tbuckley/cabot-search huggingface dataset:
The “All of Us” Research Program
Authors: Joshua C Denny, Stephanie A Devaney, Kelly A Gebo
Journal: New England Journal of Medicine (2019)

Knowledge gained from observational cohort studies has dramatically advanced the prevention and treatment of diseases. Many of these cohorts, however, are small, lack diversity, or do not provide comprehensive phenotype data. The All of Us Research Program plans to enroll a diverse group of at least 1 million persons in the United States in order to accelerate biomedical research and improve health. The program aims to make the research results accessible to participants, and it is developing new approaches to generate, access, and make data broadly available to approved researchers. All of Us opened for enrollment in May 2018 and currently enrolls participants 18 years of age or older from a network of more than 340 recruitment sites. Elements of the program protocol include health questionnaires, electronic health records (EHRs), physical measurements, the use of digital health technology, and the collection and analysis of biospecimens. As of July 2019, more than 175,000 participants had contributed biospecimens. More than 80% of these participants are from groups that have been historically underrepresented in biomedical research. EHR data on more than 112,000 participants from 34 sites have been collected. The All of Us data repository should permit researchers to take into account individual differences in lifestyle, socioeconomic factors, environment, and biologic characteristics in order to advance precision diagnosis, prevention, and treatment.
Kenneth Robert Lown
Authors: Bridget Lown Evans
Journal: BMJ (2019)

The outbreak of war in 1939 had disrupted a teenager’s schooling and his chosen career path. In 1946, as the fleet sailed homeward from the Far East via South Africa, Kenneth Robert Lown (“Ken”)—2nd Lt(A), Royal Naval Volunteer Reserve—made good use of the idle shipboard hours to renew his studies, gain a place at the London Hospital medical school, and resume the plans he had been forced to shelve five years earlier.

In 1948 Ken married Monica Johnson, a science student at QMC. In the early 1950s, after graduating, Ken and Monica left London to move to Thanet, where he …
Mortality and Rate of Hospitalization in a Colonoscopy Screening Program From a Randomized Health Services Study
Authors: Jarek Kobiela, Piotr Spychalski, Paulina Wieszczy, Malgorzata Pisera, Nastazja Pilonis, Maciej Rupinski, Marek Bugajski, Jaroslaw Regula, Michal F. Kaminski
Journal: Clinical Gastroenterology and Hepatology (2019)
A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients
Authors: Antonino Cassotta, Vincent Mikol, Thomas Bertrand, Stéphanie Pouzieux, Josiane Le Parc, Paul Ferrari, Jacques Dumas, Michael Auer, Florian Deisenhammer, Matteo Gastaldi, Diego Franciotta, Chiara Silacci-Fregni, Blanca Fernandez Rodriguez, Isabella Giacchetto-Sasselli, Mathilde Foglierini, David Jarrossay, Roger Geiger, Federica Sallusto, Antonio Lanzavecchia, Luca Piccoli
Journal: Nature Medicine (2019)
Annals Graphic Medicine - Alzheimer's Has a Funny Side Too
Authors: Denelle Mohammed
Journal: Annals of Internal Medicine (2019)

Web Exclusives17 September 2019Annals Graphic Medicine - Alzheimer's Has a Funny Side TooFREEDenelle Mohammed, MDDenelle Mohammed, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0040 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Brian R Incremona, MD, FACP, SHMnone10 September 2019 Funny side of Alzheimer's Sorry, I fail to see the humor here. I think it is in poor taste. Disclosures: none Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0040.Author/Illustrator Information: Denelle Mohammed, MD, is a recent medical school graduate and will pursue training in internal medicine (e-mail, [email protected]com). She has a penchant for the artistic side of medicine, exploring how patients experience, struggle, and cope with the challenges of illness.This article was published at Annals.org on 10 September 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 September 2019Volume 171, Issue 6Page: W31-W33KeywordsAlzheimer diseaseConflicts of interestDisclosureGraduate medical educationHealth care ePublished: 10 September 2019 Issue Published: 17 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
CD137 deficiency causes immune dysregulation with predisposition to lymphomagenesis
Authors: Ido Somekh, Marini Thian, David Medgyesi, Nesrin Gülez, Thomas Magg, Alejandro Gallón Duque, Tali Stauber, Atar Lev, Ferah Genel, Ekrem Unal, Amos J. Simon, Yu Nee Lee, Artem Kalinichenko, Jasmin Dmytrus, Michael J. Kraakman, Ginette Schiby, Meino Rohlfs, Jeffrey M. Jacobson, Erdener Özer, Ömer Akcal, Raffaele Conca, Türkan Patiroglu, Musa Karakukcu, Alper Ozcan, Tala Shahin, Eliana Appella, Megumi Tatematsu, Catalina Martinez-Jaramillo, Ivan K. Chinn, Jordan S. Orange, Claudia Milena Trujillo-Vargas, José Luis Franco, Fabian Hauck, Raz Somech, Christoph Klein, Kaan Boztug
Journal: Blood (2019)
Co-delivery of glycyrrhizin and doxorubicin by alginate nanogel particles attenuates the activation of macrophage and enhances the therapeutic efficacy for hepatocellular carcinoma
Authors: Qiang-Song Wang, Li-Na Gao, Xiao-Ning Zhu, Yan Zhang, Chuang-Nian Zhang, Dong Xu, Yuan-Lu Cui
Journal: Theranostics (2019)

Nanocarrier drug delivery systems (NDDS) have been paid more attention over conventional drug delivery system for cancer therapy. However, the efficacy is hampered by the fast clearance of activated macrophage from the blood circulation system. In this study, glycyrrhizin (GL) was introduced into alginate (ALG) nanogel particles (NGPs) to construct multifunctional delivery vehicle to decrease the fast clearance of activated macrophage and enhance the anticancer efficacy with the combination therapy of GL and doxorubicin (DOX). Methods: We firstly synthesized the GL-ALG NGPs with intermolecular hydrogen bond and ionic bond as the multifunctional delivery vehicle. The immune response and phagocytosis of macrophage on GL-ALG NGPs were investigated on RAW 264.7 macrophages. The pharmacokinetic study of DOX loaded in GL-ALG NGPs was performed in rats. The active targeting effects of GL-ALG NGPs were further studied on hepatocellular carcinoma cell (HepG2) and H22 tumor-bearing mice. Moreover, the anticancer molecular mechanism of DOX/GL-ALG NGPs was investigated on HepG2 cells in vitro and tumor-bearing mice in vivo. Results: GL-ALG NGPs could not only avoid triggering the immuno-inflammatory responses of macrophages but also decreasing the phagocytosis of macrophage. The bioavailability of DOX was increased about 13.2 times by DOX/GL-ALG NGPs than free DOX in blood. The mice with normal immune functions used in constructing the tumor-bearing mice instead of the nude mouse also indicated the good biocompatibility of NGPs. GL-mediated ALG NGPs exhibited excellent hepatocellular carcinoma targeting effect in vitro and in vivo. The results suggested that the anticancer molecular mechanism of the combination therapy of glycyrrhizin and doxorubicin in ALG NGPs was performed via regulating apoptosis pathway of Bax/Bcl-2 ratio and caspase-3 activity, which was also verified in H22 tumor-bearing mice. Conclusion: DOX/GL-ALG NGPs could attenuate the activation of macrophage and enhance the therapeutic efficacy for hepatocellular carcinoma. Our results suggest that the combination therapy would provide a new strategy for liver cancer treatment.
PNH-Phenotype Cells and HLA Class I Allele-Lacking Leukocytes Shared By Family Members Who Developed Acquire Aplastic Anemia: Studies on Six Pairs of Patients in Different Families
Authors: Hiroki Mizumaki, Hirohito Yamazaki, Kazuyoshi Hosomichi, Noriharu Nakagawa, Takeshi Yoroidaka, Tatsuya Imi, Hiromi Iwasaki, Mika Kuroiwa, Ryosuke Ogawa, Atsushi Tajima, Shinji Nakao
Journal: Blood (2017)
Lipids, Apolipoproteins, and the Risk of Parkinson Disease
Authors: Fang Fang, Yiqiang Zhan, Niklas Hammar, Xia Shen, Karin Wirdefeldt, Göran Walldius, Daniela Mariosa
Journal: Circulation Research (2019)

A complete picture of the associations of the most common lipid fractions, including total cholesterol (TC), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), triglycerides, and apolipoproteins, with the risk of Parkinson disease (PD), is lacking.To assess the associations of lipids and apolipoproteins with the future risk of PD.In the AMORIS (Apolipoprotein-Related Mortality Risk) Study, we enrolled ≈600 000 participants during 1985 to 1996 in Stockholm, Sweden, with repeated measurements of TC, LDL-C, HDL-C, triglycerides, ApoB (apolipoprotein B), and ApoA-I (apolipoprotein A-I). The cohort was followed until the end of 2011, and incident cases of PD were identified through the Swedish Patient Register. We first used Cox models to estimate the associations of these biomarkers with later risk of PD. We further applied a Mendelian randomization analysis for TC, LDL-C, and triglycerides using the GWAS (Genome-wide association study) summary statistics from the public PD GWAS data and 23andMe PD cohorts with >800 000 individuals. One SD increase of TC was associated with a lower hazard of PD (hazard ratio, 0.90; 95% CI, 0.87-0.94). Similar associations were observed for LDL-C (hazard ratio, 0.93; 95% CI, 0.88-0.98), triglycerides (hazard ratio, 0.94; 95% CI, 0.90-0.97), and ApoB (hazard ratio, 0.91; 95% CI, 0.85-0.97). A clear dose-response relation was also noted when using these biomarkers as categorical variables. A causal inverse association of TC, LDL-C, and triglycerides with PD risk was further suggested by the Mendelian randomization analysis.Our findings reinforce that higher levels of TC, LDL-C, and triglycerides are associated with a lower future risk of PD and further suggest that these associations may be causal. The findings for ApoB in relation to PD risk are novel, and whether such association is causal needs to be examined.
Euthanasia: Dutch doctor is acquitted in landmark test case
Authors: Elisabeth Mahase
Journal: BMJ (2019)

A Dutch doctor who euthanised a patient who had dementia and could not consent owing to the advanced stage of her condition has been acquitted, after a judge ruled that the patient’s previous request for euthanasia, signed when she was competent, was sufficient.1

The case, which was heard in the District Court of the Hague, sought to determine whether the geriatrician should have verified whether the patient still wanted to be euthanised at the time of death. The doctor, unnamed in the court report, had been unable to do this, as the patient’s condition had deteriorated to the point where she no longer understood the concept of euthanasia, and she was deemed no longer …
Ninth international congress on peer review and scientific publication: call for research
Authors: John P A Ioannidis, Michael Berkwits, Annette Flanagin, Fiona Godlee, Theodora Bloom
Journal: BMJ (2019)

The quantity and quality of scientific research have never been greater, but with unprecedented promise comes unprecedented peril.There are better scientific policies and processes, stronger standards for openness and transparency, and innovative technologies to collaborate and publish.However, the rapidly evolving scientific publication ecosystem that facilitates research dissemination also enables research waste, predation, and piracy.The challenge of distinguishing information from noise, innovation from dystopian-like disruption, and opportunity from threat has created new levels of excitement and angst for those engaged in research and its reporting, publication, and distribution.In these historically challenging circumstances, we announce the ninth international congress on peer review and scientific publication, which will take place on 12-14 September 2021 in Chicago, Illinois.Since the first peer review congress in 1989, founded by Drummond Rennie when he was JAMA's deputy editor, 1 the aim has been to encourage research into the quality and credibility of peer review and scientific publication.The goal is to strengthen the evidence base so that all those involved in science (including but not limited to researchers, editors, publishers, funders, policy makers, academics, and representatives of universities, industry, media, and the general public) can improve the conduct, reporting, and dissemination of scientific research. 2 A few core principles and practices have governed past congresses and the next one announced here. 3 The congresses provide a forum for research into the processes of selection, refinement, and dissemination of scientific knowledge.They do not presume
The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4
Authors: Salil Saurav Pathak, Dong Liu, Tianbao Li, Nuria de Zavalia, Lei Zhu, Jin Li, Ramanujam Karthikeyan, Tommy Alain, Andrew C. Liu, Kai-Florian Storch, Randal J. Kaufman, Victor X. Jin, Shimon Amir, Nahum Sonenberg, Ruifeng Cao
Journal: Neuron (2019)
Thank you to our high-quality peer reviewers
Authors: Zoë Mullan
Journal: The Lancet Global Health (2019)

It's Peer Review Week again, and this year the focus is on quality in peer review. This theme goes to the heart of peer review and its role in setting scholarly publishing apart from other forms of information dissemination. Peer review cannot perform its role in improving the clarity and robustness of written research works or in challenging the publication of those that are poorly designed or interpreted unless the reports generated by reviewers are thorough, considered, specific, dispassionate, and generated in the spirit of moving science forward. At The Lancet Global Health, we are indebted to our many dedicated peer reviewers who generate sometimes multiple high-quality reviews for us every year. Approaches vary of course, and we recognise that not all our reviewers will have had the same degree of mentoring in what constitutes a useful review. We were pleased, therefore, to have been involved with Elsevier Researcher Academy's certified peer reviewer course, which goes live this week. The course is free of charge and can be studied via self-directed learning at the user's own pace. We hope it will be useful in enhancing the skills and confidence of those interested in contributing to peer review, particularly in settings where access to such resources is limited. Finally, a word on diversity. Last year we revealed that only 36% of our reviewers were women and pledged to invite at least 50% women per paper over the next year. Despite a real effort to do so, only 249 (38%) of the 662 reviewers who submitted a review between September 2018 and August 2019 and whose gender we could identify were women. We will continue with our commitment and welcome ideas for how we can improve further. Thank you to all who reviewed over the past 12 months (appendix). I thank Rebecca Barksby for data analysis. Download .pdf (.29 MB) Help with pdf files Supplementary appendix
Benefit of Anakinra in Treating Pediatric Secondary Hemophagocytic Lymphohistiocytosis
Authors: Esraa M. Eloseily, Peter Weiser, Courtney B. Crayne, Hilary Haines, Melissa L. Mannion, Matthew L. Stoll, Timothy Beukelman, T. Prescott Atkinson, Randy Q. Cron
Journal: Arthritis & Rheumatology (2019)

Objective To assess the benefit of the recombinant human interleukin‐1 receptor antagonist anakinra in treating pediatric patients with secondary hemophagocytic lymphohistiocytosis ( HLH )/macrophage activation syndrome ( MAS ) associated with rheumatic and nonrheumatic conditions. Methods A retrospective chart review of all anakinra‐treated patients with secondary HLH / MAS was performed at Children's of Alabama from January 2008 through December 2016. Demographic, clinical, laboratory, and genetic characteristics, outcomes data, and information on concurrent treatments were collected from the records and analyzed using appropriate univariate statistical approaches to assess changes following treatment and associations between patient variables and outcomes. Results Forty‐four patients with secondary HLH / MAS being treated with anakinra were identified in the electronic medical records. The median duration of hospitalization was 15 days. The mean pretreatment serum ferritin level was 33,316 ng/ml and dropped to 14,435 ng/ml (57% decrease) within 15 days of the start of anakinra treatment. The overall mortality rate in the cohort was 27%. Earlier initiation of anakinra (within 5 days of hospitalization) was associated with reduced mortality ( P = 0.046), whereas thrombocytopenia (platelet count &lt;100,000/μl) and STXBP 2 mutations were both associated with increased mortality ( P = 0.008 and P = 0.012, respectively). In considering patients according to their underlying diagnosis, those with systemic juvenile idiopathic arthritis ( JIA ) had the lowest mortality rate, with no deaths among the 13 systemic JIA patients included in the study ( P = 0.006). In contrast, those with an underlying hematologic malignancy had the highest mortality rate, at 100% (n = 3). Conclusion These findings suggest that anakinra appears to be effective in treating pediatric patients with non–malignancy‐associated secondary HLH / MAS , especially when it is given early in the disease course and when administered to patients who have an underlying rheumatic disease.
Beyond the Lungs: Systemic Manifestations of Pulmonary Arterial Hypertension
Authors: Nils P. Nickel, Ke Yuan, Peter Dorfmuller, Steeve Provencher, Yen-Chun Lai, Sebastien Bonnet, Eric D. Austin, Carl D. Koch, Alison Morris, Frédéric Perros, David Montani, Roham T. Zamanian, Vinicio A. de Jesus Perez
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Section:ChooseTop of pageAbstract <<Vascular Dysfunction in t...Metabolic and Endocrine A...Skeletal and Respiratory ...Bronchopulmonary Anastomo...The Microbiome and System...ConclusionsReferencesCITING ARTICLES
Global tuberculosis prevention: should we start from the beginning?
Authors: Giovanni Sotgiu, Delia Goletti, Alberto Matteelli
Journal: European Respiratory Journal (2019)

Tuberculosis (TB), which is estimated to be the deadliest infectious disease worldwide with ∼1.6 million deaths yearly [1], is a clinical issue due to the "ancient" diagnostics and drugs currently available. If compared with the management of other highly prevalent infectious diseases, such as HIV/AIDS and hepatitis C virus infection, it is clear that the clinical approach for TB disease requires innovation, being still based on means with limited efficacy ( e.g. treatment of multidrug-resistant TB; MDR-TB), and characterised by the denominator "long duration": conventional bacteriological diagnosis, therapy for the drug-susceptible disease ( i.e. 6 months) and MDR-TB ( i.e. >20 months) [2–7]. TB prevention should be based on a global and local comprehensive assessment of LTBI burden <http://bit.ly/2YfKM0T>
Chronic Model of Inflammatory Bowel Disease in IL-10<sup>-/-</sup> Transgenic Mice: Evaluation with Ultrasound Molecular Imaging
Authors: Huaijun Wang, Jose G Vilches-Moure, Samir Cherkaoui, Isabelle Tardy, Charline Alleaume, Thierry Bettinger, Amelie Lutz, Ramasamy Paulmurugan
Journal: Theranostics (2019)

Objective: Acute mouse models of inflammatory bowel disease (IBD) fail to mirror the chronic nature of IBD in patients.We sought to develop a chronic mouse IBD model for assessing long-term anti-inflammatory effects with ultrasound molecular imaging (USMI) by using dual P-and E-selectin targeted microbubbles (MBSelectin).Materials and Methods: Interleukin 10 deficient (IL-10 -/-on a C57BL/6 genetic background; n=55) and FVB (n=16) mice were used.In IL-10 -/-mice, various experimental regimens including piroxicam, 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sulfate sodium (DSS), respectively were used for promoting colitis; colitis was induced with DSS in FVB mice.Using clinical and small animal ultrasound scanners, evolution of inflammation in proximal, middle and distal colon, was monitored with USMI by using MBSelectin at multiple time points.Imaged colon segments were analyzed ex vivo for inflammatory changes on H&E staining and for P-selectin expression on immunofluorescence staining.Results: Sustained colitis was not detected with USMI in IL-10 -/-or FVB mice with various experimental regimens.USMI signals either gradually decreased after the colitis enhancing/inducing drug/agents were discontinued, or the mortality rate of mice was high.Inflammation was observed on H&E staining in IL-10 -/-mice with piroxicam promotion, while stable overexpression of P-selectin was not found on immunofluorescence staining in the same mice.Conclusion: Sustained colitis in IL-10 -/-mice induced with piroxicam, TNBS or DSS, and in FVB mice induced with DSS, was not detected with USMI using MBSelectin, and this was verified by immunofluorescence staining for inflammation marker P-selectin.Thus, these models may not be appropriate for long-term monitoring of chronic colitis and subsequent treatment response with dual-selectin targeted USMI.