Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of Single Application of Doxycycline Hyclate in Treatment of Recurrent Aphthousstomatitis

Aim: The aim of the present study is to evaluate the efficacy of topical application of single dose of doxycycline hyclate 100mg tablet as a new therapeutic regimen in the treatment of minor RAU for pain reduction. Methods: The patients diagnosed with minor recurrent aphthous ulcers fulfilling the inclusion and exclusion criteria were enrolled. The study was conducted in the Department of ENT, H&NS, SKIMS-MC, Srinagar (J&K) India from January 2017 to January 2018 after approval by institutional ethical committee. This study included a total of 50 patients which were divided into two groups each of 25 patients. Group I: 25 patients receiving doxycycline hyclate 100 mg tablets (Doxt 100). GroupII: 25 patients receiving placebotablet. Results: The data indicated a significant reduction in pain in group A (i.e., faster reduction in pain) compared with group B. On the third day, pain score was 3.80 in the study group and 5.65 in the control group [Table 1] with P value of 0.079 and it was found highly significant on the fifth day with a P value of <0.001using unpaired t‐test. Conclusion: Healing of the ulcer was significantly faster for thedoxycycline group compared to placebogroup. The doxycycline was found to be effective in treating oral aphthousulceration. It appears advantageous because of its cost‐effectiveness, single application, and faster symptomatic relief than other drugs.
Knowledge-sharing in virtual communities: familiarity, anonymity and self-determination theory

Although the role of motivation has been emphasised in knowledge-sharing literature, traditional motivation theories, such as self-determination theory (SDT), have not been actively used as a research framework in knowledge-sharing research. The purposes of this study are twofold. The first objective is to propose a model, based on SDT, to test the effect of the three basic psychological needs – perceived competence, perceived autonomy and perceived relatedness – on knowledge-sharing behaviours in virtual communities. The second objective is to explore the effects of familiarity and anonymity on the basic psychological needs to better understand individuals’ knowledge-sharing behaviours in virtual communities. The results show that perceived competence and perceived relatedness influence knowledge-sharing behaviours in virtual communities; however, perceived autonomy does not influence knowledge-sharing behaviours; familiarity influences positively perceived competence and perceived relatedness, and anonymity influences negatively perceived autonomy and perceived relatedness.
Diagrams as Physical Models to Assist in Reasoning

Diagrams serve a variety of roles in applied reasoning. At times, they are best viewed as \sentences" in a 2-D language, with specialized rules of inference that provide new diagrams. Other times, however, they are best understood as providing a physical model, much like an architectural model of a building or a 3-D molecular model of a chemical compound, for a state of afiairs. In this paper, I discuss the notion of a physical model for a logical sentence, and the role played by the causal structure of the physical medium in making the given sentence as well as a set of implied sentences true. When the physical model is prototypical, it supports the inference of certain other sentences for which it provides a model as well. I also informally discuss a proposal that diagrams and similar physical models help to explicate a certain sense of relevance in inference, an intuition that so-called Relevance Logics attempt to capture.
Do You “Work to Live” Or “Live to Work”? the Role of Mood and Confidence in Causal Agency

The literature has suggested that wanting to feel good leads to short-term indulgent choices. We suggest that attributing happiness to the self moves individuals from focusing on external sources of happiness (e.g., chocolates) to internal sources of happiness (e.g., one’s behavior, personal development). Such liberation of the self from external sources of happiness facilitates behaviors that are beneficial in personal development. Thus, confidence in agency attribution determines whether an external or internal mode of happiness governs behavior. Implications for the literatures on emotions, self-regulation, and consumer welfare will be discussed.
Estimation and Uncertainty Analysis of Impacts of Future Heat Waves on Mortality in the Eastern United States

Background: Climate change is anticipated to influence heat-related mortality in the future. However, estimates of excess mortality attributable to future heat waves are subject to large uncertainties and have not been projected under the latest greenhouse gas emission scenarios. Objectives: We estimated future heat wave mortality in the eastern United States (approximately 1,700 counties) under two Representative Concentration Pathways (RCPs) and investigated sources of uncertainty. Methods: Using dynamically downscaled hourly temperature projections for 2057–2059, we projected heat wave days that were defined using four heat wave metrics and estimated the excess mortality attributable to them. We apportioned the sources of uncertainty in excess mortality estimates using a variance-decomposition method. Results: Estimates suggest that excess mortality attributable to heat waves in the eastern United States would result in 200–7,807 deaths/year (mean 2,379 deaths/year) in 2057–2059. Average excess mortality projections under RCP4.5 and RCP8.5 scenarios were 1,403 and 3,556 deaths/year, respectively. Excess mortality would be relatively high in the southern states and eastern coastal areas (excluding Maine). The major sources of uncertainty were the relative risk estimates for mortality on heat wave versus non–heat wave days, the RCP scenarios, and the heat wave definitions. Conclusions: Mortality risks from future heat waves may be an order of magnitude higher than the mortality risks reported in 2002–2004, with thousands of heat wave–related deaths per year in the study area projected under the RCP8.5 scenario. Substantial spatial variability in county-level heat mortality estimates suggests that effective mitigation and adaptation measures should be developed based on spatially resolved data. Citation: Wu J, Zhou Y, Gao Y, Fu JS, Johnson BA, Huang C, Kim YM, Liu Y. 2014. Estimation and uncertainty analysis of impacts of future heat waves on mortality in the eastern United States. Environ Health Perspect 122:10–16; http://dx.doi. org/10.1289/ehp.1306670
Casting a Wider Net: Whole-Cell Assays to Capture Varied and Biased Signaling

The observation of complex receptor behaviors has shown how ligands can have multiple efficacies and can also differentially stimulate certain cellular signaling pathways over others (i.e., biased signaling). Conventional pharmacological assays (usually proximal to the receptor) will detect ligands that produce the signal defined by the assay (i.e., Ca2+, cAMP, and others) but otherwise may miss biased ligands that produce little activation of pathways not measured by the assay. In theory, this is less of a hazard for generic whole-cell assays, which may be sensitive to multiple signaling inputs. Whole-cell assays have the advantage of detecting effects induced by a variety of receptor interactions with cytosolic proteins, including those that may be previously unknown. These ideas are discussed within the context of the high-throughput flow cytometry measurement of receptor internalization described by Wu et al. in the current issue of the journal (p. 645). The internalization of receptors can be a useful therapeutic modality and the article by Wu et al. illustrates how this new assay, targeted to downstream cellular effects, can uncover unique ligand efficacies linked to receptor internalization.
Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens

The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neoantigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer.
Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients

Background: Current therapies for chronic hepatitis C virus (HCV) in HIV co-infected patients have a low success rate and are poorly tolerated. We have evaluated the efficacy and safety of interferon alfa-2b (IFN) + ribavirin (RBV) versus pegylated interferon alfa-2b (PEG-INF) + RBV. Methods: Randomized, single-centre, open-label clinical trial including patients with: detectable HCV-RNA, alanine aminotransferase > 1.5-fold upper limit of normal, abnormal liver histology, CD4 cell count > 250 × 106/l and HIV RNA < 10 000 copies/ml. Patients were assigned to INF (3 × 106 units three times/week) or PEG-IFN (100–150 μg/week) plus RBV (800–1200 mg/day). Duration of treatment was 48 weeks (only 24 weeks for HCV genotypes 2 or 3 and baseline HCV RNA < 800 000 IU/ml). The primary endpoint was a sustained virological response (SVR). Results: Ninety-five patients were randomized (43 INF + RBV, 52 PEG-INF + RBV), 68% males, 82% injecting drug users; 63% genotypes 1 or 4 and 36% genotypes 2 or 3; 62% fibrosis index grade ⩾2 and 30% bridging fibrosis/cirrhosis. SVR was significantly higher in the PEG-INF + RBV arm, 44% versus 21% (intent to treat; P = 0.017). Among patients with genotypes 1 or 4, SVR were 38% versus 7% (P = 0.007) and 53% versus 47% (P = 0.730) for genotypes 2 or 3. CD4 cell count but not its percentage dropped in both arms and HIV RNA viral load did not change from baseline. Side effects were very frequent in both arms leading to treatment discontinuation in 14 patients without statistical differences between arms (P = 0.565). Conclusion: PEG-INF + RBV was significantly more effective than INF + RBV for the treatment of chronic hepatitis C in HIV co-infected patients, mainly of genotype 1 or 4.
Crop–Livestock Interactions in the West African Drylands

Many semiarid regions of Sub-Saharan Africa (SSA) are experiencing vast increases in human population pressure and urbanization. These augment the demand for agricultural products and have led to the expansion, intensification, and often closer integration of crop and livestock production systems. The transition of crop and livestock production from the current relatively extensive, low input/output modes of production to more intensive, higher input/output modes of production presents numerous challenges to the achievement of required long-term production increases from these farming systems. This paper provides an overview of the challenges facing agricultural production in semiarid SSA with a focus on West Africa. A description of mixed crop-livestock farming systems and their evolution is followed by an overview of the principal linkages between crops and livestock: income, animal power, feed, and manure. The most detailed discussions relate to nutrient cycling in these farming systems. Most livestock derive their feed almost exclusively from natural rangeland and crop residues, and livestock manure is a precious soil fertility amendment. However, most farmers have insufficient livestock and therefore manure to sustain food production. Nutrient harvests from cropland often exceed nutrient inputs, and soil nutrient depletion is a principal concern. The paper concludes with a discussion of strategies that may improve the productive capacity of these mixed farming systems.
Management of metastatic phaeochromocytoma and paraganglioma: use of iodine-131-meta-iodobenzylguanidine therapy in a tertiary referral centre.

BACKGROUND Phaeochromocytoma (phaeo) and paraganglioma (PGL) are rare conditions, which are malignant in up to 30%. Optimal treatment is controversial, but in patients with metastatic iodine-131-meta-iodobenzylguanidine ((123)I-MIBG) avid tumours, we offer (131)I-MIBG therapy. We summarize response rates, survival and safety in a cohort of such patients treated with (131)I-MIBG in our centre from 1986 to 2012. DESIGN/METHODS Retrospective analysis of the case notes of patients with metastatic phaeo/PGL who received (131)I-MIBG was undertaken; patients underwent clinical, biochemical and radiological evaluation within 6 months of each course of (131)I-MIBG therapy. RESULTS Twenty-two patients (9 males) were identified, 12 with metastatic PGL and 10 with phaeo. Overall median follow-up time after first dose of (131)I-MIBG was 53 months. In total, 68 doses of (131)I-MIBG were administered; average dose was 9967 MBq (269.4 mCi). After the first dose, >50% of patients demonstrated disease stability or partial response; progressive disease was seen in 9%. A subset of patients underwent repeated treatment with the majority demonstrating partial response or stable disease. No life-threatening adverse events were reported, but three patients developed hypothyroidism and two developed ovarian failure after repeated dosing. Five-year survival after original diagnosis was 68% and median (+inter quartile range) survival from date of diagnosis was 17 years (7.6-26.4) with no difference in survival according to diagnosis (P < 0.1). CONCLUSIONS (131)I-MIBG is well tolerated and associates with disease stabilization or improvement in the majority of patients with metastatic phaeo/PGL. However, stronger conclusions on treatment effectiveness are limited by lack of a directly comparable 'control group' as well as an alternative 'gold standard' treatment.
XB130, a New Adaptor Protein, Regulates Expression of Tumor Suppressive MicroRNAs in Cancer Cells

XB130, a novel adaptor protein, promotes cell growth by controlling expression of many related genes. MicroRNAs (miRNAs), which are frequently mis-expressed in cancer cells, regulate expression of targeted genes. In this present study, we aimed to explore the oncogenic mechanism of XB130 through miRNAs regulation. We analyzed miRNA expression in XB130 short hairpin RNA (shRNA) stably transfected WRO thyroid cancer cells by a miRNA array assay, and 16 miRNAs were up-regulated and 22 miRNAs were down-regulated significantly in these cells, in comparison with non-transfected or negative control shRNA transfected cells. We chose three of the up-regulated miRNAs (miR-33a, miR-149 and miR-193a-3p) and validated them by real-time qRT-PCR. Ectopic overexpression of XB130 suppressed these 3 miRNAs in MRO cells, a cell line with very low expression of XB130. Furthermore, we transfected miR mimics of these 3 miRNAs into WRO cells. They negatively regulated expression of oncogenes (miR-33a: MYC, miR-149: FOSL1, miR-193a-3p: SLC7A5), by targeting their 3′ untranslated region, and reduced cell growth. Our results suggest that XB130 could promote growth of cancer cells by regulating expression of tumor suppressive miRNAs and their targeted genes.
Effect of non‐pulsatile renal blood flow on plasma erythropoietin

Erythropoietin is a hormone responsible for regulation of red blood cell production. Circulating erythropoietin values are regulated by renal oxygen supply, which is determined by hemoglobin concentration, hemoglobin oxygen saturation, and renal blood flow. Previous animal and human studies regarding erythropoietin regulation have assumed pulsatile renal blood flow. During cardiopulmonary bypass, non‐pulsatile renal perfusion has been shown to result in decreased glomerular filtration rate and decreased renal blood flow in comparison to pulsatile perfusion. Repair of congenital heart disease during cardiopulmonary bypass is an attractive circumstance in which to study the effect of non‐pulsatile blood flow on erythropoietin production. The hypothesis in this study was that non‐pulsatile perfusion would result in increased erythropoietin production because of decreased renal oxygen supply. Fourteen children with congenital heart disease and without preoperative renal insufficiency or anemia were enrolled in the study. All patients underwent cardiopulmonary bypass with non‐pulsatile flow. In addition, 10 control patients without congenital heart disease were enrolled. Six cardiopulmonary bypass patients had 1.5‐ to 6‐fold increases in plasma erythropoietin concentrations from baseline. These patients had longer cardiopulmonary bypass times, more commonly performed under low flow deep hypothermic conditions. The remaining 8 patients with congenital heart disease, and all control patients, did not develop increased postoperative erythropoietin concentrations. The conditions under which cardiopulmonary bypass are performed appear to influence postoperative circulating erythropoietin concentrations. Am. J. Hematol. 57:144–147, 1998. © 1998 Wiley‐Liss, Inc.
Lack of international consensus in low-risk drinking guidelines.

INTRODUCTION AND AIMS To encourage moderate alcohol consumption, many governments have developed guidelines for alcohol intake, guidelines for alcohol consumption during pregnancy and legislation relating to blood alcohol limits when driving. The aim of this study was to determine the degree of international consensus within such guidelines. DESIGN AND METHODS Official definitions of standard drinks and consumption guidelines were searched for on government websites, including all 27 European Union Member States and countries from all global geographic regions. RESULTS There was a remarkable lack of agreement about what constitutes harmful or excessive alcohol consumption on a daily basis, a weekly basis and when driving, with no consensus about the ratios of consumption guidelines for men and women. DISCUSSION AND CONCLUSIONS International consensus in low-risk drinking guidelines is an important--and achievable--goal. Such agreement would facilitate consistent labelling of packaged products and could help to promote moderate alcohol consumption. However, there are some paradoxes related to alcohol content labelling and people's use of such information: although clearer information could increase people's capacity to monitor and regulate their alcohol consumption, not all drinkers are motivated to drink moderately or sensibly, and drinkers who intend to get drunk may use alcohol content labelling to select more alcoholic products.
Structural model and functional significance of pH-dependent talin–actin binding for focal adhesion remodeling

Actin filament binding by the focal adhesion (FA)-associated protein talin stabilizes cell-substrate adhesions and is thought to be rate-limiting in cell migration. Although F-actin binding by talin is known to be pH-sensitive in vitro, with lower affinity at higher pH, the functional significance of this pH dependence is unknown. Because increased intracellular pH (pHi) promotes cell migration and is a hallmark of metastatic carcinomas, we asked whether it increases FA remodeling through lower-affinity talin–actin binding. Talin contains several actin binding sites, but we found that only the COOH-terminal USH-I/LWEQ module showed pH-dependent actin binding, with lower affinity and decreased maximal binding at higher pH. Molecular dynamics simulations and NMR of this module revealed a structural mechanism for pH-dependent actin binding. A cluster of titratable amino acids with upshifted pKa values, including His-2418, was identified at one end of the five-helix bundle distal from the actin binding site. Protonation of His-2418 induces changes in the conformation and dynamics of the remote actin binding site. Structural analyses of a mutant talin-H2418F at pH 6.0 and 8.0 suggested changes different from the WT protein, and we confirmed that actin binding by talin-H2418F was relatively pH-insensitive. In motile fibroblasts, increasing pHi decreased FA lifetime and increased the migratory rate. However, expression of talin-H2418F increased lifetime 2-fold and decreased the migratory rate. These data identify a molecular mechanism for pH-sensitive actin binding by talin and suggest that FA turnover is pH-dependent and in part mediated by pH-dependent affinity of talin for binding actin.
Hierarchical Conflict Propagation: Sequence Learning in a Recurrent Deep Neural Network

Recurrent neural networks (RNN) are capable of learning to encode and exploit activation history over an arbitrary timescale. However, in practice, state of the art gradient descent based training methods are known to suffer from difficulties in learning long term dependencies. Here, we describe a novel training method that involves concurrent parallel cloned networks, each sharing the same weights, each trained at different stimulus phase and each maintaining independent activation histories. Training proceeds by recursively performing batch-updates over the parallel clones as activation history is progressively increased. This allows conflicts to propagate hierarchically from short-term contexts towards longer-term contexts until they are resolved. We illustrate the parallel clones method and hierarchical conflict propagation with a character-level deep RNN tasked with memorizing a paragraph of Moby Dick (by Herman Melville).
Compositional abstractions of interconnected discrete-time stochastic control systems

This paper is concerned with a compositional approach for constructing abstractions of interconnected discrete-time stochastic control systems. The abstraction framework is based on new notions of so-called stochastic simulation functions, using which one can quantify the distance between original interconnected stochastic control systems and their abstractions in the probabilistic setting. Accordingly, one can leverage the proposed results to perform analysis and synthesis over abstract interconnected systems, and then carry the results over concrete ones. In the first part of the paper, we derive sufficient small-gain type conditions for the compositional quantification of the distance in probability between the interconnection of stochastic control subsystems and that of their abstractions. In the second part of the paper, we focus on the class of discrete-time linear stochastic control systems with independent noises in the abstract and concrete subsystems. For this class of systems, we propose a computational scheme to construct abstractions together with their corresponding stochastic simulation functions. We demonstrate the effectiveness of the proposed results by constructing an abstraction (totally 4 dimensions) of the interconnection of four discrete-time linear stochastic control subsystems (together 100 dimensions) in a compositional fashion.