Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathway, in silico and tissue-specific expression quantitative analyses of oesophageal squamous cell carcinoma genome-wide association studies data.

BACKGROUND Oesophageal cancer is the fourth leading cause of cancer death in China where essentially all cases are histologically oesophageal squamous cell carcinoma (ESCC). Agnostic pathway-based analyses of genome-wide association study (GWAS) data combined with tissue-specific expression quantitative trait loci (eQTL) analysis and publicly available functional data can identify biological pathways and/or genes enriched with functionally-relevant disease-associated variants. METHOD We used the adaptive multilocus joint test to analyse 1827 pathways containing 6060 genes using GWAS data from 1942 ESCC cases and 2111 controls with Chinese ancestry. We examined the function of risk alleles using in silico and eQTL analyses in oesophageal tissues. RESULTS Associations with ESCC risk were observed for 36 pathways predominantly involved in apoptosis, cell cycle regulation and DNA repair and containing known GWAS-associated genes. After excluding genes with previous GWAS signals, candidate pathways (and genes) for ESCC risk included taste transduction (KEGG_hsa04742; TAS2R13, TAS2R42, TAS2R14, TAS2R46,TAS2R50), long-patch base excision repair (Reactome_pid; POLD2) and the metabolics pathway (KEGG_hsa01100; MTAP, GAPDH, DCTD, POLD2, AMDHD1). We identified and validated CASP8 rs13016963 and IDH2 rs11630814 as eQTLs, and CASP8 rs3769823 and IDH2 rs4561444 as the potential functional variants in high-linkage disequilibrium with these single nucleotide polymorphisms (SNPs), respectively. Further, IDH2 mRNA levels were down-regulated in ESCC (tumour:normal-fold change = 0.69, P = .75E-14). CONCLUSION Agnostic pathway-based analyses and integration of multiple types of functional data provide new evidence for the contribution of genes in taste transduction and metabolism to ESCC susceptibility, and for the functionality of both established and new ESCC risk-related SNPs.
Subscale assessment of the NEI-RQL-42 questionnaire with Rasch analysis.

PURPOSE To explore the psychometric properties of the 13 subscales of the NEI-RQL-42 questionnaire using Rasch analysis. METHODS The NEI-RQL-42 is a refractive error-related quality of life (QoL) questionnaire with a complex design; its 13 subscales contain 42 questions, which include 16 different question/response category formats. It was completed by 100 laser refractive surgery subjects (spectacle and contact lens wearers) pre- and postoperatively. Rasch analysis was used to assess the use of response categories, success in measuring a single trait per subscale (unidimensionality), ability to discriminate persons (precision), and targeting of the questions to person QoL. RESULTS Response categories were misused in four subscales (clarity of vision, diurnal fluctuation, symptoms, and appearance), which required repair before further analyses. Six subscales contained items that did not contribute to a single trait measurement (multidimensional). All subscales were found to be inadequate at distinguishing between persons (person separation >2.0), and targeting of the questions to QoL was poor for six subscales. CONCLUSIONS The NEI-RQL-42 questionnaire is deficient for all psychometric properties tested. Clinicians or researchers wishing to measure QoL related to refractive error correction should consider other questionnaires that have been rigorously developed and meet standard psychometric properties.
Translation and validation of patient-practitioner orientation scale in Sri Lanka

Background: Practice of family medicine and patient centeredness does not get the deserved attention in clinical practice and teaching in Sri Lanka. Non-availability of tools for assessment of patient centeredness deters the process of curricular development and research. The Patient-Practitioner Orientation Scale (PPOS) is a self-administered tool that assesses patient-centeredness in both health care professionals and patients. This study has translated and validated the PPOS to Sinhala language. Methods: Translation and cross-cultural adaptation were carried out using forward and backward translation method. The psychometric properties of a pretested new Sinhala version of PPOS (PPOS-Sinhala) was tested in a convenience sample of 1367 patients and health professionals. Temporal stability was tested in a sub-sample of 140 individuals. The comparability of the PPOS scores and association with sex and level of education with those reported for Western populations were examined to establish construct validity. Results: The sample included 543 medical students, 67 doctors, 335 allied health students and 422 patients. Cronbach′s alpha for these groups ranged from 0.48 to 0.53 for sharing, 0.42 to 0.53 for caring, and 0.62 to 0.65 for total score. Intraclass correlation coefficients of 0.56, 0.6, and 0.4 were observed for the Total, Sharing, and Caring sub-scales, respectively. PPOS scores did not vary significantly for men and women. Health professionals exhibited higher scores than patients. Age was negatively associated and education level was positively associated with PPOS. Discussion: PPOS-Sinhala is stable, sufficiently valid and reliable to evaluate patient centeredness among Sinhala speaking health care professionals and patients. Lower internal consistency is found for a few items in the instrument which requires further development. PPOS scores and their correlates for this Sri Lankan population were more similar to that found in other populations in this region than for scores and correlates found in the US.
Zygotic induction of plasmid ssb and psiB genes following conjugative transfer of Incl1 plasmid Collb‐P9

The Incl1 conjugative plasmid Collb‐P9 carries a psiB gene that prevents induction of the SOS response in host bacteria. This locus is located 2.5 kb downstream of the ssb (single‐stranded DNA‐binding protein) gene in the leading region. This portion of Collb is strikingly similar to part of the leading region of the otherwise distinct F plasmid. Expression of psiB and ssb is increased when the host cell is exposed to an SOS‐inducing treatment or the Collb transfer system is derepressed. Moreover, expression of both genes on a derepressed plasmid is strongly enhanced in conjugatively infected recipient cells. Carriage of the psiB gene by Collb is shown to prevent a low level of SOS induction following conjugation. Plasmid ssb and psiB genes may function to promote installation of the replicon in the new cell.
Lymphogranuloma Venereum Prevalence in Sweden among Men Who Have Sex with Men and Characterization of Chlamydia trachomatis ompA Genotypes

ABSTRACT An outbreak of lymphogranuloma venereum (LGV) infections has recently been reported from The Netherlands and other European countries. The Swedish surveillance system has identified three LGV cases since 2004, all with clinically suspected infection in men who have sex with men (MSM). In order to assess the prevalence of LGV in a high-risk group of MSM and include clinically atypical cases, retrospective analysis of 197 Chlamydia trachomatis-infected men was performed. Sequencing of the ompA gene showed a different serotype distribution compared to recent Swedish studies in heterosexual populations. The most common types were G (45%), D (27%), and J (26%), whereas the normally predominant type E accounted for only 4% of the chlamydia cases. Furthermore, certain ompA genotype variants of the dominant serotypes were highly prevalent among MSM, and the reason for this is discussed. No additional case of LGV was detected by retrospective analysis of the high-risk MSM population. This indicates that, thus far, LGV in Sweden is only a result of sporadic import from infected MSM clusters abroad.
N-Linked Glycosylation of West Nile Virus Envelope Proteins Influences Particle Assembly and Infectivity

ABSTRACT West Nile virus (WNV) encodes two envelope proteins, premembrane (prM) and envelope (E). While the prM protein of all WNV strains contains a single N-linked glycosylation site, not all strains contain an N-linked site in the E protein. The presence of N-linked glycosylation on flavivirus E proteins has been linked to virus production, pH sensitivity, and neuroinvasiveness. Therefore, we examined the impact of prM and E glycosylation on WNV assembly and infectivity. Similar to other flaviviruses, expression of WNV prM and E resulted in the release of subviral particles (SVPs). Removing the prM glycosylation site in a lineage I or II strain decreased SVP release, as did removal of the glycosylation site in a lineage I E protein. Addition of the E protein glycosylation site in a lineage II strain that lacked this site increased SVP production. Similar results were obtained in the context of either reporter virus particles (RVPs) or infectious lineage II WNV. RVPs or virions bearing combinations of glycosylated and nonglycosylated forms of prM and E could infect mammalian, avian, and mosquito cells (BHK-21, QT6, and C6/36, respectively). Those particles lacking glycosylation on the E protein were modestly more infectious per genome copy on BHK-21 and QT6 cells, while this absence greatly enhanced the infection of C6/36 cells. Thus, glycosylation of WNV prM and E proteins can affect the efficiency of virus release and infection in a manner that is cell type and perhaps species dependent. This suggests a multifaceted role for envelope N-linked glycosylation in WNV biology and tropism.
Significant ethnic variation in total and free testosterone concentration

objective Measurement of serum testosterone is an integral part of the assessment of men presenting to endocrine clinics. Little is known about the variation of total bound or bioavailable testosterone by ethnic group. The principal determinant of testosterone bioavailability is SHBG, which itself is a marker for insulin sensitivity. Our aim was to examine variations in testosterone and SHBG levels across three ethnic groups in relation to ethnic differences in insulin sensitivity.
Presynaptic inhibition differentially shapes transmission in distinct circuits in the mouse retina

Diverse retinal outputs are mediated by ganglion cells that receive excitatory input from distinct classes of bipolar cells (BCs). These classes of BCs separate visual signals into rod, ON and OFF cone pathways. Although BC signalling is a major determinant of the ganglion cell‐mediated retinal output, it is not fully understood how light‐evoked, presynaptic inhibition from amacrine cell inputs shapes BC outputs. To determine whether differences in presynaptic inhibition uniquely modulate BC synaptic output to specific ganglion cells, we assessed the inhibitory contributions of GABAA, GABAC and glycine receptors across the BC pathways. Here we show that different proportions of GABAA and GABAC receptor‐mediated inhibition determined the kinetics of GABAergic presynaptic inhibition across different BC classes. Large, slow GABAC and small, fast GABAA receptor‐mediated inputs to rod BCs prolonged light‐evoked inhibitory postsynaptic currents (L‐IPSCs), while smaller GABAC and larger GABAA receptor‐mediated contributions produced briefer L‐IPSCs in ON and OFF cone BCs. Glycinergic inhibition also varied across BC class. In the rod‐dominant conditions studied here, slow glycinergic inputs dominated L‐IPSCs in OFF cone BCs, attributable to inputs from the rod pathway via AII amacrine cells, while rod and ON cone BCs received little and no glycinergic input, respectively. As these large glycinergic inputs come from rod signalling pathways, in cone‐dominant conditions L‐IPSCs in OFF cone bipolar cells will probably be dominated by GABAA receptor‐mediated input. Thus, unique presynaptic receptor combinations mediate distinct forms of inhibition to selectively modulate BC outputs, enhancing the distinctions among parallel retinal signals.
Sensitivity to the Displacement of Facial Features in Negative and Inverted Images

Subjects have previously been reported to show difficulties in recognising faces which are either inverted or in photographic negative. Experiments are reported in which a two-alternative forced-choice technique was used to measure sensitivity for distinguishing faces which have been modified by having the eyes moved vertically or horizontally. Subjects were less sensitive to such changes for inverted faces or negative faces, and were even less sensitive for faces that were both inverted and negative. No such effects were found for a control stimulus consisting simply of three solid circles in the same positions as the eyes and mouth of a face. When the stimuli consisted of eyes, nose, and mouth, but without a surround, no evidence of inversion or negation effects was found, which suggests that a facial surround is necessary. When the stimulus consisted of a facial surround with the eyes, nose, and mouth replaced by solid circles, effects of negation were found, but no effects of inversion. This dissociation of the effects of negation and inversion may suggest that they are the result of different underlying mechanisms.
Resistance to Erythromycin and Telithromycin in Streptococcus pyogenes Isolates Obtained between 1999 and 2002 from Greek Children with Tonsillopharyngitis: Phenotypic and Genotypic Analysis

ABSTRACT Since the late 1990s, the prevalence of erythromycin-resistant Streptococcus pyogenes has significantly increased in several European countries. Between January 1999 and December 2002, 1,577 isolates of S. pyogenes were recovered from children with tonsillopharyngitis living in various areas of Western Greece. Erythromycin resistance was observed in 379 (24%) of the 1,577 isolates. All erythromycin-resistant strains along with 153 randomly selected erythromycin-susceptible S. pyogenes isolates were tested for their antimicrobial susceptibility, resistance phenotypes, and genotypes. Representative isolates underwent emm gene sequence typing. Isolates with reduced susceptibility to telithromycin (MIC, ≥2 μg/ml) were studied for multilocus sequence type, L22, L4, and 23S rRNA mutations. Of the total 379 erythromycin-resistant isolates, 193 (50.9%) harbored the mef(A) gene, 163 (43%) erm(A), 1 (0.3%) mef(A) plus erm(A), and 22 (5.8%) the erm(B) gene. Among the erythromycin-susceptible isolates, emm 1 (25%), emm 2 (12.5%), and emm 77 (12.5%) predominated. Furthermore, among the erythromycin-resistant isolates, emm 4 (30.6%), emm 28 (22.2%), and emm 77 (12.5%) prevailed. Resistance to telithromycin was observed in 22 (5.8%) of the erythromycin-resistant isolates. Sixteen (72.7%) of the 22 isolates appeared to be clonally related, since all of them belonged to emm type 28 and multilocus sequence type 52. One of the well-known mutations (T2166C) in 23S rRNA, as well as a new one (T2136C), was detected in erythromycin- and telithromycin-resistant isolates. High incidence of macrolide resistance and clonal spread of telithromycin resistance were the characteristics of the Greek S. pyogenes isolates obtained from 1999 to 2002.
RAD51 G135C genetic polymorphism and their potential role in gastric cancer induced by Helicobacter pylori infection in Bhutan

SUMMARY In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan – a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients.
ALDA: Cognitive Assistant for Legal Document Analytics

In recent times, there has been an exponential growth in digitization of legal documents such as case records, contracts, terms of services, regulations, privacy documents and compliance guidelines. Courts have been digitizing their archived cases and also making it available for e-discovery. On the other hand, businesses are now maintaining large data sets of legal contracts that they have signed with their employees, customers and contractors. Large public sector organizations are often bound by complex legal legislation and statutes. Hence, there is a need of a cognitive assistant to analyze and reason over these legal rules and help people make decisions. Today the process of monitoring an ever increasing dataset of legal contracts and ensuring regulations and compliance is still very manual and labour intensive. This can prove to be a bottleneck in the smooth functioning of an enterprise. Automating these digital workflows is quite hard because the information is available as text documents but it is not represented in a machine understandable way. With the advancements in cognitive assistance technologies, it is now possible to analyze these digitized legal documents efficiently. In this paper, we discuss ALDA, a legal cognitive assistant to analyze digital legal documents. We also present some of the preliminary results we have obtained by analyzing legal documents using techniques such as semantic web, text mining and graph analysis.
Mass spectrometric monitoring of albumin in uremia.

BACKGROUND Advanced glycation end products (AGEs) are a novel class of uremic toxins. In plasma, they are present in proteins and also in low molecular mass peptides. AGE-modified peptides are thought to bind and modify plasma proteins. Monitoring of the consequent increase in molecular mass of serum albumin may be used in surveillance of the clinical management of uremia. METHODS We investigated molecular mass changes of human serum albumin (HSA) glycated by glucose and methylglyoxal in vitro and of subjects with moderate renal impairment, end-stage renal disease (ESRD), ESRD on hemodialysis, and normal healthy controls by matrix-assisted laser desorption ionization mass spectrometry. RESULTS Fatty acid-free HSA had a molecular mass of 66,446 +/- 114 D. Mean (+/-SD) molecular mass increases were HSA minimally glycated by glucose 399 +/- 88 D (N = 5, P < 0.001), HSA highly glycated by glucose 6780 +/- 122 D (N = 5, P < 0.001), HSA minimally glycated by methylglyoxal 73 +/- 121 D (N = 5, P > 0.05), and HSA without fatty acid removal 535 +/- 90 D (N = 5, P < 0.001). For HSA of human subjects, mean (+/- SD) molecular mass increases were normal healthy controls 243 +/- 97 D (N = 5), moderate renal impairment 350 +/- 83 D (P > 0.05 with respect to controls, N = 5), ESRD 498 +/- 128 (P < 0.02 with respect to controls, N = 3), and ESRD on hemodialysis 438 +/- 85 D (P < 0.02 with respect to controls, N = 5). The mean molecular mass of albumin of all groups was increased significantly with respect to that of fatty acid free albumin (P < 0.001). CONCLUSIONS Only ESRD was associated with a significant increase in the molecular mass of HSA in vivo. Since this mass increase was very low and much lower than reported for AGE-modified peptides, it may reflect AGE formation on HSA by alpha-oxoaldehydes that accumulate in uremia, rather than modification of albumin by AGE-modified peptides. The molecular mass of HSA in vivo was indicative of a minimal and not a high extent of glycation.
DSIF and RNA Polymerase II CTD Phosphorylation Coordinate the Recruitment of Rpd3S to Actively Transcribed Genes

Histone deacetylase Rpd3 is part of two distinct complexes: the large (Rpd3L) and small (Rpd3S) complexes. While Rpd3L targets specific promoters for gene repression, Rpd3S is recruited to ORFs to deacetylate histones in the wake of RNA polymerase II, to prevent cryptic initiation within genes. Methylation of histone H3 at lysine 36 by the Set2 methyltransferase is thought to mediate the recruitment of Rpd3S. Here, we confirm by ChIP–Chip that Rpd3S binds active ORFs. Surprisingly, however, Rpd3S is not recruited to all active genes, and its recruitment is Set2-independent. However, Rpd3S complexes recruited in the absence of H3K36 methylation appear to be inactive. Finally, we present evidence implicating the yeast DSIF complex (Spt4/5) and RNA polymerase II phosphorylation by Kin28 and Ctk1 in the recruitment of Rpd3S to active genes. Taken together, our data support a model where Set2-dependent histone H3 methylation is required for the activation of Rpd3S following its recruitment to the RNA polymerase II C-terminal domain.
Irish nursing students' changing self-esteem and fear of negative evaluation during their preregistration programme.

BACKGROUND Studies on Irish nursing and midwifery professions have demonstrated that stress and bullying are frequent problems that may lead to depression and low self-esteem. Self-esteem is linked to social anxiety and is therefore related to fear of negative evaluation. It is important to study nursing students' feelings about self-esteem and negative evaluation, and to assess whether or not both these constructs change as students progress through their preregistration education programme. AIM This study explored nursing students' perceived levels of self-esteem and their fear of negative evaluation prior to, and nearing the completion of, their 3-year preregistration programme. METHODS A descriptive, quantitative, comparative survey design was used. All students in the first intake of 1995 in two general nursing schools in Southern Ireland agreed to take part (n = 72). A questionnaire developed from the Rosenberg Self-esteem Scale and the Watson and Friend Fear of Negative Evaluation Scale was used to collect data at the start of their programme and again 2 months before completion. RESULTS In general, students' reported self-esteem rose as they neared the end of their education programme and their fear of negative evaluation decreased; however, their overall self-esteem levels at their highest were only average. CONCLUSIONS Many of the studies examining self-esteem have produced contradictory results. An examination of the organizational factors that contribute to self-esteem may increase our understanding of the phenomenon. Self-esteem is a complex, multifaceted phenomenon. While there is no single factor that can increase or decrease a person's self-esteem, this study has explored the potential impact of the fear of negative evaluation on self-esteem. Nursing students' self-esteem might be increased by expansion of intrinsic job characteristics, improving their job satisfaction and providing frequent positive feedback.
Mentha pulegium extract as a natural product for the inhibition of corrosion. Part I: electrochemical studies

The inhibitory effect of Mentha pulegium extract (MPE) on steel corrosion in 1 M HCl solution was investigated using potentiodynamic polarisation and electrochemical impedance spectroscopy. The inhibition efficiency of MPE was found to increase with the concentration and reached 88% at 33% (v/v). Polarisation measurements show that the natural extract acted as a mixed inhibitor. The remarkable inhibition efficiency of MPE was discussed in terms of blocking of electrode surface by adsorption of inhibitor molecules through active centres. The adsorption of MPE was found to accord with the Temkin isotherm.