tbuckley/cabot-search huggingface dataset:
Hydroxychloroquine shortages during the COVID-19 pandemic
Authors: Arielle Mendel, Sasha Bernatsky, J Carter Thorne, Diane Lacaille, Sindhu R Johnson, Évelyne Vinet
Journal: Annals of the Rheumatic Diseases (2020)

Across the globe, concerns of hydroxychloroquine (HCQ) supply shortages for patients with rheumatic disease are growing,1 in part as a consequence of the immense scientific and public enthusiasm for HCQ as a potential COVID-19 therapy.2 3 However, published data on the occurrence of HCQ shortages during the COVID-19 pandemic are presently lacking. Therefore, we conducted a national survey of 531 Canadian rheumatologists between 14 and 24 April 2020. The 5-question electronic survey (French or English) included province of practice, whether respondents were concerned about HCQ shortages in their province, and whether they had been contacted by patients or pharmacies regarding difficulties renewing HCQ prescriptions during the COVID-19 pandemic. Physicians who answered ‘yes’ to the latter question were asked to estimate for how many patients this occurred. The McGill University Health Centre research ethics board approved this survey.

Of 134 rheumatologists who completed the survey (25% response rate), three quarters (n=102, 76%) were concerned about HCQ shortages, while 81 (60%) had been contacted by pharmacies or patients …
Targeting the innate immunoreceptor RIG-I overcomes melanoma-intrinsic resistance to T cell immunotherapy
Authors: Lina Such, Fang Zhao, Derek Liu, Beatrice Thier, Vu Thuy Khanh Le-Trilling, Antje Sucker, Christoph Coch, Natalia Pieper, Sebastian Howe, Hilal Bhat, Halime Kalkavan, Cathrin Ritter, Robin Brinkhaus, Selma Ugurel, Johannes Köster, Ulrike Seifert, Ulf Dittmer, Martin Schuler, Karl S. Lang, Thomas A. Kufer, Gunther Hartmann, Jürgen C. Becker, Susanne Horn, Soldano Ferrone, David Liu, Eliezer M. Van Allen, Dirk Schadendorf, Klaus Griewank, Mirko Trilling, Annette Paschen
Journal: Journal of Clinical Investigation (2020)

Understanding tumor resistance to T cell immunotherapies is critical to improve patient outcomes. Our study revealed a role for transcriptional suppression of the tumor-intrinsic HLA class I (HLA-I) antigen processing and presentation machinery (APM) in therapy resistance. Low HLA-I APM mRNA levels in melanoma metastases before immune checkpoint blockade (ICB) correlated with nonresponsiveness to therapy and poor clinical outcome. Patient-derived melanoma cells with silenced HLA-I APM escaped recognition by autologous CD8+ T cells. However, targeted activation of the innate immunoreceptor RIG-I initiated de novo HLA-I APM transcription, thereby overcoming T cell resistance. Antigen presentation was restored in interferon-sensitive (IFN-sensitive) but also immunoedited IFN-resistant melanoma models through RIG-I-dependent stimulation of an IFN-independent salvage pathway involving IRF1 and IRF3. Likewise, enhanced HLA-I APM expression was detected in RIG-Ihi (DDX58hi) melanoma biopsies, correlating with improved patient survival. Induction of HLA-I APM by RIG-I synergized with antibodies blocking PD-1 and TIGIT inhibitory checkpoints in boosting the antitumor T cell activity of ICB nonresponders. Overall, the herein-identified IFN-independent effect of RIG-I on tumor antigen presentation and T cell recognition proposes innate immunoreceptor targeting as a strategy to overcome intrinsic T cell resistance of IFN-sensitive and IFN-resistant melanomas and improve clinical outcomes in immunotherapy.
Covid-19 and thrombosis: what do we know about the risks and treatment?
Authors: Jacqui Wise
Journal: BMJ (2020)

Covid-19 and thrombosis: what do we know about the risks and treatment?Doctors are seeing high rates of blood clots in patients who are seriously ill with covid-19, but questions remain over best practice, reports Jacqui Wise Jacqui Wise London How common is thrombosis in critically ill patients with covid-19?A recent Dutch study of 184 patients with covid-19 pneumonia admitted to an intensive care unit (ICU) found a 49% cumulative incidence of thrombotic complications-mainly changes seen on computed tomography (CT) pulmonary angiograms. 1 The authors said that this level was "remarkably high," given that all patients received at least standard doses of thromboprophylaxis.Other studies from France and the Netherlands have also suggested that thrombosis occurs in 20-30% of critically ill covid-19 patients, even with prophylaxis. 2 3"The extent of thrombosis we are seeing with covid is extraordinary," Roopen Arya, clinical director for haematology at King's College Hospital, told The BMJ. "I would say that one third of those severely affected with covid in critical care is a conservative estimate." Why are covid-19 patients at particular risk of thrombosis?Covid-19 causes massive inflammation boosting cytokines, which increase the liver's production of clotting factors, explains Beverley Hunt, medical director of Thrombosis UK and a practising clinician.For example, fibrinogen levels in a severely ill covid-19 patient are 10-14 g/L, compared with 2-4 g/L normally and 5-6 g/L in a pregnant woman."A covid patient's blood is enormously sticky," she told The BMJ.
<i>ATRAID</i> regulates the action of nitrogen-containing bisphosphonates on bone
Authors: Lauren E. Surface, Damon T. Burrow, Jinmei Li, Jiwoong Park, Sandeep Kumar, Cheng Lyu, Niki Song, Zhou Yu, Abbhirami Rajagopal, Yangjin Bae, Brendan H. Lee, Steven Mumm, Charles C. Gu, Jonathan C. Baker, Mahshid Mohseni, Melissa Sum, Margaret Huskey, Shenghui Duan, Vinieth N. Bijanki, Roberto Civitelli, Michael J. Gardner, Chris M. McAndrew, William M. Ricci, Christina A. Gurnett, Kathryn Diemer, Fei Wan, Christina L. Costantino, Kristen M. Shannon, Noopur Raje, Thomas B. Dodson, Daniel A. Haber, Jan E. Carette, Malini Varadarajan, Thijn R. Brummelkamp, Kivanc Birsoy, David M. Sabatini, Gabe Haller, Timothy R. Peterson
Journal: Science Translational Medicine (2020)

ATRAID is essential for responses to the commonly prescribed osteoporosis drugs nitrogen-containing bisphosphonates.
Correction to: Small Molecule KRAS Agonist for Mutant KRAS Cancer Therapy
Authors: Ke Xu, Dongkyoo Park, Andrew T. Magis, Jun Zhang, Wei Zhou, Gabriel L. Sica, Suresh S. Ramalingam, Walter J. Curran, Xingming Deng
Journal: Molecular Cancer (2020)

An amendment to this paper has been published and can be accessed via the original article.
A Man in His 80s With Abnormal Arterial Line Pulse Waveforms
Authors: John E. Rubin, Christina Lee, Adam D. Lichtman
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Physical Fitness Among Swedish Military Conscripts and Long-Term Risk for Type 2 Diabetes Mellitus
Authors: Casey Crump, Jan Sundquist, Marilyn A. Winkleby, Weiva Sieh, Kristina Sundquist
Journal: Annals of Internal Medicine (2016)

The relationship between physical fitness levels during late adolescence and the development of type 2 diabetes mellitus (DM) during adulthood is uncertain. This study of male military conscripts e...
Extended Out-of-Hospital Low-Molecular-Weight Heparin Prophylaxis against Deep Venous Thrombosis in Patients after Elective Hip Arthroplasty
Authors: Russell D. Hull, Graham F. Pineo, Paul D. Stein, Andrew F. Mah, Susan M. MacIsaac, Ola E. Dahl, Matthew Butcher, Rollin F. Brant, William A. Ghali, David Bergqvist, Gary E. Raskob
Journal: Annals of Internal Medicine (2001)

Extended prophylaxis with low-molecular-weight heparin showed consistent effectiveness and safety in the trials included in this systematic review (regardless of study variations in clinical practi...
188P Impact of HIV infection (HIV+) on baseline characteristics and survival of breast cancer (BC) patients (pts): A systematic review and meta-analysis
Authors: M.D.R.A. Brandão, M. Bruzzone, M.A. Franzoi, C. de Angelis, D. Eiger, R. Caparica, N. Dauby, M. Ceppi, M. Piccart, C. Carrilho, N. Lunet, L. Buisseret, E. de Azambuja, M. Lambertini
Journal: Annals of Oncology (2020)
Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure
Authors: Huayu Yang, Lejia Sun, Yuan Pang, Dandan Hu, Haifeng Xu, Shuangshuang Mao, Wenbo Peng, Yanan Wang, Yiyao Xu, Yong-Chang Zheng, Shunda Du, Haitao Zhao, Tianyi Chi, Xin Lu, Xinting Sang, Shouxian Zhong, Xin Wang, Hongbing Zhang, Pengyu Huang, Wei Sun, Yilei Mao
Journal: Gut (2020)

Objective Shortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo. Design 3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production. Results 3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah -/- Rag2 -/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice. Conclusions Our results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.
Expression of the zinc-finger transcription factor Snail during prostate cancer progression
Authors: Xiulian Chen, Andreas I. Evangelou, Norman M. Greenberg
Journal: Cancer Research (2006)

1723  The zinc finger transcription factor Snail has been implicated in Epithelial-Mesenchymal Transition (EMT) by partly repressing the expression of E-cadherin during embryonic development and tumor progression. Elevated levels of Snail have been reported in many different tumors including breast, stomach, liver, ovarian, and colon. Snail has also been demonstrated as a major determinant of ovarian cancer invasiveness and in promoting mammary tumor recurrence. In the present study we characterize expression of Snail in prostate cancer progression in the TRAMP model using quantitative RT-PCR and immunochemistry with a new rabbit polyclonal antibody developed in our lab (AbSnail). We determine that Snail is sporadically expressed in both the glandular and basal cells in the normal prostate gland. Interestingly, expression in the ventral prostate was higher than in the other lobes. This finding was consistent with the fact that the incidence of tumors originating from the ventral prostate gland was higher than from the other lobes. As tumors progress there was a significant increase in Snail expression in PIN lesions, well- and poorly-differentiated tumors, and in metastatic lesions to the lung. Hence, we have characterized and correlated Snail expression levels with histological grade in prostate tumors and in lung metastases. We are now further exploring the possibility of using AbSnail in CHIP Assays to identify specific Snail target genes during prostate cancer progression.
3O Mutation analysis of circulating tumour DNA from baseline and study discontinuation samples in SANDPIPER, a phase III study of taselisib or placebo with fulvestrant in oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA-mutant advanced breast cancer
Authors: W. Jacot, H.M. Savage, S. Dent, J. Cortés, Y-H. Im, V.C. Dieras, N. Harbeck, I.E. Krop, J. Chen, E. Sokol, F. Schimmoller, J. Hsu, M. De Laurentiis, T.R. Wilson
Journal: Annals of Oncology (2020)
Abstract 11223: A Cost-Effectiveness Analysis of Interstage Home Monitoring for Infants With Hypoplastic Left Heart Syndrome
Authors: Bryant Priromprintr, Douglas Owens, Christopher S Almond, Tracey Hong, Renu Kondragunta, Swaril Mathur, Andrew Y Shin
Journal: Circulation (2018)

Introduction: Hypoplastic left heart syndrome (HLHS) is a congenital heart defect often managed with three stages of palliative surgery. Interstage home monitoring programs (HMP) have recently been...
Bullous and Exanthematous Lesions Associated With Chimeric Antigen Receptor T-Cell Therapy in a Patient With Diffuse Large B-Cell Lymphoma
Authors: Yongxian Hu, Weiyan Zheng, Jianjun Qiao, Qu Cui, Yuanyuan Zhu, Alex H. Chang, He Huang
Journal: JAMA Dermatology (2020)

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複雑な介入の開発と評価:新しい方法論と理論的アプローチを考慮するための医学研究審議会ガイダンスの更新【JST・京大機械翻訳】
Authors: Skivington Kathryn, Matthews Lynsay, Craig Peter, Simpson Sharon, Moore Laurence
Journal: The Lancet (2018)
The COMPASS Trial
Authors: Jan Steffel, John W. Eikelboom, Sonia S. Anand, Olga Shestakovska, Salim Yusuf, Keith A.A. Fox
Journal: Circulation (2020)

Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid (aspirin; ASA) 100 mg reduced the risk of cardiovascular events as compared with ASA monotherapy in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) but increased the risk of major bleedings. Analysis of net clinical benefit (NCB) is of key clinical relevance and represents an integrated measure of overall patient outcome.The current prespecified analysis was performed to assess the NCB of adding rivaroxaban 2.5 mg twice daily to ASA monotherapy in patients with chronic vascular disease in the COMPASS study cohort (intention-to-treat study population), with a specific focus on high-risk subgroups. The predefined NCB outcome was the composite of cardiovascular death, stroke, myocardial infarction, fatal bleeding, or symptomatic bleeding into a critical organ.A lower number of NCB adverse outcomes was observed with rivaroxaban 2.5 mg twice daily plus ASA versus ASA alone (hazard ratio, 0.80 [95% CI, 0.70-0.91], P=0.0005), which became increasingly favorable with longer treatment duration. The main drivers of NCB outcomes were "efficacy" events, in particular stroke (0.5%/y versus 0.8%/y; hazard ratio, 0.58 [95% CI, 0.44-0.76], P<0.0001) and cardiovascular death (0.9%/y versus 1.2%/y; hazard ratio, 0.78 [95% CI, 0.64-0.96], P=0.02), whereas the bleeding components of the NCB, in particular fatal bleeding (0.09%/y versus 0.06%/y; hazard ratio, 1.49 [95% CI 0.67-3.33], P=0.32), only represented a minority of NCB events. In selected high-risk subgroups, including patients with polyvascular disease (≥2 vascular beds affected with atherosclerosis), impaired renal function, heart failure, and/or diabetes mellitus, a larger absolute risk reduction for experiencing a NCB event was observed.Compared with ASA monotherapy, the combination of rivaroxaban 2.5 mg twice daily plus ASA resulted in fewer NCB events primarily by preventing adverse efficacy events, particularly stroke and cardiovascular mortality, whereas severe bleedings were less frequent and with less clinical impact. The NCB was particularly favorable in high-risk subgroups and those with multiple risk characteristics. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424.
Trends in reported antibiotic use among children under 5 years of age with fever, diarrhoea, or cough with fast or difficult breathing across low-income and middle-income countries in 2005–17: a systematic analysis of 132 national surveys from 73 countries
Authors: Gbemisola Allwell-Brown, Laith Hussain-Alkhateeb, Freddy Eric Kitutu, Susanne Strömdahl, Andreas Mårtensson, Emily White Johansson
Journal: The Lancet Global Health (2020)

BackgroundGlobal assessments of antibiotic consumption have relied on pharmaceutical sales data that do not measure individual-level use, and are often unreliable or unavailable for low-income and middle-income countries (LMICs). To help fill this evidence gap, we compiled data from national surveys in LMICs in 2005–17 reporting antibiotic use for sick children under the age of 5 years.MethodsBased on 132 Demographic and Health Surveys and Multiple Indicator Cluster Surveys from 73 LMICs, we analysed trends in reported antibiotic use among children under 5 years of age with fever, diarrhoea, or cough with fast or difficult breathing by WHO region, World Bank income classification, and symptom complaint. A logit transformation was used to estimate the outcome using a linear Bayesian regression model. The model included country-level socioeconomic, disease incidence, and health system covariates to generate estimates for country-years with missing values.FindingsAcross LMICs, reported antibiotic use among sick children under 5 years of age increased from 36·8% (uncertainty interval [UI] 28·8–44·7) in 2005 to 43·1% (33·2–50·5) in 2017. Low-income countries had the greatest relative increase; in these countries, reported antibiotic use for sick children under 5 years of age rose 34% during the study period, from 29·6% (21·2–41·1) in 2005 to 39·5% (32·9–47·6) in 2017, although it remained the lowest of any income group throughout the study period.InterpretationWe found a limited but steady increase in reported antibiotic use for sick children under 5 years of age across LMICs in 2005–17, although overlapping UIs complicate interpretation. The increase was largely driven by gains in low-income countries. Our study expands the evidence base from LMICs, where strengthening antibiotic consumption and resistance surveillance is a global health priority.FundingUppsala Antibiotic Centre, Uppsala University, Uppsala University Hospital, Makerere University, Gothenburg University.
Introductory Remarks: Microelectronics, Radiation, and Superconductivity
Authors: Michael Gochfeld
Journal: Environmental Health Perspectives (1990)

Among the costs of technology are health hazards that face employees and consumers. New advances in the highly competitive field of microelectronics involve exposure to a variety of hazards such as gallium arsenide. Small high-technology industries appear unprepared to invest in health and safety. Although stray electromagnetic fields are not a new development, researchers are beginning to assemble data indicating that such fields pose a significant cancer risk under certain circumstances. Data have been obtained on fields associated with power lines on the one hand and consumer products on the other. Although not conclusive, the data are sufficient to warrant carefully designed research into the risks posed by electromagnetic fields. Because the scientific issues require research, there is a need to make basic social value decisions that will determine which technologies will be developed and which ones may be set aside because of their danger at the present time.
Acidic fibroblast growth factor underlies microenvironmental regulation of MYC in pancreatic cancer
Authors: Sohinee Bhattacharyya, Chet Oon, Aayush Kothari, Wesley Horton, Jason Link, Rosalie C. Sears, Mara H. Sherman
Journal: The Journal of Experimental Medicine (2020)

Despite a critical role for MYC as an effector of oncogenic RAS, strategies to target MYC activity in RAS-driven cancers are lacking. In genetically engineered mouse models of lung and pancreatic cancer, oncogenic KRAS is insufficient to drive tumorigenesis, while addition of modest MYC overexpression drives robust tumor formation, suggesting that mechanisms beyond the RAS pathway play key roles in MYC regulation and RAS-driven tumorigenesis. Here we show that acidic fibroblast growth factor (FGF1) derived from cancer-associated fibroblasts (CAFs) cooperates with cancer cell–autonomous signals to increase MYC level, promoter occupancy, and activity. FGF1 is necessary and sufficient for paracrine regulation of MYC protein stability, signaling through AKT and GSK-3β to increase MYC half-life. Patient specimens reveal a strong correlation between stromal CAF content and MYC protein level in the neoplastic compartment, and identify CAFs as the specific source of FGF1 in the tumor microenvironment. Together, our findings demonstrate that MYC is coordinately regulated by cell-autonomous and microenvironmental signals, and establish CAF-derived FGF1 as a novel paracrine regulator of oncogenic transcription.
Cardiovascular Toxicities Associated With Hydroxychloroquine and Azithromycin
Authors: Lee S. Nguyen, Charles Dolladille, Milou-Daniel Drici, Charlotte Fenioux, Joachim Alexandre, Jean-Paul Mira, Javid J. Moslehi, Dan M. Roden, Christian Funck-Brentano, Joe-Elie Salem
Journal: Circulation (2020)
Abstract 12719: Diabetes and Mental Illness in Sudden Unexpected Death Victims
Authors: Murrium I Sadaf, Marie Caldwell, Laura Young, Golsa Joodi, Feng-Chang Lin, Mojtaba Mirzaei, Sarah Chen, Yunhun Wu, Ross J Simpson
Journal: Circulation (2018)

Introduction: Diabetes increases the risk of cardiovascular disease and is associated with sudden unexpected death (SUD). However, controversy exists about the risk factors for SUD in patients with...