Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and efficacy of 0.5% podofilox gel in the treatment of anogenital warts.

OBJECTIVE To determine the safety and efficacy of a new gel formulation of podofilox in the treatment of anogenital warts. DESIGN Double-blind, randomized, multicenter, vehicle-controlled investigation. SETTING Private dermatology practices, university clinics (dermatology, gynecology, and infectious diseases), and contract research organizations. PATIENTS Three hundred twenty-six patients with anogenital warts. MAIN OUTCOME MEASURE Number of patients with clearing of all treated warts (treatment success). RESULTS The 0.5% podofilox gel was significantly better than vehicle gel for successfully eliminating and reducing the number and size of anogenital warts. In the intent-to-treat population, 62 (37.1%) of 167 patients treated with 0.5% podofilox gel had complete clearing of the treated areas (treatment successes) compared with 2 (2.3%) of 86 patients who had clearing of warts with the vehicle gel (P < .001) after 4 weeks. Nineteen additional patients treated with 0.5% podofilox gel and 2 patients treated with vehicle gel had clearing of warts with continued treatment up to 8 weeks. After 8 weeks, 35.9% of the baseline anogenital warts treated with 0.5% podofilox gel remained; this was significantly fewer than in the vehicle-treated group (88.4% of the baseline number) (P = .001). The 0.5% podofilox gel was generally well tolerated, with predominantly mild or moderate local adverse reactions occurring in the majority of patients. Only 7 patients (3.2%), all receiving 0.5% podofilox gel, discontinued study treatment because of drug-related local reactions. CONCLUSIONS The results demonstrated that 0.5% podofilox gel is safe and significantly more effective than vehicle gel in the treatment of anogenital warts.
Association Between C677T Polymorphism of Methylene Tetrahydrofolate Reductase and Congenital Heart Disease: Meta-Analysis of 7697 Cases and 13 125 Controls

Background—Association between the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and congenital heart disease (CHD) is contentious. Methods and Results—We compared genotypes between CHD cases and controls and between mothers of CHD cases and controls. We placed our results in context by conducting meta-analyses of previously published studies. Among 5814 cases with primary genotype data and 10 056 controls, there was no evidence of association between MTHFR C677T genotype and CHD risk (odds ratio [OR], 0.96 [95% confidence interval, 0.87–1.07]). A random-effects meta-analysis of all studies (involving 7697 cases and 13 125 controls) suggested the presence of association (OR, 1.25 [95% confidence interval, 1.03–1.51]; P=0.022) but with substantial heterogeneity among contributing studies (I2=64.4%) and evidence of publication bias. Meta-analysis of large studies only (defined by a variance of the log OR <0.05), which together contributed 83% of all cases, yielded no evidence of association (OR, 0.97 [95% confidence interval, 0.91–1.03]) without significant heterogeneity (I2=0). Moreover, meta-analysis of 1781 mothers of CHD cases (829 of whom were genotyped in this study) and 19 861 controls revealed no evidence of association between maternal C677T genotype and risk of CHD in offspring (OR, 1.13 [95% confidence interval, 0.87–1.47]). There was no significant association between MTHFR genotype and CHD risk in large studies from regions with different levels of dietary folate. Conclusions—The MTHFR C677T polymorphism, which directly influences plasma folate levels, is not associated with CHD risk. Publication biases appear to substantially contaminate the literature with regard to this genetic association.
Fast Oscillations in Cortical Circuits

The study of cortical oscillations is of great interest to those working in many areas of neuroscience. A fast coherent EEG rhythm called gamma or "40 Hz" has been implicated in cognition, as it may play a role in binding together features of objects. This rhythm may also be important for consciousness, as a number of drugs that induce general anesthesia disrupt the synchronization of the rhythm at clinically relevant concentrations. There is also suggestive evidence implicating dysfunction of gamma rhythms in Alzheimer's disease, and perhaps in other neuropsychiatric disorders. In Fast Oscillations in Cortical Circuits, the authors use a combination of electrophysiological and computer modeling techniques to analyze how large networks of neurons can produce both epileptic seizures and functionally relevant synchronized oscillations. Specific topics covered include single hippocampal pyramid cells, hippocampal interneurons, synaptic interactions, gamma oscillations in brain slices as well as in vivo, the mechanisms of oscillation-synchronization (both local and long-range), the switch from gamma to beta frequencies and its implications for memory, and the significance of gamma oscillations for brain function.
Evidence for a CD14- and Serum-Independent Pathway in the Induction of Endotoxin-Tolerance in Human Monocytes and THP-1 Monocytic Cells

Lipopolysaccharide (LPS) stimulation of macrophages or monocytes is believed to occur via a serum- and CD14-dependent signaling pathway via toll-like receptor 4 (TLR4). We sought to determine whether serum and/or CD14 are required for LPS to induce the endotoxin-tolerant state in human monocytes. LPS treatments were performed in the presence or absence of an anti-CD14 monoclonal antibody and with or without fetal bovine serum. Endotoxin tolerance was assessed after an 18-h exposure (pretreatment) to 10 ng/mL of LPS. Medium was discarded and cells were challenged with activating (1–1000 ng/mL) doses of LPS. LPS-stimulated tumor necrosis factor (TNF) secretion into culture supernatants was determined after 5 h by ELISA and p44/p42 ERK kinase activation was measured after 30 min by Western blot. Statistical analysis was by ANOVA. LPS induced endotoxin-tolerance with a significant inhibition of LPS-stimulated TNF secretion and less p44/p42 ERK kinase activation. When LPS-stimulation of naïve (nontolerant) monocytes was performed in medium with anti-CD14 antibody or without serum, there was marked blunting of TNF release. However, LPS pretreatment in medium without serum or in medium containing anti-CD14 antibody resulted in changes in monocyte activation and function characteristic of endotoxin tolerance. LPS-stimulated p44/p42 ERK kinase activation and TNF release were diminished whether or not anti-CD14 antibody was present during LPS pretreatment. LPS-stimulated TNF secretion and p44/p42 ERK kinase activation require the presence of serum and are inhibited by anti-CD14 antibody. Our findings suggest that LPS induces endotoxin tolerance in human monocytic cells via a pathway that does not require serum or cell surface CD14.
Selective Hardening of NanoPLA Circuits

Nanoelectronic components are expected to suffer from very high error rates, implying the need for hardening techniques. We propose a fine-grained approach to harden a promising class of nanoelectronic circuits, called NanoPLAs, against errors. An analytical procedure and simulations are both incorporated into the algorithm to identify the most critical error locations. By targeting errors with the largest impact for a given circuit, the method can provide significant reliability boost at low cost. Furthermore, the method yields a plethora of alternative designs, trading off hardening costs against circuit robustness. In many cases, solutions found achieve both lower cost and higher robustness compared with the duplication-based hardening strategy introduced before.
Asset Legitimacy and Distributive Justice in the Dictator Game: An Experimental Analysis

Distributive justice seems to guide behavior in reward allocation tasks in which subjects in a group jointly produce an endowment that is then allocated by a member of the group. It has been shown that allocators aim to preserve the proportionality between inputs (e.g., effort) and outputs (e.g., monetary rewards) of those in the group, even when this comes at a cost to themselves. We experimentally investigated whether justice considerations of this kind play a role in a double-blind dictator game when the assets to be allocated are generated exclusively through the effort of the decision maker. The experiment shows that distributive justice is an important source of motivation in highly demanding social environments in which reputational concerns and reciprocity are absent. This finding has been corroborated by an independent validity check and may have important implications for previous experimental findings and for the economics of charity. Copyright © 2010 John Wiley & Sons, Ltd.
Designing a collaborative virtual environment for introducing pupils to complex subject matter

Mission Queen Maud Land (MQML) is a collaborative virtual environment that was developed to explore new ways to stimulate secondary school pupils to collaborate in grasping complex subject matter. MQML is designed for five simultaneous users (four pupils and a teacher) and it combines a collaborative virtual environment with a web site and audio narratives. Basic concepts from molecular biology and genetic engineering form the educational core in MQML, and it enables the participants to explore the DNA molecule and to unravel the genetic code by interactions both on a macroscopic and a microscopic level. A background story was developed with the purpose of adding excitement and engagement to the subject matter. The audio narratives were used to convey the story while the web site provided the necessary background information. This paper describes our design approach for making the subject matter easy to understand, and for eliciting collaborative work processes among the participants. Finally, we report results from evaluations of MQML during a field study in the secondary school.
Listening Practice Influence on the Use of Communication Strategies in Oral Translation

Effective communication plays an important role in translation. In oral translation, translation major students must understand the meaning well enough to translate orally or employ some strategies to compensate for the lack of their linguistic knowledge. Therefore, the purpose of this study was to find out the types of communication strategies undergraduate students employ during oral translation and examine the relationship between authentic listening materials’ practice and employment of these strategies. To this end, 34 senior translation major students were videotaped and represented some CNN news samples in the laboratory and their oral translation performance was recorded, for three weeks, and extracted based on Tarone’s taxonomy (1977). The students listened to the audio materials of TOFEL IBT for 5 to 10 minutes a day 4 or 5 times a week at home for two months. Then the same news was represented in the laboratory for three weeks after listening to find whether the frequency of communication strategies has changed and listening materials have affected the frequencies. Despite the unawareness of communication strategies, the students locate them in oral translation. Finally, the statistical results revealed a significant relationship between authentic listening materials’ practice and the use of communication strategies.
From Efficacy to Effectiveness and Beyond: What Next for Brief Interventions in Primary Care?

Background: Robust evidence supports the effectiveness of screening and brief alcohol interventions in primary healthcare. However, lack of understanding about their “active ingredients” and concerns over the extent to which current approaches remain faithful to their original theoretical roots has led some to demand a cautious approach to future roll-out pending further research. Against this background, this paper provides a timely overview of the development of the brief alcohol intervention evidence base to assess the extent to which it has achieved the four key levels of intervention research: efficacy, effectiveness, implementation, and demonstration. Methods: Narrative overview based on (1) the results of a review of systematic reviews and meta-analyses of the effectiveness of brief alcohol intervention in primary healthcare and (2) synthesis of the findings of key additional primary studies on the improvement and evaluation of brief alcohol intervention implementation in routine primary healthcare. Results: The brief intervention field seems to constitute an almost perfect example of the evaluation of a complex intervention. Early evaluations of screening and brief intervention approaches included more tightly controlled efficacy trials and have been followed by more pragmatic trials of effectiveness in routine clinical practice. Most recently, attention has shifted to dissemination, implementation, and wider-scale roll-out. However, delivery in routine primary health remains inconsistent, with an identified knowledge gap around how to successfully embed brief alcohol intervention approaches in mainstream care, and as yet unanswered questions concerning what specific intervention component prompt the positive changes in alcohol consumption. Conclusion: Both the efficacy and effectiveness of brief alcohol interventions have been comprehensively demonstrated, and intervention effects seem replicable and stable over time, and across different study contexts. Thus, while unanswered questions remain, given the positive evidence amassed to date, research efforts should maintain a continued focus on promoting sustained implementation of screening and brief alcohol intervention approaches in primary care to ensure that those who might benefit from screening and brief alcohol interventions actually receive such support.
Consumption-Driven Market Emergence

New market development is well theorized from a firm-centered perspective, but research has paid scant attention to the emergence of markets from consumption activity. The exceptions conceptualize market emergence as a product of consumer struggle against prevailing market logics. This study develops a model of consumption-driven market emergence in harmony with existing market offerings. Using ethnographic methods and actor-network theory the authors chronicle the emergence of a new market within the motorcycle industry that develops with neither active participation nor interference from mainstream industry players. Findings reveal a process of multiple translations wherein consumers mobilize human and nonhuman actors to co-constitute products, practices, and infrastructures. These drive the growth of interlinked communities of practice, which ultimately are translated into a fully functioning market. The study highlights the roles of distributed innovation and diffusion, embedded entrepreneurship, and market catalysts in processes of market change and development.
Dynamic criteria and the measurement of change.

The question of whether work performance criteria are dynamic has been addressed by applied psychologists for many years. Despite this attention, we have few definitive answers. This article provides both theoretical and methodological arguments for refocusing investigations into dynamic criteria toward the study of intraindividual change and interindividual differences in intraindividual change. A longitudinal sample of insurance sales personnel's performance is used to demonstrate that systematic time trends are present at the individual level and that there are interindividual differences in these change patterns
When Majority Doesn’t Rule: The Use of Discrimination Indices to Improve the Quality of MCQs

Abstract This paper outlines the use of item analysis to assist examiners in evaluating the quality and validity of their MCQ exam questions. The generation of item analysis, particularly discrimination index, has long been established practice in professional testing and credentialing organisations and some disciplines in tertiary education, but its use appears to be inconsistent among Bioscience departments. We argue that generating some form of discrimination index is an essential part of the validation of exams, in particular to help identify errors in scoring, to identify potentially flawed questions, or to confirm the validity of challenging questions. We demonstrate each of these uses through examples drawn from first year Biology exams, with interpretations of the questions in the light of post-examination item analysis.
Motion based decompositing of video

We present a method to decompose video sequences into layers that represent the relative depths of complex scenes. Our method combines spatial information with temporal occlusions to determine relative depths of these layers. Spatial information is obtained through edge detection and a customized contour completion algorithm. Activity in a scene is used to extract temporal occlusion events, which are in turn, used to classify objects as occluders or occludes. The path traversed by the moving objects determines the segmentation of the scene. Several examples of decompositing and compositing of video are shown. This approach can be applied in the pre-processing of sequences for compositing or tracking purposes and to determine the approximate 3D structure of a scene.
Higher order versus second order statistics in ultrasound image deconvolution

We recently proposed a method for the estimation of imaging distortions associated with ultrasound images, based on the higher-order statistics (HOS) of radio frequency data. In this correspondence, we utilize the HOS-based estimated distortions to deconvolve ultrasound images of the breast. We also estimate imaging distortions based on the second-order statistics (SOS) of radio frequency ultrasound data and subsequently utilize them to deconvolve the same breast images. Both subjective and objective measures suggest that deconvolution with HOS-based distortion estimates led to significantly higher resolution gains as compared to the gains achieved when SOS-based distortion estimates were used.
p21 promotes error-free replication-coupled DNA double-strand break repair

p21 is a well-established regulator of cell cycle progression. The role of p21 in DNA repair, however, remains poorly characterized. Here, we describe a critical role of p21 in a replication-coupled DNA double-strand break (DSB) repair that is mechanistically distinct from its cell cycle checkpoint function. We demonstrate that p21-deficient cells exhibit elevated chromatid-type aberrations, including gaps and breaks, dicentrics and radial formations, following exposure to several DSB-inducing agents. p21−/− cells also exhibit an increased DNA damage-inducible DNA-PKCS S2056 phosphorylation, indicative of elevated non-homologous DNA end joining. Concomitantly, p21−/− cells are defective in replication-coupled homologous recombination (HR), exhibiting decreased sister chromatid exchanges and HR-dependent repair as determined using a crosslinked GFP reporter assay. Importantly, we establish that the DSB hypersensitivity of p21−/− cells is associated with increased cyclin-dependent kinase (CDK)-dependent BRCA2 S3291 phosphorylation and MRE11 nuclear foci formation and can be rescued by inhibition of CDK or MRE11 nuclease activity. Collectively, our results uncover a novel mechanism by which p21 regulates the fidelity of replication-coupled DSB repair and the maintenance of chromosome stability distinct from its role in the G1-S phase checkpoint.
Mental Health Following Acquisition of Disability in Adulthood—The Impact of Wealth

Background Acquisition of a disability in adulthood has been associated with a reduction in mental health. We tested the hypothesis that low wealth prior to disability acquisition is associated with a greater deterioration in mental health than for people with high wealth. Methods We assess whether level of wealth prior to disability acquisition modifies this association using 12 waves of data (2001–2012) from the Household, Income and Labour Dynamics in Australia survey–a population-based cohort study of working-age Australians. Eligible participants reported at least two consecutive waves of disability preceded by at least two consecutive waves without disability (1977 participants, 13,518 observations). Fixed-effects linear regression was conducted with a product term between wealth prior to disability (in tertiles) and disability acquisition with the mental health component score of the SF–36 as the outcome. Results In models adjusted for time-varying confounders, there was evidence of negative effect measure modification by prior wealth of the association between disability acquisition and mental health (interaction term for lowest wealth tertile: -2.2 points, 95% CI -3.1 points, -1.2, p<0.001); low wealth was associated with a greater decline in mental health following disability acquisition (-3.3 points, 95% CI -4.0, -2.5) than high wealth (-1.1 points, 95% CI -1.7, -0.5). Conclusion The findings suggest that low wealth prior to disability acquisition in adulthood results in a greater deterioration in mental health than among those with high wealth.
Methylene Blue as a Cerebral Metabolic and Hemodynamic Enhancer

By restoring mitochondrial function, methylene blue (MB) is an effective neuroprotectant in many neurological disorders (e.g., Parkinson’s and Alzheimer’s diseases). MB has also been proposed as a brain metabolic enhancer because of its action on mitochondrial cytochrome c oxidase. We used in vitro and in vivo approaches to determine how MB affects brain metabolism and hemodynamics. For in vitro, we evaluated the effect of MB on brain mitochondrial function, oxygen consumption, and glucose uptake. For in vivo, we applied neuroimaging and intravenous measurements to determine MB’s effect on glucose uptake, cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) under normoxic and hypoxic conditions in rats. MB significantly increases mitochondrial complex I–III activity in isolated mitochondria and enhances oxygen consumption and glucose uptake in HT-22 cells. Using positron emission tomography and magnetic resonance imaging (MRI), we observed significant increases in brain glucose uptake, CBF, and CMRO2 under both normoxic and hypoxic conditions. Further, MRI revealed that MB dramatically increased CBF in the hippocampus and in the cingulate, motor, and frontoparietal cortices, areas of the brain affected by Alzheimer’s and Parkinson’s diseases. Our results suggest that MB can enhance brain metabolism and hemodynamics, and multimetric neuroimaging systems offer a noninvasive, nondestructive way to evaluate treatment efficacy.
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The growing interest in membrane interactions of amyloidogenic peptides and proteins emanates from the realization that lipids and membranes play important, potentially central, roles in the toxicity and pathological pathways of amyloid diseases. Expanding body of evidence indicates that lipid binding of amyloidogenic peptides and amyloid peptide association with cellular membranes is critical in the onset and progression of amyloid diseases. Advancing the understanding in this field goes hand in hand with application of varied biophysical and biological techniques designed to probe the characteristics and underlying mechanisms of membrane-peptide interactions. This review summarizes experimental approaches and technical aspects employed in recent years for investigating the interaction of amyloid peptides and fibrillar species with lipid bilayers, and the reciprocal contribution of membranes to fibrillation processes and amyloidogenesis.