tbuckley/cabot-search huggingface dataset:
Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore
Authors: Sean M. Davidson, Kirsty Foote, Suma Kunuthur, Raj Gosain, Noah Tan, Richard Tyser, Yong Juan Zhao, Richard Graeff, A. Ganesan, Michael R. Duchen, Sandip Patel, Derek M. Yellon
Journal: Cardiovascular Research (2015)

In the heart, a period of ischaemia followed by reperfusion evokes powerful cytosolic Ca(2+) oscillations that can cause lethal cell injury. These signals represent attractive cardioprotective targets, but the underlying mechanisms of genesis are ill-defined. Here, we investigated the role of the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), which is known in several cell types to induce Ca(2+) oscillations that initiate from acidic stores such as lysosomes, likely via two-pore channels (TPCs, TPC1 and 2).An NAADP antagonist called Ned-K was developed by rational design based on a previously existing scaffold. Ned-K suppressed Ca(2+) oscillations and dramatically protected cardiomyocytes from cell death in vitro after ischaemia and reoxygenation, preventing opening of the mitochondrial permeability transition pore. Ned-K profoundly decreased infarct size in mice in vivo. Transgenic mice lacking the endo-lysosomal TPC1 were also protected from injury.NAADP signalling plays a major role in reperfusion-induced cell death and represents a potent pathway for protection against reperfusion injury.
THE EFFECTS OF TROPICAL LIGHT ON WHITE MEN.
Journal: JAMA (1905)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Preventable Measles Among U.S. Residents, 2001-2004
Journal: JAMA (2005)

scribed in this report would have been substantially greater if overseas screening had not been enhanced.For Hmong refugees resettling from Thailand, mycobacterial cultures and drugsusceptibility testing helped ensure appropriate treatment of patients with TB disease.These and other enhancements to standard premigration screening guidelines are under consideration for future U.S.-bound refugees and immigrants from other countries with a high TB burden.
Columbarium Architecture (Museum of Disappearing Buildings)
Authors: Thomas B. Cole
Journal: JAMA (2015)

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
Disseminated Red Violaceous Papulonodular Lesions
Authors: Rosario Alarcón-Cabrera, Felipe Partarrieu-Mejías, Fernanda Pérez-Velásquez
Journal: JAMA Dermatology (2015)

A woman in her 40s presented with a 6-month history of a generalized, asymptomatic eruption of red violaceous, nontender, rubbery nodules and papules together with brownish-red patches without enlargement of lymph nodes or hepatosplenomegaly. What is your diagnosis?
FOCUSSING OF THE CLOT: Normal and Pathologic Mechanisms
Authors: A I Schafer
Journal: Annual Review of Medicine (1987)

Several physiologic antithrombotic mechanisms operate to prevent clot formation under normal circumstances and to focus the clot on the site of damage upon vascular injury. These mechanisms, which involve prostacyclin (PGI2), antithrombin III, protein C, and the fibrinolytic system, are interrelated, are activated by thrombin generation, and are dependent upon the integrity of normal endothelium surrounding the focus of injury. Acquired or inherited abnormalities in each of these physiologic antithrombotic systems have been linked to clinical bleeding and thrombotic disorders.
Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
Authors: Priscilla K. Brastianos, Scott L. Carter, Sandro Santagata, Daniel P. Cahill, Amaro Taylor-Weiner, Robert T. Jones, Eliezer M. Van Allen, Michael S. Lawrence, Peleg M. Horowitz, Kristian Cibulskis, Keith L. Ligon, Josep Tabernero, Joan Seoane, Elena Martinez-Saez, William T. Curry, Ian F. Dunn, Sun Ha Paek, Sung-Hye Park, Aaron McKenna, Aaron Chevalier, Mara Rosenberg, Frederick G. Barker, Corey M. Gill, Paul Van Hummelen, Aaron R. Thorner, Bruce E. Johnson, Mai P. Hoang, Toni K. Choueiri, Sabina Signoretti, Carrie Sougnez, Michael S. Rabin, Nancy U. Lin, Eric P. Winer, Anat Stemmer-Rachamimov, Matthew Meyerson, Levi Garraway, Stacey Gabriel, Eric S. Lander, Rameen Beroukhim, Tracy T. Batchelor, José Baselga, David N. Louis, Gad Getz, William C. Hahn
Journal: Cancer Discovery (2015)

Abstract Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors, and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. Significance: Decisions for individualized therapies in patients with brain metastasis are often made from primary-tumor biopsies. We demonstrate that clinically actionable alterations present in brain metastases are frequently not detected in primary biopsies, suggesting that sequencing of primary biopsies alone may miss a substantial number of opportunities for targeted therapy. Cancer Discov; 5(11); 1164–77. ©2015 AACR. See related commentary by Stricker and Arteaga, p. 1124. This article is highlighted in the In This Issue feature, p. 1111
Cardiovascular Morbidity in Long-Term Survivors of Metastatic Testicular Cancer
Authors: M.T. Meinardi, J.A. Gietema, W.T. A. van der Graaf, D.J. van Veldhuisen, M.A. Runne, W.J. Sluiter, E.G. E. de Vries, P.B. H. Willemse, N.H. Mulder, M.P. van den Berg, H. Schraffordt Koops, D. Th. Sleijfer
Journal: Journal of Clinical Oncology (2000)

To determine whether long-term survivors of metastatic testicular cancer have an increased risk of cardiovascular morbidity more than 10 years after chemotherapy.Eighty-seven patients treated with cisplatin-containing chemotherapy before 1987 who were in remission for at least 10 years and whose ages were </= 50 years at the time of analysis were evaluated for the occurrence of cardiovascular events. Sixty-two of 87 patients were additionally evaluated for cardiac damage and cardiovascular risk factors. Their cardiovascular risk profile was compared with that of 40 patients with comparable age and follow-up duration treated with orchidectomy only for stage I disease.Major cardiac events were found in five (6%) of the 87 patients (age at time of event, 30 to 42 years; time after chemotherapy, 9 to 16 years): two with myocardial infarction and three with angina pectoris with proven myocardial ischemia. An increased observed-to-expected ratio of 7.1 (95% confidence interval, 1.9 to 18.3) for coronary artery disease, as compared with the general male Dutch population, was found. In addition, one patient experienced a cerebrovascular accident. Exercise ECG did not reveal cases of subclinical coronary artery disease. Echocardiography showed normal systolic left ventricular function in most patients, but diastolic left ventricular function was disturbed in 33% of the patients. Of 62 chemotherapy patients, 79% had hypercholesterolemia, 39% had hypertension, 25% still experienced Raynaud's phenomenon, and 22% had microalbuminuria. Compared with patients with stage I disease, the chemotherapy patients had higher blood pressure and higher total cholesterol and triglyceride levels and were more insulin-resistant.In long-term survivors of metastatic testicular cancer, we observed a significantly increased risk for occurrence of cardiac events accompanied by a persisting unfavorable cardiovascular risk profile. Accurate follow-up, focused on cardiovascular complications and aimed at intervention in these young cancer survivors, seems to be important.
Reply to the letter to the editor ‘The ESMO Magnitude of Clinical Benefit Scaling Tool: from theory to practice’ by Hartmann and the letter ‘Comment on ESMO Magnitude of Clinical Benefit Scale’ by Muhonen et al.
Authors: N.I. Cherny, R. Sullivan, U. Dafni, J.M. Kerst, A. Sobrero, C. Zielinski, E.G.E. de Vries, M.J. Piccart
Journal: Annals of Oncology (2015)
Incidence of sexually transmitted infections jumps in US, CDC reports
Authors: M. McCarthy
Journal: BMJ (2015)

The number of sexually transmitted infections in the United States rose significantly from 2013 to 2014, with new cases of chlamydia rising nearly 3%, gonorrhea by 5%, and primary and secondary syphilis by more than 15%, shows a new report by the Centers for Disease Control and Prevention released on 17 November.1

“America’s worsening [sexually transmitted disease] epidemic is a clear call for better diagnosis, treatment, and prevention,” said Jonathan Mermin, director of the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and Tuberculosis Prevention. Sexually transmitted diseases affect “people in all walks of life, particularly young women and men, but these data suggest an increasing burden among gay and bisexual men,” he said.

The report found that more than 1 441 789 cases of Chlamydia trachomatis infection were reported to the CDC in 2014, making a rate of 456.1 …
Monoclonal Antibodies for the Diagnosis and Treatment of Transplant Rejection
Authors: P S Russell, R B Colvin, A B Cosimi
Journal: Annual Review of Medicine (1984)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Evidence of hospital failures was not disclosed at surgeon’s manslaughter trial
Authors: Clare Dyer
Journal: BMJ (2015)

An internal report into a patient’s death at a private hospital that identified “systemic failures” was not revealed at the trial of the surgeon who was later convicted of manslaughter over the death, it has emerged.

David Sellu, a senior consultant colorectal surgeon, was sentenced to two and a half years in prison in November 2013 for contributing to the death of James Hughes in February 2010 at the Clementine Churchill Hospital in Harrow, north London.1 The 66 year old builder had undergone knee replacement surgery at the hospital, run by BMI Healthcare, the United Kingdom’s largest private healthcare provider. But Sellu, who did private operations at the hospital alongside his NHS job at Ealing Hospital NHS Trust, was asked to step in when Hughes developed abdominal pains.

Hughes had a perforated bowel …
Global, regional, and national levels and trends in maternal mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency Group
Authors: Leontine Alkema, Doris Chou, Daniel Hogan, Sanqian Zhang, Ann-Beth Moller, Alison Gemmill, Doris Ma Fat, Ties Boerma, Marleen Temmerman, Colin Mathers, Lale Say
Journal: The Lancet (2015)
VAB-6: an effective chemotherapy regimen for patients with germ-cell tumors.
Authors: G J Bosl, R Gluckman, N L Geller, R B Golbey, W F Whitmore, H Herr, P Sogani, M Morse, N Martini, M Bains
Journal: Journal of Clinical Oncology (1986)

One hundred sixty-six patients with germ-cell tumors (GCT) of the testis, retroperitoneum, and mediastinum were treated with cyclophosphamide, vinblastine, bleomycin, dactinomycin, and cisplatin (VAB-6), with and without maintenance chemotherapy. The overall complete response (CR) rate was 78%, 67% to chemotherapy alone, and 11% after chemotherapy and resection of viable residual cancer. The CR rate in all patients with seminoma was uniformly high, while the CR rate of patients with testicular nonseminomatous germ-cell tumors (79%) was superior to that of similar tumors of extragonadal origin (60%). The overall relapse rate was 12%, and was greater in tumors of extragonadal origin (21%) than in those of testicular origin (11%). Three relapses occurred after 2 years. Maintenance chemotherapy did not prolong either relapse-free or total survival. Toxicity was tolerable, and there were no treatment deaths. No Raynaud's phenomena have occurred, with a minimum duration since start of therapy of 36 months. VAB-6 is an effective chemotherapy regimen in patients with GCT with no treatment-related deaths and a majority of patients requiring only 3 months of treatment.
Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset
Authors: Brinton Seashore-Ludlow, Matthew G. Rees, Jaime H. Cheah, Murat Cokol, Edmund V. Price, Matthew E. Coletti, Victor Jones, Nicole E. Bodycombe, Christian K. Soule, Joshua Gould, Benjamin Alexander, Ava Li, Philip Montgomery, Mathias J. Wawer, Nurdan Kuru, Joanne D. Kotz, C. Suk-Yee Hon, Benito Munoz, Ted Liefeld, Vlado Dančík, Joshua A. Bittker, Michelle Palmer, James E. Bradner, Alykhan F. Shamji, Paul A. Clemons, Stuart L. Schreiber
Journal: Cancer Discovery (2015)

Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2).We present the largest CCL sensitivity dataset yet available, and an analysis method integrating information from multiple CCLs and multiple small molecules to identify CCL response predictors robustly. We updated the CTRP to enable the cancer research community to leverage these data and analyses.
WHO Updates HIV Treatment and Prevention Guideline
Authors: M. J. Friedrich
Journal: JAMA (2015)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Drug Suppression of the Angiotensin System in Congestive Heart Failure
Authors: J M Sullivan
Journal: Annual Review of Medicine (1983)

Congestive heart failure is frequently associated with elevated systemic vascular resistance. Lowering resistance can improve cardiac performance and alleviate symptoms. The angiotensin-converting enzyme inhibitors offer a new way to lower resistance and have certain advantages, including the inhibition of compensatory mechanisms. However, skillful use of these compounds demands a thorough understanding of their pharmacologic properties and of the pathophysiology of congestive heart failure.
Signaling Through the Hematopoietic Cytokine Receptors
Authors: J N Ihle, B A Witthuhn, F W Quelle, K Yamamoto, O Silvennoinen
Journal: Annual Review of Immunology (1995)

Hematopoiesis is regulated through the interaction of a variety of growth factors with specific receptors of the cytokine receptor superfamily. Although lacking catalytic domains, all the receptors couple ligand binding to the rapid induction of protein tyrosine phosphorylation. This is mediated through a novel family of protein tyrosine kinases termed the Janus kinases (Jaks) which associate with the receptors and are activated following ligand binding. Depending upon the cytokine/receptor system, one or more of the four known Jaks (Jak1, Jak2, Jak3, Tyk2) is/are involved. The activated Jaks phosphorylate both themselves and the receptor subunits, creating docking sites for SH2-containing proteins including SHC, which couples receptor engagement to activation of the ras pathway, and HCP, a protein tyrosine phosphatase which negatively affects the response. In addition, the Jaks phosphorylate one or more of a family of signal transducers and activators of transcription (Stats). Phosphorylation of Stats induces their nuclear translocation and DNA-binding activity. Activation of Stats is independent of activation of the ras pathway and represents a novel signaling pathway correlated with mitogenesis.
Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN
Authors: Gérald Simonneau, Richard N. Channick, Marion Delcroix, Nazzareno Galiè, Hossein-Ardeschir Ghofrani, Pavel Jansa, Franck-Olivier Le Brun, Sanjay Mehta, Loic Perchenet, Tomás Pulido, B.K.S. Sastry, Olivier Sitbon, Rogério Souza, Adam Torbicki, Lewis J. Rubin
Journal: European Respiratory Journal (2015)

In SERAPHIN, a long-term, randomised, controlled trial ( NCT00660179 ) in pulmonary arterial hypertension (PAH), macitentan significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation. We evaluated disease progression and the effect of macitentan in treatment-naïve incident and prevalent cohorts. Patients allocated to placebo, or macitentan 3 mg or 10 mg were classified by time from diagnosis to enrolment as incident (≤6 months; n=110) or prevalent (&gt;6 months; n=157). The risk of morbidity/mortality and PAH-related death/hospitalisation was determined using Cox regression. The risk of morbidity/mortality (Kaplan–Meier estimates at month 12: 54.4% versus 26.7%; p=0.006) and PAH-related death/hospitalisation (Kaplan–Meier estimates at month 12: 47.3% versus 19.9%; p=0.006) were significantly higher for incident versus prevalent patients receiving placebo, respectively. There was no significant difference in the risk of all-cause death between incident and prevalent cohorts (p=0.587). Macitentan 10 mg significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation versus placebo in incident and prevalent cohorts. Incident patients had a higher risk for PAH progression compared with prevalent patients but not a higher risk of death. Macitentan delayed disease progression in both incident and prevalent PAH patients.
Coronary Artery Spasm: A New Appraisal
Authors: A A Kattus
Journal: Annual Review of Medicine (1976)

When this author was a medical student in the early 1940s, the prevailing concept of the mechanism of angina pectoris was that it was due to intermittent spasm of coronary arteries. It was not regarded as a serious, potentially deadly illness since it was so readily relieved by nitroglycerin. This opinion was no doubt based on the firm assertion by Sir William Osler (1) during his second Lumlian Lecture on Angina Pectoris to the Royal College of Physicians in March 1910, when he said, Spasm or narrowing of a coronary artery ... may so modify the action of a section of the heart that it works with disturbed tension, and there are stretching and strain sufficient to arouse painful sensations. I do not know of any better explanation of anginal pain. Then in 1940 the paper by Blumgart, Schlesinger & Davis appeared (2) in which they showed by postmortem coronary injections of X-ray contrast material that patients who had clinical angina during life had in most instances extensive narrow­ ing and often complete atheromatous occlusion of one or more coronary arteries. These findings indicating that angina pectoris is a serious manifestation of a poten­ tially life-threatening disease dominated the concept of angina during the next thirty years and as late as 1968 this author wrote in an article that the work of Blumgart and his associates had laid to rest the concept that angina was due to coronary spasm ...  (3).