Miracle-dz/UniFAR-FTUs huggingface dataset:
miRTarBase 2020: updates to the experimentally validated microRNA–target interaction database

Abstract MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18–25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA–target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA–target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk. edu.cn/.
Importance of phosphorylation/dephosphorylation cycles on lipid-dependent modulation of membrane protein topology by posttranslational phosphorylation

Posttranslational modifications of proteins, such as phosphorylation and dephosphorylation, play critical roles in cellular functions through diverse cell signaling pathways. Protein kinases and phosphatases have been described early on as key regulatory elements of the phosphorylated state of proteins. Tight spatial and temporal regulation of protein kinase and phosphatase activities has to be achieved in the cell to ensure accurate signal transduction. We demonstrated previously that phosphorylation of a membrane protein can lead to its topological rearrangement. Additionally, we found that both the rate and extent of topological rearrangement upon phosphorylation are lipid charge– and lipid environment–dependent. Here, using a model membrane protein (the bacterial lactose permease LacY reconstituted in proteoliposomes) and a combination of real-time measurements and steady-state assessments of protein topology, we established a set of experimental conditions to dissect the effects of phosphorylation and dephosphorylation of a membrane protein on its topological orientation. We also demonstrate that the phosphorylation-induced topological switch of a membrane protein can be reversed upon protein dephosphorylation, revealing a new regulatory role for phosphorylation/dephosphorylation cycles. Furthermore, we determined that the rate of topological rearrangement reversal is correlated with phosphatase activity and is influenced by the membrane's lipid composition, presenting new insights into the spatiotemporal control of the protein phosphorylation state. Together, our results highlight the importance of the compartmentalization of phosphorylation/dephosphorylation cycles in controlling membrane protein topology and, therefore, function, which are influenced by the local lipid environment of the membrane protein.
Salidroside protects the cardiac function of exhausted rats by inducing Nrf2 expression.

OBJECTIVE To investigate whether salidroside (Sal) protected the rat heart from exhaustive exercise-induced injury by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. METHODS Forty-eight male Sprague-Dawley rats were divided into four groups (n = 12 rats per group): the control, the exhaustive swimming (ES) group, the low-dose Sal plus acute exhaustive swimming (SLE) group, and the high-dose Sal plus acute exhaustive swimming (SHE) group. In the SLE and SHE groups, 15 and 30 mg/kg Sal were administered, respectively, once a day. The rats in the control and ES groups were administered the same amount of physiological saline, respectively, once a day. On the 14th day, the rats in the ES, SLE and SHE groups underwent exhaustive swimming training once. Then cardiac function parameters and electrocardiograms were recorded. Biomarkers of myocardial injury in the serum and oxidative stress factors in the myocardial tissue were evaluated using ELISA tests. The levels of Nrf2, nuclear Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) messenger RNA and proteins were assessed in the myocardium using q-PCR and Western blotting, respectively. RESULTS Compared to the control group, the ES group showed remarkable increases in serum brain natriuretic peptide (BNP), cardiac troponin I (cTnI) and reactive oxygen species levels, but significant decreases in catalase and glutathione levels (p < 0.05). Compared to the ES group, the Sal treatment decreased serum BNP and cTnI levels and alleviated the changes in levels of oxidative stress-related factors. After treatment with Sal, nuclear and intracellular levels of Nrf2 protein were increased in the myocardial cells, while the level of Keap1 protein was decreased (p < 0.05). CONCLUSIONS Sal protected the heart from exhaustive exercise induced injury, and it may improve cardiac function and cardiac bioelectricity in exhausted rats by inducing Nrf2 expression.
Specifying Future Behavior When Assessing Risk Perceptions: Implications for Measurement and Theory

Background. Many theories assert that high perceived risk motivates health behavior change; the empirical literature shows mixed findings. Purpose. To determine whether, for whom, and under what circumstances specifying a future behavior when assessing perceived risk (i.e., “conditioning” risk perception items on behavior) improves data quality and strengthens the perceived risk-intentions/behavior relationship. Methods. Internet panel participants (N = 787, 58.8% no college experience, 44.4% racial/ethnic minority, 43.7% men, 67.3% aged 18–49 years, 59.0% nonadherent to physical activity guidelines) answered 8 colon cancer perceived risk items in a within-subjects design. Participants answered 4 types of risk perception items: absolute and comparative perceived likelihood and absolute and comparative feelings of risk. Participants answered each type of item twice: once conditioned on not engaging in physical activity and once unconditioned. Results. Compared to unconditioned items, conditioned items elicited fewer “don’t know” (DK) responses (OR = 0.80; 95% CI, 0.68–0.93), higher risk perceptions (b = 0.55; 95% CI, 0.49–0.61) and stronger positive correlations with intentions (zSteiger = 5.46, P < 0.001) and behavior (zSteiger = 5.10, P < 0.001). The effect of conditioning was more pronounced for perceived likelihood than feelings of risk items (OR = 2.21; 95% CI, 1.63–3.01 and b = 0.14; 95% CI, 0.08–0.20 for DK responding and risk perception magnitude, respectively). The effect on risk perception magnitude (except absolute feelings of risk) was higher among people with higher health literacy (χ2(3) = 8.11, P = 0.04). Conclusions. Researchers who examine whether perceived risk motivates precautionary behavior should consider conditioning risk perception items on behavior to increase the validity of the statistical conclusions they draw and to gain insight into the nature of perceived risk and its relation to behavior.
Ethanol and its metabolites: update on toxicity, benefits, and focus on immunomodulatory effects

Abstract This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as the impact of genetic polymorphism in its physiopathology are also highlighted. The section dealing with the beneficial effects of low to moderate alcohol consumption (on cardiovascular system, diabetes, the nervous system and sensory organs, autoimmune diseases, and rheumatology) highlights the importance of anti-inflammatory and immunomodulatory effects in these observations. This knowledge, enriched by a focus on the immunomodulatory effects of ethanol and its metabolites, in particular on the NLRP3 inflammasome pathway, might facilitate the development of treatments that can reduce ethanol’s harmful effects or accentuate its beneficial effects.
Platelet-rich fibrin to preserve alveolar bone sockets following tooth extraction: A randomized controlled trial.

BACKGROUND Platelet-rich fibrin (PRF) can be used in the alveolar socket preservation (ARP). However, the hard tissue-regeneration property of PRF in alveolar socket preservation is still unclear. PURPOSE To compare the new bone formation ratio between using PRF as a socket preservation material and normal wound healing, by means of histomorphometric analysis. MATERIALS AND METHODS Thirty-three healthy volunteers were recruited and randomized into PRF and control group. Minimally traumatic extractions were performed. Eighteen patients were treated with ARP using PRF, while the rest were left to heal naturally. Bone specimens were harvested using trephine bur 2 months after the extraction process. Histomorphometric analysis of new bone formation area compared with total socket area was performed using the software Fiji Is Just Image J (version 2, GNU General Public License). RESULTS Thirty-three volunteers were participated. Twenty-eight bone specimens were collected. The new bone formation ratio was higher in PRF group than in control group (31.33 ± 18% and 26.33 ± 19.63%, respectively). However, there was no statistically significant difference in the ratio between the PRF and control groups (P = .431). CONCLUSIONS It may be concluded that the use of PRF in ARP does not statistically significant enhance new bone formation after tooth extraction compared to normal wound healing (P > .05).
Communicating Dynamic Behaviors in Basketball: The Role of Verbal Instructions and Arrow Symbols

ABSTRACT Purpose: Guided by cognitive load theory and cognitive theory of multimedia learning, the purpose of this study was to evaluate players' ability to integrate dynamic information presented under different conditions: a verbal condition, in which instructions were given orally; a visual condition, in which instructions were shown using arrow symbols; and a redundant condition, in which both visual and verbal instructions were presented simultaneously. Method: In a 2 × 3 design, we asked basketball players with varied levels of skill (less-skilled, skilled) to rate their invested mental effort and to perform a recall test after learning from either the verbal, visual or redundant condition. Results: Results demonstrated that the less-skilled players benefited more from the redundant condition, whereas the skilled participants benefited more from the visual condition. Conclusion: Recommendations for improving instructional design techniques aimed at the transmission of tactical instructions in team games are proposed.
Effects of deletion neighbourhood frequency and individual differences in lexical decision, progressive demasking, and naming.

This study investigates whether deletion neighbourhood frequency influences the processing of French written words, and whether it might also be influenced by individual differences in skilled adult readers. For this purpose, words with at least 1 higher-frequency deletion neighbour (e.g., pliage [folding]/plage [beach]) and others with no higher-frequency neighbour (e.g., morose [gloomy]) were presented in lexical decision (Experiment 1), progressive demasking (Experiment 2), and naming (Experiment 3) tasks. For each experiment, the participants' lexical skills were assessed by spelling, reading, and vocabulary tests. In Experiments 1-3, participants responded more slowly to words with at least 1 higher-frequency deletion neighbour than they did to words with no such neighbour. We also found evidence that the inhibitory effect of deletion neighbourhood frequency was sensitive to lexical skills in the naming task. These findings are discussed in terms of lexical competition underlying visual word recognition according to individual differences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
CECDAIic – a new useful tool in pan-intestinal evaluation of Crohn’s disease patients in the era of mucosal healing

Abstract Background: Pan-intestinal capsule endoscopy (Pan-CE) has been used to assess both the small and large bowel inflammation in Crohn’s disease (CD) patients in a single examination. The capsule endoscopy Crohn’s disease activity index (CECDAI) was initially developed to measure mucosal disease activity in the small bowel, although in 2018, it was extended to the colon for standardization of inflammatory activity (CECDAIic). The aim of this study was to apply the CECDAIic in a cohort of CD patients that underwent Pan-CE to evaluate the inter-observer agreement and the correlation between this score and inflammatory parameters. Methods: The videos were read and scored using the CECDAIic by three independent experienced operators, blinded to the results of the standard workup. Statistical analysis was performed with SPSS®, using Kendall’s coefficient to evaluate the inter-observer agreement. Spearman correlation (rs) was used to access the correlation between the score and inflammatory biomarkers. Results: Included 22 patients, 59.1% males with mean age of 30.7 ± 11.1 years. The median CECDAIic score was 9.17 (0–37). The overall CECDAIic score Kendall coefficient was 0.94, demonstrating a statistically significant (p < .001) and excellent agreement between the three observers. In addition, we found a very good correlation between CECDAIic and calprotectin (rs = 0.82; p = .012) and a moderate correlation with C-reactive protein (CRP, rs = 0.50; p = .019). Conclusions: CECDAIic is a new score with excellent inter-observer agreement and strong correlation with calprotectin levels.
Gastrointestinal helminths in dog feces surrounding suburban areas of Lower Dir district, Pakistan: A public health threat.

Data on environmental contamination of the parasites of zoonotic importance is scarce in Pakistan. Soil contamination with feces of dogs hide infective stages of the parasite represents a health-risk to humans. This study was aimed to assess the eggs of gastrointestinal parasites of stray dogs and household dogs in lower Dir district, Pakistan with special consideration to those that can be spread to humans. One hundred and fifty two stool specimens from (stray dogs=90 and household dogs=62) were collected. The helminth eggs were processed by direct smear method and centrifugation techniques and identified by microscopic examination. Of the total examined dogs 26.8% (n=41 /152) were found to be infected with one or more intestinal parasites. The intestinal helminths detected were Dipylidium caninum (n =18, 11.8%), followed by Toxocara canis (n =16, 10.5%), Taenia spp. , (n=10, 6.57%) Ancylostoma caninum (n=6, 3.94), Toxascaris spp. , Capillaria spp. , and Trichuris vulpis (n=2, 1.31% each) in order of their prevalence. Pattern of infection revealed that 27 (65.8%) dogs have single, 13(31.7%) double and 1(2.43%) triple infection. The stray dogs were highly infected 34.4% (n=31) than house hold dogs 16.1% (n=10). The prevalence of infection with intestinal parasites was significantly different among these two groups (p = 0.0097). This study highlight a severe environmental contamination by frequent parasitic stages infectious to humans. There is a higher risk of zoonotic transmission from dogs which indicate an immediate need for the controlling of these parasites and educating the public to take wise action relating to the parasites and pets.
Dissemination of Cognitive Behavioral Therapy for Substance Use Disorders in the Department of Veterans Affairs Health Care System: Description and Evaluation of Veteran Outcomes

Background As part of the nation's largest dissemination and implementation of evidence-based psychotherapies (EBPs) and the promotion of EBPs for substance use disorders (SUDs), the Veterans Health Administration (VHA) is working to nationally implement Cognitive Behavioral Therapy for SUD (CBT-SUD). The current manuscript describes the approach to system-wide training and reports Veteran outcomes associated with CBT-SUD implementation. Methods Four-hundred fifty-eight Veterans with a range of treatment goals received treatment through the Department of Veterans Affairs (VA) CBT-SUD Training Program. Veteran outcomes related to substance use, substance use-related problems, and quality of life were assessed with the Brief Addiction Monitor, the Short Inventory of Problems, and the World Health Organization Quality of Life-BREF. Results Statistically significant reductions in alcohol use, heavy alcohol use, other drug use, and substance use-related problems, as well as significant improvements in quality of life, were observed over the course of treatment. Conclusions Program evaluation findings suggest that large-scale training in and implementation of EBPs for SUDs is associated with improvements in substance use and other functional outcomes. Limitations from this real-world implementation project, including the lack of a control group and missing post-treatment data, are discussed.
Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis

Abstract Background Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. Objective To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. Methods Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). Results A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. Conclusions Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.
High expression of mesothelin in advanced serous ovarian cancer is associated with poor prognosis.

PURPOSE Mesothelin is a cell surface glycoprotein which is highly expressed in various types of epithelial cancers. Its expression level is associated with poor prognosis in many cancer types. The aim this study was to evaluate the association of the level of mesothelin expression with clinicopathological characteristics and its prognostic significance in patients with advanced serous ovarian cancer (SOC). METHODS Tissue blocks from a total 42 patients with advanced SOC treated at the medical oncology clinic of Izmir Katip Celebi University Ataturk Training and Research Hospital between 2006 and 2013 were evaluated. Immunohistochemical staining for mesothelin was performed. Clinical characteristics, optimal or suboptimal operation, response to platinum-based chemotherapy, and overall survival (OS) were analyzed. RESULTS The cut-off value of 45 for mesothelin H-score determined by ROC analysis predicted survival with 86% sensitivity and 75% specificity (p=0.020). We found a notable negative correlation between mesothelin H-score and OS (r = -0.570, p=0.0001). The median OS was 67 months (95%CI, 36.114 to 97.886) in the low-staining mesothelin H-score group and 27 months (95%CI, 22.238 to 31.762) in the high-staining mesothelin H-score group (p=0.002). Univariate analysis showed that the clinical stage IV disease (p=0.023), platinum chemoresistance (p=0.001), higher mesothelin H-score (p=0.002), and suboptimal surgery (p=0.024) were associated with worse OS. In the multivariate Cox regression model, mesothelin H-score (B=1.15, 95%CI=1.016 to 9.850, p=0.047) and the status of platinum sensitivity (B=-. 916, 95%CI=. 185 to -. 864, p=0.020 were statistically significant predictors for OS. CONCLUSION These results indicated that high mesothelin H-scores were significantly associated with poor prognosis in patients with advanced SOC.
Differences in Behavior Between Elderly and Nonelderly Captive Chimpanzees and the Effects of the Social Environment.

The population of NIH-owned or NIH-supported captive research chimpanzees is quickly becoming aged, and the 1998 NIH breeding moratorium has resulted in a skewed age distribution. As such, behavioral management programs aimed at refining the care of an aging captive chimpanzee population have become increasingly important. However, little research exists that addresses the ways in which captive chimpanzee behavior differs as a function of the interaction of age and aspects of the captive environment. We examined overall differences in behavior between elderly (35 y and older) and nonelderly(younger than 35 y) captive chimpanzees. Elderly chimpanzees exhibited significantly more rough scratching (a behavioral indicator of anxiety) and inactivity, less behavioral diversity, and less affiliation than their nonelderly counterparts. We also assessed whether elderly chimpanzee behavior and wounding rates differed as a function of housing in geriatric (groupaverage age, 35 y or older) or nongeriatric (group average age, younger than 35 y) groups. In our program, geriatric social groups were characterized by smaller group size, more females within the group, and higher levels of individual mobility impairment compared with nongeriatric groups. Furthermore, elderly chimpanzees housed in geriatric groups displayed significantly increased rough scratching, decreased locomotion and submission than nongeriatric animals but no difference in wounding. These findings suggest that housing elderly chimpanzees in nongeriatric groups may be beneficial, given thatdoing so may stimulate locomotion. However, the establishment and maintenance of geriatric groups may be unavoidable as the demographics of the population of captive former research chimpanzees continues to age. Therefore, refinements to captive geriatric care strategies for chimpanzees should focus on methods of evaluating and enhancing functionally appropriate captive environments within geriatric groups.