tbuckley/cabot-search huggingface dataset:
The Expression of ERβcx in Human Breast Cancer and the Relationship to Endocrine Therapy and Survival
Authors: Carlo Palmieri, Eric W.-F. Lam, Janine Mansi, Claire MacDonald, Sami Shousha, Peter Madden, Yoko Omoto, Andrew Sunters, Margaret Warner, Jan-Åke Gustafsson, R. Charles Coombes
Journal: Clinical Cancer Research (2004)

Estrogen receptor (ER) alpha-positive breast cancer is often treated with endocrine therapy using either antiestrogens or aromatase inhibitors. However, 30% of patients who receive endocrine therapy will derive no benefit from such treatments and may indeed suffer adverse effects. Currently, there are no ways to predict response to such treatments. ER beta cx, a variant of ER beta, has a dominant-negative effect over ER alpha, and its expression thought to modulate response to endocrine treatment may represent a predictor of response to endocrine therapy.We investigated the expression of the ER beta cx in 82 frozen breast samples (8 benign, 1 ductal carcinoma in situ, and 73 malignant) by Western blot analysis. The relationship between the expression of ER beta cx variants with prognosis and outcome of endocrine therapy was examined.There was a statistically significant association between the presence of ER beta cx and the response to endocrine therapy (Fisher's exact test, P = 0.04). We also examined the influence of the ER beta cx status of a tumor on time to progression and death. There was a relationship between the presence of ER beta cx and survival, with patients whose tumors express ER beta cx having a longer survival rate (P = 0.05). Cell-type specificity of expression was assessed by immunohistochemistry on a selection of histological samples.On the basis of this small group of patients, we conclude that the expression of ER beta cx correlated with favorable response to endocrine therapy. A larger study involving the staining of archival material is currently underway to confirm these preliminary results.
Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression
Authors: S Sandberg
Journal: Thorax (2004)

A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress.Sixty children with verified chronic asthma were followed prospectively for 18 months with continuous monitoring of asthma by daily symptom diaries and peak flow measurements, accompanied by repeated interview assessments of life events. The key outcome measures were asthma exacerbations and severely negative life events.An immediate effect evident within the first 2 days following a severely negative life event increased the risk of a new asthma attack by a factor of 4.69, 95% confidence interval 2.33 to 9.44 (p<0.001) [corrected] In the period 3-10 days after a severe event there was no increased risk of an asthma attack (p = 0.5). In addition to the immediate effect, an increased risk of 1.81 (95% confidence interval 1.24 to 2.65) [corrected] was found 5-7 weeks after a severe event (p = 0.002). This is consistent with earlier findings. There was a statistically significant variation due to unobserved factors in the incidence of asthma attacks between the children.The use of statistical methods capable of investigating short time lags showed that stressful life events significantly increase the risk of a new asthma attack immediately after the event; a more delayed increase in risk was also evident 5-7 weeks later.
Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors
Authors: Joonsoo Kang, Nidhi Malhotra
Journal: Annual Review of Immunology (2015)

Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity.
<i>Helicobacter pylori</i>is associated with lower androgen activity among men in NHANES III
Authors: C M Schooling, J B Dowd, H E Jones
Journal: Gut (2013)

Chen et al ,1 using a nationally representative sample of the US population from the National Health and Nutrition Examination Survey III (NHANES III), intriguingly suggest infection with Helicobacter (H) pylori may have positive health effects in addition to a causal role in gastric cancer. H pylori has a long history of coexistence with humans. Research on the human microbiome has also highlighted the symbiotic relation of gut microorganisms with their hosts. Animal biology suggests immune defence trades-off against reproductive success such that infections suppresses androgens.2 Correspondingly, changing the gut microbial environment in mice changes mice testosterone levels.3 The same mechanisms may also apply to humans, particularly at older ages when the immune system is less effective. H pylori could modulate androgen production and thereby affect health because androgens, and similarly endocrine disruptors, may play a role in chronic diseases.

Two androgen biomarkers (serum testosterone and androstanediol glucuronide (3-α-diol-G) (AAG)) were assayed for a male subsample (12+ years) from NHANES III who …
It's not what you say but the way that you say it . .
Authors: A O'Brien
Journal: BMJ (1994)

Once during an audition for a college play I was asked to spend two minutes saying “Hello” in as many different ways as possible. I am reminded of this since I have spent the past two months experimenting with various form of “Bonjour,” my aim being to find one which will not immediately reveal me to be a foreigner.

I have come to realise that this is not as easy as at first thought. My innate ability to distinguish a native speaker of my own language (English) after the utterance of one word is not unique and not just granted to those who live on one side of the Channel. Often it …
Sleep Disorders, Health, and Safety in Police Officers
Authors: Shantha M. W. Rajaratnam, Laura K. Barger, Steven W. Lockley, Steven A. Shea, Wei Wang, Christopher P. Landrigan, Conor S. O’Brien, Salim Qadri, Jason P. Sullivan, Brian E. Cade, Lawrence J. Epstein, David P. White, Charles A. Czeisler, for the Harvard Work Hours, Health and Safety Group
Journal: JAMA (2011)

<h3>Context</h3>Sleep disorders often remain undiagnosed. Untreated sleep disorders among police officers may adversely affect their health and safety and pose a risk to the public.<h3>Objective</h3>To quantify associations between sleep disorder risk and self-reported health, safety, and performance outcomes in police officers.<h3>Design, Setting, and Participants</h3>Cross-sectional and prospective cohort study of North American police officers participating in either an online or an on-site screening (n=4957) and monthly follow-up surveys (n=3545 officers representing 15 735 person-months) between July 2005 and December 2007. A total of 3693 officers in the United States and Canada participated in the online screening survey, and 1264 officers from a municipal police department and a state police department participated in the on-site survey.<h3>Main Outcome Measures</h3>Comorbid health conditions (cross-sectional); performance and safety outcomes (prospective).<h3>Results</h3>Of the 4957 participants, 40.4% screened positive for at least 1 sleep disorder, most of whom had not been diagnosed previously. Of the total cohort, 1666 (33.6%) screened positive for obstructive sleep apnea, 281 (6.5%) for moderate to severe insomnia, 269 (5.4%) for shift work disorder (14.5% of those who worked the night shift). Of the 4608 participants who completed the sleepiness scale, 1312 (28.5%) reported excessive sleepiness. Of the total cohort, 1294 (26.1%) reported falling asleep while driving at least 1 time a month. Respondents who screened positive for obstructive sleep apnea or any sleep disorder had an increased prevalence of reported physical and mental health conditions, including diabetes, depression, and cardiovascular disease. An analysis of up to 2 years of monthly follow-up surveys showed that those respondents who screened positive for a sleep disorder vs those who did not had a higher rate of reporting that they had made a serious administrative error (17.9% vs 12.7%; adjusted odds ratio [OR], 1.43 [95% CI, 1.23-1.67]); of falling asleep while driving (14.4% vs 9.2%; adjusted OR, 1.51 [95% CI, 1.20-1.90]); of making an error or safety violation attributed to fatigue (23.7% vs 15.5%; adjusted OR, 1.63 [95% CI, 1.43-1.85]); and of exhibiting other adverse work-related outcomes including uncontrolled anger toward suspects (34.1% vs 28.5%; adjusted OR, 1.25 [95% CI, 1.09-1.43]), absenteeism (26.0% vs 20.9%; adjusted OR, 1.23 [95% CI, 1.08-1.40]), and falling asleep during meetings (14.1% vs 7.0%; adjusted OR, 1.95 [95% CI, 1.52-2.52]).<h3>Conclusion</h3>Among a group of North American police officers, sleep disorders were common and were significantly associated with increased risk of self-reported adverse health, performance, and safety outcomes.
Nonoperative Treatment of Unilateral Renal Vein Thrombosis in the Newborn
Authors: A. Barry Belman
Journal: JAMA (1970)

Acute renal vein thrombosis in the newborn has been considered a surgical emergency. More recently, survival without surgical intervention has been reported. Seven patients were treated without operation. There were six survivors with pyelographically demonstrated return of visualization on the affected side in four. One atrophic kidney resulted. Diagnosis of renal vein thrombosis is made when flank mass and hematuria are present in association with pyelographic nonvisualization and thrombocytopenia. It occurs most often in children of diabetic mothers and in the presence of diarrhea. Dialysis is recommended in the event of bilateral involvement, as return of renal function is likely.
Fulminant Delta Hepatitis in Chronic Hepatitis B Infection
Authors: Kevin M. De Cock
Journal: JAMA (1984)

Two male homosexual patients, one an intravenous (IV) drug abuser, had hepatitis B surface antigen-positive fulminant hepatitis. On the basis of tests for IgM antibody to hepatitis B core antigen (HBcAg) and for IgM and IgG antibodies to delta agent, acute delta hepatitis in chronic hepatitis B infection was diagnosed. The delta agent appeared to have a role in producing fulminant hepatic failure. Accurate diagnosis of fulminant hepatitis may be impossible without recourse to tests for IgM antibody to HBcAg and antibodies to delta agent. Although delta hepatitis in the United States primarily affects IV drug abusers, this infection can also occur in male homosexuals. (<i>JAMA</i>1984;252:2746-2748)
Validation of the educational needs assessment tool as a generic instrument for rheumatic diseases in seven European countries
Authors: Mwidimi Ndosi, Ann Bremander, Bente Hamnes, Mike Horton, Marja Leena Kukkurainen, Pedro Machado, Andrea Marques, Jorit Meesters, Tanja A Stamm, Alan Tennant, Jenny de la Torre-Aboki, Theodora P M Vliet Vlieland, Heidi A Zangi, Jackie Hill
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To validate the educational needs assessment tool (ENAT) as a generic tool for assessing the educational needs of patients with rheumatic diseases in European Countries. <h3>Methods</h3> A convenience sample of patients from seven European countries was included comprising the following diagnostic groups: ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematosus, osteoarthritis (OA) and fibromyalgia syndrome. Translated versions of the ENAT were completed through surveys in each country. Rasch analysis was used to assess the construct validity of the adapted ENATs including differential item functioning by culture (cross-cultural DIF). Initially, the data from each country and diagnostic group were fitted to the Rasch model separately, and then the pooled data from each diagnostic group. <h3>Results</h3> The sample comprised 3015 patients; the majority, 1996 (66.2%), were women. Patient characteristics (stratified by diagnostic group) were comparable across countries except the educational background, which was variable. In most occasions, the 39-item ENAT deviated significantly from the Rasch model expectations (item–trait interaction χ<sup>2</sup> p&lt;0.05). After correction for local dependency (grouping the items into seven domains and analysing them as 'testlets'), fit to the model was satisfied (item–trait interaction χ<sup>2</sup> p&gt;0.18) in all pooled disease group datasets except OA (χ<sup>2</sup>=99.91; p=0.002). The internal consistency in each group was high (Person Separation Index above 0.90). There was no significant DIF by person characteristics. Cross-cultural DIF was found in some items, which required adjustments. Subsequently, interval-level scales were calibrated to enable transformation of ENAT scores when required. <h3>Conclusions</h3> The adapted ENAT is a valid tool with high internal consistency providing accurate estimation of the educational needs of people with rheumatic diseases. Cross-cultural comparison of educational needs is now possible.
Selenium Deficiency Abrogates Inflammation-Dependent Plasma Cell Tumors in Mice
Authors: Klaus Felix, Simone Gerstmeier, Antonios Kyriakopoulos, O. M. Zack Howard, Hui-Fang Dong, Michael Eckhaus, Dietrich Behne, Georg W. Bornkamm, Siegfried Janz
Journal: Cancer Research (2004)

Abstract The role of the micronutrient, selenium, in human cancers associated with chronic inflammations and persistent infections is poorly understood. Peritoneal plasmacytomas (PCTs) in strain BALB/c (C), the premier experimental model of inflammation-dependent plasma cell transformation in mice, may afford an opportunity to gain additional insights into the significance of selenium in neoplastic development. Here, we report that selenium-depleted C mice (n = 32) maintained on a torula-based low-selenium diet (5–8 μg of selenium/kg) were totally refractory to pristane induction of PCT. In contrast, 11 of 26 (42.3%) control mice maintained on a selenium adequate torula diet (300 μg of selenium/kg) and 15 of 40 (37.5%) control mice fed standard Purina chow (440 μg of selenium/kg) developed PCT by 275 days postpristane. Abrogation of PCT was caused in part by the striking inhibition of the formation of the inflammatory tissue in which PCT develop (pristane granuloma). This was associated with the reduced responsiveness of selenium-deficient inflammatory cells (monocytes and neutrophils) to chemoattractants, such as thioredoxin and chemokines. Selenium-deficient C mice exhibited little evidence of disturbed redox homeostasis and increased mutant frequency of a transgenic lacZ reporter gene in vivo. These findings implicate selenium, via the selenoproteins, in the promotion of inflammation-induced PCT and suggest that small drug inhibitors of selenoproteins might be useful for preventing human cancers linked with chronic inflammations and persistent infections.
Attention, Intention, and Priority in the Parietal Lobe
Authors: James W. Bisley, Michael E. Goldberg
Journal: Annual Review of Neuroscience (2010)

For many years there has been a debate about the role of the parietal lobe in the generation of behavior. Does it generate movement plans (intention) or choose objects in the environment for further processing? To answer this, we focus on the lateral intraparietal area (LIP), an area that has been shown to play independent roles in target selection for saccades and the generation of visual attention. Based on results from a variety of tasks, we propose that LIP acts as a priority map in which objects are represented by activity proportional to their behavioral priority. We present evidence to show that the priority map combines bottom-up inputs like a rapid visual response with an array of top-down signals like a saccade plan. The spatial location representing the peak of the map is used by the oculomotor system to target saccades and by the visual system to guide visual attention.
Effects of insulin on vasoconstriction induced by thromboxane A2 in porcine coronary artery.
Authors: A Yanagisawa-Miwa, H Ito, T Sugimoto
Journal: Circulation (1990)

To elucidate the role of insulin in the control of coronary artery tone, its effects on porcine coronary artery contraction evoked by thromboxane A2 (TXA2) were studied in vitro. Ring preparations of porcine proximal coronary artery were suspended in a Magnus apparatus filled with Tyrode's solution at 37 degrees C and aerated with 100% O2, and the isometric tension of the contractions was measured. Insulin itself caused neither contraction nor relaxation. Insulin had no significant effect on the coronary artery contractions evoked by 20 mM K+, norepinephrine, histamine, and serotonin; however, 120 minutes of preincubation with a physiological concentration of insulin (30-300 muunits/ml) significantly accentuated coronary artery contractions evoked by STA2 (10(-11) to 10(-7) M), a stable analogue of TXA2 that is known to act on TXA2/prostaglandin H2 receptors (141.4 +/- 10.9% of the control at 10(-7) M STA2 in the presence of 300 muunits/ml insulin; p less than 0.01). The enhancing effects of insulin on the STA2-induced contractions were affected by extracellular glucose or magnesium ion concentrations. The enhancing effects of insulin were observed only at the glucose concentrations of 100-300 mg/dl and magnesium concentrations of 0.5-1.5 mM. Therefore, insulin was suspected of enhancing TXA2-induced contraction through a process that depends on extracellular glucose and Mg2+.
Childhood Maltreatment Predicts Unfavorable Course of Illness and Treatment Outcome in Depression: A Meta-Analysis
Authors: Valentina Nanni, Rudolf Uher, Andrea Danese
Journal: American Journal of Psychiatry (2011)

Objectives: Evidence suggests that childhood maltreatment may negatively affect not only the lifetime risk of depression but also clinically relevant measures of depression, such as course of illness and treatment outcome. The authors conducted the first meta-analysis to examine the relationship between childhood maltreatment and these clinically relevant measures of depression. Method: The authors conducted searches in MEDLINE, PsycINFO, and Embase for articles examining the association of childhood maltreatment with course of illness (i.e., recurrence or persistence) and with treatment outcome in depression that appeared in the literature before December 31, 2010. Recurrence was defined in terms of number of depressive episodes. Persistence was defined in terms of duration of current depressive episode. Treatment outcome was defined in terms of either a response (a 50% reduction in depression severity rating from baseline) or remission (a decrease in depression severity below a predefined clinical significance level). Results: A meta-analysis of 16 epidemiological studies (23,544 participants) suggested that childhood maltreatment was associated with an elevated risk of developing recurrent and persistent depressive episodes (odds ratio=2.27, 95% confidence interval [CI]=1.80–2.87). A meta-analysis of 10 clinical trials (3,098 participants) revealed that childhood maltreatment was associated with lack of response or remission during treatment for depression (odds ratio=1.43, 95% CI=1.11–1.83). Meta-regression analyses suggested that the results were not significantly affected by publication bias, choice of outcome measure, inclusion of prevalence or incidence samples, study quality, age of the sample, or lifetime prevalence of depression. Conclusions: Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression.
Differential Expression of Cardiac Titin Isoforms and Modulation of Cellular Stiffness
Authors: O. Cazorla, A. Freiburg, M. Helmes, T. Centner, M. McNabb, Y. Wu, K. Trombitás, S. Labeit, H. Granzier
Journal: Circulation Research (2000)

Abstract —Extension of the I-band segment of titin gives rise to part of the diastolic force of cardiac muscle. Previous studies of human cardiac titin transcripts suggested a series of differential splicing events in the I-band segment of titin leading to the so-called N2A and N2B isoform transcripts. Here we investigated titin expression at the protein level in a wide range of mammalian species. Results indicate that the myocardium coexpresses 2 distinct titin isoforms: a smaller isoform containing the N2B element only (N2B titin) and a larger isoform with both the N2B and N2A elements (N2BA titin). The expression ratio of large N2BA to small N2B titin isoforms was found to vary greatly in different species; eg, in the left ventricle the ratio is ≈0.05 in mouse and ≈1.5 in pig. Differences in the expression ratio were also found between atria and ventricles and between different layers of the ventricular wall. Immunofluorescence experiments with isoform-specific antibodies suggest that coexpression of these isoforms takes place at the single-myocyte level. The diastolic properties of single cardiac myocytes isolated from various species expressing high levels of the small (rat and mouse) or large (pig) titin isoform were studied. On average, pig myocytes are significantly less stiff than mouse and rat myocytes. Gel analysis indicates that this result cannot be explained by varying amounts of titin in mouse and pig myocardium. Rather, low stiffness of pig myocytes can be explained by its high expression level of the large isoform: the longer extensible region of this isoform results in a lower fractional extension for a given sarcomere length and hence a lower force. Implications of our findings to cardiac function are discussed.