Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacological Profile of Lurasidone, a Novel Antipsychotic Agent with Potent 5-HT 7 and 5-HT 1A Receptor Activity

Lurasidone ((3a R ,4 S ,7 R ,7a S ,2 R H -isoindole-1,3-dione hydrochloride, SM-13496) is an azapirone derivative, and a novel antipsychotic candidate. The objective of the current studies was to investigate the in vitro and in vivo pharmacological properties of lurasidone. Receptor binding affinities of lurasidone and several antipsychotic drugs were tested under comparable assay conditions using cloned human receptors or membrane fractions prepared from animal tissue. Lurasidone was found to have potent binding affinity for dopamine D 2, 5-HT 2A , 5-HT 7 , 5-HT 1A and noradrenaline α 2C receptors. Affinity for noradrenaline α 1 , α 2A and 5-HT 2C receptors was weak, while affinity for histamine H 1 and muscarinic acetylcholine receptors was negligible. In vitro functional assays demonstrated that lurasidone acts as an antagonist at D 2 and 5-HT 7 receptors and a partial agonist at the 5-HT 1A receptor subtype. Lurasidone showed potent effects predictive of antipsychotic activity such as inhibition of methamphetamine (MAP)-induced hyperactivity and apomorphine (APO)-induced stereotyped behavior in rats, similar to other antipsychotics. Furthermore, lurasidone had only weak extrapyramidal effects in rodent models. In animal models of anxiety disorders and depression, treatment with lurasidone was associated with significant improvement. Lurasidone showed a preferential effect on the frontal cortex (vs. striatum) in increasing dopamine turnover. Anti- α 1 -noradrenergic, anticholinergic and central nervous system (CNS) depressant actions of lurasidone were also very weak. These results demonstrate that lurasidone possesses antipsychotic activity, and antidepressant- or anxiolytic-like effects with potentially reduced liability for extrapyramidal and CNS depressant side effects. the profiles (receptor binding affinities functional the receptor binding affinities, functional activities, behavioral pharmacological characteristics of lurasidone, in various animal models. The current results demonstrate that lurasidone possesses potent antipsychotic, anxiolytic- and antidepressant-like activity, with a low propensity for EPS, motor impairment and CNS depressant side effects. These findings suggest that could improve the symptoms of schizophrenia, especially the positive symptoms, through blocking dopamine D 2 receptors, similar to marketed antipsychotics.
Improvement in quality of life in patients with Fistula-In-Ano, following surgical management, a prospective observational study

Background: Fistula-in-ano may lead to significant worsening of quality of life of affected person. But studies documenting the impact of treatment quality of life are very limited in Indian population. Hence the current study was conducted with an objective of assessing the improvement in quality of life in patients undergoing surgical management of fistuala-in-ano in a tertiary care teaching hospital in south India. Methodology: The current study was a prospective observational study, conducted in the department of general surgery of Dr. SMCSI Medical college hospital, between February and December 2016. A total of 45 subjects aged between 20 to 80 years, suffering from various types of fistual in ano, managed with surgical intervention were included in the study. Quality of life was before and after surgery was assessed by GIQLI questionnaire. Results: Among the 45 subjects, 71.11% were males majority were aged between 41 to 60 years. The proportion of Inter sphincteric fistula was 48.88% whereas Trans-sphincteric fistula and Supra sphincteric fistula were 33.33% and 17.77% respectively. Fistulectomy was conducted in 44.44% of cases. Fistulotomy and insertion of cutting setons were done in 31.11% and 24.44% cases. Mean values of symptoms pre and post-operative were 49.50 and 66.25 and the association was statistically significant (P=<0.01). Mean associated physical disease was 14.25 before surgery and the post - operative mean was 22.76 with a statistically significant mean difference (P=<0.01). Preoperative Mean values for emotions, social integration, and effects of treatment were 7.65, 8.26 and 3.00 respectively, whereas Post-operative means were 15.27, 14.40 and 3.65. There were statistically significant mean differences for Emotions, social integration and effects of treatment. Mean Total score of pre-surgery was 89.05 and post-surgery was 120.26 with a statistically significant mean difference. (P=<0.01). Conclusions: 1) There is a significant improvement in the quality of life postoperatively in patients of Fistula in ano. 2) GIQLI score is a useful tool to assess the quality of life in Fistula in ano patients.
Comparison of Computation Period for Some Newtonian Fluid Flow Problems by Elzaki, Sumudu and Laplace Transform

Newtonian Fluid Flow Problems (NFFPs) of Stokes’ first theorem for suddenly started and suddenly stopped plate are solved by Elzaki Transform Method and the results are identical to those of Laplace Transform and Sumudu Transform. It shows that the said method is very effective due to smaller computation period. The results are verified by graphing the outcome of all the transforms and by calculating their computation period, so that NFFP can be easily solved by Elzaki Transform Method to avoid lengthy calculations.
in Business and Management Studies Revisiting Barriers to External Finance for SMEs

After the Global Financial Crises in 2008, obtaining finance has become more complicated. This study reviews the literature on barriers in accessing external finance given to the importance of availability of finance for all business firms specifically SMEs. Literature over 20 years is searched while reviewing the research question by using Google scholar. Both demand and supply related barriers in accessing external finance has been searched. The study reviewed the factors influencing accessing external finance in the context of developed as well as developing countries with unique conditions and include the issues pre-and post-crises using available literature. The findings of the study discuss the hindrances for SME’s financing mentioned in the literature and highlights the frequently mentioned barriers. Moreover, barriers in accessing external finance in developed and developing countries are different depending upon country environment. It also depends on industry specific effects, firm’s specific effects, and owner’s specific effects. This review provides the problems faced by SME’s in obtaining external finance. Key barriers in accessing finance are also highlighted in the light of available studies. Moreover, it will give further insight to the barriers of small sized firms in developed and developing countries. It has practical value for policy makers while addressing the problem. Future research recommendations will contribute to the literature.
Measurement of Choriogonadotropin Free Choriogonadotropin in Screening for Fetal

it is now unequivocally established that concentrations of human choriogonadotropin (hCG) in maternal serum in cases of fetal Down’s syndrome average about twice that in unaffected pregnancies (1 14). 1 Use of a woman’s hCG concentration at 15-20 weeks’ gestation, in combination with certain other biochemical measurements, can significantly enhance the effectiveness of screening for fetal Down’s syndrome. In this issue, Spencer (15) reports that for Down’s syndrome screening, measurements of the free /3-subunit of hCG may be equivalent to, or possibly better than, other types of hCG measurements-whether evaluated univariately, or in a multivariate risk analysis with maternal serum a-fetoprotein (AFP), unconjugated estriol (uE3), and maternal age. Although the data are not sufficient to sustain a claim of superiority, measurements of free /3-subunit do appear preliminarily to offer an alternative to assays based on intact or total hCG.
Divine Omdasji Sound Meditation – a cure for mental depression, sleep disorders, anxiety, drug addiction and loss of immunity

: This research work is a sustained attempt to scientifically interpret the Meditative Guidance of the Divine Omdasji Sound Meditation (SR0000398348 dated 2006-09-13, United States Copyright Office) renowned to bring peace and calm to the meditating human subject. It is the outcome of inspiration dawned on the authors to scientifically investigate such phenomena connected with the Divine Omdasji Sound Meditation. The Divine Omdasji Sound Meditation has been found to have many properties that Science can explain. accompanied with BioPhotonic Communication, Meditative Consciousness & BioAcoustic Fields and Multiple Phase Locked Loops are used to analyze the Divine Omdasji Sound Meditation. Meditative guidance characteristics for multiple subjects at various levels are exhibited by the inference from the experimental results including a unique phenomenon of guided dual consciousness state awareness in meditation. Further analysis and inference indicates that the Divine Omdasji Sound Meditation can be used as a cure for mental depression, sleep disorders, anxiety, drug addiction and loss of immunity.
PRESCRIBING PATTERN OF ANTIHYPERTENSIVE MEDICATIONS AMONG PHYSICIANS AT KING ABDULAZIZ MEDICAL CITY

: Objective: To investigate the antihypertensive prescribing patterns among physicians at KAMC-R. Methods: After each scheduled clinic, a data collector will check all patients who have a diagnosis of hypertension, and then we will screen the patients for eligibility by checking the patient's chart. All patients who were above 18 years, have been diagnosed with hypertension and are taking at least one antihypertensive agent were included. Results: the study included 632 patients where the frequency of the six antihypertensive drug classes were as follow: CCBs (25.14%), Diuretics (21.36%), ARBs (19.57%), ACE inhibitors (16.29%), b-Blockers (14.71%) and other antihypertensive agents (2.93%). Amlodipine was the most common prescribed drug (23.36%) followed by furosemide (12.64%), lisinopril (12.50%), valsartan (10.14%) and metoprolol (9.71%). Conclusion: The most prescribed antihypertensive class was CCBs, and the most prescribed drug is amlodipine. It was also evident that diabetes is the most common co-morbidity in our patients, but CKD is more common in males, in some instances, physicians didn’t adhere to guidelines.
Spontaneous Thought and Vulnerability to Mood Disorders: The Dark Side of the Wandering Mind

There is increasing interest in spontaneous thought, namely task-unrelated or rest-related mental activity. Spontaneous thought is an umbrella term for processes like mindwandering, involuntary autobiographical memory, and daydreaming, with evidence elucidating adaptive and maladaptive consequences. In this theoretical framework, we propose that, apart from its positive functions, spontaneous thought is a precursor for cognitive vulnerability in individuals who are at-risk for mood disorders. Importantly, spontaneous thought mostly focuses on unattained goals and evaluates the discrepancy between current and desired status (Klinger, 1971, 2013a). In individuals who stably (i.e., trait negative affectivity) or transitorily (i.e., stress) experience negative emotions in reaction to goal-discrepancy, spontaneous thought fosters major cognitive vulnerabilities (e.g., rumination, hopelessness, low self-esteem, and cognitive reactivity) which, in turn, enhance depression. Furthermore, we also highlight preliminary links between spontaneous thought and bipolar disorder. The evidence for this framework is reviewed and we discuss theoretical and clinical implications of our proposal.
Eating Disorder Examination Questionnaire (EDE-Q): Factor structure for adolescent girls and boys.

Objective: To examine the factor structure of the EDE-Q among a sample of adolescents. Method: A community-based sample of 917 adolescents (522 girls and 395 boys) aged 14 to 18 years completed the EDE-Q version 6.0 as part of a larger study. Participants were randomly assigned to one of two subsamples to enable separate analyses. Results: A confirmatory factor analysis on the original four factor model of the EDE-Q produced an inadmissible model with a poor fit. Exploratory factor analysis using principal axis factoring produced an alternative three factor model of the EDE-Q among adolescents. The Shape and Weight Concerns, Restriction and Preoccupation and Eating Concern subscales accounted for 65% of the total variance. Subscale and global scores were significantly higher for girls than for boys. A high proportion of both girls (53.6%) and boys (30.5%) reported participating in at least one key eating disordered behaviour during the previous 28 days. Discussion: The results of this study present three new subscales ( Shape and Weight Concerns, Restriction and Preoccupation and Eating Concern ) which are suggested for use in future research which uses the EDE-Q with community samples of adolescents.
Bridge performance indicators based on traffic load monitoring

Abstract The assessment of the existing road bridges as a part of bridge management networks has been a subject of several European research projects and actions in the last few decades. Bridge management includes a series of activities, interconnected in order to achieve optimal balancing of required costs, potential risks and overall bridge performance. This paper discusses a valuable link between a specific indicator (traffic load information calculated using Bridge Weigh-in-Motion measurement data) and the corresponding structural performance (reliability of existing bridge). It is shown that implementation of weigh-in-motion measurements in the probabilistic assessment of existing road bridges can reveal hidden bridge reserves and predict bridge reliability development over the required lifetime. Consequently, such approach can yield an unrestricted use of the bridge over a much longer remaining service life. Broader advantages lie in an improved road network management, road bridges in particular, and in a more sustainable development of infrastructure network and greater satisfaction of road users and owners.
University of Birmingham Lexical variation and change in British Sign Language

This paper presents results from a corpus-based study investigating lexical variation in BSL. An earlier study investigating variation in BSL numeral signs found that younger signers were using a decreasing variety of regionally distinct variants, suggesting that levelling may be taking place. Here, we report findings from a larger investigation looking at regional lexical variants for colours, countries, numbers and UK placenames elicited as part of the BSL Corpus Project. Age, school location and language background were significant predictors of lexical variation, with younger signers using a more levelled variety. This change appears to be happening faster in particular sub-groups of the deaf community (e.g., signers from hearing families). Also, we find that for the names of some UK cities, signers from outside the region use a different sign than those who live in the region. and RES-620-28-0002: Deafness Cognition and Language Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Localization and mRNA expression of CY3A and P-gp in human duodenum as a function of age

Cytochromes P450 3A (CYP3A) and P-glycoprotein (P-gp) are mainly located in enterocytes and hepatocytes. The CYP3A/P-gp system contributes to the first pass metabolism of many drugs, resulting in a limited bioavailability. During the neonatal period, a shift between CYP3A7, the fetal form, and CYP3A4 occurs in the liver but data on the expression of the CYP3A/P-gp complex in the intestine are very limited. 59 normal duodenal biopsies from Caucasian children aged 1 month to 17 years were studied. Localization of the proteins by immunohistochemistry analysis was performed using a polyclonal antibody “Nuage” anti-CYP3A and a monoclonal antibody “C494” anti-P-gp. The mRNA quantification was performed using highly specific real time RT-PCR. Villin mRNA quantification was used for normalization. CYP3A protein was detected in all enterocytes in the samples from patients over 6 months of age while it was not in younger samples. P-gp protein was expressed at the apical and upper lateral surfaces of the enterocytes. CYP3A isoforms and P-gp mRNA levels were highly variable. CYP3A4 and CYP3A5 mRNA levels were high during the first year of life and decreased with age while CYP3A7 was detected at a low level in 64% of samples, whatever the age. P-gp mRNA expression level was also highly variable. Our results showed that neonates and infants had a significant expression of CYP3A and P-gp mRNA in the intestine, suggesting a different maturation profile of CYP3A and P-gp with age in the liver and the intestine. Abstract presentation: this work was presented as an abstract: “Ontogeny of cytochrome 3A and P-glycoprotein in the human intestine” in Clinical Pharmacology & Therapeutics, Volume 75, Issue 2, February 2004, Page P50 following its acceptance as a poster at the 2004 annual meeting of the American Society of Clinical Pharmacology and Therapeutics.
Zebra Fish as a Cancer Model

The zebra fish has developed into an important model organism in biomedical research over the last two decades. Although the main focus of zebra fish research has habitually been on developmental biology, observing zebra fish in the lab led to the identification of diseases similar to humans, such as cancer, which subsequently became a subject for study. As a result, about more than 50 articles have been published since 2000 in which zebra fish were used as a cancer model. Strategies used include carcinogenic treatments, transplantation of mammalian cancer cells, forward genetic screens for proliferation or genomic instability, reverse genetic target-selected mutagenesis to inactivate known tumor suppressor genes, and the generation of transgenics to express human oncogenes. Zebra fish found to develop almost all type of tumor known from human, with similar morphology and, accordance to gene expression array studies, equivalent signaling pathways. However, tumor incidences were found to be relatively low, although highly comparable between different mutants, and tumors develop late in life. In addition, tumor spectra are sometimes different when compared with mice and humans. However, the zebra fish model has created its own slot in cancer research, complementing existing models with its specific experimental advantages and characteristics. Examples of these are imaging of tumor progression in living fish by fluorescence, treatment with chemical compounds, and screening possibilities not only for chemical modifiers but also for genetic enhancers and suppressors. This review aims to provide a comprehensive overview of the state of the art of zebra fish as a model in cancer research.
Acute lymphoblastic leukemia The NUP 98-HOXD 13 fusion oncogene induces thymocyte self-renewal via Lmo 2 / Lyl 1

T cell acute lymphoblastic leukaemia (T-ALL) cases include subfamilies that overexpress the TAL1/LMO, TLX1/3 and HOXA transcription factor oncogenes. While it has been shown that TAL1/LMO transcription factors induce self-renewal of thymocytes, whether this is true for other transcription factor oncogenes is unknown. To address this, we have studied NUP98-HOXD13-transgenic (NHD13-Tg) mice, which overexpress HOXA transcription factors throughout haematopoiesis and develop both myelodysplastic syndrome (MDS) progressing to acute myeloid leukaemia (AML) as well as T-ALL. We find that thymocytes from preleukaemic NHD13-Tg mice can serially transplant, demonstrating that they have self-renewal capacity. Transcriptome analysis shows that NHD13-Tg thymocytes exhibit a stem cell-like transcriptional programme closely resembling that induced by Lmo2, including Lmo2 itself and its critical cofactor Lyl1. To determine whether Lmo2/Lyl1 are required for NHD13-induced thymocyte self-renewal, NHD13-Tg mice were crossed with Lyl1 knockout mice. This showed that Lyl1 is essential for expression of the stem cell-like gene expression programme in thymocytes and self-renewal. Surprisingly however, NHD13 transgenic mice lacking Lyl1 showed accelerated T-ALL and absence of transformation to AML, associated with a loss of multipotent progenitors in the bone marrow. Thus multiple T cell oncogenes induce thymocyte self-renewal via Lmo2/Lyl1; however, NHD13 can also promote T-ALL via an alternative pathway.
Admission Gatekeeping and Safe Discharge for the Elderly: Referral by the Emergency Department to the Community Nursing Service for Home Visits

Objective To assess the gatekeeping effect and discharge safety in elderly referrals to the community nursing service (CNS) in a major accident & emergency department (AED). Methods Descriptive review analysis of the referrals in 2002–2004. Results Altogether 333 patients were accepted, comprising 5% of the total CNS referrals in the hospital: 323 were aged ≥65 (median age 81), 13.8% were living alone, 21.6% had unscheduled return to the AED within 14 days, and 11.7% in 15–28 days. The ≤14 days and 15–28 days admission to hospital was 15.0% and 6.0%, with 4.8% and 0.6% patients admitted with the same or related diagnosis as the first visit respectively, including missed fractures and stroke. One patient died 17 days after discharge. Eight of the 162 falls returned within 28 days with a second fall. Overall, 317 admissions were avoided with 1,978 bed-days saved. Living alone was strongly associated with unscheduled return and admission ≤14 and ≤28 days, while age was not. The six categories of community nursing care were fall-related, tube care, skin and soft tissue care, pain control, medical and diabetic care. Injections were given for cellulitis, pain, and diabetics. Forty-nine patients had phone follow-ups. Conclusion The gatekeeping effect of AED referrals to CNS remained small. The commonest referrals were falls with head injury. It was safe to discharge the elderly for CNS care. A wide range of home nursing care was feasible. CNS referral could decrease elderly return visits with falls. Living alone was strongly associated with return visit and admission.
H∞ control system design attenuating initial state uncertainties: evaluation by a magnetic suspension system

This paper deals with an H1 control attenuating initial-state uncertainties, and its application to a magnetic suspension system. An H1 control problem, which treats a mixed attenuation of disturbance and initial-state uncertainty for linear time-invariant systems in the in(cid:12)nite-horizon case, is examined. The mixed attenuation supplies H1 controls with good transients or assures H1 controls of robustness against initial-state uncertainty. We apply this method to a magnetic suspension system, and evaluate attenuation property of the proposed disturbance and initial-state uncertainty via simulations and experiments.
Eleventh International Foamy Virus Conference 2016 Meeting Report

: The Eleventh International Foamy Virus Conference took place on 9–10 June 2016 at the Institut Pasteur, Paris, France. The meeting reviewed progress on foamy virus (FV) research, as well as related current topics in retrovirology. FVs are complex retroviruses that are widespread in several animal species. Several research topics on these viruses are relevant to human health: cross-species transmission and viral emergence, vectors for gene therapy, development of antiretroviral drugs, retroviral evolution and its inﬂuence on the human genome. In this article, we review the conference presentations on these viruses and highlight the major questions to be answered.