symptoms from 1,000 patients presenting to a palliative medicine program were recorded prospectively. Possible clustering of pain, depression and fatigue was tested (Spearman correlations). Univariate and multivariate logistic regression analyses were performed of demographics, disease site, laboratory and clinical risk factors for the presence all three symptoms. Results: No association was found between pain and depression (r=0.051, p=0.13), or pain and fatigue (r=0.001, p=0.97) and little between depression and fatigue (r=0.173, p&lt;0.001). 27% (n=261) had all three symptoms and in 9% (n=71) all were moderate or severe. Univariate predictors for the presence of all three were: anorexia-cachexia, anxiety, dyspnea, nausea, sleep problems (all p&lt;0.001), vomiting (p=0.007), and younger age (p=0.007). Univariate predictors of moderate-severe pain, depression and fatigue were: anorexia and early satiety (p&lt;0.001), anxiety (p&lt;0.001), dyspnea (p=0.004), low creatinine (p=0.07), poor performance status (p=0.002), sleep problems (p=0.002), &gt;10% weight loss (p=0.046) and vomiting (p=0.047). Those with pain, depression and fatigue had a median 12 (range 2–24) other symptoms vs. 5 (range 1–14) if none were present (p&lt;0.001). Multivariate predictors of pain, depression and fatigue were: anxiety OR 3.81 (95% CI 2.74–5.30, p&lt;0.001); early satiety OR 1.86 (1.35–2.56, p&lt;0.001); nausea OR 1.44 (1.05–1.97, p=0.023); sleep problems OR 1.52 (1.11–2.08, p=0.009); weight loss OR 1.47 (1.08–2.01, p=0.016). Multivariate predictors of moderate-severe pain, depression and fatigue were anorexia OR 3.11 (1.74–5.55, p&lt;0.001); anxiety OR 6.53 (3.64–11.73, p&lt;0.001); poor performance status OR 1.49 (1.09–2.04, p=0.012). Conclusions: The 3 symptoms co-occur in 1 in 4 advanced cancer patients. Risk factors include younger age, symptom burden and the anorexia-cachexia syndrome. Pain, depression and fatigue do not cluster in advanced cancer. No significant financial relationships to disclose.
Beyond GDP as a measure of welfare: introducing the health-adjusted income metric
Authors: Angela Y Chang, Dean T Jamison
Journal: The Lancet Global Health (2020)

BackgroundGross domestic product (GDP) is often used as a proxy for quality of life. Yet, material gain is only one of the many aspects of life that enhance the wellbeing of a population. One of the most important aspects of welfare is the value of human lifespan. A full-income approach can capture both monetary income and the value of changes in mortality. However, existing literature estimating full-income has two shortcomings: first, the concepts of levels of life expectancy with changes in life expectancy are often conflated, assigning monetary values estimated for changes to levels instead; second, existing approaches apply only to high-income countries and cannot be expanded to low-income countries. Here, we present our framework for a health-adjusted income that captures both the GDP and the monetary values of health and longevity of populationsMethodsIn developing the health-adjusted income framework, we distinguish the differences between levels and changes in mortality, and assign proper values to each. We also explore several approaches for assigning values for changes in mortality for all countries. We compare changes in health-adjusted income across time and countries, and break down the changes into four parts (changes in income, life expectancy, and willingness to pay due to changes in income or changes in life expectancy).FindingsWe provide health-adjusted income estimates for 195 countries between 1970 and 2015, and highlight several interesting comparisons. For example, in the USA, per capita GDP has been approximately 20% greater than that in France for the past 30 years. Yet, the health-adjusted incomes of the two countries have been converging due to France's greater improvements in life expectancy. Other comparisons, such as India versus China, and within China over time, are discussed in detail.InterpretationCompared with GDP, health-adjusted income provides a more comprehensive picture of how countries' welfare has changed over time and allows for comparisons between countries. In a time of worldwide political change, a comprehensive welfare metric that captures population health should be provided to, and used by, policymakers.FundingNone
Droplet Digital PCR Quantification of Mantle Cell Lymphoma Follow‐up Samples From Four Prospective Trials of the European MCL Network
Authors: Daniela Drandi, Marion Alcantara, Ichrafe Benmaad, Arian Söhlbrandt, Ludovic Lhermitte, GianMaria Zaccaria, Martina Ferrante, Elisa Genuardi, Barbara Mantoan, Patrick Villarese, Morgane Cheminant, Irene della Starza, Elena Ciabatti, Riccardo Bomben, Cristina Jimenez, Mary Callanan, Chrystelle Abdo, Cornelia Eckert, Vincent Ribrag, Sergio Cortelazzo, Martin Dreyling, Olivier Hermine, Marie‐Hélène Delfau‐Larue, Christiane Pott, Marco Ladetto, Simone Ferrero, Elizabeth Macintyre
Journal: HemaSphere (2020)

Supplemental Digital Content is available in the text
Identification of tetranectin-targeting monoclonal antibodies to treat potentially lethal sepsis
Authors: Weiqiang Chen, Xiaoling Qiang, Yongjun Wang, Shu Zhu, Jianhua Li, Ariella Babaev, Huan Yang, Jonathan Gong, Lance Becker, Ping Wang, Kevin J. Tracey, Haichao Wang
Journal: Science Translational Medicine (2020)

An antibody strategy prevents harmful TN/HMGB1 interaction and resultant macrophage pyroptosis and immunosuppression in sepsis.
Wet-adhesive, haemostatic and antimicrobial bilayered composite nanosheets for sealing and healing soft-tissue bleeding wounds
Authors: Chengkai Xuan, Lijin Hao, Xuemin Liu, Ye Zhu, Huishang Yang, Yipeng Ren, Lin Wang, Toshinori Fujie, Hongkai Wu, Yunhua Chen, Xuetao Shi, Chuanbin Mao
Journal: Biomaterials (2020)
Semi-quantitative cultures of throat and rectal swabs are efficient tests to predict ESBL-Enterobacterales ventilator-associated pneumonia in mechanically ventilated ESBL carriers
Authors: Olivier Andremont, Laurence Armand-Lefevre, Claire Dupuis, Etienne de Montmollin, Stéphane Ruckly, Jean-Christophe Lucet, Roland Smonig, Eric Magalhaes, Etienne Ruppé, Bruno Mourvillier, Jordane Lebut, Mathilde Lermuzeaux, Romain Sonneville, Lila Bouadma, Jean-François Timsit
Journal: Intensive Care Medicine (2020)