tbuckley/cabot-search huggingface dataset:
Alcohol Consumption and Risk of Incident Atrial Fibrillation in Women
Authors: David Conen
Journal: JAMA (2008)

Previous studies suggest that consuming moderate to high amounts of alcohol on a regular basis might increase the risk of developing atrial fibrillation in men but not in women. However, these studies were not powered to investigate the association of alcohol consumption and atrial fibrillation among women.To prospectively assess the association between regular alcohol consumption and incident atrial fibrillation among women.Participants were 34 715 initially healthy women participating in the Women's Health Study, a completed randomized controlled trial conducted in the United States. Participants were older than 45 years and free of atrial fibrillation at baseline and underwent prospective follow-up from 1993 to October 31, 2006. Alcohol consumption was assessed via questionnaires at baseline and at 48 months of follow-up and was grouped into 4 categories (0, > 0 and < 1, > or = 1 and < 2, and > or = 2 drinks per day). Atrial fibrillation was self-reported on the yearly questionnaires and subsequently confirmed by electrocardiogram and medical record review.Time to first episode of atrial fibrillation.Over a median follow-up of 12.4 years, 653 cases of incident atrial fibrillation were confirmed. Age-adjusted incidences among women consuming 0 (n = 15,370), more than 0 and less than 1 (n = 15,758), 1 or more and less than 2 (n = 2228), and 2 or more (n = 1359) drinks per day were 1.59, 1.55, 1.27, and 2.25 events/1000 person-years of follow-up. Thus, compared with nondrinking women, women consuming 2 or more drinks per day had an absolute risk increase of 0.66 events/1000 person-years. The corresponding multivariate-adjusted hazard ratios (HRs) for incident atrial fibrillation were 1, 1.05 (95% CI, 0.88-1.25), 0.84 (95% CI, 0.58-1.22), and 1.60 (95% CI, 1.13-2.25), respectively. The increased hazard in the small group of women consuming 2 or more drinks per day persisted when alcohol intake was updated at 48 months (HR, 1.49; 95% CI, 1.05-2.11) or when women were censored at their first cardiovascular event (HR, 1.68; 95% CI, 1.18-2.39).Among healthy middle-aged women, consumption of up to 2 alcoholic beverages per day was not associated with an increased risk of incident atrial fibrillation. Heavier consumption of 2 or more drinks per day, however, was associated with a small but statistically significant increased risk of atrial fibrillation.
Molecular Characterization of Breast Cancer with High-Resolution Oligonucleotide Comparative Genomic Hybridization Array
Authors: Fabrice Andre, Bastien Job, Philippe Dessen, Attila Tordai, Stefan Michiels, Cornelia Liedtke, Catherine Richon, Kai Yan, Bailang Wang, Gilles Vassal, Suzette Delaloge, Gabriel N. Hortobagyi, W. Fraser Symmans, Vladimir Lazar, Lajos Pusztai
Journal: Clinical Cancer Research (2009)

Abstract Purpose: We used high-resolution oligonucleotide comparative genomic hybridization (CGH) arrays and matching gene expression array data to identify dysregulated genes and to classify breast cancers according to gene copy number anomalies. Experimental Design: DNA was extracted from 106 pretreatment fine needle aspirations of stage II-III breast cancers that received preoperative chemotherapy. CGH was done using Agilent Human 4 × 44K arrays. Gene expression data generated with Affymetrix U133A gene chips was also available on 103 patients. All P values were adjusted for multiple comparisons. Results: The average number of copy number abnormalities in individual tumors was 76 (range 1-318). Eleven and 37 distinct minimal common regions were gained or lost in &amp;gt;20% of samples, respectively. Several potential therapeutic targets were identified, including FGFR1 that showed high-level amplification in 10% of cases. Close correlation between DNA copy number and mRNA expression levels was detected. Nonnegative matrix factorization (NMF) clustering of DNA copy number aberrations revealed three distinct molecular classes in this data set. NMF class I was characterized by a high rate of triple-negative cancers (64%) and gains of 6p21. VEGFA, E2F3, and NOTCH4 were also gained in 29% to 34% of triple-negative tumors. A gain of ERBB2 gene was observed in 52% of NMF class II and class III was characterized by a high rate of estrogen receptor–positive tumors (73%) and a low rate of pathologic complete response to preoperative chemotherapy (3%). Conclusion: The present study identified dysregulated genes that could classify breast cancer and may represent novel therapeutic targets for molecular subsets of cancers.
Identity Disturbance in Borderline Personality Disorder: An Empirical Investigation
Authors: Tess Wilkinson-Ryan, Drew Westen
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Identity disturbance is one of the nine criteria for borderline personality disorder in DSM-IV, yet the precise nature of this disturbance has received little empirical attention. This study examines 1) the extent to which identity disturbance is a single construct, 2) the extent to which it distinguishes patients with borderline personality disorder, and 3) the role of sexual abuse in identity disturbance in patients with borderline personality disorder. METHOD: The authors constructed an instrument that consisted of 35 indicators of identity disturbance culled from relevant clinical and theoretical literature and asked clinicians to rate a patient on each of the items. The patient group consisted of 95 subjects diagnosed with borderline personality disorder (N=34), another personality disorder (N=20), or no personality disorder (N=41). Relevant diagnostic, demographic, and developmental history data were also collected. The authors used factor analysis to ascertain whether identity disturbance is a unitary construct and then examined the relation between dimensions of identity disturbance and borderline diagnosis after controlling for sexual abuse history. RESULTS: Four identity disturbance factors were identified: role absorption (in which patients tend to define themselves in terms of a single role or cause), painful incoherence (a subjective sense of lack of coherence), inconsistency (an objective incoherence in thought, feeling, and behavior), and lack of commitment (e.g., to jobs or values). All four factors, but particularly painful incoherence, distinguished patients with borderline personality disorder. Although sexual abuse was associated with some of the identity factors, particularly painful incoherence, borderline pathology contributed unique variance beyond abuse history to all four identity disturbance factors. The data also provided further evidence for an emerging empirical distinction between two borderline personality disorder types: one defined by emotional dysregulation and dysphoria, the other by histrionic characteristics. CONCLUSIONS: Identity disturbance is a multifaceted construct that distinguishes patients with borderline personality disorder from other patients. Some of its components are related to a history of sexual abuse, whereas others are not. Identity disturbance appears to be characteristic of borderline patients whether or not they have an abuse history.
Does Hyperinsulinemia Preserve Bone?
Authors: Elizabeth Barrett-Connor, Donna Kritz-Silverstein
Journal: Diabetes Care (1996)

OBJECTIVE Obesity and NIDDM are each associated with increased bone mineral density (BMD). We therefore hypothesize that hyperinsulinemia is an osteogenic factor. RESEARCH DESIGN AND METHODS Subjects consisted of 411 men and 559 women aged 50–89 years who were participants in the Rancho Bernardo Heart and Chronic Disease Study and were not diabetic by history or oral glucose tolerance test. Fasting and 2-h postchallenge insulin were measured by radioimmunoassay. Bone mineral density was measured at the midshaft radius with single photon absorptiometry and at the lumbar spine and hip with dual energy X-ray absorptiometry. RESULTS Multiple regression analyses indicated that among men, a significant insulin-BMD association at the hip was no longer apparent after adjusting for covariates. Among women, fasting insulin was significantly and positively associated with bone density of the radius and spine (P &amp;lt; 0.05), independent of age, BMI, waist-hip ratio, postmenopausal estrogen use, age at menopause, thiazide use, family history of diabetes, current cigarette smoking, and exercise. Each 10 μU/ml increase in fasting insulin was associated with an increase of 0.33 and 0.57 g/cm2 of the radius and spine, respectively. CONCLUSIONS Hyperinsulinemia may be responsible for part of the observed association of both diabetes and obesity with BMD in women.
Nonlinear relations between house dust mite allergen levels and mite sensitization in farm and nonfarm children
Authors: D. Schram‐Bijkerk, G. Doekes, M. Boeve, J. Douwes, J. Riedler, E. Üblagger, E. Von Mutius, J. Budde, G. Pershagen, M. Van Hage, M. Wickman, C. Braun‐Fahrländer, M. Waser, B. Brunekreef
Journal: Allergy (2006)

Low sensitization rates to common allergens have been observed in farm children, which might be due to high exposure to microbial agents. It is not known how microbial agents modify the association between specific allergen exposure and sensitization.To examine the relations between house dust mite allergen exposure and mite sensitization in farm and nonfarm children and to assess the effects of microbial agents levels on this association.Major mite allergens of Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1), endotoxin, beta(1,3)-glucans and fungal extracellular polysaccharides were measured in mattress dust of 402 children participating in a cross-sectional study in five European countries. Mite allergen (Der p 1 + Der f 1) levels were divided into tertiles with cut-offs 1.4 and 10.4 microg/g. Sensitization was assessed by measurement of allergen-specific immunoglobulin E against house dust mite.Prevalence ratios of mite sensitization for medium and high when compared with low mite allergen levels were 3.1 [1.7-5.7] and 1.4 [0.7-2.8] respectively. Highest mite sensitization rates at intermediate exposure levels were consistently observed across country (except for Sweden) and in both farm and nonfarm children. The shape of the dose-response curve was similar for above and below median mattress microbial agent levels, but the 'sensitization peak' appeared to be lower for above median levels.Our data suggest a bell-shaped dose-response relationship between mite allergen exposure and sensitization to mite allergens. In populations with high microbial agent levels and low sensitization rates, the curve is shifted down.
Prevention and Treatment of Major Blood Loss
Authors: Pier Mannuccio Mannucci, Marcel Levi
Journal: New England Journal of Medicine (2007)

The most common medical cause of major blood loss is surgery, particularly cardiovascular procedures, liver transplantation and hepatic resection, and major orthopedic procedures. Excessive blood loss may also occur for other reasons, such as trauma. This article reviews the benefits of hemostatic drugs and considers the associated risk of adverse events, particularly thrombotic complications.
Mastoiditis without Middle-ear Signs
Authors: W. S. T. Neville
Journal: BMJ (1943)

MIEDICAL JOURNALand labium minus there were raised indurated areas of inflammation about 1 in.by 1 in.covered with thin grey adherent membrane.Smears taken from the mouth showed no evidence of Vincent's angina.Swabs and pieces of membrane were later reported to reveal.thepresence of the true diphtheria bacillus.
Estrogen Enhances Angiogenesis through a Pathway Involving Platelet-Activating Factor-Mediated Nuclear Factor-κB Activation
Authors: Kook Heon Seo, Hyun-Suk Lee, Bongnam Jung, Hyun-Mi Ko, Jung-Hwa Choi, Sung Jun Park, Il-Hwan Choi, Hern-Ku Lee, Suhn-Young Im
Journal: Cancer Research (2004)

Abstract In this study, we investigated the molecular events involved in estrogen-induced angiogenesis. Treatment of the human endometrial adenocarcinoma cells, HEC-1A, with estrogen up-regulated mRNA expression and protein synthesis of various angiogenic factors such as tumor necrosis factor-α, interleukin-1, basic fibroblast growth factor, and vascular endothelial growth factor. The estrogen-dependent induction of the expression was blocked by the platelet-activating factor (PAF) antagonists, WEB 2170. Estrogen treatment caused the activation of nuclear factor (NF)-κB in HEC-1A cells and was also blocked by PAF antagonist. Inhibitors of NF-κB activation inhibited estrogen-induced mRNA expression and protein synthesis of the angiogenic factors. Estrogen led to a pronounced angiogenesis as assessed by a mouse Matrigel model in vivo and endothelial cell sprouting in vitro. PAF antagonists or NF-κB inhibitors significantly inhibited this estrogen-dependent angiogenesis. Estrogen caused phospholipase A2 (PLA2) gene and protein expression. Estrogen-induced vascular endothelial growth factor mRNA expression and sprouting were significantly inhibited by PLA2 inhibitors, suggesting PLA2 expression is the upstream pathway in the estrogen-induced angiogenesis. Taken together, these results suggest that estrogen induces the production of angiogenic factors via a mechanism involving PAF-mediated NF-κB activation.
C. elegans phototransduction requires a G protein–dependent cGMP pathway and a taste receptor homolog
Authors: Jie Liu, Alex Ward, Jingwei Gao, Yongming Dong, Nana Nishio, Hitoshi Inada, Lijun Kang, Yong Yu, Di Ma, Tao Xu, Ikue Mori, Zhixiong Xie, X Z Shawn Xu
Journal: Nature Neuroscience (2010)
Gestalt isomorphism and the primacy of the subjective perceptual experience
Authors: Steven Lehar
Journal: Behavioral and Brain Sciences (1998)

The Gestalt principle of isomorphism reveals the primacy of subjective experience as a valid source of evidence for the information encoded neurophysiologically. This theory invalidates the abstractionist view that the neurophysiological representation can be of lower dimensionality than the percept to which it gives rise.
Dyspnoea at rest and at the end of different exercises in patients with near-fatal asthma
Authors: E. Barreiro, J. Gea, C. Sanjuás, R. Marcos, J. Broquetas, J. Milic-Emili
Journal: European Respiratory Journal (2004)

Blunted perception of dyspnoea under resistive loading has been observed in patients with a history of near-fatal asthma (NFA). The perception of dyspnoea at rest and at the end point of various exercises was assessed in such patients. Respiratory function and exercise capacity (6-min walking distance, incremental cycloergometry and inspiratory threshold loading) were assessed in seven NFA and eight non-NFA patients. Dyspnoea (Borg scale) was measured at rest and at the end point of the various exercises. Dyspnoea at rest was significantly lower in NFA patients. Although exercise tolerance was similarly reduced in both the NFA and non-NFA groups, dyspnoea at peak cycle exercise was significantly lower in the former (2.6+/-2 versus 6.1+/-3.8 (Borg scale; mean+/-SD)), who mainly (86%) stopped because of leg discomfort. A similar trend was observed in the 6-min walking distance and inspiratory threshold loading tests. Dyspnoea at peak exercise was the best indicator of the NFA condition, with a sensitivity of 100% and specificity of 63% for a Borg scale score of < or = 6. Perception of dyspnoea is blunted in near-fatal asthma patients at both rest and the end point of various forms of exercise. Dyspnoea at peak exercise is the best indicator of the near-fatal asthma condition.
Long-Term Menstrual and Reproductive Function in Patients With Bulimia Nervosa
Authors: Scott J. Crow, Paul Thuras, Pamela K. Keel, James E. Mitchell
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Menstrual dysfunction occurs frequently in patients with bulimia nervosa. Whether this is associated with diminished fertility is unknown. This study examined menstrual and reproductive function in bulimia nervosa patients retrospectively, with 10–15-year follow-ups. METHOD: A total of 173 women with bulimia nervosa were interviewed an average of 11.5 years (SD=1.9) after initial assessment with the Structured Clinical Interview for DSM-IV and a questionnaire about menstruation, pregnancy, and eating disorder symptoms. RESULTS: At baseline assessment, 38.2% of the subjects reported regular menses, and 4.6% reported amenorrhea. At follow-up, the rate of amenorrhea was 16.8% (2.9% because of pregnancy). At baseline, 34.7% of the subjects had experienced at least one pregnancy. At follow-up, 74.6% had been pregnant at least once, and 1.7% reported an inability to conceive. CONCLUSIONS: These results suggest that while menstrual irregularities are common, bulimia nervosa appears to have little impact on later ability to achieve pregnancy.
Legionnaires’ disease in Europe, 2009-2010
Authors: J Beauté, P Zucs, B de Jong, Collective on behalf of the European Legionnai
Journal: Eurosurveillance (2013)

The surveillance of Legionnaires' disease (LD) in Europe is carried out by the European Legionnaires' Disease Surveillance Network (ELDSNet) and coordinated by the European Centre for Disease Prevention and Control (ECDC). All cases reported in 2009 and 2010 and meeting the European case definition were electronically transmitted to The European Surveillance System (TESSy) database. A total of 5,551 and 6,305 cases were reported by 29 European countries in 2009 and 2010, respectively. The age-standardised rate of all cases was 1.20 per 100,000 inhabitants in 2010, 12% higher than in 2009, which was consistent with the increasing trend observed since 2005. Most of this increase consisted of community-acquired cases reported by France, Germany and the Netherlands with dates of onset in August–September. The exceptionally hot summer of 2010 in some parts of Europe may have played a role in this increase.
IL-13Rα2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis
Authors: Ivan J Fuss, Bharat Joshi, Zhiqiong Yang, Heba Degheidy, Stefan Fichtner-Feigl, Heitor de Souza, Florian Rieder, Franco Scaldaferri, Anja Schirbel, Melania Scarpa, Gail West, Chuli Yi, Lili Xu, Pamela Leland, Michael Yao, Peter Mannon, Raj K Puri, Claudio Fiocchi, Warren Strober
Journal: Gut (2014)

Objective Previous studies have shown that ulcerative colitis (UC) is associated with the presence of lamina propria non-invariant (Type II) NKT cells producing IL-13 and mediating epithelial cell cytotoxicity. Here we sought to define the antigen(s) stimulating the NKT cells and to quantitate these cells in the UC lamina propria. Design Detection of Type II NKT cells in UC lamina propria mononuclear cells (LPMC) with lyso-sulfatide loaded tetramer and quantum dot-based flow cytometry and staining. Culture of UC LPMCs with lyso-sulfatide glycolipid to determine sulfatide induction of epithelial cell cytotoxicity, IL-13 production and IL-13Rα2 expression. Blinded quantum dot-based phenotypic analysis to assess UC LPMC expression of IL-13Rα2, CD161 and IL-13. Results Approximately 36% of UC LPMC were lyso-sulfatide tetramer positive, whereas few, if any, control LPMCs were positive. When tested, the positive cells were also CD3 and IL-13Rα2 positive. Culture of UC LPMC with lyso-sulfatide glycolipid showed that sulfatide stimulates UC LPMC production of IL-13 and induces UC CD161 LPMC-mediated cytotoxicity of activated epithelial cells; additionally, lyso-sulfatide induces enhanced expression of IL-13Rα2. Finally, blinded phenotypic analysis of UC LP MC using multicolour quantum dot-staining technology showed that approximately 60% of the LPMC bear both IL-13Rα2 and CD161 and most of these cells also produce IL-13. Conclusions These studies show that UC lamina propria is replete with Type II NKT cells responsive to lyso-sulfatide glycolipid and bearing IL-13Rα2. Since lyso-sulfatide is a self-antigen, these data suggest that an autoimmune response is involved in UC pathogenesis.
KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer
Authors: YingYing Qian, Shoujie Chai, Zuyu Liang, Yongfang Wang, You Zhou, Xia Xu, Chenchen Zhang, Min Zhang, Jingxing Si, Feiteng Huang, Zhangdan Huang, Wei Hong, Kai Wang
Journal: Molecular Cancer (2014)

Lung cancer in nonsmokers tends to be driven by a single somatic mutation or a gene fusion. KIF5B-RET fusion is an oncogene identified in non-small cell lung cancers. In this study, we verified the oncogenic activity of KIF5B-RET fusion and investigated how KIF5B-RET activates the specific signaling pathways for cellular transformation. We aimed to provide a basis for the further development of the therapy for KIF5B-RET positive lung cancer patients. RT-PCR was used to screen for KIF5B-RET fusions in Chinese lung cancer patients. To verify the oncogenic activity of KIF5B-RET kinase in lung cancer cells, we manipulated its expression genetically followed by colony formation and tumor formation assays. The mechanism by which KIF5B-RET kinase induces proliferation was investigated by western blot, coimmunoprecipitation, and administration of RET, MAPK and STAT3 inhibitors. Our study identified a KIF5B-RET fusion in Chinese NSCLC patients and demonstrated that KIF5B-RET transfected cells showed a significantly increased proliferation rate and colony-forming ability. Furthermore, we found that KIF5B-RET fusion kinase induced multilevel activation of STAT3 at both Tyr705 and Ser727, and KIF5B-RET-STAT3 signaling related inhibitors repressed the proliferation and tumorigenicity of lung cancer cells significantly. Our data suggest that KIF5B-RET promotes the cell growth and tumorigenicity of non-small cell lung cancers through multilevel activation of STAT3 signaling, providing possible strategies for the treatment of KIF5B-RET positive lung cancers.
The Risk of Myocardial Infarction Associated with Inhaled β -Adrenoceptor Agonists
Authors: DAVID H. AU, ROZENN N. LEMAITRE, J. RANDALL CURTIS, NICHOLAS L. SMITH, BRUCE M. PSATY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Beta-adrenoceptor agonists (beta-agonists), in widespread clinical use for obstructive lung disease, have been associated with an increased risk of cardiovascular mortality. The objective of this study was to assess the association between incident myocardial infarction and the use of inhaled beta-agonists. We performed a case-control study within the Group Health Cooperative of Puget Sound (GHC). Between 1989 and 1994, we identified 1,444 cases with an incident myocardial infarction and 4,094 control subjects frequency-matched on age, sex, hypertension, and index date. The computerized pharmacy database of the health maintenance organization (HMO) was used to assess the use of beta-agonists by metered dose inhaler (MDI). Cardiovascular risk factor information was obtained from medical record review. In comparison to subjects who did not fill a beta-agonist prescription, subjects who had filled one beta-agonist MDI prescription in the 3 mo prior to their index date had an elevated estimated risk of myocardial infarction (adjusted odds ratio [OR]: 1.67 [95% CI, 1.07 to 2.60]). The elevated risk was limited to those subjects who had a history of cardiovascular disease (adjusted OR: 3.22 [95% CI, 1.63 to 6.35]) and among those with cardiovascular disease, to new users of beta-agonists (adjusted OR: 7.32 [95% CI, 2.34 to 22.8]). There was no dose-response relationship between beta-agonists use and risk of myocardial infarction. In this study, new use of beta-agonists was associated with an increased risk of myocardial infarction, although we cannot determine if the association is causal. Our study suggests that clinicians should exercise caution when giving an initial beta-adrenoceptor agonist prescription to patients with cardiovascular disease.