Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Neuronal Nicotinic Acetylcholine Receptor Subtypes by α-Conotoxin GID and Analogues*

α-Conotoxins are small disulfide-rich peptides from the venom of the Conus species that target the nicotinic acetylcholine receptor (nAChR). They are valuable pharmacological tools and also have potential therapeutic applications particularly for the treatment of chronic pain. α-Conotoxin GID is isolated from the venom of Conus geographus and has an unusual N-terminal tail sequence that has been shown to be important for binding to the α4β2 subtype of the nAChR. To date, only four conotoxins that inhibit the α4β2 subtype have been characterized, but they are of considerable interest as it is the most abundant nAChR subtype in the mammalian brain and has been implicated in a range of diseases. In this study, analysis of alanine-scan and truncation mutants of GID reveals that a conserved proline in α-conotoxins is important for activity at the α7, α3β2, and α4β2 subtypes. Although the proline residue was the most critical residue for activity at the α3β2 subtype, Asp3, Arg12, and Asn14 are also critical at the α7 subtype. Interestingly, very few of the mutations tested retained activity at the α4β2 subtype indicating a tightly defined binding site. This lack of tolerance to sequence variation may explain the lack of selective ligands discovered for the α4β2 subtype to date. Overall, our findings contribute to the understanding of the structure-activity relationships of α-conotoxins and may be beneficial for the ongoing attempts to exploit modulators of the neuronal nAChRs as therapeutic agents.
Fundamental Information Analysis

Fundamental analysis is aimed at determining the value of corporate securities by a careful examination of key value-drivers, such as earnings, risk, growth, and competitive position. In the context of such analysis, we identify below a set of financial variables (fundamentals) claimed by analysts to be useful in security valuation and examine these claims by estimating the incremental value-relevance of these variables over earnings. Our findings support the incremental value-relevance of most of the identified fundamentals; in fact, for the 1980s, the fundamentals add approximately 70%, on average, to the explanatory power of earnings with respect to excess returns. We also show that the returns-fundamentals relation is considerably strengthened when it is conditioned on macroeconomic variables, thereby demonstrating the importance of a contextual capital market analysis. For example, several fundamentals that appear only weakly value-relevant or even irrelevant in the unconditional analysis exhibit strong association with returns under specific economic conditions (e.g., the accounts receivable and the provision for doubtful receivables signals during high inflation). From a general examination of the role of fundamentals in security valuation we turn to the related issues of earnings persistence, growth, and the earnings response coefficient. We hypothesize that the funda-
PKC-Dependent Phosphorylation May Regulate the Ability of Connexin43 to Inhibit DNA Synthesis

Phosphorylation affects several biological functions of connexin43 (Cx43), although its role on Cx43-mediated inhibition of DNA synthesis is not known. Previous studies showed increased Cx43 phosphorylation on serine in response to growth factor stimulation of cardiomyocytes, mediated by protein kinase C-epsilon (PKCε). Here we report that activation of PKCε is also necessary for stimulation of cardiomyocyte DNA synthesis and mitosis. We have investigated the participation of specific serine residues that are putative PKC targets in producing phosphorylated Cx43 species and also in regulating DNA synthesis in cardiomyocytes. Interference with the PKC signaling system and/or the phosphorylation of specific amino-acids of Cx43 may allow regulation of the mitogenic response.
Randomized Comparison of Cavotricuspid Isthmus Ablation for Atrial Flutter Using an Open Irrigation‐Tip versus a Large‐Tip Radiofrequency Ablation Catheter

Ablation of Typical Atrial Flutte. Background: Large‐tip (10 mm) catheters (LTCs) and open‐irrigation‐tip catheters (OITCs), both capable of creating large lesions, are more effective than conventional catheters for cavotricuspid isthmus (CTI) ablation. However, it is not clear whether complete CTI block can be achieved more efficiently using an LTC or an OITC. The purpose of this study was to compare the efficiency of radiofrequency catheter ablation (RFA) of the CTI using LTC versus OITC to eliminate atrial flutter (AFL).
Upper Extremity Replantation: Current Concepts

Background: Upper extremity replantation is a procedure that has revolutionized hand surgery. Since its introduction, a rapid evolution has occurred with a shifting focus from implant survival to optimization of functional outcomes and surgical efficiency. In this review, the current concepts surrounding the indications for replantation, variations in surgical technique, the factors affecting outcomes, and future directions of the specialty are analyzed. Methods: A literature review was performed of all recent articles pertaining to digit, hand, and upper extremity replantation surgery. Particular emphasis was placed on comparative studies and recent meta-analyses. Results: The indications and contraindications for replantation surgery are largely unchanged, with mechanism of injury remaining one of the most important determinants of implant survival. With advances in surgical technique, improved outcomes have been observed with avulsion injuries. Distal tip replantations appear to be more common with improved microsurgical techniques, and for these distal injuries, digital nerve and vein repair may not be necessary. Cold ischemia time for a digit amputation should not preclude transfer to a replantation facility or significantly affect the decision to perform a replantation. However, transferring physicians should thoroughly review the options with patients to prevent unnecessary transfers, which is an area where telemedicine may be useful. Conclusion: This review provides an update on the current concepts of the practice of replantation and the treatment and management of patients with upper extremity amputations.
Exploring the Impact of Social Norms and Perceptions on Women's Participation in Customary Forest and Land Governance in the Democratic Republic of Congo—Implications for REDD+

SUMMARY The Democratic Republic of Congo (DRC) with its extensive forest cover is the biggest target country for the Reducing Emissions from Deforestation and Forest Degradation (REDD+) mechanism in Africa. Despite high levels of gender inequality in rural DRC, the impacts of REDD+ interventions on gender have not been sufficiently addressed. This study examines the gender dimension at two project sites in the Equateur Province. Focus group discussions and individual interviews reveal that women spend as much time as men in the forest. Nonetheless, men's activities in the forest are often much more highly valued. This systemic devaluation of women's work, and their knowledge about the forest, legitimises men's dominance in forest governance. The results of this study finds that alongside investment in women's education, which is central for women's empowerment and their participation in forest management, local opinion leaders who shape social norms and perceptions, such as church-based organisations, are indispensable partners to make REDD+ more equitable.
Prevalence of metabolic syndrome among professional and office workers in Bangkok, Thailand.

OBJECTIVE To estimate the prevalence of metabolic syndrome (MetS) among Thai professional and office workers and to compare the prevalence with other populations. MATERIAL AND METHOD The authors conducted a cross-sectional study of 1,339 professional and office workers (535 men and 804 women) who participated in the annual health examinations at the Mobile Health Checkup Unit of King Chulalongkorn Memorial Hospital in Bangkok, Thailand during the period of August through December 2001. MetS was defined using the modified NCEP ATP III criteria. Chi-square tests were used to evaluate differences in distribution of covariates for affected and unaffected patients. RESULTS The prevalence of MetS among Thai professional and office workers was 15.2% and approximately 3 times more common among men than women (25.8% vs. 8.2%). Men and women with MetS were older (p < 0.05) and were less well-educated (p < 0.05) than those without MetS. The three most common metabolic abnormalities in men were high blood pressure (45.0%), BMI > or = 25 kg/m2 (40.7%) and hypertriglyceridemia (38.7%). Among women, high blood pressure (22.8%), BMI > or = 25 kg/m2 (20.9%) and low HDL-Cholesterol (18.4%) were the most common metabolic abnormalities noted. CONCLUSION The prevalence of MetS in this cohort of Thai professional and office workers was as high as those observed in developed countries. These findings emphasize the urgent need to develop strategies for the detection, treatment, and prevention of MetS. Such efforts will contribute to attenuating the incidence of cardiovascular disease and diabetes.
Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

CONTEXT The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. METHODS Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. MAIN OUTCOME MEASURES Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. RESULTS Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. CONCLUSIONS Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.
Effect of a denture base acrylic resin containing silver nanoparticles on Candida albicans adhesion and biofilm formation.

OBJECTIVE The objective of this study was to evaluate the effect of denture base resin containing silver nanoparticles (nano-silver) on Candida albicans adhesion and biofilm formation. BACKGROUND Epidemiological studies report that approximately 70% of removable denture wearers suffer from denture stomatitis. Candida albicans adhesion and biofilm formation are regarded as essential prerequisites for denture stomatitis. MATERIALS AND METHODS The bioactivity and biomass of C. albicans biofilm, which was incubated in a series of twofold dilutions of nano-silver suspension at 37°C for 24 h, were determined using XTT reduction and crystal violet assays, respectively. The denture base resin specimens containing nano-silver were then used in C. albicans adhesion (37°C; 90 min; n = 9) and biofilm formation assays (37°C; 72 h; n = 9). Confocal laser scanning microscopy was used to evaluate the architectural properties of average thickness and live/dead cell ratio in the different biofilm stages that developed on the specimens. RESULTS The bioactivity and biomass of C. albicans biofilm successively decreased with increasing nano-silver solution concentration. Denture base resin containing nano-silver had no effect on adhesion at low concentrations, but it exhibited anti-adhesion activity at a high concentration (5%). For 72 h biofilm formed on the resin specimens, the thickness and live/dead cell ratio were successively reduced with increasing nano-silver concentrations. CONCLUSION Nano-silver had antifungal activity and inhibited C. albicans biofilm formation. Antifungal activity and an inhibitory effect on adhesion and biofilm formation by denture base resin containing nano-silver were discovered, especially at a higher concentration.
Stenting versus aggressive medical therapy for intracranial arterial stenosis.

BACKGROUND Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial. METHODS We randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus PTAS with the use of the Wingspan stent system. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days. RESULTS Enrollment was stopped after 451 patients underwent randomization, because the 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non-stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group. CONCLUSIONS In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected. (Funded by the National Institute of Neurological Disorders and Stroke and others; SAMMPRIS ClinicalTrials.gov number, NCT00576693.).
Does Forest Certification Enhance Forest Structure? Empirical Evidence from Certified Community-Based Forest Management in Kilwa District, Tanzania

SUMMARY Forest Stewardship Council (FSC) standards support enhancement of certified forests. However, the performance of certified forests in enhancing forest structure has rarely been examined empirically. Forest structure, human forest use and forest governance indicators are assessed in a comparative study of FSC-certified community forests, open access forests (non-FSC) and state forest reserves (non-FSC) in Kilwa District, Tanzania. The FSC-certified forests have better forest structure, appropriate regeneration, and lower fire incidences than open access forests and state forest reserves. Certified forests also provide more economic benefits to communities compared to non-FSC forests. These findings imply that forest certification could be an appropriate management intervention, and that adoption of FSC standards may lead to more effective management in human-dominated landscapes. However, because of the short time certification has been operational, it is hard to precisely identify all effects of certification. Further empirical evidence on effects, in space and time, is therefore desirable.
Fama and French Factors and Their Regression Tendencies: Improving the Accuracy of Risk Assessments

The Fama and French three-factor model aids investors in making investment decisions. Historical data is often used to extrapolate past trends into the future. But what if historical estimates are not accurate predictors for future values? Blume (1971) found that market betas in a CAPM tend to regress to the mean, i.e. the overall market beta of one. Similarly, this study tests to what extent beta, SMB, and HML coefficients in a Fama and French three-factor model are subject to mean reversion. Using a 1990-2010 U.K. sample, I demonstrate that all three coefficients regress to the mean. In addition, while the regression rates of beta and SMB coefficients are fairly stable over time, for HML coefficients these are highly volatile. The results are robust for composing portfolios based on median BE/ME splits, including negative-BE firms, and analyzing longer periods with lower frequency data.
Tonsillectomy for IgA nephropathy: a meta-analysis.

BACKGROUND The efficacy of tonsillectomy in immunoglobulin A nephropathy (IgAN) remains controversial. Our meta-analysis was intended to investigate its efficacy as an adjunct or independent treatment. STUDY DESIGN Meta-analysis of prospective and retrospective studies using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. SETTING & POPULATION Patients with IgAN treated with or without tonsillectomy. SELECTION CRITERIA FOR STUDIES Studies that compared clinical remission or end-stage renal disease (ESRD) in patients with IgAN with or without tonsillectomy. INTERVENTION Tonsillectomy. OUTCOMES Clinical remission and ESRD. RESULTS 14 studies (1,794 patients) were included and a random-effects model was applied. There were significantly greater odds of clinical remission with tonsillectomy (10 studies, 1,431 patients; pooled OR, 3.40; 95% CI, 2.58-4.48; P<0.001). Sensitivity analysis to exclude the effects of renin-angiotensin system inhibitors yielded consistent results (6 studies, 671 patients; pooled OR for remission, 2.80; 95% CI, 1.91-4.09; P<0.001). In subgroup analysis of the remission outcome, tonsillectomy plus steroid pulse therapy was superior to steroid pulse therapy alone (7 studies, 783 patients; pooled OR, 3.15; 95% CI, 1.99-5.01; P<0.001), and tonsillectomy plus conventional steroid therapy was superior to conventional steroid therapy alone (2 studies, 159 patients; pooled OR, 4.13; 95% CI, 1.23-13.94; P=0.02). Tonsillectomy was superior to general treatment (3 studies, 187 patients; pooled OR for remission, 2.21; 95% CI, 1.20-4.05; P=0.01). In addition, tonsillectomy was associated with decreased odds of ESRD (9 studies, 873 patients; pooled OR, 0.25; 95% CI, 0.12-0.52; P<0.001). 2 sensitivity analyses, one excluding studies with less than 5 years' follow-up and another excluding the confounding effect of renin-angiotensin system inhibitors, yielded nearly the same reduction in ESRD risk (6 studies, 691 patients; pooled OR, 0.20; 95% CI, 0.11-0.36; P<0.001; and 6 studies, 547 patients; pooled OR, 0.24; 95% CI, 0.14-0.44; P<0.001). LIMITATIONS Most included studies were retrospective cohort studies; we were unable to adjust uniformly for potential confounding variables. CONCLUSIONS As adjunct or independent therapy, tonsillectomy may induce clinical remission and reduce the rates of ESRD in patients with IgAN.
Peroxisome proliferator‐activated receptor γ C161T polymorphisms and survival of Japanese patients with immunoglobulin A nephropathy

Peroxisome proliferator‐activated receptor γ (PPARγ) plays an important role in lipid metabolism, insulin sensitivity, atherogenesis, and immune regulation. A genetic polymorphism (C161T) at exon 6 of PPARγ gene (PPARG) was reported to be associated with the onset of coronary artery disease. However, there has been no report of an association with renal disease. Genomic DNAs were isolated from 225 Japanese patients with histologically confirmed immunoglobulin A nephropathy (IgAN). The PPARG C161T genotype was determined by polymerase chain reaction‐restriction fragment length polymorphism. The association of the polymorphism with renal prognosis in IgAN patients was analyzed using the Kaplan–Meier method and Cox proportional hazard regression model. The PPARG polymorphism was not associated with the renal survival rate. However, when patients were stratified into those either with or without hypertension at the time of diagnosis, the renal survival of the CT/TT genotypes was significantly better in those without hypertension than those with the CC genotype. We report that the PPARG C161T polymorphism is associated with the survival of IgAN patients without hypertension. The T allele of the polymorphism might have a protective effect on the progression of IgAN.
Quality of life of older Chinese adults receiving primary care in Wuhan, China: a multi-center study

Background Quality of life (QOL) is an important primary care outcome, but the QOL of older adults treated in primary care is understudied in China. This study examined QOL and its associated factors in older adults treated in Chinese primary care. Methods A total of 752 older patients (65+ years) were consecutively recruited from 13 primary care centers in Wuhan, China, and interviewed with a standardized questionnaire, concerning socio-demographics, major medical conditions, loneliness, and depression. QOL and depression were measured with the Chinese six-item QOL questionnaire and the shortened Geriatric Depression Scale, respectively. Multiple linear regression was used to identify factors associated with poor QOL. Results The average QOL score of primary care older adults was (20.7 ± 2.5), significantly lower than that of the Chinese general population. Factors significantly associated with poor QOL of Chinese primary care older adults included engaging in manual labor before older adulthood (unstandardized coefficient [β]: −0.702, P < 0.001), no living adult children (β: −1.720, P = 0.001), physical inactivity (β: −0.696, P < 0.001), having ≥ four major medical conditions (β: −1.813, P < 0.001), hearing problem (β: −1.004, P = 0.017), depression (β: −1.153, P < 0.001), and loneliness (β: −1.396, P < 0.001). Conclusions Older adults treated in Chinese primary care have poorer QOL than the general population. Addressing psychosocial problems at Chinese primary care settings could be helpful in improving QOL in Chinese older adults.