Miracle-dz/UniFAR-FTUs huggingface dataset:
Hydrogen Sulfide Represses Androgen Receptor Transactivation by Targeting at the Second Zinc Finger Module*

Background: Androgen receptor (AR) signaling is indispensable for the development of castration-resistant prostate cancer. Results: Hydrogen sulfide (H2S) inhibits AR transactivation, and the expression of cystathionine γ-lyase (CSE) and H2S production in antiandrogen-resistant prostate cancer cells is lower. Conclusion: Lower level of H2S contributes to antiandrogen-resistant status in prostate cancer cells. Significance: CSE/H2S system can serve as a valuable prognosis indicator for treatment of prostate cancer. Androgen receptor (AR) signaling is indispensable for the development of prostate cancer from the initial androgen-dependent state to a later aggressive androgen-resistant state. This study examined the role of hydrogen sulfide (H2S), a novel gasotransmitter, in the regulation of AR signaling as well as its mediation in androgen-independent cell growth in prostate cancer cells. Here we found that H2S inhibits cell proliferation of both androgen-dependent (LNCaP) and antiandrogen-resistant prostate cancer cells (LNCaP-B), with more significance on the latter, which was established by long term treatment of parental LNCaP cells with bicalutamide. The expression of cystathionine γ-lyase (CSE), a major H2S-producing enzyme in prostate tissue, was reduced in both human prostate cancer tissues and LNCaP-B cells. LNCaP-B cells were resistant to bicalutamide-induced cell growth inhibition, and CSE overexpression could rebuild the sensitivity of LNCaP-B cells to bicalutamide. H2S significantly repressed the expression of prostate-specific antigen (PSA) and TMPRSS2, two AR-targeted genes. In addition, H2S inhibited AR binding with PSA promoter and androgen-responsive element (ARE) luciferase activity. We further found that AR is post-translationally modified by H2S through S-sulfhydration. Mutation of cysteine 611 and cysteine 614 in the second zinc finger module of AR-DNA binding domain diminished the effects of H2S on AR S-sulfhydration and AR dimerization. These data suggest that reduced CSE/H2S signaling contributes to antiandrogen-resistant status, and sufficient level of H2S is able to inhibit AR transactivation and treat castration-resistant prostate cancer.
Generalist and subspecialist care for children with chronic conditions.

OBJECTIVE To determine, among Medicaid-enrolled children with chronic conditions, associations of indicators of morbidity and expenditures with different patterns of generalist, subspecialist, and pediatric subspecialist use. DESIGN AND SETTING Cross-sectional analysis of Medicaid claims, enrollment, and provider data from 4 states (California, Georgia, Michigan, and Tennessee). SAMPLE All children enrolled in Supplemental Security Income (aged 0-21 years) and a sample of other Medicaid-enrolled children matched for age and gender. We included 11 chronic conditions, including both uncommon conditions (eg, spina bifida, hemophilia) and common ones (eg, asthma, attention deficit hyperactivity disorder). MAIN OUTCOME MEASURES We determined the number of visits per year to generalists and subspecialists (pediatric and other), using only subspecialists relevant to that condition. We categorized patterns of care as generalist only, predominantly generalist, or predominantly subspecialist, and examined patterns by condition and an indicator of morbidity. Among children seeing subspecialists, we also compared morbidity by pediatric and other subspecialists. We used linear regression to determine per-year total expenditures, controlling for demographic characteristics and morbidity. RESULTS Most children (60.7%) saw generalists only. Twenty-eight percent were in predominantly generalist arrangements, and 11% were in predominantly subspecialist arrangements. Children in predominantly generalist arrangements had higher morbidity than children in generalist-only or predominantly subspecialist arrangements. Among children seeing subspecialists, those seeing pediatric subspecialists had generally higher morbidity than those seeing other subspecialists. Mean yearly expenditures varied from 1306 dollars (attention deficit hyperactivity disorder) to 11,633 dollars (acquired immunodeficiency syndrome). Children who saw only generalists had significantly lower expenditures for 6 of the 11 conditions, after adjusting for morbidity. CONCLUSIONS Medicaid-enrolled children in predominantly generalist arrangements appear to have more complicated conditions than children in generalist-only or predominantly subspecialist arrangements, engendering also higher expenditures. Although children who saw generalists only had lower expenditures than those seeing subspecialists, this finding may reflect unmeasured variations in morbidity.
TGFBI and CHST6 gene analysis in Chinese stromal corneal dystrophies.

AIM To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies (CD) in 8 Chinese probands. METHODS Eight unrelated patients with stromal corneal dystrophies were recruited in this study; all affected members were assessed by completely ophthalmologic examinations. Genomic DNA was extracted from peripheral leukocytes, 17 exons of TGFBI gene and the exon of CHST6 gene were amplified by polymerase chain reaction (PCR), sequenced directly and compared with the reference database. RESULTS Three heterozygous mutations in TGFBI gene were identified in six patients: c. 370C>T (p.Arg124Cys) was found in exon 4 of TGFBI gene in three members, c. 371G>A (p.Arg124His) was found in one patient; c. 1663C>T (p.Arg555Trp) was found in exon 12 in other two members. In addition, four polymorphisms with the nucleotide changes rs1442, rs1054124, rs4669, and rs35151677 were found in TGFBI gene. Mutations were not identified in the rest of 2 affected individuals in TGFBI gene or CHST6 gene. CONCLUSION Within these patients, R124C, R124H and R555W mutations were co-segregated with the disease phenotypes and were specific mutations for lattice corneal dystrophy type I (LCD I), Avellino corneal dystrophy (ACD, GCD II), granular corneal dystrophy type I (GCD I), respectively. Our study highlights the prevalence of codon 124 and codon 555 mutations in the TGFBI gene among the Chinese stromal corneal dystrophies patients.
Existence of intrinsic reflection asymmetry at low spin in odd and odd-odd mass nuclei in the Pm/Eu region.

The low-spin features of odd-mass nuclei in the [ital Z][similar to]62, [ital N][similar to]90 region, for which stable octupole deformations has been previously suggested, are studied without introducing the static intrinsic reflection asymmetry (SIRA). Calculations using a Woods-Saxon potential and taking into account the Coriolis mixing show that most properties can be described in this approximation. Furthermore, the calculated polarization energies of octupole-driving orbitals are not large enough to support the existence of SIRA at low spin in this region.
Targeting tumor suppressor genes for cancer therapy

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.
Zung Scale Factor Invariance in Male Coronary Patients and Healthy People

Abstract The objective of this study was, firstly, to determine the factor structure and factor invariance of the Zung Self-Rating Depression Scale (ZSDS) and, secondly, to justify its use in coronary patients (CPs) and healthy people (HP). Two comparable samples of males were studied: 217 CPs and 191 HP. Exploratory and confirmatory factor analyses (EFA and CFA) for ordinal data were carried out with Mplus. Two models obtained from all participants in this study and another two, the model of Shafer (2006) from a meta-analysis and that of Barefoot et al. (2000) with CPs, were analyzed in CFA. A two-factor structure was supported by EFA in both samples, but none of the models showed adequate goodness-of-fit for the CPs and the HP in CFA. Only the two and three-factor models obtained from the combined sample of CPs and HP showed adequate goodness-of-fit for HP. The ZSDS showed good reliability, replicated the prevalence of depressive symptoms found in other studies and was able to distinguish between CPs and HP. We conclude that the best fit is obtained from the two-factor solution in HP, that the factor structure of the ZSDS is not invariant and is linked to positively and negatively worded items.
Re-Engineering of Health Care: Opportunity or Threat for Occupational Therapists?

The health care system is responding to a paradigm shift from the industrial era to the knowledge society. The rapidly changing administrative structures of some hospitals and increasing numbers of proposals for new models of care are disconcerting for therapists who are used to working in traditional organizational structures and models of care. However, with a broader understanding of the shift that is occurring, it becomes apparent that this paradigm shift is pushing the system toward care practices that are more consistent with occupational therapy practices than those of the traditional medical model. This paper describes the factors influencing the direction of the paradigm shift, the major emerging models of care and organizational structures associated with the paradigm shift, and then discusses the issue of whether the paradigm shift presents a threat or a challenge to occupational therapists.
Systemic lupus erythematosus and pregnancy outcomes: an update and review of the literature

Purpose of reviewThis review synthesizes new data from the studies published between 2011 and 2013, with particular focus on the different information gleaned by various study types. Recent findingsPopulation-based cohorts have demonstrated that women with systemic lupus erythematosus (SLE) have fewer live births and more pregnancy complications, but can have successful live births after having a poor outcome. A retrospective study suggests that only 4 months, not the traditional 6 months of disease quiescent SLE prior to pregnancy improves outcomes. Prospective studies identified several novel predictors of poor pregnancy outcomes, including uterine Doppler and laboratory findings. A prospective study found great success in transitioning to azathioprine from mycophenolate mofetil prior to pregnancy in patients with quiet lupus nephritis. Two retrospective analyses suggest that hydroxychloroquine may prevent congenital heart block in pregnancies exposed to SSA/Ro antibodies. Finally, the initial pregnancy data for belimumab suggest a high degree of transplacental transfer, but thus far no definitive link between belimumab and congenital abnormalities. SummaryRecent studies suggest both novel markers of poor pregnancy outcomes and new approaches to the management of lupus during pregnancy.
The least worst option: user experiences of antipsychotic medication and lack of involvement in medication decisions in a UK community sample

Abstract Background: Treatment decision-making that fully involves service users is an aim across medicine, including mental health. Aim: To explore service users experiences of taking antipsychotic medication for psychotic disorders and their perceptions of decision-making about this. Method: Semi-structured interviews with 20 users of community mental health services, conducted by service user researchers and analysed using thematic analysis. Results: Antipsychotic medication was perceived to have beneficial effects on symptoms and relapse risk, but adverse effects were prominent, including a global state of lethargy and demotivation. Weighing these up, the majority viewed antipsychotics as the least worst option. Participants were split between positions of “willing acceptance”, “resigned acceptance” and “non-acceptance” of taking antipsychotics. Many felt their choices about medication were limited, due to the nature of their illness or pressure from other people. They commonly experienced their prescribing psychiatrist as not sufficiently acknowledging the negative impacts of medication on life quality and physical health concerns and described feeling powerless to influence decisions about their medication. Conclusion: The study highlights the complexity of agendas surrounding antipsychotic medication, including the pervasive influence of coercive processes and the challenges of implementing collaborative decision-making for people with serious mental health problems.
Enhanced firefly algorithm for constrained numerical optimization

Firefly algorithm is one of the recent and very promising swarm intelligence metaheuristics for tackling hard optimization problems. While firefly algorithm has been proven on various numerical and engineering optimization problems as a robust metaheuristic, it was not properly tested on a wide set of constrained benchmark functions. We performed testing of the original firefly algorithm on a set of standard 13 benchmark functions for constrained problems and it exhibited certain deficiencies, primarily insufficient exploration during early stage of the search. In this paper we propose enhanced firefly algorithm where main improvements are correlated to the hybridization with the exploration mechanism from another swarm intelligence algorithm, introduction of new exploitation mechanism and parameter-based tuning of the exploration-exploitation balance. We tested our approach on the same standard benchmark functions and showed that it not only overcame weaknesses of the original firefly algorithm, but also outperformed other state-of-the-art swarm intelligence algorithms.
Effects of oocyte age, cumulus cells and injection methods on in vitro development of intracytoplasmic sperm injection rabbit embryos

This study assessed the effects of oocyte age, cumulus cells and injection methods on in vitro development of intracytoplasmic sperm injection (ICSI) rabbit embryos. Oocytes were recovered from female rabbits superovulated with PMSG and hCG, and epididymal sperm were collected from a fertile male rabbit. The oocyte was positioned with the first polar body at 12 o'clock position, and a microinjection needle containing a sperm was inserted into the oocyte at 3 o'clock. Oolemma breakage was achieved by aspirating ooplasm, and the aspirated ooplasm and sperm were re-injected into the oocyte. The injected oocytes were cultured in M199 medium containing 10% fetal calf serum at 38 °C with 5% CO2 in air. The results showed that oocytes injected at 1 h post-collection produced a higher (p<0.05) fertilization rate than those injected at 4 or 7 h post-collection. Blastocyst rate in the 1 h group was higher (p<0.05) than in the 7 h group. Denuded oocytes (group A) and oocytes with cumulus cells (group B) were injected, respectively. Rates of fertilization and development of ICSI embryos were not significantly different (p<0.05) between the two groups. Four ICSI methods were applied in this experiment. In methods 1 and 2, the needle tip was pushed across half the diameter of the oocyte, and oolemma breakage was achieved by either a single aspiration (method 1) or repeated aspiration and expulsion (method 2) of ooplasm. In methods 3 and 4, the needle tip was pushed to the oocyte periphery opposite the puncture site, and oolemma breakage was achieved by either a single aspiration (method 3) or repeated aspiration and expulsion (method 4) of ooplasm. Fertilization rate in method 2 was significantly higher (p<0.05) than in methods 1 and 3. Blastocyst rates were not significantly different (p<0.05) among methods 1, 3 and 4, but method 2 produced a higher (p<0.05) blastocyst rate than method 3.
GABA and Glutamate in Human Epilepsies

8 INTRODUCTION . 10 REVIEW OF THE LITERATURE . 12 1. Epilepsy . 12 1.1. Definition . 12 1.2. Epidemiology and etiology . 12 1.3. Classification.12 1.4. Outcome of seizures in epilepsy . 16 1.5. Antiepileptic medication . 16 2. Epilepsy and the concentrations of amino acid transmitters . 17 2.1. GABA . 18 2.2. Glutamate . 22 3. Platelet model . 24 AIMS OF THE STUDY . 26 MATERIAL AND METHODS.27 1. Patients . 27 1.1. Adult patients . 27 1.2. Children.27 1.3. Ethical aspects.27 2. Samples.27 3. Assays.28 3.1. GABA transaminase activity . 28 3.2. GABA uptake.28 3.3. Glutamate uptake . 29 3.4. Amino acid concentrations.29 3.5. In vitro analyses with antiepileptic drugs . 30 3.6. Isolation of mRNA from human platelets.30 3.7. Reverse transcription-polymerase chain reaction . 31 3.8. Protein measurements . 31 4. Calculation of kinetic parameters.31 5. Statistical analysis . 31
Whose end is destruction: cell division and the anaphase-promoting complex.

Cell proliferation depends on the duplication of chromosomes followed by the segregation of duplicates (sister chromatids) to opposite poles of the cell prior to cell division (cytokinesis). How cells ensure that chromosome duplication, chromosome segregation, and cell division occur in the correct order and form an immortal reproductive cycle is one of the most fundamental questions in cell biology. Without such coordination, cells would not maintain a constant chromosome number and sexual reproduction as we know and love it would not be possible.
Strategies to enhance chronic disease self-management: How can we apply this to stroke?

Purpose. Social Cognition Theory and the cognitive construct of self-efficacy often form the theoretical basis for many chronic disease self-management programmes. Self-efficacy can be influenced through these programmes and has been shown to be predictive of greater levels of functioning and psychological well-being. Stroke is regarded as a complex chronic disability, and individuals may share many of the same concerns as those living with other chronic diseases such as arthritis and chronic pulmonary disease. However there has been minimal reported research on the utility of self-management programmes following stroke. Search strategy. To comprehend the composition of chronic disease self-management programmes which could be applied to stroke, this paper examined the theoretical basis of self-management and particularly the evidence relating to interventions which have utilized self-efficacy enhancing strategies. Selected papers were retrieved from an extensive search of literature using Medline, Cinahl, PsychInfo and Web of Science databases and the Cochrane Collaboration. The search request focused on literature that specifically related to chronic disease, self-management and self-efficacy that had been published since 1995. However, seminal literature on self-efficacy produced prior to this date was also included. Discussion and conclusions. There is strong evidence to support the use of self-management programmes and their effect on self-efficacy and associated health outcomes. While there are differences in the nature of each chronic condition, there are similarities in the core skills required for self-management. Many effective strategies could be incorporated into current stroke rehabilitation programmes or used to develop targeted self-management interventions. Future research which informs stroke rehabilitation should utilize the evidence relating to other chronic conditions. This could be used to develop the most effective methods of equipping individuals following stroke to cope confidently with the transition from being discharged from therapy towards effective self-management in the longer term.
The Impact of Prophylactic Dexamethasone on Nausea and Vomiting After Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis

Objective:To determine the impact of prophylactic corticosteroid administration on postoperative nausea, vomiting, pain and complications in patients undergoing laparoscopic cholecystectomy. Data Sources:We searched 4 bibliographic databases, conference proceedings, reference lists of articles and textbooks, and contacted experts in the field of anesthesia and hepatobiliary surgery. Review Methods:We evaluated the methodologic quality of trials and extracted data regarding baseline characteristics, interventions, and outcomes. We pooled results from the studies using a random-effects model, evaluated the degree of heterogeneity, and explored potential explanations for heterogeneity. Results:Seventeen trials met eligibility criteria and provided high quality evidence regarding steroid effectiveness. Irrespective of the co-interventions (other antiemetic medications), dexamethasone reduced the incidence of nausea (RR 0.59, 95% CI, 0.48–0.72), vomiting (RR 0.41, 95% CI, 0.30–0.55), and postoperative nausea or vomiting (RR 0.55, 95% CI, 0.44–0.67) relative to placebo. Dexamethasone also seemed to reduce the severity of postoperative pain (Ratio of Means 0.87, 95% CI, 0.78–0.98), although substantial unexplained heterogeneity was present (I2 90.4%). The incidence of headache and dizziness was similar between groups. Conclusions:Prophylactic dexamethasone decreases the incidence of nausea and vomiting after LC relative to placebo and may decrease the severity of postoperative pain. Dexamethasone does not increase the incidence of headaches or dizziness. Surgeons should consider administering prophylactic corticosteroids to patients undergoing laparoscopic cholecystectomy, particularly those at high risk of postoperative nausea and vomiting.
Association of Arterial Hypertension With Renal Target Organ Damage in Kidney Transplant Recipients: The Predictive Role of Ambulatory Blood Pressure Monitoring

Background. Although arterial hypertension is a powerful predictor of graft failure, only few studies have evaluated 24-hr blood pressure (BP) profile in renal transplant recipients (RTRs). Methods. We performed ambulatory blood pressure monitoring (ABPM) in 94 RTRs (65 men; age 28-71 years) with 1-year functioning grafts. Serum biochemical parameters, daily proteinuria, and transplantation-related data were evaluated in all subjects. Results. ABPM showed that only 5% of RTRs were normotensives (BP<130/80 mm Hg) and identified 29% of patients with nocturnal hypertension. A strong, direct correlation was shown between each set of both systolic BP and diastolic BP measured by ABPM and serum creatinine, daily proteinuria, and serum triglycerides (P at least <0.025 for each). Serum creatinine immediately after transplantation and 1-yr asleep diastolic BP were the only significant predictors of 1-yr creatinine (P<0.0001; r2=0.49), whereas awake systolic BP was the only predictor of daily proteinuria (r2=0.39; P=0.005) by multiple regression analysis. Conclusions. BP assessed by ABPM proved to be a stronger predictor of renal graft damage than traditional immunologic factors. ABPM improved the diagnostic accuracy of arterial hypertension in RTRs and was the only effective tool in disclosing the association of BP with 1-year renal transplant outcome.