Miracle-dz/UniFAR-FTUs huggingface dataset:
Alternative polyadenylation in a family of paralogous EPB41 genes generates protein 4.1 diversity

ABSTRACT Alternative polyadenylation (APA) is a step in mRNA 3′-end processing that contributes to the complexity of the transcriptome by generating isoforms that differ in either their coding sequence or their 3′-untranslated regions (UTRs). The EPB41 genes, EPB41, EPB41L2, EPB41L3 and EPB41L1, encode an impressively complex array of structural adaptor proteins (designated 4.1R, 4.1G, 4.1B and 4.1N, respectively) by using alternative transcriptional promoters and tissue-specific alternative pre-mRNA splicing. The great variety of 4.1 proteins mainly results from 5′-end and internal processing of the EPB41 pre-mRNAs. Thus, 4.1 proteins can vary in their N-terminal extensions but all contain a highly homologous C-terminal domain (CTD). Here we study a new group of EPB41-related mRNAs that originate by APA and lack the exons encoding the CTD characteristic of prototypical 4.1 proteins, thereby encoding a new type of 4.1 protein. For the EPB41 gene, this type of processing was observed in all 11 human tissues analyzed. Comparative genomic analysis of EPB41 indicates that APA is conserved in various mammals. In addition, we show that APA also functions for the EPB41L2, EPB41L3 and EPB41L1 genes, but in a more restricted manner in the case of the latter 2 than it does for the EPB41 and EPB41L2 genes. Our study shows alternative polyadenylation to be an additional mechanism for the generation of 4.1 protein diversity in the already complex EPB41-related genes. Understanding the diversity of EPB41 RNA processing is essential for a full appreciation of the many 4.1 proteins expressed in normal and pathological tissues.
miR-148a and miR-17–5p synergistically regulate milk TAG synthesis via PPARGC1A and PPARA in goat mammary epithelial cells

ABSTRACT MicroRNA (miRNA) are a class of ‘18–25’ nt RNA molecules which regulate gene expression and play an important role in several biologic processes including fatty acid metabolism. Here we used S-Poly (T) and high-throughput sequencing to evaluate the expression of miRNA and mRNA during early-lactation and in the non-lactating (“dry”) period in goat mammary gland tissue. Results indicated that miR-148a, miR-17–5p, PPARGC1A and PPARA are highly expressed in the goat mammary gland in early-lactation and non-lactating periods. Utilizing a Luciferase reporter assay and Western Blot, PPARA, an important regulator of fatty acid oxidation, and PGC1a (PPARGC1A), a major regulator of fat metabolism, were demonstrated to be targets of miR-148a and miR-17–5p in goat mammary epithelial cells (GMECs). It was also revealed that miR-148a expression can regulate PPARA, and miR-17–5p represses PPARGC1A in GMECs. Furthermore, the overexpression of miR-148a and miR-17–5p promoted triacylglycerol (TAG) synthesis while the knockdown of miR-148a and miR-17–5p impaired TAG synthesis in GMEC. These findings underscore the importance of miR-148a and miR-17–5p as key components in the regulation of TAG synthesis. In addition, miR-148a cooperates with miR-17–5p to regulate fatty acid metabolism by repressing PPARGC1A and PPARA in GMECs. Further studies on the functional role of miRNAs in lipid metabolism of ruminant mammary cells seem warranted.
Condom use during most recent vaginal intercourse event among a probability sample of adults in the United States.

INTRODUCTION Correct and consistent condom use remains the most effective way to reduce sexually transmissible infection/HIV transmission during sex and is a highly effective contraceptive method. Understanding correlates of condom use is vital to public health programs. AIM To explore sociodemographic, event characteristics, and experiential correlates of condom use at last penile-vaginal intercourse (PVI). METHODS Survey data were collected from a nationally representative probability sample of adults in the United States as part of the National Survey of Sexual Health and Behavior. MAIN OUTCOME MEASURES Condom use/non-use at most recent PVI was the main outcome. Logistic regression analyses predicted condom use from sociodemographic variables (i.e., age, education, race/ethnicity, sexual orientation, health status, type of relationship with sexual partner) and event characteristics (i.e., location of sexual encounter, prior intercourse experience with partner, whether partner had other sex partners in the 6 months prior to sex with the participant; other contraceptive use, alcohol use, marijuana use, and for men, erection medication use). Logistic regression analyses examined evaluations of the sexual aspects of the experience (pleasure, arousal, erection/lubrication difficulty, participant orgasm, partner orgasm) in light of condom use. RESULTS Condom-protected PVI was significantly greater among younger people, blacks and Hispanics, and those having PVI with a nonrelationship partner. Statistically adjusting for these differences, condom use was significantly associated with fewer previous intercourse experiences with the partner and not using other forms of contraception. The sexual aspects of experience were evaluated similarly regardless of whether or not a condom was used. CONCLUSION Public health programs among youths and minorities may underlie higher condom use rates among these groups. Condom use may be further improved by continuing such programs and also expanding outreach to older persons and whites, suggesting prolonging use as relationships develop, and highlighting that condom use does not necessarily interfere with the sexual experience.
Altered hepatic gene expression in nonalcoholic fatty liver disease is associated with lower hepatic n‐3 and n‐6 polyunsaturated fatty acids

In nonalcoholic fatty liver disease, hepatic gene expression and fatty acid (FA) composition have been reported independently, but a comprehensive gene expression profiling in relation to FA composition is lacking. The aim was to assess this relationship. In a cross‐sectional study, hepatic gene expression (Illumina Microarray) was first compared among 20 patients with simple steatosis (SS), 19 with nonalcoholic steatohepatitis (NASH), and 24 healthy controls. The FA composition in hepatic total lipids was compared between SS and NASH, and associations between gene expression and FAs were examined. Gene expression differed mainly between healthy controls and patients (SS and NASH), including genes related to unsaturated FA metabolism. Twenty‐two genes were differentially expressed between NASH and SS; most of them correlated with disease severity and related more to cancer progression than to lipid metabolism. Biologically active long‐chain polyunsaturated FAs (PUFAs; eicosapentaenoic acid + docosahexaenoic acid, arachidonic acid) in hepatic total lipids were lower in NASH than in SS. This may be related to overexpression of FADS1, FADS2, and PNPLA3. The degree and direction of correlations between PUFAs and gene expression were different among SS and NASH, which may suggest that low PUFA content in NASH modulates gene expression in a different way compared with SS or, alternatively, that gene expression influences PUFA content differently depending on disease severity (SS versus NASH). Conclusion: Well‐defined subjects with either healthy liver, SS, or NASH showed distinct hepatic gene expression profiles including genes involved in unsaturated FA metabolism. In patients with NASH, hepatic PUFAs were lower and associations with gene expression were different compared to SS. (Hepatology 2015;61:1565–1578)
Mutational landscape of RNA-binding proteins in human cancers

ABSTRACT RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which are increasingly documented to be dysfunctional in cancer genomes. However, our current understanding of these alterations is limited. Here, we delineate the mutational landscape of ∼1300 RBPs in ∼6000 cancer genomes. Our analysis revealed that RBPs have an average of ∼3 mutations per Mb across 26 cancer types. We identified 281 RBPs to be enriched for mutations (GEMs) in at least one cancer type. GEM RBPs were found to undergo frequent frameshift and inframe deletions as well as missense, nonsense and silent mutations when compared to those that are not enriched for mutations. Functional analysis of these RBPs revealed the enrichment of pathways associated with apoptosis, splicing and translation. Using the OncodriveFM framework, we also identified more than 200 candidate driver RBPs that were found to accumulate functionally impactful mutations in at least one cancer. Expression levels of 15% of these driver RBPs exhibited significant difference, when transcriptome groups with and without deleterious mutations were compared. Functional interaction network of the driver RBPs revealed the enrichment of spliceosomal machinery, suggesting a plausible mechanism for tumorogenesis while network analysis of the protein interactions between RBPs unambiguously revealed the higher degree, betweenness and closeness centrality for driver RBPs compared to non-drivers. Analysis to reveal cancer-specific Ribonucleoprotein (RNP) mutational hotspots showed extensive rewiring even among common drivers between cancer types. Knockdown experiments on pan-cancer drivers such as SF3B1 and PRPF8 in breast cancer cell lines, revealed cancer subtype specific functions like selective stem cell features, indicating a plausible means for RBPs to mediate cancer-specific phenotypes. Hence, this study would form a foundation to uncover the contribution of the mutational spectrum of RBPs in dysregulating the post-transcriptional regulatory networks in different cancer types.
The effect of MCQ vetting on students' examination performance

Context: Question vetting is important to ensure validity, reliability, and other quality indicators of assessment tools, including the MCQ. Faculty members invest a substantial amount of time and effort into the MCQ vetting process. However, there is shortage of scientific evidence showing its effectiveness and at which level it needs to be focused on. This study aimed to provide scientific evidence regarding the effects of question vetting process on students’ examination performance by looking at their scores and pass-fail outcomes. Method: A parallel randomized control trial was conducted on third year medical students in a medical school. They were randomly assigned into two equal groups (i.e. control and experimental). Two mock examinations were conducted (i.e. time I and time II). At time I, non-vetted MCQs were administered to both groups as a baseline measurement. At time II, vetted MCQs were administered to the experimental group, while the same non-vetted MCQs were administered to the control group. Results: Out of 203 students, 129 (63.5%) participated in both mock examinations. 65 students were in the control group and 64 students were in the experimental group. Statistical analysis showed no significant differences (p > 0.05) in mean examination scores and pass-fail outcomes between or within the control and experimental groups. Conclusion: This study indicated that the MCQ vetting process did not influence examination performance. Despite these findings, the MCQ vetting process should still be considered an important activity to ensure that test items are developed at the highest quality and standards. However, it can be suggested that such activity can be done at the departmental level rather than at the central level.
Versatility and HIV vulnerability: investigating the proportion of Australian gay men having both insertive and receptive anal intercourse.

INTRODUCTION There is a lack of recent data on the extent to which gay men engage in insertive anal intercourse (IAI) and receptive anal intercourse (RAI). Accurate assessments of the overall risk of infection from HIV and other sexually transmitted infections (STIs) require such data because versatile men who engage in both roles have heightened vulnerability for becoming infected and infecting others. AIM To investigate the extent to which gay men are versatile with regard to having IAI and RAI. MAIN OUTCOME MEASURES Percentages of gay men who reported engaging in IAI, RAI, or both during the past 12 months and in their most recent sexual encounter. METHODS Eight hundred fifty-six Australian gay men completed an online survey to retrospectively report on their sexual practices over the past 12 months. RESULTS Of men who had anal intercourse in the past 12 months, 83% had both IAI and RAI, of whom 57% were highly versatile in that they had approximately equal numbers of partners for IAI and RAI. Of men who had anal intercourse in their most recent sexual encounter, as many as one in five (20%) had reciprocal anal intercourse, having both IAI and RAI with the same partner in a single encounter. Condom use was significantly less likely with reciprocal (38%) than nonreciprocal anal intercourse (50%; P = 0.04). While highly versatile men were less likely to know their HIV status, practices at most recent sexual encounter such as reciprocal anal intercourse and condom use were not significantly related to either their HIV status or that of their partner. CONCLUSIONS Engaging in both IAI and RAI appears to be common among gay men. HIV/STI prevention strategies would benefit from paying attention to the implications of high rates of versatile sexual practices, particularly the tendency for condoms to be used less often when having reciprocal anal intercourse.
Ledipasvir/sofosbuvir regimens for chronic hepatitis C infection: Insights from a work productivity economic model from the United States

Patients with chronic hepatitis C (CHC) exhibit reduced work productivity owing to their disease. Historically, most regimens indicated for CHC genotype 1 (GT1) patients were administered with pegylated interferon (Peg‐IFN) and/or ribavirin (RBV), which further compromised work productivity during treatment. The aim of this study was to model the impact of LDV/SOF (ledipasvir/sofosbuvir), the first Peg‐IFN‐ and RBV‐free regimen for CHC GT1 patients, on work productivity from an economic perspective, compared to receiving no treatment. The WPAI‐SHP (Work Productivity and Activity Index–Specific Health Problem) questionnaire was administered to patients across the ION clinical trials (N = 1,923 U.S. patients). Before initiation of treatment, patients with CHC GT1 in the ION trials exhibited absenteeism and presenteeism impairments of 2.57% and 7.58%, respectively. Patients with cirrhosis exhibited greater work productivity impairment than patients without cirrhosis. In total, 93.21% of U.S. patients in the ION trials achieved SVR; these patients exhibited absenteeism and presenteeism impairments of 2.62% (P = 0.76, when compared to baseline) and 3.53% (P < 0.0001), respectively. Monetizing these data to the entire U.S. population, our model projects an annual societal cost of $7.1 billion owing to productivity loss in untreated GT1 CHC patients. Our model projects that, when compared to no treatment, treating all CHC GT1 patients with a regimen with very high viral eradication rates (LDV/SOF) would translate to annual productivity loss savings of $2.7 billion over a 1‐year time horizon. Conclusions: Patients with untreated HCV impose a substantial societal burden owing to reduced work productivity. As a result of improvements in work productivity, treatment of CHC GT1 patients with LDV/SOF‐based regimens is likely to result in significant cost savings from a societal perspective, relative to no treatment. (Hepatology 2015;61:1471–1478)
Perceptions of Teamwork Among Code Team Members

Background: Cardiopulmonary arrest (CPA) teams, known as code teams, provide coordinated and evidenced-based interventions by various disciplines during a CPA. Teamwork behaviors are essential during CPA resuscitation and may have an impact on patient outcomes. Objectives: The purpose of this study was to explore the perceptions of teamwork during CPA events among code team members and to determine if differences in perception existed between disciplines within the code team. Methods: A prospective, descriptive, comparative design using the Code Teamwork Perception Tool online survey was used to assess the perception of teamwork during CPA events by medical residents, critical care nurses, and respiratory therapists. Results: Sixty-six code team members completed the Code Teamwork Perception Tool. Mean teamwork scores were 2.63 on a 5-point scale (0–4). No significant differences were found in mean scores among disciplines. Significant differences among scores were found on 7 items related to code leadership, roles and responsibilities between disciplines, and in those who had participated on a code team for less than 2 years and certified in Advanced Cardiac Life Support for less than 4 years. Conclusions: Teamwork perception among members of the code team was average. Teamwork training for resuscitation with all disciplines on the code team may promote more effective teamwork during actual CPA events. Clinical nurse specialists can aid in resuscitation efforts by actively participating on committees, identifying opportunities for improvement, being content experts, leading the development of team training programs, and conducting research in areas lacking evidence.
Cd11b+ myeloid cells support hepatic metastasis through down‐regulation of angiopoietin‐like 7 in cancer cells

Myeloid cells are known to mediate metastatic progression. Here, we attempted to elucidate the mechanisms underlying these effects by identifying gene expression alterations in cancer cells forming hepatic metastases after myeloid cell depletion. Hepatic metastases are heavily infiltrated by CD11b+ myeloid cells. We established hepatic metastases in transgenic CD11b‐diphtheria toxin receptor mice by intrasplenic injection of MC38 colon and Lewis lung carcinoma cells before depleting myeloid cells with diphtheria toxin. Myeloid cell depletion inhibited metastatic growth with a marked diminishment of tumor vasculature. Expression of ANGPTL7 (angiopoietin‐like 7), a protein not previously linked to metastasis, was highly up‐regulated in cancer cells after myeloid cell depletion. This effect was duplicated in tissue culture, where coculture of cancer cells with tumor‐conditioned myeloid cells from liver metastases or myeloid cell conditioned media down‐regulated ANGPTL7 expression. Analogous to myeloid cell depletion, overexpression of ANGPTL7 in cancer cells significantly reduced hepatic metastasis formation and angiogenesis. We found that ANGPTL7 itself has strong antiangiogenic effects in vitro. Furthermore, analysis of The Cancer Genome Atlas colorectal and breast cancer data sets revealed striking ANGPTL7 underexpression in cancerous compared to normal tissues. Also, ANGPTL7 was down‐regulated in metastatic liver colonies of colorectal cancer patients compared to their adjacent liver tissue. Conclusion: Myeloid cells promote liver metastasis by down‐regulating ANGPTL7 expression in cancer cells; our findings implicate ANGPTL7 as a mediator of metastatic progression and a potential target for interference with liver metastases. (Hepatology 2015;62:521–533
Two Case Studies on Data Sensitivity of Wireless Sensor Network Algorithms and our Proposal on Scalable, Synthetic Data Generation

Sensor network research is still in its infancy. There is a large volume of exploratory research. From lack of experimental data and sophisticated models derived from such data, many sensor network publications continue to use data generated from simple models in their algorithm evaluation. It is commonly agreed that data processing algorithms in sensor networks are sensitive to input data. However, no previous efforts have been devoted to quantitatively characterize the range of the algorithm performance when evaluated using different data input. In this paper, we made the first attempt to quantify the algorithm's sensitivity to data. Our evaluation results demonstrated that different data input could change the algorithm performance by as much as an order of magnitude or even change the relative performance order of two alternative algorithms. This pointed out the need to evaluate sensor network systems with data representing a wide range of real-world scenarios. For each algorithm in our case study, we identified a small set of data characteristics essential to the algorithm's performance. This defined a unique feature of our synthetic data generation framework and made both synthetic data generation and evaluation scalable. To support systematic algorithm evaluation and robust algorithm design and deployment, our synthetic data generation toolbox can generate 1. irregular topology data based on empirical models which will maintain important features of the experimental data; and 2. data corresponding to a wide range of parameter values.
Impact of clinically evident portal hypertension on the course of hepatocellular carcinoma in patients listed for liver transplantation

Liver transplantation (LT) is the best curative treatment for early hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the current shortage of organs causes prolonged waiting times and poorer intention‐to‐treat (ITT) survival (i.e., after listing) owing to tumor progression and dropout. Portal hypertension (PH) is a recognized risk factor of HCC development in patients with cirrhosis and its recurrence after resection. The aim of this study was to evaluate the potential impact of PHT on the results of LT on an ITT basis. Patients with cirrhosis listed for LT for HCC were included and their outcomes after listing were compared according to the presence or absence of PH defined as presence of esophageal varices or ascites or low platelet count and splenomegaly. Among 243 consecutively listed patients, 70% were affected by PH, which was associated with a significantly higher risk of tumor progression (38% vs. 22%; P = 0.017) and a higher risk of dropout (22% vs. 8%; P = 0.01). Transarterial chemoembolization (TACE) was similarly applied to the two groups (60% vs. 67%; P = 0.325). An absence of TACE was the only other independent risk factor of dropout owing to tumor progression. Under an ITT analysis, PH reduced overall survival (OS), but there was no difference in OS and time to recurrence post‐LT. The only pathological feature that could potentially explain this observation was the lower complete response to TACE in the PHT group (12% vs. 36%; P = 0.001). Conclusion: PH should be regarded as a major risk factor of dropout owing to tumor progression and should be taken into consideration when managing patients with HCC who are waiting for LT. (Hepatology 2015;62:179‐187)
Real-Time Communications for Wireless Sensor Networks: A Two-Tiered Architecture

While many approaches have been proposed to deal with energy/latency trade-offs, they are likely to be insufficient for the applications where reduced delay guarantee is the main concern. In this article, we investigated the potential application of a decentralized two-tiered network architecture, in large-scale wireless sensor networks, where an upper layer Wireless Local Area Network (WLAN), offering more powerful capabilities, serves as a backbone to an adaptively-clustered Low-Energy Adaptive Clustering Hierarch (LEACH)-based wireless sensor network. The WLAN layer will be involved in the communication between the sensor network and the control station, mitigating the impact of the limited capacities of the sensor nodes. With this two-tiered architecture we target to provide more reliable data delivery with reduced delay bounds, and lower energy consumption in the underlying sensor network, thereby increasing its lifetime. Simulation results show that the two-tiered network architecture achieved a relatively long lifetime, while preserving remarkably low latencies, compared to a single-tiered LEACH and a super-clustered LEACH-based network architectures.