tbuckley/cabot-search huggingface dataset:
Letrozole Therapy for Unexplained Infertility
Authors: Anita Slomski
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
Serial Assessment of Trauma Care Capacity in Ghana in 2004 and 2014
Authors: Barclay T. Stewart, Robert Quansah, Adam Gyedu, Godfred Boakye, Francis Abantanga, James Ankomah, Peter Donkor, Charles Mock
Journal: JAMA Surgery (2015)

IMPORTANCETrauma care capacity assessments in developing countries have generated evidence to support advocacy, detailed baseline capabilities, and informed targeted interventions.However, serial assessments to determine the effect of capacity improvements or changes over time have rarely been performed.OBJECTIVE To compare the availability of trauma care resources in Ghana between 2004 and 2014 to assess the effects of a decade of change in the trauma care landscape and derive recommendations for improvements.DESIGN, SETTING, AND PARTICIPANTS Capacity assessments were performed using direct inspection and structured interviews derived from the World Health Organization's Guidelines for Essential Trauma Care.In Ghana, 10 hospitals in 2004 and 32 hospitals in 2014 were purposively sampled to represent those most likely to care for injuries.Clinical staff, administrators, logistic/procurement officers, and technicians/biomedical engineers who interacted, directly or indirectly, with trauma care resources were interviewed at each hospital.MAIN OUTCOMES AND MEASURES Availability of items for trauma care was rated from 0 (complete absence) to 3 (fully available).Factors contributing to deficiency in 2014 were determined for items rated lower than 3.Each item rated lower than 3 at a specific hospital was defined as a hospital-item deficiency.Scores for total number of hospital-item deficiencies were derived for each contributing factor.RESULTS There were significant improvements in mean ratings for trauma care resources: district-level (smaller) hospitals had a mean rating of 0.8 for all items in 2004 vs 1.3 in 2014 (P = .002);regional (larger) hospitals had a mean rating of 1.1 in 2004 vs 1.4 in 2014 (P = .01).However, a number of critical deficiencies remain (eg, chest tubes, diagnostics, and orthopedic and neurosurgical care; mean ratings Յ2).Leading contributing factors were item absence (503 hospital-item deficiencies), lack of training (335 hospital-item deficiencies), and stockout of consumables (137 hospital-item deficiencies). CONCLUSIONS AND RELEVANCEThere has been significant improvement in trauma care capacity during the past decade in Ghana; however, critical deficiencies remain and require urgent redress to avert preventable death and disability.Serial capacity assessment is a valuable tool for monitoring efforts to strengthen trauma care systems, identifying what has been successful, and highlighting needs.
‘Hypoxio-spondin’: thrombospondin and its emerging role in pulmonary hypertension
Authors: Larissa A. Shimoda, Wolfgang M. Kuebler
Journal: Cardiovascular Research (2015)

This editorial refers to ‘HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction’ by D. Labrousse-Arias et al. , doi:10.1093/cvr/cvv243. 

In 1971, Baenziger et al. 1 identified a 190 kDa membrane protein in intact platelets that rapidly (within <2 min) disappeared after treatment with thrombin, while a new 107 kDa protein emerged. They concluded that this transition represented hydrolysis of a thrombin-sensitive protein, which likely triggered the physiological effects of thrombin on platelets. Accordingly, the protein was named ‘thrombospondin’ (currently known as thrombospondin-1 or TSP1).2 Since then, TSP1 has emerged as a multifunctional protein playing important roles in numerous physiological and pathological processes, including thrombosis, angiogenesis, tumorigenesis, inflammation, apoptosis, and fibrosis.

Recently, TSP1 was linked to pulmonary hypertension (PH), a progressive disease of multiple origins characterized by increased pulmonary artery pressure (>25 mmHg at rest) and extensive lung vascular remodelling that ultimately leads to death due to decompensating right heart failure.3 Despite important advancements in the pharmacotherapy of PH, there is still no cure for this fatal disease. Notably, all of the TSP1 regulated processes listed above, including tumour-like monoclonal proliferation of endothelial cells,4 are implicated in PH pathogenesis. Indeed, the functional role of TSP1 in PH was recently evidenced in independent studies showing partial protection of mice deficient in TSP1 ( tsp1 −/−) from the classic hallmarks of hypoxia-induced PH, i.e. right ventricular pressure elevation …
Book Review: An Intelligent Person's Guide to Medicine
Authors: Adrian Marston
Journal: Journal of the Royal Society of Medicine (2001)

The book forms part of a series called The Intelligent Person's Guide — to ethics, philosophy, culture, and so forth. Most of these guides are designed as route maps, but when the publishers chose Dr Dalrymple to contribute the volume on medicine, they knew very well that they would not get a route map but something quite different—a witty polemic written from a decidedly non-politically-correct standpoint. Those who have been amused or infuriated by Dalrymple's columns in magazines and newspapers will not be disappointed: this is vintage Dalrymple, grumpy, iconoclastic, well informed and immensely readable.
Seasonality of avian influenza A(H7N9) activity and risk of human A(H7N9) infections from live poultry markets
Authors: Jie Wu, Eric H.Y. Lau, Qinbin Xing, Lirong Zou, Hongbin Zhang, Hui-Ling Yen, Yinchao Song, Haojie Zhong, Jinyan Lin, Min Kang, Benjamin J. Cowling, Guofeng Huang, Changwen Ke
Journal: Journal of Infection (2015)
Oiling vascular growth: adipokines can induce (pathological) angiogenesis by using the VEGF/VEGFR system: EXPERTS' PERSPECTIVE
Authors: J. Waltenberger, E. Pardali
Journal: Cardiovascular Research (2012)

Obesity is a major cardiovascular risk factor that has been associated with serious complications such as hypertension, dyslipidaemia, insulin resistance, diabetes, and the development of cardiovascular disease.Adipokines, bioactive peptides and cytokines produced by adipose tissue, play important roles in glucose and lipid metabolism, cell viability, energy homeostasis, immunity and-most importantly-in cardiovascular function.Interestingly, it was shown that the adipokine profiles of different adipose tissues are different and they are further modified depending on the pathological condition.To date, several adipokines have been identified and characterized, including adiponectin, leptin, chemerin, vaspin, and visfatin.Visfatin has been identified as a novel adipokine that is highly expressed in visceral fat.Visfatin is also known as pre-B-cell colony-enhancing factor [PBEF, a pre-B cell colony-enhancing factor that enhances the effects of interleukin (IL)-7 and stem cell factor on pre-B-cell colony formation] and as nicotinamide phosphoribosyltransferase (NAMPT; a nicotinamide phosphoribosyltransferase, an enzyme involved in nicotinamide adenine dinucleotide biosynthesis).Visfatin was shown to be increased in obese subjects and in patients with metabolic syndrome as well as in type 2 diabetics. 1 -5 It was also shown that visfatin regulates insulin secretion and insulin receptor signalling in the pancreas. 6Visfatin exerts a cardioprotective effect during myocardial infarction and it has been suggested to play a protective role in non-alcoholic fatty liver disease. 7,8Visfatin exhibits direct cardioprotective effects in vivo in a murine ischaemia-reperfusion model, since the infarct size was reduced following treatment with a single intravenous dose of visfatin. 8Visfatin-induced myocardial protection was shown to be dependent upon phosphoinositide 3-kinase (PI3K) and MEK 1/2 activation.Furthermore, visfatin reduces death of murine
Prevalence, awareness, treatment, and control of diabetes in relation to hypertension status in Chinese adults: a nationwide cross-sectional survey
Authors: Baihui Xu, Limin Wang, Lin Ding, Yu Xu, Yong Jiang, Mei Zhang, Maigeng Zhou, Yichong Li, Min Xu, Jieli Lu, Shenghan Lai, Yufang Bi, Weiqing Wang, Linhong Wang, Guang Ning
Journal: The Lancet (2015)
The Role of Radiation Therapy in the Definitive Treatment of Adenocarcinoma of the Prostate
Authors: G R Ray, M A Bagshaw
Journal: Annual Review of Medicine (1975)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Structural Brain Connectivity as a Genetic Marker for Schizophrenia
Authors: Marc M. Bohlken, Rachel M. Brouwer, René C. W. Mandl, Martijn P. Van den Heuvel, Anna M. Hedman, Marc De Hert, Wiepke Cahn, René S. Kahn, Hilleke E. Hulshoff Pol
Journal: JAMA Psychiatry (2015)

<h3>Importance</h3> Schizophrenia is accompanied by a loss of integrity of white matter connections that compose the structural brain network, which is believed to diminish the efficiency of information transfer among brain regions. However, it is unclear to what extent these abnormalities are influenced by the genetic liability for developing the disease. <h3>Objective</h3> To determine whether white matter integrity is associated with the genetic liability for developing schizophrenia. <h3>Design, Setting, and Participants</h3> In 70 individual twins discordant for schizophrenia and 130 matched individual healthy control twins, structural equation modeling was applied to quantify unique contributions of genetic and environmental factors on brain connectivity and disease liability. The data for this study were collected from October 1, 2008, to September 30, 2013. The data analysis was performed between November 1, 2013, and March 30, 2015. <h3>Main Outcome Measures</h3> Structural connectivity and network efficiency were assessed through diffusion-weighted imaging, measuring fractional anisotropy (FA) and streamlines. <h3>Results</h3> The sample included 30 monozygotic twins matched to 72 control participants and 40 dizygotic twins matched to 58 control participants. Lower global FA was significantly correlated with increased schizophrenia liability (phenotypic correlation, −0.25; 95% CI, −0.38 to −0.10;<i>P</i> = .001), with 83.4% explained by common genes. In total, 8.1% of genetic variation in global FA was shared with genetic variance in schizophrenia liability. Local reductions in network connectivity (as defined by FA-weighted local efficiency) of frontal, striatal, and thalamic regions encompassed 85.7% of genetically affected areas. Multivariate genetic modeling revealed that global FA contributed independently of other genetic markers, such as white matter volume and cortical thickness, to schizophrenia liability. <h3>Conclusions and Relevance</h3> Global reductions in white matter integrity in schizophrenia are largely explained by the genetic risk of developing the disease. Network analysis revealed that genetic liability for schizophrenia is primarily associated with reductions in connectivity of frontal and subcortical regions, indicating a loss of integrity along the white matter fibers in these regions. The reported reductions in white matter integrity likely represent a separate and novel genetic vulnerability marker for schizophrenia.
MET Receptor Juxtamembrane Exon 14 Alternative Spliced Variant: Novel Cancer Genomic Predictive Biomarker
Authors: Patrick C. Ma
Journal: Cancer Discovery (2015)

Abstract Clinical studies on MET-targeting cancer therapeutics have yielded mixed results in recent years, and MET-relevant predictive biomarkers remain elusive. New studies now reveal METex14 alternative splicing aberrations to represent potential predictive cancer genomic biomarker, hence renewing optimism and directions in the quest for optimized MET-targeting personalized cancer therapy. Cancer Discov; 5(8); 802–5. ©2015 AACR. See related article by Paik et al., p. 842. See related article by Frampton et al., p. 850.
The psychiatrist and solvent-inhalant abuse: recognition, assessment, and treatment
Authors: J Westermeyer
Journal: American Journal of Psychiatry (1987)

Solvent-inhalant abuse, existent for a century, has been gradually increasing in several sectors of our society over the last few decades. This form of substance abuse involves a variety of pharmacological agents as well as several target groups at risk. A key strategy for effective intervention is early recognition in clinical as well as other settings. Psychiatrists should appreciate the clinical manifestations of these substances because they often appear in psychiatric settings. Assessment and treatment of the solvent-inhalant abuser must take into account the special pharmacological, demographic, and ecological factors associated with this particular form of substance abuse.
Ranolazine antagonizes catecholamine-induced dysfunction in isolated cardiomyocytes, but lacks long-term therapeutic effects<i>in vivo</i>in a mouse model of hypertrophic cardiomyopathy
Authors: Frederik Flenner, Felix W. Friedrich, Nele Ungeheuer, Torsten Christ, Birgit Geertz, Silke Reischmann, Stefan Wagner, Konstantina Stathopoulou, Klaus-Dieter Söhren, Florian Weinberger, Edzard Schwedhelm, Friederike Cuello, Lars S. Maier, Thomas Eschenhagen, Lucie Carrier
Journal: Cardiovascular Research (2015)

Hypertrophic cardiomyopathy (HCM) is often accompanied by increased myofilament Ca2+ sensitivity and diastolic dysfunction. Recent findings indicate increased late Na+ current density in human HCM cardiomyocytes. Since ranolazine has the potential to decrease myofilament Ca2+ sensitivity and late Na+ current, we investigated its effects in an Mybpc3-targeted knock-in (KI) mouse model of HCM. Unloaded sarcomere shortening and Ca2+ transients were measured in KI and wild-type (WT) cardiomyocytes. Measurements were performed at baseline (1 Hz) and under increased workload (30 nM isoprenaline (ISO), 5 Hz) in the absence or presence of 10 µM ranolazine. KI myocytes showed shorter diastolic sarcomere length at baseline, stronger inotropic response to ISO, and drastic drop of diastolic sarcomere length under increased workload. Ranolazine attenuated ISO responses in WT and KI cells and prevented workload-induced diastolic failure in KI. Late Na+ current density was diminished and insensitive to ranolazine in KI cardiomyocytes. Ca2+ sensitivity of skinned KI trabeculae was slightly decreased by ranolazine. Phosphorylation analysis of cAMP-dependent protein kinase A-target proteins and ISO concentration–response measurements on muscle strips indicated antagonism at β-adrenoceptors with 10 µM ranolazine shifting the ISO response by 0.6 log units. Six-month treatment with ranolazine (plasma level >20 µM) demonstrated a β-blocking effect, but did not reverse cardiac hypertrophy or dysfunction in KI mice. Ranolazine improved tolerance to high workload in mouse HCM cardiomyocytes, not by blocking late Na+ current, but by antagonizing β-adrenergic stimulation and slightly desensitizing myofilaments to Ca2+. This effect did not translate in therapeutic efficacy in vivo.
Hsc70-4 Deforms Membranes to Promote Synaptic Protein Turnover by Endosomal Microautophagy
Authors: Valerie Uytterhoeven, Elsa Lauwers, Ine Maes, Katarzyna Miskiewicz, Manuel N. Melo, Jef Swerts, Sabine Kuenen, Rafaël Wittocx, Nikky Corthout, Siewert-Jan Marrink, Sebastian Munck, Patrik Verstreken
Journal: Neuron (2015)
Effects of the Adenosine A1 Receptor Antagonist Rolofylline on Renal Function in Patients With Acute Heart Failure and Renal Dysfunction
Authors: Adriaan A. Voors, Howard C. Dittrich, Barry M. Massie, Paul DeLucca, George A. Mansoor, Marco Metra, Gad Cotter, Beth D. Weatherley, Piotr Ponikowski, John R. Teerlink, John G.F. Cleland, Christopher M. O'Connor, Michael M. Givertz
Journal: Journal of the American College of Cardiology (2011)
Managing acute renal colic
Authors: A Hindle
Journal: BMJ (2003)

Media influence on suicide Television programme makers have an ethical responsibilityEditor-We agree with Hawton and Williams that training courses for careers in the media offer the potential for improved portrayal of suicide in the media. 1 The media, however, clearly can affect many facets of health related behaviour.We recently reported the effect of the death from cervical cancer of a character (Alma) in the television soap opera Coronation Street on the NHS cervical screening programme in the north west of England. 2 3 Our studies showed an excess of 14 000 cervical smear tests performed as a result of the storyline (a 21% increase on the previous year), although only 2000 of them were in women whose test was overdue or who had had no previous smear test.The remaining 12 000 smear tests were performed on women attending for an early, unscheduled test or who were due a smear test anyway and brought their appointment forward.The large increase in the number of smear tests led to a strain on local laboratories, with the time taken to report results increasing to beyond acceptable quality assurance limits-a factor likely to provoke excess anxiety in women.We also found that many women were prompted to attend for a cervical smear test because the storyline made them worry.This anxiety generating approach contrasts with current initiatives to encourage women to make an informed choice about screening.Television programme makers should realise the power of such stories not only to achieve maximal viewing figures but also to cause fear and anxiety, as well as the consumption of scarce healthcare resources.Those responsible for promoting health need to engage programme makers in a full ethical debate.
Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation
Authors: Sophia X. Pfister, Enni Markkanen, Yanyan Jiang, Sovan Sarkar, Mick Woodcock, Giulia Orlando, Ioanna Mavrommati, Chen-Chun Pai, Lykourgos-Panagiotis Zalmas, Neele Drobnitzky, Grigory L. Dianov, Clare Verrill, Valentine M. Macaulay, Songmin Ying, Nicholas B. La Thangue, Vincenzo D’Angiolella, Anderson J. Ryan, Timothy C. Humphrey
Journal: Cancer Cell (2015)
Pharmacological Salvage of Myocardium
Authors: L G Lange, B E Sobel
Journal: The Annual Review of Pharmacology and Toxicology (1982)

During the past decade, efforts to limit the extent of myocardium exhibiting infarction once ischemia has been initiated have focused on manipulation of myocardial oxygen supply and demand as well as the process of injury itself. Interventions of promise range from the conventional, moderate increase in inspired oxygen content, to administration of hyaluronidase or intracoronary thrombolysis to augment oxygen supply; use of beta-adrenergic blocking drugs and nitroglycerin to diminish demand; and administration of calcium antagonists and prostaglandin synthesis inhibitors to limit the injury process. The ultimate effects on infarct size and long-term mortality have yet to be established unequivocally for any of these approaches in the clinical setting of acute myocardial infarction, but significant preservation of ischemic myocardium with hypothermia and with administration of nifedipine during coronary-artery bypass surgery have been documented. Several prospective, large-scale, blinded, and random sample selection clinical trials are currently in progress. Their results should definitively elucidate the clinical utility of specific interventions under defined conditions and should help to further improve the management of patients with ischemic heart disease.
Prevention of Thrombocytopenia and Neutropenia in a Nonhuman Primate Model of Marrow Suppressive Chemotherapy by Combining Pegylated Recombinant Human Megakaryocyte Growth and Development Factor and Recombinant Human Granulocyte Colony-Stimulating Factor
Authors: Laurence A. Harker, Ulla M. Marzec, Andrew B. Kelly, Ellen Cheung, Aaron Tomer, Janet L. Nichol, Stephen R. Hanson, Richard B. Stead
Journal: Blood (1997)
Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies
Authors: M. Ilie, E. Long-Mira, C. Bence, C. Butori, S. Lassalle, L. Bouhlel, L. Fazzalari, K. Zahaf, S. Lalvée, K. Washetine, J. Mouroux, N. Vénissac, M. Poudenx, J. Otto, J.C. Sabourin, C.H. Marquette, V. Hofman, P. Hofman
Journal: Annals of Oncology (2015)
Drug Pharmacokinetics in Cardiac and Hepatic Disease
Authors: R L Williams, L Z Benet
Journal: The Annual Review of Pharmacology and Toxicology (1980)

The rational administration of a drug to a patient requires knowledge of the anticipated efficacy and toxicity of the drug dose that is administered. When knowledge of how a given patient will absorb and eliminate a drug is coupled with knowledge of the pharmacologic effect of a given amount of the drug, a drug dose can be selected that will result in clinical efficacy with minimal toxicity. After a dosing regimen is instituted, direct clinic.!l obser­ vations for efficacy and toxicity and laboratory measurements of drug con­ centrations in plasma or blood may then be used to modify the initial regimen (1). These observations are especially important when drugs with low therapeutic indices are used. To assist the physician in the development of a rational dosing regimen, the science of pharmacokinetics provides information about the time course of the amount of drug in the body in the expectation that this information will correlate, directly or indirectly, with the time course of drug efficacy and toxicity. Investigations of drug absorption into the body, distribution within, and elimination from the body (the latter two processes defined as drug disposition) have been performed frequently in healthy subjects on the assumption that kinetic parameters defi ned in a small number of healthy individuals would apply to various patient populations (2). Although this assumption forms the basis for many pharmacokinetic investigations that are performed to evaluate drugs for clinical use, several clinical investiga­ tions have now documented that drug absorption and disposition parame­ ters in healthy individuals may differ widely from those observed in patients
Neuromodulation Techniques for Medically Refractory Chronic Pain
Authors: B Landau, R M Levy
Journal: Annual Review of Medicine (1993)

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