Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential interactions between HIV drugs, ritonavir and efavirenz and anticancer drug, nilotinib—a study in primary cultures of human hepatocytes that is applicable to HIV patients with cancer

Nilotinib is used to treat chronic myeloid leukemia (CML), and is metabolized by CYP3A. With a black‐box warning for QT prolongation, which is exposure dependent, controlling for drug interactions is clinically relevant. Treatments of HIV patients with CML are with HAART drugs, ritonavir and efavirenz, may cause complex drug interactions through CYP3A inhibition or induction. We evaluated the interactions of ritonavir or efavirenz on nilotinib using human hepatocytes and compared these interactions with those of ketoconazole or rifampin, classical CYP3A inhibitor and inducer, respectively. Hepatocytes were treated with vehicle, ritonavir (10 μM), ketoconazole (10 μM), efavirenz (10 μM), or rifampin (10 μM) for 5 days. On day 5, nilotinib (3 μM) was coincubated for an additional 24–48 hours. The concentrations of nilotinib were quantitated in collected samples (combined lysate and medium) by LC‐MS. Apparent intrinsic clearance (CLint,app) of nilotinib was lowered 5.8‐ and 3.1‐fold, respectively, by ritonavir and ketoconazole. Efavirenz and rifampin increased the CLint,app of nilotinib by 2.1‐ and 4.1‐fold, respectively. The clinically recommended dose (300 mg twice daily) of nilotinib may have to be reduced substantially (150 mg once daily) or increased (400 mg thrice daily), respectively, to achieve desired drug exposure, when ritonavir or efavirenz is co‐administered.
A Test of Two Procedures for Increasing Responses to Mail Surveys

This paper examines the effectiveness of two procedures used in combination in an attempt to increase responses to a mail survey in a cost effect manner: a first reminder letter without a replacement questionnaire, coupled with a time-bounded prize draw for $100 worth of petrol vouchers. The prize draw elicited a faster response to the first two mail-outs, but produced only a slightly higher response rate by the end of the survey (43% vs. 41%). The use of a letter without a replacement questionnaire for the first reminder resulted in a lower response to that mail-out, but a slightly higher response rate by the end of the survey, and was the most cost-effective procedure. A combination of prize draw plus letter-only first reminder gave the highest response rate overall, but the differences between combinations were not statistically significant. A much higher level of agreement to be re-interviewed was obtained when the prize draw was used.
Oxidative Stress as a Mechanism of Valproic Acid-Associated Hepatotoxicity

Valproic acid (2-n-propylpentanoic acid; VPA) has several therapeutic indications, but it is used primarily as an anticonvulsant. VPA is a relatively safe drug, but its use is associated with idiosyncratic hepatotoxicity, which in some cases may lead to fatality. The underlying mechanism responsible for the hepatotoxicity is still not well understood, but various hypotheses have been proposed, including oxidative stress. This article discusses the experimental evidence on the effect of VPA on the various indices of oxidative stress and on the potential role of oxidative stress in VPA-associated hepatotoxicity.
Higher serum uric acid associated with decreased Parkinson's disease prevalence in a large community‐based survey

A large community‐based cross‐sectional survey provided an opportunity to evaluate a previously reported association between Parkinson's disease (PD) and low serum uric acid (UA) levels in this population. The association between a self‐reported PD diagnosis with treatment (n = 59) and serum UA level was examined using logistic and linear regression models, controlling for key covariates. In adjusted models, participants with UA levels at or above the median had a significantly lower odds of reporting PD with treatment compared with those with lower UA levels (OR 0.33, 95% CI 0.19–0.60, P = 0.0002). This association was observed for both men and women. The mean UA level among participants reporting PD with treatment was 0.78 mg/dl lower than the mean UA level among those not reporting PD (P ≤ 0.0001). These findings concur with several previous longitudinal studies that found an association between higher UA levels and decreased PD risk. © 2010 Movement Disorder Society
Can Artifact Mimic the Pathology of the Peritoneal Mesothelium?

Objective A peritoneal biopsy registry was established to examine morphological and functional changes to the peritoneum during peritoneal dialysis (PD). During the early stages of this study, it became clear that surgical trauma to the peritoneum at the time of biopsy could cause a variety of changes to the surface. We examined the effects of surgical trauma in a rat biopsy model. Design Rat peritoneum was subjected to a variety of traumas that might occur at biopsy and compared with peritoneal biopsies that had been collected, using the suture method described here, from PD patients. Changes in the quality of non-PD biopsies taken before and after the development of the suture technique were evaluated. Results In the rat model, external massaging of the peritoneum induced moderate loss of microvilli. Brief light touching caused distortion of the mesothelial surface. Pressing resulted in mesothelial denudation and thin strands of presumed cellular remains. Rubbing caused complete loss of mesothelial cells and their basement membrane. Air drying caused progressive loss of microvilli and eventual cellular distortion. Comparison with peritoneal biopsies from PD patients revealed similarities with certain types of trauma, namely, air drying and pressing. Collection of peritoneal biopsies using the suture method significantly improved specimen quality compared with specimens taken before its introduction (p < 0.025%). Conclusion These results illustrate the sensitivity of the mesothelium to mechanical trauma, the possibility of confusing trauma with genuine pathology, and, hence, the necessity of employing a trauma-free method of biopsy collection, such as the technique described here.
Non-literary in the Light of Literary Translation

The purpose of this article is to contrast non-literary with literary translation. An example from the opening pages of Kafka’s Amerika is used to illustrate how literary texts may be translated differently from non-literary ones. They differ essentially through intention (literary texts belong to the world of imagination whereas non-literary ones belong to the world of facts) and through the fact literary texts are about persons while non-literary ones are about objects. Nevertheless, both texts are concerned with the fundamental truths of translation: factual, aesthetic, allegorical truth, logical and linguistic truth.
The influence of HLA-DRB1 alleles and rheumatoid factor on disease outcome in an inception cohort of patients with early inflammatory arthritis.

OBJECTIVE There are conflicting data concerning the role of HLA-DRB1 alleles in disease outcome in early rheumatoid arthritis. The exact role of these alleles in short-term outcome is determined in this large, prospective, population-based study. METHODS We recruited 532 patients with inflammatory polyarthritis from the Norfolk Arthritis Register and typed their sera for HLA-DRB1 alleles using polymerase chain reaction-based methods. Disease outcome was assessed at 2 years in terms of persistent joint inflammation, functional disability, and radiologic erosions. Results are expressed as risk ratios (RR) with 95% confidence intervals (95% CI). RESULTS There was no influence of HLA-DRB1 alleles, in any combination, on the likelihood of disease persistence, and only a modest effect on functional disability (Health Assessment Questionnaire score > or = 1). The most obvious effect was on the development of erosions (RR 1.9, 95% CI 1.4-2.6 for those who carried at least 1 DRB1 shared epitope [SE] allele), with slightly greater effects for those who were homozygous for SE-bearing alleles (RR 2.5, 95% CI 1.8-3.6). This effect of HLA-DRB1 was restricted to patients whose sera were negative for rheumatoid factor. Among patients with erosions, HLA-DRB1 had no influence on the severity of radiologic damage (defined as the number of eroded joints, or total Larsen score). CONCLUSION These data do not support routine HLA-DRB1 screening of patients with early arthritis to identify those at risk for subsequent severe disease.
HOSTILE ATTRIBUTION BIAS FOR PHYSICAL AND RELATIONAL PROVOCATIONS AND AGGRESSION IN ADOLESCENT GIRLS AND BOYS : THE MODERATING ROLE OF NARCISSISM AND SELF-ESTEEM

The role of hostile attribution bias for physical and relational provocations was linked to level of physical and relational aggressivity in adolescent boys and girls. In addition, the moderating roles of narcissism and self-esteem on the relation between hostile attribution bias and aggression were examined. Our findings suggest that relational provocations predict relational aggression for girls, and overt provocations predict overt aggression for boys. Results also indicated that the relationship between hostile attribution bias for both overall aggression (relational and overt aggression combined) and relational aggression was moderated by the interaction between self-esteem and narcissism. These findings are consistent with previous research and have implications for developing effective strategies for intervention. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Transient up-regulation of miR-155-3p by lipopolysaccharide in primary human monocyte-derived macrophages results in RISC incorporation but does not alter TNF expression

Background: The innate immune response is a tightly regulated process that reacts rapidly in response to pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS). Evidence is accumulating that microRNAs contribute to this, although few studies have examined the early events that constitute the “primary” response. Methods: LPS-dependent changes to miRNA expression were studied in primary human monocyte-derived macrophages (1°MDMs). An unbiased screen by microarray was validated by qPCR and a method for the absolute quantitation of miRNAs was also developed, utilising 5’ phosphorylated RNA oligonucleotide templates. RNA immunoprecipitation was performed to explore incorporation of miRNAs into the RNA-induced silencing complex (RISC). The effect of miRNA functional inhibition on TNF expression (mRNA and secretion) was investigated. Results: Of the 197 miRNAs expressed in 1°MDMs, only five were induced >1.5-fold. The most strongly induced was miR-155-3p, the partner strand to miR-155-5p, which are both derived from the MIR155HG/BIC gene (pri-miR-155). The abundance of miR-155-3p was induced transiently ~250-fold at 2-4hrs and then returned towards baseline, mirroring pri-miR-155. Other PAMPs, IL-1β, and TNF caused similar responses. IL-10, NF-κB, and JNK inhibition reduced these responses, unlike cytokine-suppressing mycolactone. Absolute quantitation revealed that miRNA abundance varies widely from donor-to-donor, and showed that miR-155-3p abundance is substantially less than miR-155-5p in unstimulated cells. However, at its peak there were 446-1,113 copies/cell, and miR-155-3p was incorporated into the RISC with an efficiency similar to miR-16-5p and miR-155-5p. Inhibition of neither miRNA affected TNF secretion after 2hrs in 1°MDMs, but technical challenges here are noted. Conclusions: Dynamic regulation of miRNAs during the primary response is rare, with the exception of miR-155-3p. Further work is required to establish whether its low abundance, even at the transient peak, is sufficient for biological activity and to determine whether there are specific mechanisms determining its biogenesis from miR-155 precursors
Numerical Simulation of Helically Coiled Closed Loop Pulsating Heat Pipe

This paper addresses the numerical simulation of helically coiled closed loop pulsating heat pipe which is carried in ANSYS Fluent. The values of thermal resistance for constant heat fluxes vs. transient heat fluxes are analyzed. Phase change visualization after the end of simulation is carried out to observe the phenomenon in liquid at its saturation temperature and pressure. Finally, helical heat pipes are found to have thermal resistance less by 2.7K/W, 0.56 K/W, and 0.227 K/W for 8W, 40W and 80W heat inputs than circular pipes. Helical heat pipes are found more efficient than circular heat pipes.
miR-10b-3p, miR-8112 and let-7j as potential biomarkers for autoimmune inner ear diseases

Circulating microRNAs (miRNAs) have been suggested as non-invasive biomarkers for the diagnosis of several autoimmune diseases. However, to the best of our knowledge, no studies have yet examined the miRNA expression profiles in autoimmune inner ear disease (AIED). The present study aimed to use an miRNA sequencing assay to detect the miRNA expression profiles of serum samples from 3 control mice and 3 antigen-induced AIED model mice. Differentially expressed miRNAs (DE-miRNAs) were screened using a t-test. miRNA target prediction was performed using TargetScan Mouse. Then, the miRNA-target gene interaction network was constructed and visualized using Cytoscape software. The underlying functions of the target genes of the DE-miRNAs were predicted using the clusterProfiler package. As a result, 22 miRNAs were identified as DE-miRNAs between AIED and control mice, including 10 upregulated and 12 downregulated genes. Based on the TargetScan Mouse prediction, 1,958 genes were identified as the targets for the 22 DE-miRNAs. Functional analysis indicated that only the target genes of 8 miRNAs were respectively enriched for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, among which miR-10b-3p, let-7j and miR-8112 were shared between the two pathway analyses. These 3 miRNAs may be involved in AIED by affecting inflammatory chemokine (miR-10b-3p-C-C motif chemokine 12), Wnt signaling (miR-8112-Wnt9b/Wnt 3a/Wnt2b) and Mucin type O-glycan biosynthesis pathways (let-7j-Galnt2/Galnt12). In conclusion, miR-10b-3p, miR-8112 and let-7j may be underlying biomarkers for diagnosing AIED.
Spectrum and antimicrobial resistance of common pathogenic bacteria isolated from patients with acute exacerbation of chronic obstructive pulmonary disease in mainland of China

Background Bacteria‐induced respiratory infection has been long considered to be the major cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, a clear picture about the distribution and drug‐resistance of pathogenic bacteria in the lower airways should be helpful for treatment of the disease. So far, data on this topic among Chinese are lacking. Methods A surveillance study was performed in consecutive patients with AECOPD at five areas in China between October 2006 and April 2008. The sputum from these patients was cultured and isolated for bacteria. Agar dilution method was used to determine the minimal inhibitory concentrations (MICs) of levofloxacin and other 15 antibiotics against these strains. Results Three hundred and fifty‐nine pathogenic bacterial strains were isolated among 884 patients with AECOPD. The predominant bacteria were Pseudomonas aeruginosa (21.7%), Klebsiella pneumoniae (12.3%), Haemophilus influenzae (14.2%) and Streptococcus pneumoniae (11.7%), followed by Haemophilus parainfluenzae (9.5%), Acinetobacter baumannii (7.8%), Moraxella catarrhalis (6.4%) and Escherichia coli (3.6%). The majority of bacterial pathogens isolated in this study were susceptible to fluoroquinolones, ceftazidime, cefepime and imipenem. Conclusions Gram‐negative bacilli are the leading pathogens in patients with AECOPD in China. Haemophilus parainfluenzae may be one of the most important pathogens in AECOPD. This study provides evidence for local surveillance of AECOPD pathogens and appropriate choice of antimicrobials in China.
MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol

Introduction The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence. Methods and analysis Randomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps. Ethics and dissemination Ethical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via usual scientific forums. Trial registration number ACTRN12616000661471; Pre-results
Osteoprotegerin is up-regulated in pancreatic cancers and correlates with cancer-associated new-onset diabetes.

New-onset diabetes might help to yield biomarkers for the early diagnosis of pancreatic cancer (PaC). In this study, we computationally predicted and experimentally validated osteoprotegerin (OPG) being associated with pancreatic cancer related new-onset diabetes. We first performed a meta-analysis on microarray datasets to search for genes specifically highly expressed in PaC, and then filtered for cytokines involved in islet dysfunction. The expression of OPG in PaC and normal pancreas were validated by immunohistochemistry. Serum OPG levels in healthy controls, non-cancerous diabetes and PaC patients with or without diabetes were detected by enzyme-linked immunosorbent assay (ELISA). In silico assay found that OPG up-regulated in PaC tissues in comparison to normal pancreas. Immunohistochemical data further confirmed that OPG was overexpressed in PaC samples. Furthermore, increased expression of OPG in PaC tissues correlated to the occurrence of new-onset diabetes, and adversely affected the patients' overall survival in both univariate and multivariate analysis. In addition, the serum levels of OPG were significantly higher in pancreatic cancer patients with new-onset diabetes than other groups including pancreatic patients without diabetes, new-onset type 2 diabetes and healthy controls. In conclusion, there is a close association between OPG and pancreatic cancer related new-onset diabetes, and OPG might serve as a potential biomarker for the early diagnosis of pancreatic cancer from populations with new-onset diabetes.
Possibility of early diagnosis in a fetus affected by Prader-Willi syndrome with maternal hetero-UPD15: A lesson to be learned

Prader-Willi syndrome (PWS), a complicated neurodevelopmental disorder arising from errors in genomic imprinting, is characterized by evident hypotonia along with feeding difficulties and the absence of crying in early infancy. Hyperphagia and obesity are not uncommon in patients with PWS, usually accompanied by intellectual disability, cognitive impairment, short stature, small hands and feet, as well as hypogonadism and typical facial features. Due to the severe complications associated with PWS, a thorough understanding of its features and an early diagnosis, preferably in the fetal period, are important for clinical management. According to previous studies, prenatal diagnosis has been confirmed in only a few cases of PWS, using ultrasound, or as an accidental finding by cytogenetic molecular techniques, as no precise fetal phenotype has been defined. In this present study, an infant with PWS arising from maternal heterodisomy of chromosome 15 is described. This is a typical case of missed diagnosis by fetal ultrasound examination, chromosome karyotype analysis and chromosome microarray (CMA) conducted during the pregnancy. To delineate the complex prenatal characteristics of a fetus with PWS, prenatally-diagnosed cases of PWS described in the literature were reviewed. This present study indicated that although prenatal signs are not sufficient for a diagnosis to be confirmed, a comprehensive consideration of these signs is important in leading to a diagnosis of suspected PWS, and thus prompts further prenatal investigations using molecular genetic tools. Furthermore, this present study also suggested that CMA can lead to a missed diagnosis of PWS/Angelman syndrome and other imprinting disorders despite its high value in the detection of copy-number variants in individuals with developmental delay. If clinical signs strongly suggest PWS, other prenatal molecular genetic investigations, including methylation tests and short tandem repeat-based linkage analysis for uniparental disomy, are recommended as an additional tool to aid diagnosis.
Models for Relating Science and Religion

Rival models in science often become the focus of vigorous debate. The term ‘model’ has a rather broad range of meanings within science, but generally refers to one key idea that incorporates a particular set of data in a satisfactory manner. For example, during the early 1950s there were several rival models describing the structure of DNA, the molecule that encodes genes, but in the end the issue was settled by Watson and Crick: the double-helical model in fact provides the best way of describing the structure of DNA. Could there be one single model that in like manner encapsulates the relationship between science and religion? This seems very unlikely. For a start, both science and religion are highly complex enterprises. Furthermore, both are in a constant state of flux. Unlike the unchanging structure of DNA, described by a single well-established model, now discovered, no one all-encompassing model describing the relationship between science and religion awaits discovery. It has therefore been argued, with good reason, that the safest approach when investigating science and religion is simply to describe the complexity of the relationship. Yet life is short and models retain their conceptual usefulness in mapping out ways of relating different bodies of knowledge, useful at least as introductory tools to what is a vast literature. Furthermore, highly vocal advocates continue to sustain the view that a single model is sufficient to encompass the science-religion relationship. This paper therefore has two main goals: the first is to present four of the major models whereby science-faith interactions can be visualised and the second to critique the notion that any one of these models is in itself adequate for the task, albeit highlighting one model in particular that has proved to be most fruitful. Fuller accounts, presenting more nuanced collections of models, can be found elsewhere.