Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic and environmental factors and serum hormones, and risk of estrogen receptor-positive breast cancer in pre- and postmenopausal Japanese women

Breast cancer incidence in Japanese women has more than tripled over the past two decades. We have previously shown that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive, HER2-negative subtype. We conducted a case–control study; ER-positive, HER2-negative breast cancer patients who were diagnosed since 2011 and women without disease were recruited. Environmental factors, serum levels of testosterone and 25-hydroxyvitamin D, and common genetic variants reported as predictors of ER-positive breast cancer or found in Asian women were evaluated between patients and controls in pre- and postmenopausal women. To identify important risk predictors, risk prediction models were created by logistic regression models. In premenopausal women, two environmental factors (history of breastfeeding, and history of benign breast disease) and four genetic variants (TOX3-rs3803662, ESR1-rs2046210, 8q24-rs13281615, and SLC4A7-rs4973768) were considered to be risk predictors, whereas three environmental factors (body mass index, history of breastfeeding, and hyperlipidemia), serum levels of testosterone and 25-hydroxyvitamin D, and two genetic variants (TOX3-rs3803662 and ESR1-rs2046210) were identified as risk predictors. Inclusion of common genetic variants and serum hormone measurements as well as environmental factors improved risk assessment models. The decline in the birthrate according to recent changes of lifestyle might be the main cause of the recent notable increase in the incidence of ER-positive breast cancer in Japanese women.
Impact of Treatment Time on Chemoradiotherapy in Locally Advanced Cervical Carcinoma.

BACKGROUND Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco- regional control with a conventional schedule. MATERIALS AND METHODS Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin 40 mg/m2. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7 Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7 Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin 20 mg/m2/day was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months. RESULTS A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were 65±12 and 48±4 days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade≥3 toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome. CONCLUSIONS In the setting of concurrent chemo- radiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.
ALIPHATIC CHLORINATED HYDROCARBONS ALTER THE CONTRACTILE RESPONSES OF TRACHEAL SMOOTH MUSCLE IN PIGLET

Aliphatic chlorinated hydrocarbons (ACHs) are widely used in several industrial processes and are also found in many commercial household products. They are classified as hazardous air pollutants, since ACHs exposure induces respiratory complications including airway hyperactivity. However, the contribution of airway smooth muscle tone to ACH-induced respiratory dysfunction has not been elucidated. Thus, the effects of ACHs such as dichloromethane (DCM), dichloroethane (DCE), and trichloromethane (TCM), on the basal and stimulant-induced contractile responses in piglet tracheal smooth muscle were investigated. ACHs at 100-1000 ppm were found to evoke the basal contraction of tracheal smooth muscle strips. Although DCM, DCE, and TCM enhanced the muscle tone precontracted by KCl, they exerted differential effects on acetylcholine- or histamineinduced muscle contraction. DCE did not alter the muscle tone activated by acetylcholine and histamine. DCM at 1000 ppm enhanced the muscle tension precontracted by acetylcholine but not by histamine. TCM at 30-1000 ppm increased the histamine-induced muscle contraction, but at 1000 ppm relaxed the muscle precontracted by acetylcholine. DCE and TCM at the highest concentration (1000 ppm) provoked a biphasic response with an initial increase in KCl-induced muscle tension followed by a decrease. Furthermore, pretreatment with DCE potentiated the acetylcholine-, histamine-, and KCl-induced muscle contractile responses. Pretreatment with TCM potentiated the histamine-, and KCl-induced response, but DCM only potentiated the KCl-induced response. The results suggest that ACH exposure altering the basal and spasmogen-induced contractile responses might participate in airway impairment with hyperresponsiveness.
Considerations on the measurement of follicular squamous cell carcinoma.

To The Editor: Follicular squamous cell carcinoma (SCC) is a rare variant. It is briefly mentioned in some textbooks of dermatopathology, and Diaz-Cascajo et al published a series of 16 cases in 2004. In the 31st symposium of the International Society of Dermatopathology in Barcelona, Carter et al presented a series of 56 cases emphasizing some of the morphologic features of this variant. Follicular SCC shows the following features as most remarkable: 1. It arises from the pre-existing hair follicles. 2. The interfollicular epidermis is not involved and there is a minimal spread of the tumor beyond the follicular ostium. 3. The tumor totally or partially involves the infundibullum or the sebaceous glands. 4. In some tumors, palisade of the tumoral cells is seen.
Short-term treatment of urinary tract infections with trimethoprim/sulphamethoxazole: a clinical and bacteriological study.

Abstract The clinical effects of treatment with a trimethoprim (TMP)-sulphamethoxazole (SM) combination were studied in 40 patients with urinary tract infection. The indication for treatment was symptoms of urinary tract infection with > 10(5) colonies per ml of urine. The dosage was 160 mg of TMP and 800 mg of SM administered orally twice daily for 10 days. The bacteriological in vitro examination revealed synergic effect of the two agents on 30 out of 55 bacterial strains (55%). Out of 32 strains which were resistant or slightly sensitive to SM, synergy was revealed in 14 instances (44%). Development of resistance to TMP was seen in one case. In 20 patients with non-complicated urinary tract infections, sterile urine was found 3 and 14 days after termination of treatment in 100% and 89%, respectively. In one case there was recurrence, and in one case reinfection occurred. In 20 patients with complicated urinary tract infections, sterile urine was found 3 and 14 days after termination of treatment in 80% and 55%, respectively. In 4 cases infection recurred, and in 5 cases the treatment had no effect. Side effects were seen in 3 patients; one case of exanthem, one of nausea, and one of leucopenia. In one case treatment had to be withdrawn because of exanthem, in another because of nausea.
The Lys469glu/K469E Polymorphism of the Inflammatory Gene Intercellular Adhesion Molecule-1 Lacks any Apparent Role in the Polycystic Ovary Syndrome in Kashmiri Women: A Case Control Study

Background: Polycystic ovary syndrome (PCOS), associated with a state of low grade chronic inflammation, depends on multiple genetic and environmental factors. Elevated levels of inflammatory markers including intercellular adhesion molecule-1 (ICAM-1) have been demonstrated in affected women. Recent evidence indicates a significant linkage between chromosome 19p13 loci and multifactorial diseases that have an inflammatory component. The aim of this study was to assess the possible association of the lys469glu (K469E) polymorphism of the ICAM-1 gene located on chromosome 19p13 with risk of PCOS in Kashmiri women. Material and Methods: The K469E single nucleotide polymorphism (SNP) was analysed with DNA from peripheral blood leukocytes of 220 PCOS cases and 220 age matched non-PCOS healthy controls using PCR-RFLP. Results: Genotypic frequencies in cases were found to be 32 (14.5%) for EE, 98 (44.5%) for KE, and 90 (40.9%) for KK, with 130 (59.1%) for the KE+EE genotypes compared to healthy control values of 29 (13.2%) for EE, 113 (51.4%) for KE, 78 (35. 5%) for KK and 142 (64.5%) for KE+EE combined. The odds ratios for the EE, KE and KE: EE genotypes were 0.95(95% CI= 0.53-1.71)[p= 0.88], 0.75(95% CI= 0.50-1.12)[p =0.168] and 0.79 (95% CI =0.53-1.16) [p = 0.23], no statistically significant differences being found between cases and controls (χ2 =2.07; p=0.35). Conclusion: In conclusion, there was no apparent significant influence of the K469E polymorphism on risk of PCOS, or any clinical or laboratory parameters.
Three years’ experience of focused cardiovascular ultrasound in the peri‐operative period

Ultrasound applications in peri‐operative medicine have become common place in modern anaesthesia practice. Anaesthetists have performed transoesophageal echocardiography in cardiac and selected non‐cardiac surgery for over two decades. We aimed to assess the indications, impact on clinical management and accuracy of focused cardiovascular ultrasound performed by anaesthetists in the peri‐operative period. One hundred and seventy patients over a 3‐year period had a focused transthoracic echocardiogram. Adequate images to answer the clinical question were obtained in 167 out of 170 patients (98%). The undifferentiated systolic murmur was the commonest indication (98 out of 170, 58%). Some degree of aortic stenosis was present in 47 out of 170 (26%) of patients; mitral valve disease (30 out of 170 (18%)) and pulmonary hypertension (25 out of 170 (14%)) were also common. Changes in peri‐operative management occurred in 140 out of 170 (82%) patients and major findings correlated with a formal cardiology transthoracic echocardiogram in 52 out of 57 (92%) patients. Focused cardiovascular ultrasound performed by anaesthetists in the peri‐operative period accurately detects major cardiac pathology and significantly alters peri‐operative management.
Adaptive PID controller based on model predictive control

Model Predictive Control (MPC) is very suitable controller for many industrial applications especially for constrained systems. However, it requires high computation burden. On the other side, PID controller is simple and popular for industrial applications in particular for Single Input Single Output (SISO) systems but it is difficult to be tuned especially for constrained systems. To gain the benefits of the two controllers and reduce their limitations, a hierarchical control structure (two levels) is proposed. The algorithm concept focuses on the adaptation of PID controller parameters (lower level) according to the MPC performance (higher level). The algorithm is tested on two constrained systems; separately excited DC motor as a SISO system and three tank system as Multi Input Multi Output (MIMO) benchmark system.
Widespread Recruitment of Ancient Domain Structures in Modern Enzymes during Metabolic Evolution

Protein domains sometime combine to form multidomain proteins and are acquired or lost in lineages of organisms. These processes are ubiquitous in modern metabolism. To sort out evolutionary patterns of domain recruitment, we developed an algorithm that derives the most plausible ancestry of an enzyme from structural and evolutionary annotations in the MANET database. We applied this algorithm to the analysis of 1,163 enzymes with structural assignments. We then counted the number of enzymes along a time series and analyzed enzyme distribution in organisms belonging to superkingdoms Archaea, Bacteria, and Eukarya. The generated timelines described the evolution of modern metabolic networks and showed an early build-up of metabolic activities associated with metabolism of nucleotides, cofactors, and vitamins, followed by enzymes involved in carbohydrate and amino acid metabolism. More importantly, we find that existing domain structures were pervasively co-opted to perform more modern enzymatic tasks, either singly or in combination with other domains. This occurred differentially in lineages of the superkingdoms as the world diversified and organisms adapted to various environments. Our results highlight the important role of recruitment and domain organization in metabolic evolution.
Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression

Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung pairs, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent down-regulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways, and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and down-regulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell–cell and cell–matrix interactions, was recently shown to be a tumor suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by identifying novel epigenetically deregulated genes potentially involved in lung adenocarcinoma development/progression, and by describing an epigenetic subgroup of lung adenocarcinoma associated with characteristic molecular alterations.
A critical evaluation of the relationship between sustained attentional abilities and hypnotic susceptibility

During hypnosis, highly susceptible individuals report a loss of awareness of their surroundings and a narrowing of their awareness to the events suggested by the hypnotist. These individuals also report more frequent occurrences of deeply involving experiences in daily life. It has been widely theorized that the ability to strongly maintain the focus of attention underlies hypnotic susceptibility (Crawford, 1994). Studies making use of a range of behavioural measures are widely cited as supporting this view. However, lack of replication and uncertainty about the nature of the measures makes interpretation difficult. The present study uses a factor analytic design (n = 182) to explore the structure of the relationship between hypnotic susceptibility, imagery, absorption and a range of behavioural measures said in the hypnosis literature to correlate with susceptibility and to index sustained attentional abilities. If the general claims are correct, similar relationships should be found here. Further, an identifiable sustained attention factor should emerge from the covariance structure, including a substantial loading from susceptibility. These predictions were not supported. Results showed that only absorption correlated significantly with susceptibility. A sustained attention factor did emerge but was independent of the hypnosis absorption factor. Linkages between susceptibility and sustained attention remain undemonstrated.
Nutritional support in intensive care units in England and Wales: a survey.

OBJECTIVE To assess current practice in nutritional support in intensive care units (ICUs) in England and Wales. DESIGN A three-section questionnaire about feeding practice was sent to all adult ICUs in England and Wales; this requested information on nutritional support provided for all patients during a single designated 24-h study period. RESULTS 66% of the questionnaires were completed and returned. 43% of patients received nutritional support. Of these, 46% received only parenteral nutrition, 34% only enteral nutrition, 4% received sip feeds and the remaining 16% received more than one form of feeding. 81% of patients fed by the nasogastric route had a large-bore tube in place. More than 40% of patients were fed parenterally via the central route, of these 54% had a dedicated feeding line. CONCLUSIONS Despite the complications of central venous feeding and the advantages of and developments in enteral feeding these findings suggest there could be further improvement in our provision of nutrition for the critically ill patient.
Effects of exercise of different intensities on the angiogenesis, infarct healing, and function of the left ventricle in postmyocardial infarction rats

BackgroundLifestyle interventions, including physical exercise, are feasible options for the prevention and treatment of cardiovascular diseases. In this study, the effects of exercise of different intensities on the infarct region, function, and angiogenesis of the left ventricle (LV) in postmyocardial infarction (MI) rats were investigated and the levels of vascular endothelial growth factor (VEGF) proteins in the LV and plasma were examined. Materials and methodsMale Sprague–Dawley rats were randomly assigned to six groups. The exercise-trained rats observed a daily 60-min treadmill routine 5 days/weeks for 6 weeks. Different treadmill speeds were used in the high-intensity exercise (HIE), moderate-intensity exercise (MIE), and low-intensity exercise (LIE) groups, whereas the untrained rats remained sedentary (Sed). At 6 weeks, all rats underwent either an acute MI operation or a sham (Sh) MI operation 24 h after their last treadmill exercise or the corresponding Sed protocol. They were then killed 7 days after recovery. Echocardiographic and hemodynamic measurements were taken at the end of the experimental protocol. The infarct regions were analyzed using Masson's trichrome staining, whereas intramyocardial microvessels were detected using Factor VIII-related antigen staining. The cardiac VEGF protein levels were determined by western blotting analysis, and plasma VEGF concentrations were examined by enzyme-linked immunosorbent assay. ResultsCompared with the corresponding parameters in the Sed-Sh group, LV function did not significantly ameliorate and microvessel density did not increase in the MIE-Sh group. Compared with the Sed-MI group, the MIE-MI and HIE-MI groups had significantly reduced LV infarct size, improved hemodynamic parameters, and increased fractional shortening, scar thickness, and microvessel density, these parameters did not significantly change in the LIE-MI group. In addition, the MIE-MI and HIE-MI rats had significant differences in hemodynamic parameters and microvessel density. Compared with those of the Sed-MI group, the heart and plasma of the exercise-trained rats in the MIE-MI and HIE-MI groups displayed higher levels of VEGF protein, but the difference between the MIE-MI and HIE-MI groups was not significant. ConclusionsModerate-intensity running before acute MI improved LV function, reduced scar size, and increased scar thickness and microvessel density in post-MI rats. Exercise at a higher intensity could have further small effects. LIE may be beneficial, but it would not be sufficient to improve MI. Moderate-intensity and high-intensity running upregulated the expression of VEGF protein and increased microvessels, which may have partly improved cardiac function after MI in this study.
Factors associated with sexual arousal, sexual sensation seeking and sexual satisfaction among female African American adolescents.

BACKGROUND Sexuality-related constructs, such as sexual arousal, sexual sensation seeking (SSS) and sexual satisfaction, have been related to sexual behaviours that place one at risk of adverse consequences, such as sexually transmissible infections, HIV and unintended pregnancy. The biopsychosocial model posits an array of factors, ranging from social environmental factors to biological and psychological predispositions, that may be associated with these sexuality constructs in adolescents. METHODS Female African Americans aged 14-20 years were recruited from reproductive health clinics for an HIV intervention. Baseline survey and follow-up DNA data (n=304) were used to assess biological, psychological and social environmental associations with the sexuality constructs of arousal, SSS and sexual satisfaction. RESULTS Multivariate linear regression analysis revealed that a higher depressive symptom rating was associated with higher arousability, whereas short serotonin transporter gene allele(s) status was associated with lower arousability. Impulsivity and perceived peer norms supportive of unsafe sexual behaviours were associated with increased SSS, whereas short serotonin transporter gene allele(s) status was associated with lower SSS. Higher social support was associated with higher levels of sexual satisfaction, whereas short serotonin transporter gene allele(s) status was associated with lower satisfaction. The sexuality constructs were also significantly related to the number of sex partners, the frequency of vaginal sex and the number of unprotected vaginal sex acts in the past 6 months. CONCLUSIONS The findings emphasise the importance of understanding biopsychosocial factors, including the role of serotonin as an indicator of natural variations in sexual inclination and behaviours, that influence sexuality constructs, which, in turn, are associated with sexual behaviours, to allow further refinement of sexual health clinical services and programs and promote the development of healthy sexuality.