tbuckley/cabot-search huggingface dataset:
Exploiting the tumor-suppressive activity of the androgen receptor by CDK4/6 inhibition in castration-resistant prostate cancer
Authors: Wanting Han, Mingyu Liu, Dong Han, Anthia A. Toure, Muqing Li, Anna Besschetnova, Zifeng Wang, Susan Patalano, Jill A. Macoska, Hung-Ming Lam, Eva Corey, Housheng Hansen He, Shuai Gao, Steven P. Balk, Changmeng Cai
Journal: Molecular Therapy (2022)

The androgen receptor (AR) plays a pivotal role in driving prostate cancer (PCa) development. However, when stimulated by high levels of androgens, AR can also function as a tumor suppressor in PCa cells. While the high-dose testosterone (high-T) treatment is currently being tested in clinical trials of castration-resistant prostate cancer (CRPC), there is still a pressing need to fully understand the underlying mechanism and thus develop treatment strategies to exploit this tumor-suppressive activity of AR. In this study, we demonstrate that retinoblastoma (Rb) family proteins play a central role in maintaining the global chromatin binding and transcriptional repression program of AR and that Rb inactivation desensitizes CRPC to the high-dose testosterone treatment in vitro and in vivo. Using a series of patient-derived xenograft (PDX) CRPC models, we further show that the efficacy of high-T treatment can be fully exploited by a CDK4/6 inhibitor, which strengthens the chromatin binding of the Rb-E2F repressor complex by blocking the hyperphosphorylation of Rb proteins. Overall, our study provides strong mechanistic and preclinical evidence on further developing clinical trials to combine high-T with CDK4/6 inhibitors in treating CRPC. The androgen receptor (AR) plays a pivotal role in driving prostate cancer (PCa) development. However, when stimulated by high levels of androgens, AR can also function as a tumor suppressor in PCa cells. While the high-dose testosterone (high-T) treatment is currently being tested in clinical trials of castration-resistant prostate cancer (CRPC), there is still a pressing need to fully understand the underlying mechanism and thus develop treatment strategies to exploit this tumor-suppressive activity of AR. In this study, we demonstrate that retinoblastoma (Rb) family proteins play a central role in maintaining the global chromatin binding and transcriptional repression program of AR and that Rb inactivation desensitizes CRPC to the high-dose testosterone treatment in vitro and in vivo. Using a series of patient-derived xenograft (PDX) CRPC models, we further show that the efficacy of high-T treatment can be fully exploited by a CDK4/6 inhibitor, which strengthens the chromatin binding of the Rb-E2F repressor complex by blocking the hyperphosphorylation of Rb proteins. Overall, our study provides strong mechanistic and preclinical evidence on further developing clinical trials to combine high-T with CDK4/6 inhibitors in treating CRPC.
Tobacco Tax
Authors: Eric L. Dyer
Journal: Annals of Internal Medicine (1997)

Ad Libitum1 August 1997Tobacco TaxEric L. Dyer, MDEric L. Dyer, MDNashville, TN 37203Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-3-199708010-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail “Their bodies fill a crumbling room with light”-Allen TateThe ultimate burley tariff came duethat dark-fired afternoonwhen many would have paidon his behalf if coins would clear his debt.Yet, lungs aged thirty years beyondthe hand which had held his cigarettesdemanded currency stronger than thatas pneumonia red-penciledhis life's works like first drafts.Around his hospital bed that nightstood boys in white, unsure, ascending,starched, fervent, answering their pagesfull of hope and healing, readingone last biting essay from the sagewho taught a lesson in dyspnea as he diedin that spare classroom where he forgotthe first lines of his own poems,breathing the common air.... Author, Article, and Disclosure InformationAffiliations: Nashville, TN 37203Corresponding Author: Eric L. Dyer, MD, 2400 Patterson Street, Nashville, TN 37203. Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1997Volume 127, Issue 3Page: 241KeywordsBreathingDyspneaLungsPneumoniaTaxes ePublished: 15 August 2000 Issue Published: 1 August 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Hypothalamus-habenula potentiation encodes chronic stress experience and drives depression onset
Authors: Zhiwei Zheng, Chen Guo, Min Li, Liang Yang, Pengyang Liu, Xuliang Zhang, Yiqin Liu, Xiaonan Guo, Shuxia Cao, Yiyan Dong, Chunlei Zhang, Min Chen, Jiamin Xu, Hailan Hu, Yihui Cui
Journal: Neuron (2022)
P1.01-010 Circulating Cell-Free DNA of Cerebrospinal Fluid May Function as Liquid Biopsy for Leptomeningeal Metastases of ALK Rearrangement NSCLC
Authors: Y. Li, B. Jiang, J.J. Yang, X. Zhang, Z. Zhang, W. Zhong, Q. Zhou, H. Tu, Z. Wang, H. Chen, C. Xu, B. Wang, Y. Wu
Journal: Journal of Thoracic Oncology (2017)
Caregiver treatment preferences for children and adolescents with asthma: a discrete choice experiment
Authors: Nabeel Farooqui, Elliot Israel, Maureen George, Ileen Gilbert, Hitesh Gandhi, Tommi Tervonen, Zaneta Balanta, Caitlin Thomas, Nicolas Krucien, Chris Gillette
Journal: Journal of Allergy and Clinical Immunology (2022)
Dupilumab reduces asthma disease burden and recurrent SCS use in patients with CRSwNP and coexisting asthma
Authors: Mark Gurnell, Andrew Menzies-Gow, Claus Bachert, Njira Lugogo, Seong Cho, Shahid Siddiqui, Scott Nash, Haixin Zhang, Asif Khan, Juby Jacob Nara, Paul Rowe, Yamo Deniz
Journal: Journal of Allergy and Clinical Immunology (2022)
Association between household size and COVID-19: A UK Biobank observational study
Authors: Clare L Gillies, Alex V Rowlands, Cameron Razieh, Vahé Nafilyan, Yogini Chudasama, Nazrul Islam, Francesco Zaccardi, Daniel Ayoubkhani, Claire Lawson, Melanie J Davies, Tom Yates, Kamlesh Khunti
Journal: Journal of the Royal Society of Medicine (2022)

To assess the association between household size and risk of non-severe or severe COVID-19.
Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis
Authors: Steven R. Ytterberg, Deepak L. Bhatt, Ted R. Mikuls, Gary G. Koch, Roy Fleischmann, Jose L. Rivas, Rebecca Germino, Sujatha Menon, Yanhui Sun, Cunshan Wang, Andrea B. Shapiro, Keith S. Kanik, Carol A. Connell
Journal: New England Journal of Medicine (2022)

Increases in lipid levels and cancers with tofacitinib prompted a trial of major adverse cardiovascular events (MACE) and cancers in patients with rheumatoid arthritis receiving tofacitinib as compared with a tumor necrosis factor (TNF) inhibitor.We conducted a randomized, open-label, noninferiority, postauthorization, safety end-point trial involving patients with active rheumatoid arthritis despite methotrexate treatment who were 50 years of age or older and had at least one additional cardiovascular risk factor. Patients were randomly assigned in a 1:1:1 ratio to receive tofacitinib at a dose of 5 mg or 10 mg twice daily or a TNF inhibitor. The coprimary end points were adjudicated MACE and cancers, excluding nonmelanoma skin cancer. The noninferiority of tofacitinib would be shown if the upper boundary of the two-sided 95% confidence interval for the hazard ratio was less than 1.8 for the combined tofacitinib doses as compared with a TNF inhibitor.A total of 1455 patients received tofacitinib at a dose of 5 mg twice daily, 1456 received tofacitinib at a dose of 10 mg twice daily, and 1451 received a TNF inhibitor. During a median follow-up of 4.0 years, the incidences of MACE and cancer were higher with the combined tofacitinib doses (3.4% [98 patients] and 4.2% [122 patients], respectively) than with a TNF inhibitor (2.5% [37 patients] and 2.9% [42 patients]). The hazard ratios were 1.33 (95% confidence interval [CI], 0.91 to 1.94) for MACE and 1.48 (95% CI, 1.04 to 2.09) for cancers; the noninferiority of tofacitinib was not shown. The incidences of adjudicated opportunistic infections (including herpes zoster and tuberculosis), all herpes zoster (nonserious and serious), and adjudicated nonmelanoma skin cancer were higher with tofacitinib than with a TNF inhibitor. Efficacy was similar in all three groups, with improvements from month 2 that were sustained through trial completion.In this trial comparing the combined tofacitinib doses with a TNF inhibitor in a cardiovascular risk-enriched population, risks of MACE and cancers were higher with tofacitinib and did not meet noninferiority criteria. Several adverse events were more common with tofacitinib. (Funded by Pfizer; ORAL Surveillance ClinicalTrials.gov number, NCT02092467.).
Evaluation of the Quality of Evidence of the Association of Foods and Nutrients With Cardiovascular Disease and Diabetes
Authors: Victoria Miller, Renata Micha, Erin Choi, Dimitra Karageorgou, Patrick Webb, Dariush Mozaffarian
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Poor diet is a leading global factor associated with cardiometabolic disease (CMD). Understanding the quality of evidence of the associations between specific dietary factors and CMD, including effect size (relative risk [RR]) and uncertainty, is essential to guide policy and consumer actions to achieve healthy diet and public health goals. <h3>Objective</h3> To assess the quality of evidence of the associations between specific dietary factors and CMD as well as the quantitative evidence for RRs and the uncertainty of these risk estimates. <h3>Evidence Review</h3> PubMed and the reference lists of eligible articles were searched between May 1, 2015, and February 26, 2021, for systematic reviews with meta-analyses of randomized clinical trials and prospective cohort studies that analyzed the consumption of 1 or more of the dietary factors of interest; reported dose-response meta-analyses; included healthy adults; and assessed 1 or more of the outcomes of interest. Study characteristics and RR estimates were extracted in duplicate. For identified associations, quality of evidence was assessed using the Bradford-Hill criteria for causation. <h3>Findings</h3> A total of 2058 potentially relevant reports were identified, from which 285 full-text articles were assessed for eligibility. The final selection of articles included 28 meta-analyses representing 62 associations between diet and CMD. Among these associations, 10 foods, 3 beverages, and 12 nutrients had at least probable evidence of associations with coronary heart disease, stroke, and/or diabetes. Most RRs ranged from 0.87 to 0.96 per daily serving change for protective associations and from 1.06 to 1.15 per daily serving change for harmful associations. Most identified associations were protective (n = 38) and a smaller number were harmful (n = 24), with a higher risk associated with higher intake. <h3>Conclusions and Relevance</h3> This systematic review summarized the current quality of evidence of the associations of specific dietary factors with coronary heart disease, stroke, and diabetes. These findings may inform dietary guidance, the assessment of disease burden in specific populations, policy setting, and future research.
Myocarditis after BNT162b2 Vaccination in Israeli Adolescents
Authors: Dror Mevorach, Emilia Anis, Noa Cedar, Tal Hasin, Michal Bromberg, Lital Goldberg, Elchanan Parnasa, Rita Dichtiar, Yael Hershkovitz, Nachman Ash, Manfred S Green, Lital Keinan-Boker, Sharon Alroy-Preis
Journal: New England Journal of Medicine (2022)
Long-term safety and effectiveness of mepolizumab for severe eosinophilic asthma
Authors: Fernando Mendez de Paz, Monica Mochales, Cristina Lopez-Fernandez, Beatriz Moya, Rocio Diaz-Campos, Consuelo Fernandez, Jesus Fernandez Crespo, Ismael Garcia-Moguel
Journal: Journal of Allergy and Clinical Immunology (2022)
From the NIH: Otitis media
Journal: JAMA (1980)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The Silverway Guidewire: An Observational Study on Successful Crossing when a Conventional J-tip Wire has failed
Authors: Jo Dens, Van Den Buijs DMF, Poels EM, Ferdinande B, Cottens D, Vrolix M, Holvoet W, Ameloot K
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

Aim: The aim of this observational study was to evaluate the Silverway guidewire [Asahi Intecc Co.] that is designed to guide catheters during cardiac catheterization towards the aortic valve when the standard J-tip guidewire fails because of anatomical anomalies. Materials and Methods: A total of 50 consecutive patients, in which the Silverway guidewire was used, were analyzed: procedural characteristics, such as anatomical challenges, crossing of the vessel and deliverability of the catheters were prospectively collected. This sample size was considered reasonable to describe the success, because this was the first observational study on the performance of the Silverway guidewire. Results: In the majority of procedures, transradial access was used (47 cases; 94%). The Silverway guidewire was able to cross the vessel in 98% and to deliver catheters in 92% of patients. Most anatomical challenges occurred at the radial artery level (39 cases). No clinical important complications occurred after use of the Silverway guidewire. Conclusion:The Silverway guidewire is highly successful in overcoming anatomical obstacles without vascular complications during cardiac catheterization when the J-tip guidewire fails to cross the vascular anatomy.
Transformable Gallium‐Based Liquid Metal Nanoparticles for Tumor Radiotherapy Sensitization
Authors: Ruixue Liu, Linji Gong, Xianyu Zhu, Shuang Zhu, Xiaochen Wu, Tingyu Xue, Liang Yan, Jiangfeng Du, Zhanjun Gu
Journal: Advanced Healthcare Materials (2022)

The past decades have witnessed an increasing interest in the exploration of room temperature gallium-based liquid metal (LM) in the field of microfluidics, soft robotics, electrobiology, and biomedicine. Herein, this study for the first time reports the utilization of nanosized gallium-indium eutectic alloys (EGaIn) as a radiosensitizer for enhancing tumor radiotherapy. The sodium alginate (Alg) functionalized EGaIn nanoparticles (denoted as EGaIn@Alg NPs) are prepared via a simple one-step synthesis method. The coating of Alg not only prevents the aggregation and oxidation of EGaIn NPs in an aqueous solution but also enables them low cytotoxicity, good biocompatibility, and in-situ formation of gels in the Ca2+ enriched tumor physiological microenvironment. Due to the metallic nature and high density, EGaIn can increase the generation of reactive oxygen species under the irradiation of X-ray, which can not only directly promote DNA damage and cell apoptosis, but also show an efficient tumor inhibition rate in vivo. Moreover, EGaIn@Alg NPs hold good performance as computed tomography (CT) and photoacoustic tomography (PAT) imaging contrast agents. This work provides an alternative nanotechnology strategy for tumor radiosensitization and also enlarges the biomedical application of gallium-based LM.
Meadow faces GMC over evidence given in child death cases
Journal: BMJ (2004)

these qualities.However, we saw no differences in previous academic performance by group (table 2).A further argument against selection bias being a serious limitation in this study is the school's selection procedure.The three elements that contribute to this process are performance in a national admission test of reasoning and problem solving in the basic sciences and humanities, performance in a previous undergraduate degree, and performance at a standardised interview that rewards evidence of self directedness, teamwork, communication skills, compassion, resourcefulness, and broad life skills.Thus, all medical students at Flinders are likely to be resourceful and talented high achievers.Other qualities that could be over-represented in students in the rural programme and Darwin groups, such as seeking adventure, interest in rural medicine as a career, being suited to rural life, and having fewer ties with the city, show only the student centred benefits of offering different environments to suit the needs of different students.There is no suggestion that such qualities inherently affect academic performance, but when a student's self perceived traits are matched to an environment that supports them, their academic performance may be enhanced.This should, however, have been equally true for students who chose to study in the tertiary centre.Our analysis accounted for the other possible biases of student age, sex, year 2 score, and cohort effect.The results cannot be explained by the Hawthorne effect as they have been sustained over five years and during this time the rural and Darwin programmes have become a routine part of the school's study options.The results may also be criticised for reflecting the effect of group size rather than location.However, on a day to day basis, students in all of the locations were allocated to practices or wards in pairs or alone, and tutorial group sizes were also similar.
Oxidative pentose phosphate pathway controls vascular mural cell coverage by regulating extracellular matrix composition
Authors: Nicola Facchinello, Matteo Astone, Matteo Audano, Roxana E. Oberkersch, Marianna Spizzotin, Enrica Calura, Madalena Marques, Mihaela Crisan, Nico Mitro, Massimo M. Santoro
Journal: Nature Metabolism (2022)
Correction Notices Added to Articles Related to Retracted Article
Authors: Katherine Hill, Cary Gross, Dowin Boatright
Journal: JAMA Internal Medicine (2020)

However, medical schools must also grapple with the ethical concerns involved with recruiting marginalized groups into environments that may be deleterious, without simultaneously developing and implementing interventions to ensure that their educational environment is supportive.Rather than solely focusing on increasing the quantity of diverse students, medical schools and accrediting bodies must place greater emphasis on and allocate more resources toward creating a climate of diversity, equity, and inclusion.
Exploiting CD22 on Memory B Cells to Induce Tolerance to Peanut Allergens
Authors: Lakeya Hardy, Johanna Smeekens, Gour Daskhan, Susmita Sarkar, Stephen Rogers, Soheila Maleki, A. Wesley Burks, James Paulson, Matthew Macauley, Michael Kulis
Journal: Journal of Allergy and Clinical Immunology (2022)
The peripheral white blood cells and metronidazole
Authors: Y. Lefebvre
Journal: JAMA (1965)

A group of 386 patients was studied for the possible effects of metronidazole on the white blood cell (WBC), relative percentage of polymorphonuclear leukocytes to lymphocytes, and absolute polymorphonuclear cell counts. The only change directly attributable to metronidazole is the occurrence of neutropenia in ten of the cases. This neutropenia in all instances was transient. In the event of a failure of cure or of a reinfection, WBC and differential counts should be made before instituting another course of therapy. It would seem logical (1) to do a leukocyte and differential count before and after each metronidazole treatment in those persons showing some evidence of health deficiency, (2) to treat only proven cases of trichomoniasis, and (3) to await further studies before giving metronidazole to pregnant patients.
Developing Structured Data Entry Forms for Food Allergy Clinical Documentation in The Electronic Health Record
Authors: Shruti Sehgal, Ruchi Gupta, Mark Wlodarski, Lucy Bilaver, Firas Wehbe, Jonathan Spergel, Julie Wang, Christina Ciaccio, Sai Nimmagadda, Melanie Makhija, Justin Starren
Journal: Journal of Allergy and Clinical Immunology (2022)
Surveillance of leishmaniasis cases from 15 European centres, 2014 to 2019: a retrospective analysis
Authors: Gert Van der Auwera, Leigh Davidsson, Pierre Buffet, Marie-Thérèse Ruf, Marina Gramiccia, Stefania Varani, Carmen Chicharro, Aldert Bart, Gundel Harms, Peter L. Chiodini, Hanne Brekke, Florence Robert-Gangneux, Sofia Cortes, Jaco J Verweij, Alessandra Scarabello, Sara Karlsson Söbirk, Romain Guéry, Saskia van Henten, Trentina Di Muccio, Elena Carra, Pieter van Thiel, Martin Vandeputte, Valeria Gaspari, Johannes Blum
Journal: Eurosurveillance (2022)

Background Surveillance of human leishmaniasis in Europe is mostly limited to country-specific information from autochthonous infections in the southern part. As at the end of 2021, no integrated analysis has been performed for cases seen across centres in different European countries. Aim To provide a broad perspective on autochthonous and imported leishmaniasis cases in endemic and non-endemic countries in Europe. Methods We retrospectively collected records from cutaneous, mucosal and visceral leishmaniasis cases diagnosed in 15 centres between 2014 and 2019. Centres were located in 11 countries: Belgium, France, Germany, Italy, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom. Data on country of infection, reason for travelling, infecting species, age and sex were analysed. Results We obtained diagnostic files from 1,142 cases, of which 76%, 21% and 3% had cutaneous, visceral, and mucosal disease, respectively. Of these, 68% were men, and 32% women, with the median age of 37 years (range: 0–90) at diagnosis. Visceral leishmaniasis was mainly acquired in Europe (88%; 167/190), while cutaneous leishmaniasis was primarily imported from outside Europe (77%; 575/749). Sixty-two percent of cutaneous leishmaniasis cases from outside Europe were from the Old World, and 38% from the New World. Geographic species distribution largely confirmed known epidemiology, with notable exceptions. Conclusions Our study confirms previous reports regarding geographic origin, species, and traveller subgroups importing leishmaniasis into Europe. We demonstrate the importance of pooling species typing data from many centres, even from areas where the aetiology is presumably known, to monitor changing epidemiology.
SEX DIFFERENCES IN OUTPATIENT PERFORMANCE MEASURES: A REPORT OF THE FIRST 14,000+ PATIENTS IN THE AMERICAN COLLEGE OF CARDIOLOGY’S IC3 (IMPROVING CONTINUOUS CARDIAC CARE) PROGRAM
Authors: Paul Chan, Donna Buchanan, Fran F. Fiocchi, Philip G. Jones, Kristi Mitchell, Tracie Breeding, William J. Oetgen, John S. Rumsfeld, John A. Spertus
Journal: Journal of the American College of Cardiology (2010)