Miracle-dz/UniFAR-FTUs huggingface dataset:
The Multifaceted Mast Cell in Inflammatory Bowel Disease

Abstract:Mast cells (MCs) are tissue-resident immune cells that carry out protective roles against pathogens. In disease states, such as inflammatory bowel disease, these granulocytes release a diverse array of mediators that contribute to inflammatory processes. They also participate in wound repair and tissue remodeling. In this review, the composition of MCs and how their phenotypes can be altered during inflammation of the gastrointestinal tract is detailed. Animal and human clinical studies that have implicated the participation of MCs in inflammatory bowel disease are reviewed, including the contribution of the cell's mediators to clinical symptoms, stress-triggered inflammation, and fistula and strictures. Studies that have focused on negating the proinflammatory roles of MCs and their mediators in animal models suggest new targets for therapies for patients with inflammatory bowel disease.
Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects.

BACKGROUND Nausea and vomiting of pregnancy (NVP) occurs in up to 80% of pregnant women, but its association with birth outcomes is not clear. Several medications are used for the treatment of NVP; however, data are limited on their possible associations with birth defects. METHODS Using data from the National Birth Defects Prevention Study (NBDPS)-a multi-site, population-based, case-control study-we examined whether NVP or its treatment was associated with the most common noncardiac defects in the NBDPS (nonsyndromic cleft lip with or without cleft palate [CL/P], cleft palate alone [CP], neural tube defects, and hypospadias) compared with randomly selected nonmalformed live births. RESULTS Among the 4524 cases and 5859 controls included in this study, 67.1% reported first-trimester NVP, and 15.4% of them reported using at least one agent for NVP. Nausea and vomiting of pregnancy was not associated with CP or neural tube defects, but modest risk reductions were observed for CL/P (adjusted odds ratio [aOR] = 0.87; 95% confidence interval [CI], 0.77-0.98) and hypospadias (aOR = 0.84; 95% CI, 0.72-0.98). Regarding treatments for NVP in the first trimester, the following adjusted associations were observed with an increased risk: proton pump inhibitors and hypospadias (aOR = 4.36; 95% CI, 1.21-15.81), steroids and hypospadias (aOR = 2.87; 95% CI, 1.03-7.97), and ondansetron and CP (aOR = 2.37; 95% CI, 1.18-4.76), whereas antacids were associated with a reduced risk for CL/P (aOR = 0.58; 95% CI, 0.38-0.89). CONCLUSIONS NVP was not observed to be associated with an increased risk of birth defects; however, possible risks related to three treatments (i.e., proton pump inhibitors, steroids and ondansetron), which could be chance findings, warrant further investigation.
COMPARISON OF MODERATE-TO-VIGOROUS PHYSICAL ACTIVITY LEVELS BETWEEN PHYSICAL EDUCATION, SCHOOL RECESS AND AFTER-SCHOOL TIME IN SECONDARY SCHOOL STUDENTS: AN ACCELEROMETER-BASED STUDY

Regular physical activity is an important factor of health in youth. Unfortunately, in Chile 85% of adolescents do not achieve the 60 min daily recommendation of moderate-to-vigorous physical activity. Physical education, school recess and after-school time are considered crucial environments for adolescents to meet the recommended moderate-to-vigorous physical activity levels. This study compared the moderateto-vigorous physical activity levels between physical education, school recess and after-school time in Chilean secondary school students, and examined the influence of gender and weight status. A hundred and fifty-six Chilean secondary school students (finally 89 participants were included), aged 13-14 years, were monitored by objective measures of moderate-to-vigorous physical activity during physical education, school recess and after-school time. Results indicated statistically significant differences in moderate-to-vigorous physical activity between contexts (total minutes: After-school time>physical education>school recess; percentage: Physical education>after-school time=school recess, p girls, p<.05). Policy-makers are encouraged to increase the number of physical education classes and teachers to ensure that more physical education class time is spent in moderate-to-vigorous physical activity, especially among girls. The increase in students’ moderate-to-vigorous physical activity levels during school recess and after-school time should also be promoted. Key words: accelerometry, exercise, healthy behavior, public health, adolescence, youth
Front-line erlotinib in unselected patients with advanced NSCLC and poor performance status - the TOPICAL study.

Lung cancer has long been recognized as an extremely heterogeneous disease since its development, in terms of clinical characterizations, prognosis, response and tolerance to treatment, is unique in every patient. Eastern Cooperative Oncology Group performance status (ECOG PS) is the most important predictor of outcome in advanced non-small-cell lung cancer (NSCLC). Patients with PS ≥2 tend to tolerate treatment poorly and have significantly inferior survival compared with patients with PS 0 to 1 (1).
Alterations in Plasma Triglyceride Concentrations Following Two Oral Meals with Different Fat Content in Patients with Type 2 Diabetes Mellitus.

BACKGROUND Enhanced postprandial lipaemia has been reported in patients with obesity, hypertension, metabolic syndrome and type 2 diabetes mellitus (T2DM). We compared 2 oral fat meal tests (LIPOLD: 149g of fat, 56g of carbohydrates and 11.7g of proteins administrated per 2m2 of body surface) and LIPOTEST: 75g of fat, 25g of carbohydrates and 10g of protein with the addition of 15g common sugar) with regard to changes in triglycerides (TGs) as well as other cardiometabolic parameters between baseline and 4 h after the meals. METHODS We studied 21 men [median age (interquartile range; IQR) = 65 (16) years] with well-controlled T2DM [median glycated haemoglobin (HbA1c) (IQR) = 6.6 (0.9) %]. All participants performed the meals with 1 week interval between the 2 meals. RESULTS Median (IQR) TG differences in mg/dl were 86 (100) and 46 (60) for LIPOLD and LIPOTEST meals, respectively, whereas the % differences in TGs were 105 (105) and 48 (55), respectively. The differences (in mg/dl and %) between TGs before ingesting the test meal and after 4h were significant for both LIPOLD and LIPOTEST meals (p = 0.003 for mg/dl differences and p = 0.005 for % differences). Patients who had a positive response to the LIPOLD meal (i.e. TGs > 220 mg/dl at 4 h) also had increased postprandial TGs with LIPOTEST. The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) correlated with TG differences (in mg/dl) following the LIPOLD meal consumption (Spearman's rho = (+) 0.527, p = 0.02). C-peptide correlated with TG differences (in mg/dl) following the LIPOTEST meal consumption (Spearman's rho = (+) 0.538, p = 0.032). There were no differences in TGs and glucose response postprandially in both testing meals according to body mass index (except for TGs between tertile 21.3-24.5 and 25-26.8 kg/m2, p=0.046, in LPOTEST group) and body surface area. CONCLUSION An oral fat tolerance test (OFTT), which contains 75g fat, and represents the everyday habits of Western societies, could provide additional information regarding the postprandial state of the individuals with well-controlled T2DM. The consumption of meals with very high fat content may lead to over diagnosing PPL. TG differences after the consumption of a high fat meal correlated with HOMA-IR. This may be useful to evaluate the role of HOMA-IR in T2DM patients. A standardized the OFTT will help clinicians to better define postprandial TG abnormalities, leading to more appropriate therapeutic options to improve postprandial dysmetabolism.
Hypogonadism and metabolic syndrome

Background: The relationship between metabolic syndrome (MetS), male hypogonadism and their possible interaction in cardiovascular (CV) risk stratification are not completely understood. Aim: We reviewed relationships between testosterone (T) and MetS emphasizing their possible interaction in the pathogenesis of CV diseases. Materials and methods: A systematic search of published evidence was performed using Medline (1969 to January 2011). Results: Cross-sectional data have shown that subjects with MetS have lower levels of total T (TT) (about 3 nmol/l), as hypogonadism is more evident in subjects with than in those without erectile dysfunction (ED) than in those without. Longitudinal evidence shows that low T is allocated with a higher risk of subsequent development of MetS, although the reverse condition is also possible. Which are the factors in MetS responsible for the low T is not completely clarified. In clinical studies, increased waist circumference is the major determinant of MetS-associated hypogonadism. Our experiments in rabbits do not support the idea that visceral fat is the main determinant of MetS-associated male hypogonadism. Only few randomized clinical trials have evaluated the impact of T replacement therapy (TRT) in patients with MetS. Available evidence suggests that TRT decreases visceral fat accumulation and ameliorates insulin sensitivity, whereas androgen deprivation increases abdominal adiposity. Conclusions: The clinical significance of the MetS-associated hypogonadism needs further clarifications. In particular, it has not been completely clarified if low T might be considered a cause or a consequence of MetS. The benefit of TRT in term of the reduction of CV risk needs to be confirmed in larger and longer studies.
Sexual function and depressive symptoms among male North American medical students.

INTRODUCTION The role of sexuality as an association of medical student well-being has not been extensively studied. AIM We explored the relationship between depressive symptoms, sexuality, and sexual dysfunction in male North American medical students. MAIN OUTCOME MEASURE North American medical students were invited to participate in an Internet-based survey. The Center for Epidemiological Studies Depression Scale (CES-D) was utilized to screen for depressive symptoms. METHODS Subjects completed an ethnodemographic survey, a sexuality survey, and instruments for the quantification of anxiety, sexuality, and psychosocial function. Descriptive statistics, odds ratios (ORs), and logistic regression were used to analyze our data. RESULTS There were 844 male subjects with complete data on the CES-D and the Spielberger State-Trait Anxiety Index. Depressive symptoms (CES-D ≥ 16) were present in 37% of respondents and were more common in subjects with greater levels of anxiety. Subjects who were in sexual relationships and/or had frequent sexual activity were less likely to be depressed compared to other subjects. Erectile dysfunction (ED) was associated with significantly greater likelihood of depressive symptoms (OR 2.90 and 9.27 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED, P < 0.01). After adjusting for ethnodemographic and sexual history factors, ED remained significantly positively associated with depressive symptoms (OR 2.87 and 6.59 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED after adjustment, P ≤ 0.01). Inclusion of data related to psychosocial/relationship factors in the multivariate model eliminated the significant association between ED and depressive symptoms (OR 1.59 and 2.29 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED after adjustment with the Self-Esteem and Relationship quality instrument, P > 0.05), suggesting that psychosocial factors were more strongly associated with depressive symptoms than erectile function. CONCLUSION Healthy sexuality and relationships may be protective against depressive symptoms in medical students. Attention to these factors may enhance medical student well-being.
Azoospermia: incidence, and biochemical evaluation of seminal plasma by the differential pH method.

BACKGROUND Recent artificial reproductive technologies (ART) have enabled even azoospermic subjects to take part in "in vitro fertilization" programs. The aim of the present study was: a) to evaluate the incidence of azoospermic male partners of infertile couples; b) to determine whether biochemical evaluation of such azoospermic males can help to discriminate between obstructive and secretory azoospermia. METHODS Semen samples (n. 28,339; period 1990-1997) were analyzed according to WHO guidelines. In addition, in 108 azoospermic subjects, fructose, citric acid and L-carnitine (taken respectively as markers of seminal vesicle, prostate and epididymal function) were assayed using a new, faster technique, the differential pH method. RESULTS The incidence of azoospermic semen samples was 4.76%. The biochemical analyses were indicative diagnostically, especially with regard to obstructive azoospermia. However, in secretory azoospermia, biochemical analysis of seminal plasma did not offer particularly helpful indications, except in cases of hypogonadism. CONCLUSIONS Azoospermia accounts for a relatively high number of cases and justifies detailed attention to the diagnostic and therapeutic approach. Biochemical analysis of the seminal markers is a valid support for differential diagnosis between secretory obstructive azoospermia. It can therefore help in the correct recruitment of such patients for ART programs.
A Fatty Acid Synthase Blockade Induces Tumor Cell-cycle Arrest by Down-regulating Skp2*

In eukaryotes, fatty acid synthase (FAS) is the enzyme responsible for synthesis of palmitate, the precursor of long-chain nonessential fatty acids. FAS is up-regulated in a wide range of cancers and has been suggested as a relevant drug target. Here, two independent approaches are taken toward knocking down FAS and then probing its connection to tumor cell proliferation. In one approach, Orlistat, a drug approved for treating obesity, is used as a potent inhibitor of the thioesterase function of FAS. In a separate strategy, the expression of FAS is suppressed by targeted knock-down with small interfering RNA. In both circumstances, the ablation of FAS activity causes a dramatic down-regulation of Skp2, a component of the E3 ubiquitin ligase that controls the turnover of p27Kip1. These effects ultimately tie into the retinoblastoma protein pathway and lead to a cell-cycle arrest at the G1/S boundary. Altogether, the findings of the study reveal unappreciated links between fatty acid synthase and ubiquitin-dependent proteolysis of cell-cycle regulatory proteins.
Heavy use of acute in‐patient psychiatric services: the challenge to translate a utilization pattern into service provision

Objective: There is an inequality in resource utilization among acute psychiatric in‐patients. About 20–30% of them absorb 60–80% of the total resources allocated to this form of treatment. This study intends to summarize findings related to heavy in‐patient service use and to illustrate them by means of utilization data for acute psychiatric wards.
Risk factors for periodontal

The aim of this study was to identify the risk factors for periodontal disease progression by individual characteristics at baseline among elderly people over a 2-year period. Subjects were selected from 4542 people aged 70years residing in Niigata who were in good general health and who did not require special care for their daily activities. Gender, smoking and alcohol drinking habits were obtained using a questionnaire, while serum levels of disease markers were investigated and attachment levels were clinically recorded. For the assessment of periodontal disease progression, additional attachment loss was used if one or more sites had a 3-mm or more increase in probing attachment level over a 2-year period. In all, 394 subjects (208 males and 186 females) were surveyed. Approximately 75% of subjects exhibited additional attachment loss over a 2-year period. Significant associations were found between additional attachment loss and smoking, and attachment level of 6mm or more at baseline, with odds ratios of 3.75
Smooth estimation of survival functions and hazard ratios from interval‐censored data using Bayesian penalized B‐splines

We discuss the use of Bayesian P‐spline and of the composite link model to estimate survival functions and hazard ratios from interval‐censored data. If one further assumes proportionality of the hazards, the proposed strategy provides a smoothed estimate of the baseline hazard along with estimates of global covariate effects. The frequentist properties of our Bayesian estimators are assessed by an extensive simulation study. We further illustrate the methodology by two examples showing that the proportionality of the hazards might also be found inappropriate from interval‐censored data. Copyright © 2010 John Wiley & Sons, Ltd.
In vitro models of the blood-brain barrier.

In this literature review on in vitro models of the blood-brain barrier (BBB), it is concluded that there is a need to identify a unified in vitro model for the BBB. The best evaluated model at present is based on the use of primary cultures of bovine brain endothelial cells. Primary cell cultures are usually shown to retain several BBB characteristics, but are time-consuming and difficult to establish. To make a unified in vitro model for the BBB more generally available, it is strongly suggested that such a model should be based on the use of an established cell line. To identify the best in vitro model, an evaluation of the most promising immortalised BBB-derived endothelial cell lines, as well as other established cell lines presently used as BBB models, is highly recommended. An evaluation of possible species variation is also important, in order to establish the most relevant species to be used. Furthermore, it is also suggested that the specific properties of in vitro BBB models, as compared to models for the "intestinal barrier", for example, should be evaluated. Finally, it is recommended that an evaluation of available computer models is performed, to further improve early predictions for drug candidates with regard to BBB permeability.
The cellular transfer in humans of delayed cutaneous reactivity to hemolytic streptococci.

In a series of 472 adult patients without apparent streptococcal disease or its complications, the incidence of positive delayed cutaneous reactions was as follows: To intact Streptococcal cells—39% of 67 patients. To SK-SD—69% of 112 patients. To M Substance—36% of 293 patients. Of the total 472 patients, the overall incidence of positive reactions to the streptococcal materials was 45%. It has been possible to transfer passively, in 14 consecutive instances, generalized cutaneous streptococcal reactivity of the delayed tuberculin type to streptococcus-negative human recipients by means of viable leucocytes obtained from streptococcus-positive human donors. This was accomplished with intact streptococcal cells as the test material in 4 instances, with SK-SD as the test material in 6 instances, and with M Substance as the test material in 3 instances. In one instance it was possible to induce delayed cutaneous reactions to intact streptococcal cells, SK-SD and M Substance simultaneously in the same negative recipient. Delayed cutaneous reactions did not develop in the streptococcus-negative recipient when the transferred leucocytes were obtained from streptococcus-negative donors. The endowment of the negative recipient with the capacity to develop generalized delayed cutaneous reactivity to streptococcal materials, following leucocytic transfer, is a transient phenomenon. The results of leucocytic transfer of delayed cutaneous reactivity to hemolytic streptococcal materials in humans generally appear to parallel those reported in humans using tuberculin as the test substance.
Dynamics of Vaginal Bacterial Communities in Women Developing Bacterial Vaginosis, Candidiasis, or No Infection, Analyzed by PCR-Denaturing Gradient Gel Electrophoresis and Real-Time PCR

ABSTRACT The microbial flora of the vagina plays a major role in preventing genital infections, including bacterial vaginosis (BV) and candidiasis (CA). An integrated approach based on PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR was used to study the structure and dynamics of bacterial communities in vaginal fluids of healthy women and patients developing BV and CA. Universal eubacterial primers and Lactobacillus genus-specific primers, both targeted at 16S rRNA genes, were used in DGGE and real-time PCR analysis, respectively. The DGGE profiles revealed that the vaginal flora was dominated by Lactobacillus species under healthy conditions, whereas several potentially pathogenic bacteria were present in the flora of women with BV. Lactobacilli were the predominant bacterial population in the vagina for patients affected by CA, but changes in the composition of Lactobacillus species were observed. Real-time PCR analysis allowed the quantitative estimation of variations in lactobacilli associated with BV and CA diseases. A statistically significant decrease in the relative abundance of lactobacilli was found in vaginal fluids of patients with BV compared to the relative abundance of lactobacilli in the vaginal fluids of healthy women and patients with CA.
Celebrity Contagion and the Value of Objects

Why do people purchase objects that were once owned by celebrities, such as film stars or politicians, and also by despised individuals, such as serial killers and notorious dictators? The present studies examine three potential explanations: mere associations, market demands, and contagion (the belief that these objects contain some remnants of their previous owners). Results indicate that while market demands do play a role, contagion appears to be the critical factor affecting the valuation of celebrity possessions. Manipulating the degree of physical contact that a celebrity has with an object dramatically influences consumers’ willingness to purchase it, and individual differences in sensitivity to contagion moderate this effect. Additionally, the valuation of celebrity possessions is principally explained by measures of contagion, and subliminally activating the concept of contagion changes consumers’ willingness to purchase celebrity objects. Theoretical and practical implications of these findings.
Coupling electrophysiological and hemodynamic responses to errors

Performance errors are associated with distinct electrophysiological and hemodynamic signatures: a fronto‐central error‐related negativity (ERN) is seen in the event‐related potentials and a network of activations including medio‐frontal, parietal, and insular cortex is revealed by functional magnetic resonance imaging. We used simultaneous electroencephalography and functional magnetic resonance imaging (fMRI) to characterize the relationship between the electrophysiological and hemodynamic responses to errors. Participants performed a modified Flanker task. When analyzed independently, we found the ERN and hemodynamic activations in dorsal anterior cingulate cortex, superior frontal gyrus, precentral gyrus, inferior frontal gyrus, and inferior parietal lobule. fMRI‐informed dipole modeling and joint independent component analysis (ICA) were used to couple electrophysiological and hemodynamic data. Both techniques revealed a temporal evolution of the areas found in the fMRI analysis, with the right hemisphere activations peaking before the left hemisphere. However, joint ICA added information, revealing a number of cortical and subcortical areas that had not been shown with parametric mapping. This technique also uncovered how these areas evolve over time. All together, these analyses provide a more detailed picture of the spatiotemporal dynamics of the processing of performance errors. Hum Brain Mapp 33:1621–1633, 2012. © 2011 Wiley Periodicals, Inc.