Miracle-dz/UniFAR-FTUs huggingface dataset:
Abnormal LH pulsatility in women with hyperprolactinaemic amenorrhoea normalizes after bromocriptine treatment: deconvolution-based assessment.

OBJECTIVE The present study examines the LH secretory process in hyperprolactinaemic women before, during and after bromocriptine therapy, using restrictive clinical selection criteria as well as improved methodological tools. PATIENTS AND DESIGN Six women (aged 20-40 years) with microprolactinomas (mean +/- SE prolactin, PRL: 2478 +/- 427 mU/l, range: 1370-3800 mU/l) and four age- and sex-matched healthy controls were admitted to the study. After an overnight fast, all patients and controls had blood samples withdrawn at 10 minute intervals for 6 h (during saline infusion) from 0800 h to 1400 h to determine serum LH and PRL concentrations. After baseline evaluation, patients were treated with bromocriptine, which was started at a daily dose of 1.25 mg for 7 days; the dose was then increased to 2.5 mg daily for the next 7 days and subsequently to 2.5 mg twice daily. PRL levels were evaluated at weekly intervals after the beginning of bromocriptine therapy for the duration of the study. The 6 h pulsatility study was repeated on four patients during treatment at a time when PRL levels were decreased, although not normalized (PRL range: 450-1350 mU/l) and, on four patients, with the attainment of normal serum PRL levels (PRL < 450 mU/l) in the early follicular phase of the menstrual cycle (days 2-5). The LH instantaneous secretion rate was reconstructed by a nonparametric deconvolution method. In addition to pulse analysis made using the program DETECT, the evaluation of the secretion rate yielded the pulse frequency as well as the pulse amplitude distribution. RESULTS Each time series was submitted to deconvolution analysis using a nonparametric method in order to estimate the instantaneous secretion rate (ISR). Hyperprolactinaemic patients had very few high-amplitude LH pulses above 0.2 IU/(l minutes) before treatment (average frequency: 0.83 +/- 0.40 pulses/6 h) and at the intermediate evaluation (0.25 +/- 0.25 pulses/6 h). In both cases, the pulse frequency was significantly lower than in controls (P < 0.05 and P < 0.01, respectively). When PRL was normalized, the number of high-amplitude LH pulses (4.25 +/- 1.03 pulses/6 h), became statistically different from the pulse number before (P < 0.01) and during (P < 0.01) therapy; in particular the pulse frequency after therapy rose to a level not statistically different from that in controls. CONCLUSION The present study shows the presence of reduced LH pulsatility in hyperprolactinaemic women that recovers completely to within the physiological distribution when PRL levels are normalized by bromocriptine therapy.
Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis

Abstract Introduction: The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. Methods: We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran’s Q for heterogeneity and I2 to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger’s test to assess for publication bias in studies. Results: Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1–0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models. Discussion: Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.
Adducin Is Required for Desmosomal Cohesion in Keratinocytes*

Background: The cortical actin cytoskeleton is necessary for keratinocyte adhesion by unclear mechanisms. Results: The actin-binding protein adducin modulates desmosomal adhesion and is a target of protective PKC phosphorylation in response to autoantibodies of the blistering skin disease pemphigus. Conclusion: Adducin promotes adhesion by regulating desmosomes and is part of a protective pathway in pemphigus. Significance: Novel mechanism how cortical actin modulates desmosomal adhesion. Adducin is a protein organizing the cortical actin cytoskeleton and a target of RhoA and PKC signaling. However, the role for intercellular cohesion is unknown. We found that adducin silencing induced disruption of the actin cytoskeleton, reduced intercellular adhesion of human keratinocytes, and decreased the levels of the desmosomal adhesion molecule desmoglein (Dsg)3 by reducing its membrane incorporation. Because loss of cell cohesion and Dsg3 depletion is observed in the autoantibody-mediated blistering skin disease pemphigus vulgaris (PV), we applied antibody fractions of PV patients. A rapid phosphorylation of adducin at serine 726 was detected in response to these autoantibodies. To mechanistically link autoantibody binding and adducin phosphorylation, we evaluated the role of several disease-relevant signaling molecules. Adducin phosphorylation at serine 726 was dependent on Ca2+ influx and PKC but occurred independent of p38 MAPK and PKA. Adducin phosphorylation is protective, because phosphorylation-deficient mutants resulted in loss of cell cohesion and Dsg3 fragmentation. Thus, PKC elicits both positive and negative effects on cell adhesion, since its contribution to cell dissociation in pemphigus is well established. We additionally evaluated the effect of RhoA on adducin phosphorylation because RhoA activation was shown to block pemphigus autoantibody-induced cell dissociation. Our data demonstrate that the protective effect of RhoA activation was dependent on the presence of adducin and its phosphorylation at serine 726. These experiments provide novel mechanisms for regulation of desmosomal adhesion by RhoA- and PKC-mediated adducin phosphorylation in keratinocytes.
Channel-number-compressed multi-channel acoustic echo canceller for high-presence teleconferencing system with large display

Sound localization is important to make conversation easy between local and remote sites in a teleconference. This requires a multi-channel sound system having a multi-channel acoustic echo canceller (MAEC). The appropriate number of channels is determined from a trade-off between high presence and MAEC performance, so it is not possible to increase the channel number by much. We propose a channel-number-compressed MAEC to provide teleconferencing systems that exhibit high presence. The channel number of the MAEC inputs is compressed and that of its outputs is expanded.
Community health worker incentives and disincentives: how they affect motivation retention and sustainability.

This paper examines the experience with using various incentives to motivate and retain community health workers (CHWs) serving primarily as volunteers in child health and nutrition programs in developing countries. It makes recommendations for more systematic use of multiple incentives based on an understanding of the functions of different kinds of incentives and emphasizes the importance of the relationship between a CHW and community. Case studies from Afghanistan El Salvador Honduras and Madagascar illustrate effective use of different incentives to retain CHWs and sustain CHW programs. (authors)
Herpes Simplex Virus Infection Induces Phosphorylation and Delocalization of Emerin, a Key Inner Nuclear Membrane Protein

ABSTRACT The inner nuclear membrane (INM) contains specialized membrane proteins that selectively interact with nuclear components including the lamina, chromatin, and DNA. Alterations in the organization of and interactions with INM and lamina components are likely to play important roles in herpesvirus replication and, in particular, exit from the nucleus. Emerin, a member of the LEM domain class of INM proteins, binds a number of nuclear components including lamins, the DNA-bridging protein BAF, and F-actin and is thought to be involved in maintaining nuclear integrity. Here we report that emerin is quantitatively modified during herpes simplex virus (HSV) infection. Modification begins early in infection, involves multiple steps, and is reversed by phosphatase treatment. Emerin phosphorylation during infection involves one or more cellular kinases but can also be influenced by the US3 viral kinase, a protein whose function is known to be involved in HSV nuclear egress. The results from biochemical extraction analyses and from immunofluorescence of the detergent-resistant population demonstrate that emerin association with the INM significantly reduced during infection. We propose that the induction of emerin phosphorylation in infected cells may be involved in nuclear egress and uncoupling interactions with targets such as the lamina, chromatin, or cytoskeletal components.
Endocrine-Metabolic Function in Remission-Phase IDDM During Administration of Cyclosporine

We have studied the endocrine-metabolic status of patients in non–insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6–60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels <7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute β-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects. This was associated with substantial increases in plasma IRI and C-peptide in both groups, whereas the responses of both hormones were significantly reduced in the patients with diabetes. Plasma IRGI did not change in response to Sustacal in nondiabetic or NIR subjects. Thus, patients in NIR remission of diabetes as defined exhibited grossly subnormal responses of the μ-cells to intravenous glucose, with relatively well-preserved responses to oral glucose, intravenous arginine, and a mixed meal. Evidence is cited that cyclosporine does not affect the endocrine-metabolic responses examined in this study. It appears that patients in this condition revert to a state similar to that in the interval shortly preceding manifestation of overt hyperglycemia.
Barriers to post exposure prophylaxis (PEP) completion after rape: a South African qualitative study

Sexual violence and HIV are two serious public health problems in South Africa. Post exposure prophylaxis (PEP) to prevent HIV after rape was introduced into the South African public health services in 2002 but many questions on the completion of PEP medication remain. A qualitative study involving in-depth interviews was conducted with 29 women attending sexual assault services in an urban and a rural site to explore PEP use after rape. It showed how PEP adherence was a complex and challenging experience, with survivors experiencing disruptions in their lives and unable to adhere to the medication adequately. Only nine completed their prescribed drug regimes. Rape stigma and perceptions of rape impacted on adherence, which became a lesser priority if the rape was contested by important others. Being blamed and not receiving social support had profound psychological impact. Stigma of rape and fear of HIV played very powerful roles in debilitating women's ability to take medication to prevent HIV infection. Further research is needed to support the development of interventions that acknowledge the complex barriers to adherence of PEP after rape.
Distribution of Dekkera bruxellensis in a sugarcane‐based fuel ethanol fermentation plant

We investigated the presence of the yeast Dekkera bruxellensis in samples collected at three points surrounding the industrial alcoholic fermentation plants of two distilleries where there are often cases of contamination caused by this yeast: this involved sugar cane wash water, feeding sugar cane juice and vinasse from the treatment pond. Total yeast was isolated in WLN medium with bromocresol green and cycloheximide and further selected on the basis of its ability to grow in synthetic medium containing nitrate. Following this, colonies were selected from the distribution on nitrate plates and identified by amplification with species‐specific primers and DNA sequencing of the 26S‐D1/D2 locus. The results showed that D. bruxellensis is introduced through the feeding substrate, which suggests that its cells originated with the harvested cane. Subsequently, its population circulates as a result of the reuse of water for washing the cane, in a continuous re‐inoculation of the plant with yeasts. Furthermore, the yeast population is formed in the vinasse by the addition of wash water into the treatment ponds and then reintroduced to the culture fields by fertigation, so that the process can be renewed in the following season. It is now possible to adopt sanitation procedures that can prevent the entry of the contamination to the fermentation process.
Longitudinal Changes in Body Fat and Its Distribution in Relation to Cardiometabolic Risk in Black South African Women.

BACKGROUND Ethnic differences in body composition and cardiometabolic risk have been reported in cross-sectional studies. This study aimed to investigate changes in body composition over 5.5 years, and its association with cardiometabolic risk in premenopausal black South African (SA) women. METHODS Changes in body composition and body fat distribution (dual-energy x-ray absorptiometry and computerized tomography), fasting glucose, insulin, and lipid concentrations, were measured in 63 black SA women at baseline (age: 27 ± 8 years), and 5.5 years later. RESULTS Body weight and fat mass (FM) increased by 6.9 ± 9.9 kg and 4.3 ± 6.9 kg, respectively, over the 5.5 years with a relative (%FM) increase in central and decrease in peripheral FM (all P < 0.05). Fasting glucose and lipid concentrations (except HDL-cholesterol) increased over the follow-up period (all P < 0.05). Both baseline and changes in body fat distribution were associated with cardiometabolic risk. Independent of baseline age, FM and insulin sensitivity, baseline trunk:leg was associated with reduced insulin sensitivity at follow-up (Matsuda index; β = -0.41, P = 0.002). Increasing trunk:gynoid ratio was associated with higher plasma insulin levels (β = 0.31, P = 0.023) and reduced insulin sensitivity (Matsuda index; β = -0.52, P < 0.001) at follow-up. CONCLUSIONS Weight gain in free-living black SA women over 5.5 years was associated with a centralization of fat mass, which predicted an increase in cardiometabolic risk.
Assessment of the serological relatedness of genital human papillomaviruses by hemagglutination inhibition

To assess the potential for cross-protection among genital human papillomavirus (HPV) types in virus-like particle (VLP)-based vaccinations, inhibition of HPV VLP-mediated hemagglutination by rabbit antisera raised against HPV type 6b (HPV-6b), HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, and HPV-45 was analyzed. Only highly homologous types (HPV-6b and HPV-11, and HPV-18 and HPV-45) exhibited detectable serological cross-reaction for the class of antibodies that inhibit virion-to-cell surface binding. However, analysis of neutralizing monoclonal antibodies to several animal and human papillomaviruses indicated that over half of these antibodies do not prevent cell surface binding, but these latter antibodies do not appear to be more cross-reactive in enzyme-linked immunosorbent assays than those that mediate inhibition of hemagglutination. The data strongly suggest that while there may be limited cross-protection between highly (>85% L1 amino acid identity) homologous types, protection by HPV VLP-based vaccines will be predominantly type specific.
AMG 925 Is a Dual FLT3/CDK4 Inhibitor with the Potential to Overcome FLT3 Inhibitor Resistance in Acute Myeloid Leukemia

Resistance to FLT3 inhibitors is a serious clinical issue in treating acute myelogenous leukemia (AML). AMG 925, a dual FLT3/CDK4 inhibitor, has been developed to overcome this resistance. It is hypothesized that the combined inhibition of FLT3 and CDK4 may reduce occurrence of the FLT3 resistance mutations, and thereby prolong clinical responses. To test this hypothesis, we attempted to isolate AML cell clones resistant to AMG 925 or to FLT3 inhibitors. After a selection of over 8 months with AMG 925, we could only isolate partially resistant clones. No new mutations in FLT3 were found, but a 2- to 3-fold increase in total FLT3 protein was detected and believed to contribute to the partial resistance. In contrast, selection with the FLT3 inhibitors sorafenib or AC220 (Quizartinib), led to a resistance and the appearance of a number of mutations in FLT3 kinase domains, including the known hot spot sites D835 and F691. However, when AC220 was combined with the CDK4 inhibitor PD0332991 (palbociclib) at 0.1 μmol/L or higher, no resistance mutations were obtained, indicating that the CDK4-inhibiting activity of AMG 925 contributed to the failure to develop drug resistance. AMG 925 was shown to potently inhibit the FLT3 inhibitor–resistant mutation D835Y/V. This feature of AMG 925 was also considered to contribute to the lack of resistance mutations to the compound. Together, our data suggest that AMG 925 has the potential to reduce resistance mutations in FLT3 and may prolong clinical responses. Mol Cancer Ther; 14(2); 375–83. ©2014 AACR.
Hypotheses generation using link prediction in a bipartite graph

The large volume of scientific publications is likely to have hidden knowledge which can be discovered dealing with the massive information altogether using a system which can cover the huge amount of data. We propose a method for generating hypotheses in the field of physics using the massive publications of physics journals. We convert the text data of titles and abstracts in publications to a bipartite graph extracting words of matter and keywords and suggest methods for predicting links between matter and keywords node. Those links generate hypotheses for research by suggesting the new possible relationship between some matter and phenomena or properties. Suggested methods have better performance than existed methods for link prediction in the bipartite graph. The experiments also show the detail application of our system for specific purpose: suggesting new matter which will be related with the concept of antiferromagnetism, superconductor and NMR spectroscopy.
PENGARUH UKURAN PERUSAHAAN, PROFITABILITAS, DAN UMUR PERUSAHAAN PADA PENGUNGKAPAN INFORMASI LINGKUNGAN

Amount of environmental damage problem that occurred in Indonesia, making a lot of environmental aspect become a hot discussion among the public. To show the company’s attetion and awareness about environmental then the company makes environmental activities disclosure that contained in yearly repots that they publish. This research purposed to find out the effect of the company’s size, profitability, and the company’s age on the environmental disclosure. The population in this research are all companies that was registered on the Indonesia Stock Exchange in 2012-2014 and was registered in the PROPER. Sampling method used was purposive sampling. Amount of sampling used was 29 companies. Data collection method used non participant observation and documentation. Analytical techniques used was multiple linier regression. Based on analystical result was found that the company’s size and the company’s age has positive effect on the environmental disclosure. While profitability has no effect on the environmental disclosure.
Long-term efficacy and safety of Chinese made sirolimus eluting stents: results, including off label usage, from two centres over three years.

BACKGROUND Multiple randomized clinical trials have demonstrated that drug eluting stents can significantly reduce the rates of restenosis and subsequent adverse events across lesion and patient. We investigated the medium term clinical efficacy and safety of Firebird sirolimus eluting stent (SES) in coronary artery disease. METHODS The sample was 509 consecutive patients with coronary artery disease (CAD) who were treated by Firebird SES and finished three-year clinical follow-up. The occurrences of major adverse cardiac events (MACE) and Academic Research Consortium defined stent thrombosis (ST) were evaluated in patients with and without diabetes mellitus. RESULTS Three hundred and thirty three patients (65.4%) were treated by Firebird SES by off label indications. Angiographic success was achieved in 98.3% of the lesions. MACE and target vessel revascularization rates at 6-month, 1 year's and 3 years' clinical follow-up were 2.4% and 1.4%, 4.1% and 2.8%, 7.9% and 5.1%, respectively. The cumulative 3-year MACE free survival rate was 92.1%. After 3 years, DM patients had significantly higher rates of MACE (13.7% vs 6.4%, P < 0.05) and TVR (9.8% vs 4.0%, P < 0.05) and the cumulative MACE free survival rate was very significantly lower in the DM group (86.4% vs 93.6%, P < 0.05). ST occurred in 7 patients (1.4%) at the end of 3 years' follow-up, 5 of them had definite ST with 4 cases presenting with myocardial reinfarction and 1 with unstable angina, the other 2 with probable ST had reinfarction in the stented coronary territory without angiographic follow-up. There was no difference in occurrence of ST between off label (1.5%) and on label groups (1.1%, P = 0.07). CONCLUSIONS In daily practice, about 2/3 of patients were treated by Firebird SES by off label indications. Medium term clinical follow-up of 3 years indicated CAD patients treated by Firebird SES had a low MACE and acceptable ST rate. DM patients had higher rates of adverse events and than non DM.