tbuckley/cabot-search huggingface dataset:
The T-box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer
Authors: I. Atreya, C. C Schimanski, C. Becker, S. Wirtz, H. Dornhoff, E. Schnurer, M. R Berger, P. R Galle, W. Herr, M. F Neurath
Journal: Gut (2007)

An efficient cytolytic T cell function is essential for immune mediated rejection of colorectal cancer. However, the molecular mechanisms driving T cell mediated cancer rejection are still poorly understood. Here, we assessed the relevance of the T-box transcription factor eomesodermin in colorectal cancer. METHODS/ RESULTS: By analysing tissue probes from 88 different colorectal tumours, a significant (p<0.02) inverse correlation between eomesodermin expression in colorectal cancers and the presence of lymph node metastases could be shown, whereas no such correlation was noted for the master transcription factor of regulatory T cells, FoxP3 and CD8 alpha expression. To evaluate whether this effect might be due to effects of eomesodermin on tumour infiltrating CD8 T cells, we subsequently analysed the regulated expression and function of this transcription factor in human T cells. Whereas overexpression of this factor induced perforin but not granzyme expression, siRNA mediated suppression of eomesodermin expression led to significantly reduced IFN-gamma production, perforin levels and cytolytic activity of CD8 T cells. Furthermore, TGF-beta and IL4 could be identified as important inducer of eomesodermin expression.
Statistics Notes: Bootstrap resampling methods
Authors: J. M. Bland, D. G. Altman
Journal: BMJ (2015)

In medical research we study a sample of individuals to make inferences about a target population. Estimates of interest, such as a mean or a difference in proportions, are calculated, usually accompanied by a confidence interval derived from the standard error. The data from a single sample are used here to quantify the variation in the estimate of interest across (hypothetical) multiple samples from the same population.1 As we have only one sample we need to make assumptions about the data. Most methods of analysis are called parametric because they incorporate assumptions about the distribution of the data, such as that observations follow a normal distribution. Non-parametric methods avoid assumptions about distributions but generally provide only P values and not estimates of quantities of interest.2 

For a given dataset the assumptions may not be met. In such cases there is an alternative way to estimate standard errors and confidence intervals without any reliance on assumed probability distributions. We use the sample dataset and apply a resampling procedure called …
A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer
Authors: B. Glimelius, H. Sørbye, L. Balteskard, P. Byström, P. Pfeiffer, K. Tveit, R. Heikkilä, N. Keldsen, M. Albertsson, H. Starkhammar, H. Garmo, Å. Berglund
Journal: Annals of Oncology (2008)
Cultural Competence and Student Body Composition Among US Medical Students—Reply
Authors: Somnath Saha, LuAnn Wilkerson
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
Pathobiology of Severe Asthma
Authors: Humberto E. Trejo Bittar, Samuel A. Yousem, Sally E. Wenzel
Journal: Annual Review of Pathology Mechanisms of Disease (2014)

Severe asthma (SA) afflicts a heterogeneous group of asthma patients who exhibit poor responses to traditional asthma medications. SA patients likely represent 5-10% of all asthma patients; however, they have a higher economic burden when compared with milder asthmatics. Considerable research has been performed on pathological pathways and structural changes associated with SA. Although limitations of the pathological approaches, ranging from sampling, to quantitative assessments, to heterogeneity of disease, have prevented a more definitive understanding of the underlying pathobiology, studies linking pathology to molecular markers to targeted therapies are beginning to solidify the identification of select molecular phenotypes. This review addresses the pathobiology of SA and discusses the current limitations of studies, the inflammatory cells and pathways linked to emerging phenotypes, and the structural and remodeling changes associated with severe disease. In all cases, an effort is made to link pathological findings to specific clinical/molecular phenotypes.
Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis
Authors: Junpei Shibata, Jo Hasegawa, Hans-Joachim Siemens, Eva Wolber, Leif Dibbelt, Dechun Li, Dörthe M. Katschinski, Joachim Fandrey, Wolfgang Jelkmann, Max Gassmann, Roland H. Wenger, Klaus F. Wagner
Journal: Blood (2003)
Low Cortisol and Risk for PTSD in Adult Offspring of Holocaust Survivors
Authors: Rachel Yehuda, Linda M. Bierer, James Schmeidler, Daniel H. Aferiat, Ilana Breslau, Susan Dolan
Journal: American Journal of Psychiatry (2000)

The study examined the association between cortisol and putative risk factors for posttraumatic stress disorder (PTSD) in a sample of subjects at increased risk for the development of PTSD.Twenty-four-hour urinary cortisol excretion was measured in 35 adult offspring of Holocaust survivors and 15 healthy comparison subjects who were not offspring of Holocaust survivors. Subjects were also characterized with regard to clinical symptoms, presence or absence of psychiatric diagnoses including PTSD, and presence or absence of PTSD in their parents.Low cortisol levels were significantly associated with both PTSD in parents and lifetime PTSD in subjects, whereas having a current psychiatric diagnosis other than PTSD was relatively, but nonsignificantly, associated with higher cortisol levels. Offspring with both parental PTSD and lifetime PTSD had the lowest cortisol levels of all study groups.Parental PTSD, a putative risk factor for PTSD, appears to be associated with low cortisol levels in offspring, even in the absence of lifetime PTSD in the offspring. The findings suggest that low cortisol levels in PTSD may constitute a vulnerability marker related to parental PTSD as well as a state-related characteristic associated with acute or chronic PTSD symptoms.
Weight Loss Is a Reversible Factor in the Prognosis of Chronic Obstructive Pulmonary Disease
Authors: ANNEMIE M. W. J. SCHOLS, JOS SLANGEN, LEX VOLOVICS, EMIEL F. M. WOUTERS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The objective of the study was to further unravel the prognostic significance of body weight changes in patients with COPD. Two survival analyses were performed: (1) a retrospective study, including 400 patients with COPD none of whom had received nutritional therapy; (2) a post hoc analysis of a prospective study, including 203 patients with COPD who had participated in a randomized placebo-controlled trial. There was no overlap between the patient groups. Baseline characteristics of all patients were collected on admission to a pulmonary rehabilitation center in stable clinical condition. In the prospective randomized placebo-controlled trial, the physiologic effects of nutritional therapy alone (n = 71) or in combination with anabolic steroid treatment (n = 67) after 8 wk was studied in patients with COPD prestratified into a depleted group and a nondepleted group. Mortality was assessed as overall mortality. The Cox proportional hazards model was used to quantify the relationship between the baseline variables age, sex, spirometry, arterial blood gases, body mass index (BMI), smoking, and subsequent overall mortality. Additionally, the influence of treatment response on mortality was investigated in the prospective study. The retrospective study revealed that low BMI (p < 0.001), age (p < 0.0001) and low PaO2 (p < 0.05) were significant independent predictors of increased mortality. After stratification of the group into BMI quintiles a threshold value of 25 kg/m2 was identified below which the mortality risk was clearly increased. In the prospective study, weight gain ( > 2 kg/8 wk) in depleted and nondepleted patients with COPD, as well as increase in maximal inspiratory mouth pressure during the 8-wk treatment, were significant predictors of survival. On Cox regression analysis weight change entered as a time-dependent covariate remained an independent predictor of mortality in addition to all variables that were entered in the retrospective study. The combined results of the two survival analyses provide evidence to support the hypothesis that body weight has an independent effect on survival in COPD. Moreover the negative effect of low body weight can be reversed by appropriate therapy in some of the patients with COPD.
GPs and criminal justice staff to receive training as part of national strategy to improve offenders' health
Authors: A. O'Dowd
Journal: BMJ (2009)

GPs and other professionals involved in the care of offenders are to receive training in England to improve the health of lawbreakers in prison and in the community.

The care services minister Phil Hope launched a cross government action plan on 17 November to tackle health inequalities in this population.

The plan draws together recommendations made by the Labour peer Keith Bradley in his review of people with mental health and learning disabilities in the criminal justice system, which was published on 30 April.

The plan is designed to protect the public, reduce health inequalities, and cut levels of reoffending.

It aims to ensure that offenders have access to the same levels of health care as …
Sulindac versus ibuprofen in sprains and strains.
Authors: T. B. Hayes, A. Fyvie, P. G. Janke, M. J. Vandenburg, W. J. Currie
Journal: British Journal of Sports Medicine (1984)

In a double-blind parallel group randomised study 191 patients with acute sprains and strains of ankle, hip, shoulder or knees were treated with either 400 mg sulindac or 1200 mg ibuprofen per day for 4 days; of these, 176 completed the trial. Spontaneous pain (day and night), pain on active movement, swelling and tenderness were assessed before and after the treatment period along with a physician's and patient's assessment of therapy at the end of the study. The vast majority of patients had a successful outcome whichever treatment they were taking. No patients reported any adverse effect during the study.
Age-dependent increase in c-fos activity and cyclin A expression in vascular smooth muscle cells A potential link between aging, smooth muscle cell proliferation and atherosclerosis
Authors: A Rivard
Journal: Cardiovascular Research (2000)

Objective: Aging can be defined as a progressive deterioration of biological functions after the organism has attained its maximal reproductive competence, which is usually associated with a decrease in proliferative ability in most cell types. However, in certain pathological situations such as atherosclerosis and restenosis, aging has been shown to be associated with a higher level of vascular smooth muscle cell (VSMC) proliferation and neointimal lesion formation after angioplasty. In the present study, we investigated potential mechanisms involved in the age-dependent increase in VSMC proliferation. Methods and results: Primary cultures of VSMCs were isolated from young (6–8-month-old) and old (4–5-year-old) New Zealand rabbits. Results from cell counting assays and FACS analysis were consistent with a shortening of the cell cycle in old VSMCs. Western blot analysis in serum stimulated cells showed a significant increase in the level of cyclin A and cyclin-dependent kinase 2 proteins in the old vs. young VSMCs. In marked contrast, expression of cyclin E in VSMCs was not influenced by aging. Transient transfection assays showed an age-dependent increase in transcription from the human cyclin A promoter. Parallel studies demonstrated that the expression of the AP1 transcription factor c-fos, which interacts with the cyclin A promoter and stimulates VSMC proliferation, was also increased in old VSMCs. Consistent with this notion, electrophoretic mobility shift assays demonstrated an increase in AP1 DNA-binding activity in old VSMCs. Conclusions: These studies suggest that age-associated increase in c-fos activity contributes to augmented cyclin A expression and VSMC proliferation in old animals. These mechanisms might contribute to the higher prevalence and severity of atherosclerosis in the elderly.
Lack of de novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish
Authors: Prakash C. Thakur, Carsten Stuckenholz, Marcus R. Rivera, Jon M. Davison, Jeffrey K. Yao, Adam Amsterdam, Kirsten C. Sadler, Nathan Bahary
Journal: Hepatology (2011)

Hepatic steatosis is the initial stage of nonalcoholic fatty liver disease (NAFLD) and may predispose to more severe hepatic disease, including hepatocellular carcinoma. Endoplasmic reticulum (ER) stress has been recently implicated as a novel mechanism that may lead to NAFLD, although the genetic factors invoking ER stress are largely unknown. During a screen for liver defects from a zebrafish insertional mutant library, we isolated the mutant cdipt hi559Tg /+ ( hi559 ). CDIPT is known to play an indispensable role in phosphatidylinositol (PtdIns) synthesis. Here we show that cdipt is expressed in the developing liver, and its disruption in hi559 mutants abrogates de novo PtdIns synthesis, resulting in hepatomegaly at 5 days postfertilization. The hi559 hepatocytes display features of NAFLD, including macrovesicular steatosis, ballooning, and necroapoptosis. Gene set enrichment of microarray profiling revealed significant enrichment of endoplasmic reticulum stress response (ERSR) genes in hi559 mutants. ER stress markers, including atf6 , hspa5 , calr , and xbp1 , are selectively up-regulated in the mutant liver. The hi559 expression profile showed significant overlap with that of mammalian hepatic ER stress and NAFLD. Ultrastructurally, the hi559 hepatocytes display marked disruption of ER architecture with hallmarks of chronic unresolved ER stress. Induction of ER stress by tunicamycin in wild-type larvae results in a fatty liver similar to hi559 , suggesting that ER stress could be a fundamental mechanism contributing to hepatic steatosis. Conclusion: cdipt -deficient zebrafish exhibit hepatic ER stress and NAFLD pathologies, implicating a novel link between PtdIns, ER stress, and steatosis. The tractability of hi559 mutant provides a valuable tool to dissect ERSR components, their contribution to molecular pathogenesis, and evaluation of novel therapeutics of NAFLD. (Hepatology 2011;)
Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone
Authors: Chien-Chang Lee, Meng-tse Gabriel Lee, Yueh-Sheng Chen, Shih-Hao Lee, Yih-Sharng Chen, Shyr-Chyr Chen, Shan-Chwen Chang
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Fluoroquinolones have been associated with collagen degradation, raising safety concerns related to more serious collagen disorders with use of these antibiotics, including aortic aneurysm and dissection. <h3>Objective</h3> To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection. <h3>Design, Setting, and Participants</h3> We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwan’s National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex. <h3>Exposures</h3> Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection. <h3>Main Outcomes and Measures</h3> Risk of developing aortic aneurysm or dissection. <h3>Results</h3> A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score–adjusted RR, 2.15; 95% CI, 0.97-4.60). <h3>Conclusions and Relevance</h3> Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.
Tennis elbow: incidence in local league players.
Authors: R. Carroll
Journal: British Journal of Sports Medicine (1981)

Seventy-four local league players were surveyed through a questionnaire and interview to establish the incidence of tennis elbow, the perceived causes, preventive measures taken and their perceived effectiveness. Of these 35% suffered from tennis elbow, 77% of those critically. The tennis racquet used, technique and timing and the condition of the court were perceived as the main causes, whilst playing tennis frequently was seen as the main contributory factor. The effectiveness of both medical treatment and non-medical measures are noted, but only 5 cases of complete recovery from the injury are reported. Medical help was not sought in almost 50% of the cases, and lack of faith in the GP's interest or advice was noted. Information about tennis elbow did not appear to be easily accessible. More sports injury clinics and wider dissemination of information are suggested. The American research is reviewed.
Study of tetrahydrobiopterin in idiopathic pulmonary fibrosis and COPD
Authors: Patricia Almudéver Folch, Alfredo De Diego Damia, Julio Cortijo Gimeno, Montserrat Leόn Fábregas, M.J. Fandόs, Xavier Milara
Journal: European Respiratory Journal (2011)

Introduction: Tetrahydrobiopterin (BH4) is an essential cofactor for the activity of nitric oxide synthase enzyme (eNOS). Deficiency of BH4 induced by oxidative stress could produce eNOS uncoupling and contribute to pulmonary damage.

Objective: To study the role of endogenous BH4 in patients with stable idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD).

Materials and methods: Twenty eight patients (15 IPF, 13 COPD; 61 (13) years) and 9 healthy controls were studied. Lung function tests (spirometry, pletismography and lung diffusion capacity), HRCT (High Resolution Computed Tomography) lung scan and 6-min. walk test were performed in all patients. Blood neutrophils, plasma BH4 (reverse-phase high-performance liquid chromatographic (RP-HPLC) with fluorescence detection), hemoglobin, fibrinogen, and CRP were also measured. Differences in BH4 levels between groups and its relationship with clinical, functional or biological parameters of disease severity were analized.

Results: BH4 was significantly reduced in IPF 1.32 (0.16)), and COPD (1.44 (0.27)) patients versus controls (2.42 (0.29)). There were no differences in BH4 levels between either IPF and COPD or bronchitis and emphysema phenotypes. BH4 levels were not related with parameters of lung function, radiological extension, inflammatory markers or smoking severity. In patients with COPD, BH4 levels were related with the number of previous exacerbations.

Conclusions: Plasma BH4 levels are reduced in IPF and COPD, which may be of potential value as a future biomarker of oxidative stress related diseases.

Supported by grant SVN 2010 and CIBERES (CB06/06/0027)
Enhancing Comprehension of Consent for Research in Older Patients With Psychosis: A Randomized Study of a Novel Consent Procedure
Authors: Laura B. Dunn, Laurie A. Lindamer, Barton W. Palmer, Lawrence J. Schneiderman, Dilip V. Jeste
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The ability of individuals with schizophrenia to provide informed consent for research has become the focus of public debate. The authors examined whether a novel consent procedure improved the comprehension of consent for older patients with psychosis. METHOD: Fifty outpatients with schizophrenia or other psychotic disorders and 19 normal comparison subjects aged 40–80 were randomly assigned to groups given either a routine or an enhanced consent procedure. The latter utilized a computerized presentation that included sequential bullet points and summaries of key information. A posttest measured comprehension of consent-relevant information. RESULTS: A significantly greater proportion of patients who received the enhanced consent procedure scored 100% on first and second trials of the posttest, compared to those receiving the routine procedure (trial 1: 42.3% versus 8.3%; trial 2: 80.8% versus 45.8%, respectively). CONCLUSIONS: The enhanced consent method improved comprehension of information relevant for consent in older patients with psychosis.