Miracle-dz/UniFAR-FTUs huggingface dataset:
Steroid Endocrinology after the Menopause: A Review 1

The menopause is defined as the last menstrual period in a woman's life. It is the inevitable consequence of the natural rate of atresia of ovarian follicles. Because in premenopausal women 95% of circulating oestradiol-171B is secreted by these follicles, the menopause is associated with a reduction of oestrogen secretion. Measurement of oestrogens by biological techniques showed, many years ago, that blood levels in postmenopausal and castrate women were lower than in preimenopausal women. However, even 40 years ago it was realized that oestrogens were not always undetectable in postmenopausal women (Fluhmann 1936). The development of biochemical methods of measurement made it possible to investigate extraovarian sources of steroids after the menopause. Direct secretion of oestrogens by the adrenal gland had been inferred by Brown et al. (1959) after noting premenopausal levels of urinary oestrogens in an ovariectomized woman who had been treated with corticotrophin (ACTH). Direct ovarian and adrenal secretion of steroids after the menopause has since been studied by determining hormone concentrations in the blood draining these glands. Although this method of collection of blood samples itself may disturb glandular secretion, the studies reported have suggested that neither the adrenal cortex nor the ovarian stroma makes a significant direct contribution to circulating oestrogens after the menopause (Baird, Uno & Melby 1969, Judd et al. 1974). Extraglandular production of oestrogens through aromatization of androgens was first recognized in humans by West et al. (1956), who identified oestrone and oestradiol in the urine of 2 adrenalectomized, ovariectomized women after injections of testosterone propionate. The subsequent development ofisotopic techniques has allowed this aspect ofsteroid endocrinology to be studied in greater detail. The peripheral pathways of conversion and interconversion of androgen and oestrogens suggested by the isotopic studies of Baird, Horton et al. (1969) are as follows: Androstenedione Oestrone
A non-canonical DNA structure is a binding motif for the transcription factor SP1 in vitro

SP1 is a ubiquitous transcription factor that is involved in the regulation of various house-keeping genes. It is known that it acts by binding to a double-stranded consensus motif. Here, we have discovered that SP1 binds also to a non-canonical DNA structure, a G-quadruplex, with high affinity. In particular, we have studied the SP1 binding site within the promoter region of the c-KIT oncogene and found that this site can fold into an anti-parallel two-tetrad G-quadruplex. SP1 pull-down experiments from cellular extracts, together with biophysical binding assays revealed that SP1 has a comparable binding affinity for this G-quadruplex structure and the canonical SP1 duplex sequence. Using SP1 ChIP-on-chip data sets, we have also found that 87% of SP1 binding sites overlap with G-quadruplex forming sequences. Furthermore, while many of these immuoprecipitated sequences (36%) even lack the minimal SP1 consensus motif, 5′-GGGCGG-3′, we have shown that 77% of them are putative G-quadruplexes. Collectively, these data suggest that SP1 is able to bind both, canonical SP1 duplex DNA as well as G-quadruplex structures in vitro and we hypothesize that both types of interactions may occur in cells.
Role of Extracellular Vesicles in Hematological Malignancies

In recent years the role of tumor microenvironment in the progression of hematological malignancies has been widely recognized. Recent studies have focused on how cancer cells communicate within the microenvironment. Among several factors (cytokines, growth factors, and ECM molecules), a key role has been attributed to extracellular vesicles (EV), released from different cell types. EV (microvesicles and exosomes) may affect stroma remodeling, host cell functions, and tumor angiogenesis by inducing gene expression modulation in target cells, thus promoting cancer progression and metastasis. Microvesicles and exosomes can be recovered from the blood and other body fluids of cancer patients and contain and deliver genetic and proteomic contents that reflect the cell of origin, thus constituting a source of new predictive biomarkers involved in cancer development and serving as possible targets for therapies. Moreover, due to their specific cell-tropism and bioavailability, EV can be considered natural vehicles suitable for drug delivery. Here we will discuss the recent advances in the field of EV as actors in hematological cancer progression, pointing out the role of these vesicles in the tumor-host interplay and in their use as biomarkers for hematological malignancies.
Triangle factors of graphs without large independent sets and of weighted graphs

The classical Corrádi‐Hajnal theorem claims that every n‐vertex graph G with δ(G)≥2n/3 contains a triangle factor, when 3|n . In this paper we present two related results that both use the absorbing technique of Rödl, Ruciński and Szemerédi. Our main result determines the minimum degree condition necessary to guarantee a triangle factor in graphs with sublinear independence number. In particular, we show that if G is an n‐vertex graph with α(G)=o(n) and δ(G)≥(1/2+o(1))n , then G has a triangle factor and this is asymptotically best possible. Furthermore, it is shown for every r that if every linear size vertex set of a graph G spans quadratically many edges, and δ(G)≥(1/2+o(1))n , then G has a Kr‐factor for n sufficiently large. We also propose many related open problems whose solutions could show a relationship with Ramsey‐Turán theory.
EXPERIMENTAL-COMPUTATIONAL ANALYSIS OF VIGILANCE DYNAMICS FOR APPLICATIONS IN SLEEP AND EPILEPSY

Clinical sleep scoring involves tedious visual review of overnight polysomnograms by a human expert. Many attempts have been made to automate the process by training computer algorithms such as support vector machines and hidden Markov models (HMMs) to replicate human scoring. Such supervised classifiers are typically trained on scored data and then validated on scored out-of-sample data. Here we describe a methodology based on HMMs for scoring an overnight sleep recording without the benefit of a trained initial model. The number of states in the data is not known a priori and is optimized using a Bayes information criterion. When tested on a 22-subject database, this unsupervised classifier agreed well with human scores (mean of Cohen's kappa > 0.7). The HMM also outperformed other unsupervised classifiers (Gaussian mixture models, k-means, and linkage trees), that are capable of naive classification but do not model dynamics, by a significant margin (p < 0.05).
A MULTICENTRE STUDY OF THE SAFETY AND EFFICACY OF AMLODIPINE IN MILD TO MODERATE HYPERTENSION

SUMMARY An open, non‐comparative study of 10 weeks' duration was conducted in general practice to assess the safety of amlodipine in patients with mild to moderate hypertension. Of the 5352 patients entering the study, 5135 received amlodipine; 4621 patients (90%) with a mean age of 58.2 years completed the study. Normalisation of blood pressure was achieved in over 80% of patients with a mean reduction of 21/15 mmHg. The mean final dose of amlodipine was 6.8 mg/day. Adverse experiences possibly related to amlodipine were reported by 19.3% of patients, and overall adverse events led to withdrawal in 6.7% of patients. The most common reported side‐effect was oedema. The frequency of headache was almost identical in older and younger patients and oedema, flushing and dizziness were seen only slightly more often in elderly patients. Ninety per cent of patients were considered by their GP to have shown excellent or good toleration of therapy. Over 85% of patients elected to continue on amlodipine therapy after completion of the study.
Relationships of self-efficacy beliefs to executive functions, hyperactivity-impulsivity and inattention in school-aged children

Abstract Executive function deficits, hyperactivity-impulsivity, and inattention can have a negative impact on a child’s self-efficacy beliefs. Forty-eight children with high intensity ADHD symptoms and 56 children with low intensity symptoms in ages 8 to 10 years completed the Self-Efficacy Scale for Children and executive function tests. Rating Scales for Teachers and Parents were completed for each child to measure the ADHD symptoms. ADHD symptoms and executive function deficits were associated with lower self-efficacy beliefs especially in two spheres: academic achievement and self-control. Implications of these findings for child therapy are discussed.
Qualitative Marketing Research

PART ONE: SOCIAL SCIENCE RESEARCH AND MARKETING Philosophy of Research Scope of Research in Marketing Design of a Research Problem Academic, Business and Practitioner Research PART TWO: QUALITATIVE RESEARCH METHODOLOGIES Justification of a Qualitative Research Methodology In-Depth Interviewing Case-Based Research Focus Group Interviewing Observation Studies Ethnography and Grounded Theory Action Research and Action Learning PART THREE: APPLICATIONS AND OUTCOMES OF QUALITATIVE RESEARCH Organizing, Processing and Visualizing Data Writing Qualitative Research Reports Integrative Multiple Mixes of Methodologies Qualitative Research Future Evolution
Remifentanil for procedural sedation: a systematic review of the literature

Objective We sought to determine the performance characteristics of remifentanil as an agent of procedural sedation and analgesia (PSA) for adult and paediatric patients undergoing procedures similar to those executed in the ED. Methods We systematically reviewed electronically published literature, grey literature, conference proceedings and trial registries from 1946 to 2015. Outcome measures included PSA effectiveness, recovery time, patient safety and resource management. We performed narrative summary analyses. Heterogeneity among selected studies precluded meta-analysis. Results We found 1525 citations, reviewed 34 full manuscripts (kappa=0.64) and included 10 studies (kappa=0.71). Seven were randomised controlled trials and three studies took place in the ED. Included procedures were lumbar puncture (80), cardioversion (66), orthopaedic manipulation (63), incision and drainage (15), thoracostomy (8) and nasal packing (2). There was extensive variation in remifentanil dosing (0.15– 1.5 μg/kg), administration protocols and use of additional PSA drugs. All studies noted superior or equivalent sedation effectiveness compared withcontrols. Several studies, including all those performed in the ED, noted faster procedure completion or patient recovery with remifentanil compared with control groups. The most commonly reported adverse event was respiratory depression, especially in paediatric patients. All studies were found to carry significant risk of bias. Conclusions There is currently a lack of high-quality data on the use of remifentanil in the ED. Physicians should exert caution when using remifentanil in the absence of published standardised dosing protocols in light of frequently reported paediatric respiratory depression. However, PSA efficacy combined with faster recovery times merit ongoing investigations into its use.
Treatment of elderly advanced gastric cancer patients with 5-fluorouracil and leucovorin combination.

In September 1987 a phase II study was begun to verify if elderly symptomatic patients affected by advanced gastric cancer could benefit from a combination of 5-fluorouracil (5FU) and leucovorin (LV). We employed Machover's regimen: 5FU 370 mg/m2 i.v. infusion daily for 5 days; LV 200 mg/m2 i.v. bolus daily for 5 days; cycles were repeated every 3 weeks. 23 patients entered the study and 22 were evaluable for response and toxicity. We obtained only one partial response; 9 had stable disease and 12 progressed on therapy. The median duration of survival was 6 months. Symptoms were not affected by treatment. These data reflect the absence of significant improvement in the quality of life, which was further lessened by the presence of treatment side effects. Because of this we think that this regimen cannot be recommended for the treatment of elderly advanced gastric cancer patients.
Difficulties in Emotion Regulation and Mindfulness in Psychological and Somatic Symptoms of Functional Gastrointestinal Disorders

Background: Negative emotions are the best predictors for psychological and physical health. Objectives: We aimed to investigate the role of difficulties in emotion regulation and mindfulness on psychological and somatic symptoms of patients with functional gastrointestinal disorders (FGID). Patients and Methods: In this cross-sectional study, the studied sample was selected using census method. A total of 167 patients with FGID completed a demographic questionnaire, difficulties in emotion regulation scale (DERS), mindful attention awareness scale (MAAS), depression, anxiety and stress scale (DASS), and gastrointestinal symptom rating scale (GSRS). To examine the relationship between studied variables, Pearson correlation coefficients and multiple regression analyses were used. Results: The findings of the study indicate that difficulties in emotion regulation and mindfulness are significantly correlated to both increased psychological and somatic symptoms. Some factors of difficulties in emotion regulation positively predicted those symptoms. Among these factors, only lack of awareness was not significantly correlated with both symptoms as well as decreased mindfulness. Conclusions: The findings suggest some potential targets to reduce symptoms. Patients with FGID may benefit from treatments that facilitate emotional experience, functional status, and ability to control impulsive behaviors and behave according to the goals when experiencing negative emotions.
‘Not just right experience’ (NJRE) in obsessive-compulsive disorder: Is NJRE a manifestation of autistic traits?

Aims: Harm avoidance (HA) and ‘not just right experience’ (NJRE) have been proposed to be two core motivational processes underlying obsessive-compulsive disorder (OCD). This study was interested in exploring the less well understood construct NJRE in OCD. The study hypothesized that NJRE demarcates a neurodevelopmental OCD subgroup distinct from HA related to autistic traits and/or to a broader phenotype of cognitive rigidity and sensory processing difficulties. In addition, it was hypothesized that NJRE would be associated with an earlier age of OCD onset. It was also predicted that HA, unlike NJRE, would be related to responsibility attitudes, which are characteristic of the traditional cognitive behavioural understanding of OCD. Method: The constructs of NJRE and HA were assessed in an outpatient OCD sample (N=25). A correlational design investigated whether NJRE and HA are distinct entities in OCD and explored their relationships to a range of variables including ASD traits, sensory processing, set-shifting, age of OCD onset, and responsibility attitudes. Results: NJRE was found to be only moderately (r=.34) correlated to HA. Significance was not established in this study. Consistent with predictions, NJRE was associated with sensory processing difficulties and an earlier age of OCD onset, but was not related to responsibility beliefs. No significant relationships were found between NRJE and ASD traits or set-shifting difficulties. Conclusions: There was a lack of evidence demonstrating NJRE as a manifestation of autistic traits. However, NJRE was associated with sensory abnormalities and early onset of OCD, suggesting it may be a marker for difficulties of developmental origin. The role of NJRE as a developmental, and possibly neurodevelopmental, risk factor for OCD warrants further investigation.
Continuous regression testing for component resource utilization

Unintended changes in the utilization of resources like CPU and memory can lead to severe problems for the operation of robotics and intelligent systems. Still, systematic testing for such performance regressions has largely been ignored in this domain. We present a method to specify and execute performance tests for individual components of component-based robotics systems based on their component interfaces. The method includes an automatic analysis of each component revision against previous ones that reports potential changes to the resource usage characteristics. This informs developers about the impact of their changes. We describe the design of the framework and present evaluation results for the automatic detection of performance changes based on tests for a variety of robotics components.
Multimodal Molecular Imaging of Integrin αvβ3 for In Vivo Detection of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable or metastasized tumors emphasizes the need for novel imaging approaches. Here, we report on so far nonexploited potentials of αvβ3 integrin–targeted molecular imaging technologies for detection of PDAC using genetically engineered mouse models. Methods: Immunohistochemistry and Western blot were used for characterization of αvβ3 expression in murine and human PDAC. We applied IntegriSense 680 fluorescence molecular tomography, intraoperative fluorescence imaging, and 68Ga-NODAGA-RGD PET for αvβ3 integrin molecular in vivo imaging of spontaneous PDAC occurring in Ptf1a+/Cre;Kras+/LSL-G12D;p53LoxP/LoxP mice. (NODAGA is 1,4,7-triazacyclononane-1,4-bis[acetic acid]-7-[2-glutaric acid] and RGD is arginine-glycine-aspartic acid.) Results: αvβ3 integrin is expressed in tumor cells of human and murine PDAC. IntegriSense fluorescence molecular tomography and 68Ga-NODAGA-RGD PET enabled faithful visualization of PDAC. Furthermore, intraoperative optical imaging with IntegriSense 680 allowed good delineation of tumor borders. Conclusion: Imaging approaches targeting αvβ3 integrin expand the potential of molecular imaging for identification of αvβ3-positive PDAC with potential implications in early detection, fluorescence-guided surgery, and therapy monitoring.
Safer Wards: reducing violence on older people's mental health wards

Abstract Through the Safer Wards project we aimed to reduce the number of incidents of physical violence on older people’s mental health wards. This was done using quality improvement methods and supported by the Trust’s extensive programme of quality improvement, including training provided by the Institute for Healthcare Improvement. Violence can be an indicator of unmet needs in this patient population, with a negative effect on patient care and staff morale. Reducing harm to patients and staff is a strategic aim of our Trust. We established a multi-disciplinary group who led on the project on each ward and used a Pareto diagram to establish the focus of our work. We established a dashboard of measures based on our incident reporting system Datix, including number of incidents of violence, days between incidents, days of staff sickness, days between staff injury, use of restraint, and use of rapid tranquilisation (the last two being balancing measures in the reduction of violence). Each team identified factors driving physical violence on the wards, under headings of unmet patient needs, staff needs and staff awareness, which included lack of activity and a safe and therapeutic environment. Using driver diagrams, we identified change ideas that included hourly rounding (proactive checks on patient well-being), the addition of sensory rooms, flexible leave for patients, and a structured activity programme. We also introduced exercise to music, therapeutic groups led by patients, and focused on discharge planning and pet therapy, each of which starting sequentially over the course of a one year period from late 2013 and subject to a cycle of iterative learning using PDSA methods. The specific aim was a 20% decrease in violent incidents on three wards in City and Hackney, and Newham. Following our interventions, days between violent incidents increased from an average of three to an average of six. Days between staff injury due to physical violence rose from an average of eight (one violent incident resulting in staff injury every eight days) to 22 (one incident every 22 days). Incidents of physical violence reduced from 63 in 2013 to 39 in 2014. We were also able to quantify reduced costs associated with reduction in violence. The success of this project in our view lay in the involvement of ward staff in understanding the problems and generating local solutions which were also broadly evidenced based. Patients were also closely involved in generating ideas. We are currently incorporating much of this work into routine practice in order to sustain improvement, as well as continuing to generate new ideas for further improvement while using the skills learnt in this process to address other problems.
A Randomized Controlled Study of Neurofeedback for Chronic PTSD

Introduction Brain/Computer Interaction (BCI) devices are designed to alter neural signals and, thereby, mental activity. This study was a randomized, waitlist (TAU) controlled trial of a BCI, EEG neurofeedback training (NF), in patients with chronic PTSD to explore the capacity of NF to reduce PTSD symptoms and increase affect regulation capacities. Study Design 52 individuals with chronic PTSD were randomized to either NF (n = 28) or waitlist (WL) (n = 24). They completed four evaluations, at baseline (T1), after week 6 (T2), at post-treatment (T3), and at one month follow up (T4). Assessment measures were:1. Traumatic Events Screening Inventory (T1); 2. the Clinician Administered PTSD Scale (CAPS; T1, T3, T4); 3. the Davidson Trauma Scale (DTS; T1-T4) and 4. the Inventory of Altered Self-Capacities (IASC; T1-T4). NF training occurred two times per week for 12 weeks and involved a sequential placement with T4 as the active site, P4 as the reference site. Results Participants had experienced an average of 9.29 (SD = 2.90) different traumatic events. Post-treatment a significantly smaller proportion of NF (6/22, 27.3%) met criteria for PTSD than the WL condition (15/22, 68.2%), χ2 (n = 44, df = 1) = 7.38, p = . 007. There was a significant treatment condition x time interaction (b = -10.45, t = -5.10, p< .001). Measures of tension reduction activities, affect dysregulation, and affect instability exhibited a significant Time x Condition interaction. The effect sizes of NF (d = -2.33 within, d = - 1.71 between groups) are comparable to those reported for the most effective evidence based treatments for PTSD. Discussion Compared with the control group NF produced significant PTSD symptom improvement in individuals with chronic PTSD, as well as in affect regulation capacities. NF deserves further investigation for its potential to ameliorate PTSD and to improve affect regulation, and to clarify its mechanisms of action.
The Effect of Theory Based Nutritional Education on Fat Intake, Weight and Blood Lipids

Introduction Though Nutrition plays a key role in the control of hypertension, it is often forgotten in Iranian patients’ diet. In fact, dietary behavior can be regarded as unsatisfactory among Iranian patients. This study was aimed to assess the effectiveness of theory based educational intervention on fat intake, weight, and blood lipids among rural hypertensive patients. Methods This quasi experimental study was conducted on 138 hypertensive patients who had referred to Ardabil rural health centers during 2014. The nutritional education based on DASH and Health Promotion Model (HPM) was treated for six sessions. The pre-test and post-test had intervals of two and six months. Data were analyzed using SPSS-18 and Chi-square, independent-samples t-test, paired-samples t-test and repeated measure ANOVA. Results After treating intervention, weight, dietary fat, LDL_C and Total cholesterol, systolic and diastolic blood pressures decreased significantly in the intervention group compared with the control group (p < 0.001). In contrast, HDL_C increased significantly in the intervention group. Conclusion Educational intervention, provided based on Pender’s health promotion model, affecting fat intake, blood lipids, and blood pressure, led to their decrease