tbuckley/cabot-search huggingface dataset:
NICE hears appeals over dementia drugs
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

Computational analyses of pathogen genomes are increasingly used to unravel the dispersal history and transmission dynamics of epidemics. Here, we show how to go beyond historical reconstructions and use spatially-explicit phylogeographic and phylodynamic approaches to formally test epidemiological hypotheses. We illustrate our approach by focusing on the West Nile virus (WNV) spread in North America that has been responsible for substantial impacts on public, veterinary, and wildlife health. WNV isolates have been sampled at various times and locations across North America since its introduction to New York twenty years ago. We exploit this genetic data repository to demonstrate that factors hypothesised to affect viral dispersal and demography can be formally tested. Specifically, we detail and apply an analytical workflow consisting of state-of-the art methods that we further improve to test the impact of environmental factors on the dispersal locations, velocity, and frequency of viral lineages, as well as on the genetic diversity of the viral population through time. We find that WNV lineages tend to disperse faster in areas with higher temperatures and we identify temporal variation in temperature as a main predictor of viral genetic diversity through time. Using a simulation procedure, we find no evidence that viral lineages preferentially circulate within the same migratory bird flyway, suggesting a substantial role for non-migratory birds or mosquito dispersal along the longitudinal gradient. Finally, we also separately apply our testing approaches on the three WNV genotypes that circulated in North America in order to understand and compare their dispersal ability. Our study demonstrates that the development and application of statistical approaches, coupled with comprehensive pathogen genomic data, can address epidemiological questions that might otherwise be difficult or impractically expensive to answer.
Doxycycline and hydroxypropyl-β-cyclodextrin complex in poloxamer thermal sensitive hydrogel for ophthalmic delivery
Authors: Zi-xin He, Zhou-hua Wang, Hao-hao Zhang, Xin Pan, Wen-ru Su, Dan Liang, Chuan-bin Wu
Journal: Acta Pharmaceutica Sinica B (2011)

The present study aimed to prepare a chemically and physically stable formulation of doxycycline (Doxy) in an in situ thermally sensitive hydrogel for ophthalmic delivery. An inclusion complex of Doxy and hydroxypropyl-β-cyclodextrin (HP-β-CD) was first developed to increase the stability of Doxy in aqueous solution. The physical characteristics (phase solubility profiles, thermal analysis, X-ray powder diffractograms and infrared spectra) of the Doxy-HP-β-CD inclusion complex indicated the formation of a stable 1:1 complex. Poloxamers P407 (16–22%) and P188 (0–5%) were mixed to obtain a hydrogel with an appropriate gelation temperature for opthalmic use. Formulation of the inclusion complex in the poloxamer hydrogel exhibited a suitable gelation temperature (33.3 °C) after dilution with simulated tear fluid (Gel:STF=40:7, v/v). The release of Doxy from the poloxamer hydrogel followed a zero order equation suggesting it occurs through corrosion of the poloxamer hydrogel. Stability studies demonstrated that the inclusion of Doxy by HP-β-CD markedly improved its stability in aqueous solution both at 8 and 40 °C. This formulation of a doxycycline-HP-β-CD inclusion complex in an in situ thermally sensitive poloxamer hydrogel represents a potentially effective ophthalmic Doxy delivery system.
The ShcA Phosphotyrosine Docking Protein Uses Distinct Mechanisms to Regulate Myocyte and Global Heart Function
Authors: Rachel D. Vanderlaan, W. Rod Hardy, M. Golam Kabir, Adrian Pasculescu, Nina Jones, Pieter P. deTombe, Peter H. Backx, Tony Pawson
Journal: Circulation Research (2010)

Although tyrosine kinases (TKs) are important for cardiac function, their relevant downstream targets in the adult heart are unknown. The ShcA docking protein binds specific phosphotyrosine (pTyr) sites on activated TKs through its N-terminal pTyr-binding (PTB) and C-terminal SH2 domains and stimulates downstream pathways through motifs such as pTyr sites in its central CH1 region. Therefore, ShcA could be a potential hub for downstream TK signaling in the myocardium.To define the role of ShcA, a TK scaffold, in the adult heart using a myocardial-specific knockout of murine ShcA (ShcA CKO) and domain knock-in models.ShcA CKO mice developed a dilated cardiomyopathy phenotype involving impaired systolic function with enhanced cardiomyocyte contractility. This uncoupling of global heart and intrinsic myocyte functions was associated with altered collagen and extracellular matrix compliance properties, suggesting disruption of mechanical coupling. In vivo dissection of ShcA signaling properties revealed that selective inactivation of the PTB domain in the myocardium had effects resembling those seen in ShcA CKO mice, whereas disruption of the SH2 domain caused a less severe cardiac phenotype. Downstream signaling through the CH1 pTyr sites was dispensable for baseline cardiac function but necessary to prevent adverse remodeling after hemodynamic overload.These data demonstrate a requirement for TK-ShcA PTB domain signaling to maintain cardiac function. In addition, analysis of the SH2 domain and CH1 pTyr sites reveals that ShcA mediates pTyr signaling in the adult heart through multiple distinct signaling elements that control myocardial functions and response to stresses.
The Elusive Quest for Quality and Cost Savings in the Medicare Program
Authors: J. Z. Ayanian
Journal: JAMA (2009)

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
Serum and Urinary Amino Acids in Hyperuricemic and Normouricemic Subjects.
Authors: David Kaplan
Journal: Annals of Internal Medicine (1964)

s1 April 1964Serum and Urinary Amino Acids in Hyperuricemic and Normouricemic Subjects.David Kaplan, M.D., Stanley L. Wallace, M.D., F.A.C.P., David Bernstein, M.D., David Halberstam, M.S.David Kaplan, M.D.Search for more papers by this author, Stanley L. Wallace, M.D., F.A.C.P.Search for more papers by this author, David Bernstein, M.D.Search for more papers by this author, David Halberstam, M.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-719_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOn the supposition that (1) there is a renal defect in hyperuricemia, and that (2) based on evidence indicating that uric acid and some amino acids are handled similarly by the renal tubule, such a defect would not be specific for uric acid alone, we have studied the serum levels and renal clearances of amino acids in patients with hyperuricemia as compared to control patients. Renal function was evaluated with either creatinine or inulin and PAH clearances, and the studies performed after either an overnight fast or after 2 days on a 40 g protein diet. Six hyperuricemic and 14... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGout 1 April 1964Volume 60, Issue 4Page: 719-720KeywordsAmino acidsCreatinineDietProteinsUric acid Issue Published: 1 April 1964 PDF downloadLoading ...
Assessment of Reliability of Lung Function Screening Programs or Longitudinal Studies
Authors: EVA HNIZDO, GAVIN CHURCHYARD, DAVE BARNES, ROB DOWDESWELL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The aim was to determine reliability of lung function measurements performed according to recommendations of the American Thoracic Society (ATS) at a screening program in a large South African gold mine and to determine the usefulness of the reliability coefficient G for monitoring the reliability of lung function measurements in a mass screening program. The reliability coefficient G estimates the amount of random error of measurement, relative to the total variation in a measurement. The coefficient G was calculated as a correlation coefficient between two consecutive lung function tests performed within 6 mo, over a period of 43 mo on 3,378 miners. There was significant temporal variability in the reliability. For FEV1, the coefficient G showed increased variability over the first 5 mo and stabilized at a value of 0.93 for the next 23 mo, after which it systematically declined over the next 15 mo. We estimated that in a large screening program, an optimal sample size of around 900 miners, examined randomly throughout the year, on a yearly basis, would provide a sufficient sample to examine monthly or quarterly fluctuation in the reliability. The value of the reliability coefficient G did not change when the time between two consecutive tests increased up to 15 mo. In conclusion, monitoring of lung function reliability in a screening program by the reliability coefficient G should improve data quality, and provide a measure on which the confidence in a decision-making process could be based when examining temporal changes in lung function for individual subjects. Hnizdo E, Churchyard G, Barnes D, Dowdeswell R. Assessment of reliability of lung function screening programs or longitudinal studies.
αvβ6 Integrin Promotes the Invasion of Morphoeic Basal Cell Carcinoma through Stromal Modulation
Authors: Daniel Marsh, Sarah Dickinson, Graham W. Neill, John F. Marshall, Ian R. Hart, Gareth J. Thomas
Journal: Cancer Research (2008)

Abstract Basal cell carcinoma (BCC) is the most prevalent cancer in the Western world and its incidence is increasing. The pathogenesis of BCC involves deregulated Sonic hedgehog signaling, leading to activation of the Gli transcription factors. Most BCCs have a nodular growth pattern, and are indolent, slow-growing, and considered “low-risk” lesions. In contrast, the “high-risk” morphoeic variant, which causes significant morbidity, has an infiltrative growth pattern, and is so-called because of its densely fibrous stroma. As αvβ6 is capable of promoting both carcinoma invasion and fibrosis, we examined the expression of this integrin in BCCs and found that the morphoeic type showed significantly higher αvβ6 expression than the nodular type (P = 0.0009). In order to examine the function of αvβ6, we transfected the transcription factors Gli1 or Gli2 into NTERT, human keratinocytes to generate a BCC model. These cells expressed αvβ6 and were invasive, although inhibition of αvβ6 had no direct effect on cell invasion. However, the cells showed αvβ6-dependent activation of transforming growth factor-β1, which induced transdifferentiation of human fibroblasts into myofibroblasts. Paracrine secretion of hepatocyte growth factor/scatter factor by these myofibroblasts promoted c-Met–dependent tumor invasion in both Transwell and three-dimensional organotypic assays. These experimental in vitro findings were confirmed using human clinical samples in which we showed that the stroma of morphoeic BCC is myofibroblast-rich compared with nodular BCC (P = 0.0036), that myofibroblasts express hepatocyte growth factor/scatter factor, and that morphoeic BCCs are strongly c-Met–positive. These data suggest that αvβ6-dependent transforming growth factor-β1 activation induces both the infiltrative growth pattern and fibrotic stroma so characteristic of morphoeic BCC. [Cancer Res 2008;68(9):3295–303]
Hepatitis B Vaccine for Medical Students
Authors: Mitchell T. Wallin
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The article by Mr McRae and Dr Stephens<sup>1</sup>in<i>JAMA</i>advocated that medical schools provide and pay for their students' hepatitis B virus (HBV) vaccinations. The article cited the 1992 Occupational Safety and Health Administration (OSHA) blood-borne pathogens standard promulgated to limit occupational transmission of infectious agents.<sup>2</sup>The authors believed that medical students are "noticeably missing" from the scope of the standard, and they concluded that OSHA standards should be extended to require medical schools to cover their students. All medical students need to be protected from blood-borne pathogens. However, OSHA standards can be applied only to employees because the Occupational Safety and Health Act, which provides the legal authority under which OSHA sets workplace standards, is limited to employers and employees.<sup>3</sup>Since medical students are not employed by their medical schools, OSHA cannot legally extend its standards to cover them. Medical schools need
CSF-1R inhibition alters macrophage polarization and blocks glioma progression
Authors: Stephanie M Pyonteck, Leila Akkari, Alberto J Schuhmacher, Robert L Bowman, Lisa Sevenich, Daniela F Quail, Oakley C Olson, Marsha L Quick, Jason T Huse, Virginia Teijeiro, Manu Setty, Christina S Leslie, Yoko Oei, Alicia Pedraza, Jianan Zhang, Cameron W Brennan, James C Sutton, Eric C Holland, Dylan Daniel, Johanna A Joyce
Journal: Nature Medicine (2013)
Abstract 2416: Protein expression analysis of premature termination codon containing mutant proteins in colon cancers with high microsatellite instability
Authors: SeongJu Yoon, Won Kyu Kim, Jeon Han Park, Hoguen Kim
Journal: Cancer Research (2014)

Abstract Frameshift mutations at coding mononucleotide repeats (cMNR) are common in the tumors with high microsatellite instability (MSI-H). These mutations invariably generate mRNAs containing abnormal coding sequences and premature termination codons (PTC). Normally, these mRNAs containing PTC are degraded by nonsense mediated mRNA decay (NMD) system. However, mRNAs containing PTC located in the last exon are not subject to be degraded by NMD system, and thus expected to generate truncated mutant proteins. We identified 29 novel mutations at coding region mononucleotide repeats (cMNR) genes by a PCR based method and sequencing. The frequency was varying (10% to 90%) in the 10 MSI-H colon cancer cell lines. To confirm the mRNA level, we analyzed the mutant mRNAs from identified genes in colon cancer cell lines and found that the mutant mRNAs were not degraded in cells. For mutant protein detection, we adopted both immunobloting and a target mass method to detect endogenous mutant proteins in cells. By immunobloting analysis, we found rare level of endogenous mutant proteins in cells. Using a target mass method, however, we could detect potential mutant protein candidates and confirmed one of the mutant candidates (VPS37B mutant proteins) is stably expressed in cells by in vitro overexpression experiments. When mutated, VPS37B mutant proteins came to acquire very short neopeptides (only two novel amino acids) which mainly disturb the stable expression of mutant proteins and this might explain the intact expression of VPS37B mutant proteins. Taken together, our findings suggest that frameshift mutations at cMNR of genes usually lead to the rare expression of the mutant proteins in tumor cells but, some mutant proteins with short neopeptides could be stably detected by a highly sensitive target mass method. Citation Format: SeongJu Yoon, Won Kyu Kim, Jeon Han Park, Hoguen Kim. Protein expression analysis of premature termination codon containing mutant proteins in colon cancers with high microsatellite instability. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2416. doi:10.1158/1538-7445.AM2014-2416
Dr Todd, newly named EVP, will work for friendlier, wiser AMA
Authors: D. L. Breo
Journal: JAMA (1990)

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
A Cold Spot of IDDM Incidence in Europe: Macedonia
Authors: Mirjana Kocova, Massimo Trucco, Marina Konstantinova, Janice S Dorman
Journal: Diabetes Care (1993)

Objective— To determine, for the first time, the incidence of IDDM among children 0–15 yr of age in Macedonia, the south republic of former Yugoslavia, and to compare these rates with those from neighboring countries. Research Design and Methods— Children &amp;lt;15 yr of age, with IDDM diagnosed between January 1985 and December 1991, were registered using the criteria established for the WHO Multinational Project for Childhood Diabetes. The primary source of case ascertainment consisted of clinical records from the University Pediatric Clinic in Skopje, the capital of Macedonia. The secondary source consisted of records for insulin supplies from the pharmacy in Skopje and from 15 local hospitals. Results— During 1985–1991, 112 children &amp;lt;15 yr of age were diagnosed with IDDM in Macedonia. The completeness of case ascertainment was 96.6%. The age-adjusted IDDM incidence rate was very low, only 2.45/100,000 per yr. No significant sex difference in incidence was observed. The highest incidence rate occurred in the 10- to 15-yr age-group. No temporal trends were observed. Conclusions— The incidence of IDDM in Macedonia is the lowest in Europe and among the lowest reported for Caucasian populations. However, the descriptive epidemiology is similar to that for high incidence populations. Further etiological studies are required to evaluate potential reasons for the very low incidence of IDDM in Macedonia.
Adenovirus Protein IX: A New Look at an Old Protein
Authors: Robin J. Parks
Journal: Molecular Therapy (2004)

The success of gene therapy depends in part on our understanding of the biology of gene therapy vectors. This knowledge must be used to improve the function, safety, and versatility of the vector system. For decades, we have known which viral proteins are involved in formation of the adenovirus (Ad) capsid, but we are still learning how these proteins can be altered or manipulated to improve vector function. The Ad protein IX (pIX) was originally identified as a minor component of the Ad capsid, but was not essential for virion formation. However, more recent studies have suggested that pIX may have multiple roles in the Ad life cycle, including acting as a transcriptional activator and reorganizing nuclear proteins to provide an environment more conducive to virus replication. In gene therapy studies, removal of pIX from the Ad vector backbone was used to increase the cloning capacity of E1-deleted Ad vectors and to develop a new method for preparing helper-dependent Ad vectors. pIX has also been at the center of numerous attempts to eliminate the problem of replication-competent Ad in Ad vector preparations. Finally, pIX represents a versatile platform for the presentation of polypeptides on the surface of the viral capsid, including ligands for virus retargeting and fluorescent proteins for visualizing the virus in vitro and in vivo. Thus, the importance and uses of this "minor" capsid protein have changed significantly over the past few years.
Indian health minister convenes experts to tackle fetal sex selection
Authors: S. Bagcchi
Journal: BMJ (2014)

Indian health minister Harsh Vardhan has announced that he will establish an expert group to examine new methods that are being used to determine the sex of fetuses. These new methods—some of which are non-invasive—bypass existing regulations that ban the use of ultrasonography to find out the sex of a fetus.

“While misuse of ultrasound machines is still prevalent because it is cheap, newer medical technologies are increasingly being used in the name of ‘genetic testing,’” Vardhan told members of the reconstituted Central Supervisory Board on 13 October in New Delhi. The …
Coronary occlusion before, during, and after strenuous exercise
Authors: P. L. THOMPSON, B. LOWN
Journal: Cardiovascular Research (1976)

Groups of dogs were exercised immediately before, and immediately after occlusion of the left anterior descending coronary artery. Coronary occlusion by a staged procedure resulted in a low mortality and rare ventricular ectopic beats. The combination of simultaneous exercise with coronary occlusion reproducibly provoked ventricular fibrillation (VF). Exercise before and after occlusion frequently produced ventricular tachycardia but no VF. The risk of major arrhythmias was related to the peak heart rate resulting from the exercise.
HEMORRHAGIC INFECTION IN AN INFANT DUE TO THE TYPHOID BACILLUS.
Authors: GEORGE BLUMER
Journal: JAMA (1900)

The case herein reported, while differing in some respects from the hitherto recorded ones of congenital typhoid infection, probably belongs in the same category. It seems proper, therefore, before detailing the history and findings to review briefly the literature of this somewhat rare class of cases. It seems hardly necessary to refer to the cases reported in the pre-bacteriologic era, inasmuch as they are so imperfectly recorded, according to modern standards, that considerable doubt must necessarily hang over their authenticity. Even the earlier cases recorded after the discovery of the typhoid bacillus are open to question, on account of the difficulty at the time of their discovery of distinguishing the typhoid bacillus from the organisms of the colon group. Eberth<sup>1</sup>indirectly hints, and Dürk<sup>2</sup>positively states that the cases of Reher,<sup>3</sup>Neuhauss<sup>4</sup>and Chantemesse and Widal<sup>5</sup>are open to doubt on these grounds, and this