Miracle-dz/UniFAR-FTUs huggingface dataset:
Parental occupational exposure to potential endocrine disrupting chemicals and risk of hypospadias in infants

Objectives Hypospadias is a urogenital birth defect affecting infant boys. Periconceptual parental occupational exposure to endocrine disrupting chemicals (EDCs) with oestrogenic or anti-androgenic properties may adversely affect male genital development in utero. The aim of this study was to investigate the association between both maternal and paternal occupational exposures to EDCs and hypospadias. Methods This registry-based case–control study considered 1202 cases of hypospadias in children born in Western Australia between 1980 and 2000 and 2583 male controls randomly selected from birth records for whom information regarding parental occupation was available from the Western Australian Maternal and Child Health Research Database. Occupational exposures to seven groups of potential EDCs were independently coded by two researchers according to a validated job–exposure matrix. Results Multivariable analysis showed a strong association with potential maternal occupational exposure to heavy metals with an over twofold increased risk of hypospadias (OR 2.6; 95% CI 1.3 to 5.2), and women exposed to phthalates were more likely to have an affected son (OR 1.2; 95% CI 0.8 to 1.7). Compared with mild or isolated cases, the risks of moderate–severe hypospadias or multiple defects were increased up to two- and fivefold, respectively, with maternal exposure to most types of EDCs. Paternal occupational exposures to polychlorinated organic (OR 1.3; 95% CI 1.0 to 1.8) and bi-phenolic (OR 1.6; 95% CI 1.0 to 2.6) compounds were also possible risk factors. Conclusions Our findings provide preliminary evidence of an association between exposure to EDCs with oestrogenic or anti-androgenic properties and increased risk of hypospadias.
Manifestation of theme as a point of departure in the result and discussion section of academic research articles

Theme is the element which serves as the point of departure of the message in a clause. It plays a major role in text organization, enabling a text to be communicated and understood clearly (Halliday, 1994). One issue in research article writing is how the writer deals with this important textual feature. This study did an analysis of theme types used in result and discussion section of research articles using Halliday's (2004) model of thematic organization. The study was carried out on the corpus of 16 result and discussion sections that were sourced from 16 research articles published in UPM journals in 2010 and 2011 from four disciplines, which are English Language Teaching, Economics, Biology, and Civil Engineering (4 from each discipline). The results revealed disciplinary differences in the use of theme across the four disciplines. These differences are supported by the claim that writing in each discipline is shaped by the discipline's own rules and conventions (Hyland, 2009; North, 2005). The results also supported the idea proposed by Gosden (1992) that theme types are important in fulfilling rhetorical functions of research article sections.
Requirement of Histone Methyltransferase SMYD3 for Estrogen Receptor-mediated Transcription*

SMYD3 is a SET domain-containing protein with histone methyltransferase activity on histone H3–K4. Recent studies showed that SMYD3 is frequently overexpressed in different types of cancer cells, but how SMYD3 regulates the development and progression of these malignancies remains unknown. Here, we report the previously unrecognized role of SMYD3 in estrogen receptor (ER)-mediated transcription via its histone methyltransferase activity. We demonstrate that SMYD3 functions as a coactivator of ERα and potentiates ERα activity in response to ligand. SMYD3 directly interacts with the ligand binding domain of ER and is recruited to the proximal promoter regions of ER target genes upon gene induction. Importantly, our chromatin immunoprecipitation analyses provide compelling evidence that SMYD3 is responsible for the accumulation of di- and trimethylation of H3–K4 at the induced ER target genes. Furthermore, RNA interference-directed down-regulation of SMYD3 reveals that SMYD3 is required for ER-regulated gene transcription in estrogen signaling pathway. Thus, our results identify SMYD3 as a new coactivator for ER-mediated transcription, providing a possible link between SMYD3 overexpression and breast cancer.
Role of Glucoxidation and Lipid Oxidation in the Development of Atherosclerosis

Abstract: Previous data have indicated that modification of proteins/lipids by glucoxidation and/or lipid oxidation may initiate/propagate the formation of atherosclerotic plaques. Although the biomarker carboxymethyllysine (CML) has been detected in these lesions, the origin of the reactive oxygen species (ROS) leading to its formation and the source of its carbon backbone are unknown. As presented here, the stimulation of cultured monocytes by phorbol‐12‐myristate‐13‐acetate (TPA), an activator of protein kinase C that can mimic the effects of high glucose, angiotensin II, and other physiological stimuli, leads to cellular ROS generation and concomitant formation of intracellular CML. Inhibitors of ROS‐generating cellular systems such as NO synthase, xanthine oxidase, or cytochrome P450 oxidase had no effect on CML formation. Likewise, in cells with inactive NAD(P)H oxidase no reduced CML formation was found. In cells exhibiting a high glycolysis rate, CML formation was unaffected. Because we found rapid CML formation in the presence of unsaturated fatty acids, it appears that lipid oxidation is quantitatively more important. In vivo studies revealed strong intracellular CML staining in areas of histiocytic/monocytic infiltration or proliferation, mostly associated with atheroma formation. Corresponding CML staining patterns were found in healing wounds of different ages, indicating that formation of atherosclerosis is a chronic wound repair associated with a low‐grade inflammatory reaction. In summary, CML is formed concomitantly with oxidative stress in activated monocytes and can be regarded as a biomarker for a low‐grade inflammatory tissue reaction in the atherosclerotic plaque. Its formation via lipid oxidation may be involved in the development of atherosclerosis.
Sensitivity of changes in chronic graft-versus-host disease activity to changes in patient-reported quality of life: results from the Chronic Graft-versus-Host Disease Consortium

Background The 2005 National Institute of Health Chronic Graft-versus-Host Disease Consensus Conference recommended collection of patient-reported outcomes in clinical trials on chronic graft-versus-host disease. We assessed whether changes in chronic graft-versus-host disease severity, determined using National Institute of Health criteria, clinicians’ assessment or patients’ self-evaluation, correlated with patient-reported quality of life as measured by the Short Form-36 and Functional Assessment of Cancer Therapy – Bone Marrow Transplant (FACT-BMT) instruments. Design and Methods Three-hundred and thirty-six adult patients (median age 52 years; range, 19 – 79) with chronic graft-versus-host disease from six transplant centers contributed baseline and follow-up data (from 936 visits overall). Results While the majority of the patients had stable chronic graft-versus-host disease, improvement or worsening was noted in approximately 40% of follow-up visits. Multivariable analysis demonstrated no association between change in chronic graft-versus-host disease severity evaluated by National Institute of Health criteria and change in quality of life, while clinician-reported changes in severity were associated with changes in some quality of life measures. Patient-reported changes in the severity of chronic graft-versus-host disease were associated with changes in all quality of life measures. Comparison of the Short Form-36 and the FACT-BMT suggested that the data collected in the Functional Assessment of Cancer Therapy – General (FACT-G) core survey are sufficient without the need for the Short Form-36 or the FACT–BMT subscale. Conclusions We conclude that serial National Institute of Health and clinician-reported chronic graft-versus-host disease severity assessments cannot substitute for patient-reported outcomes in clinical trials. Collection of just the FACT-G instead of the Short Form-36 and the full FACT-BMT will decrease respondent burden without compromising quality of life assessment.
Common Genetic Variants of PSCA, MUC1 and PLCE1 Genes are not Associated with Colorectal Cancer.

BACKGROUND Polymorphisms of genes encoding PSCA, PLCE1 and MUC1 have been associated with the risk of different cancers in genome wide association studies (GWAS). Up to date there are limited data on the role of these genetic alterations in colorectal cancer (CRC) development. The aim of this study was to evaluate potential associations between single nucleotide polymorphisms (SNPs) of genes encoding PSCA, PLCE1 and MUC1 and the presence of CRC in European populations. MATERIALS AND METHODS Gene polymorphisms were analyzed in 574 European subjects (controls: n=382; CRC: n=192). PSCA C>T (rs2294008), PSCA G>A (rs2976392), MUC1 A>G (rs4072037) and PLCE1 A>G (rs2274223) SNPs were genotyped by RT-PCR. RESULTS The distribution of genotypes for all four SNPs was in line with the Hardy-Weinberg equilibrium (rs2294008, P=0.153; rs2976392, P=0.269; rs4072037, P=0.609; rs2274223, P=0.858). The distribution of genotypes and alleles of PSCA C>T, PSCA G>A, MUC1 A>G and PLCE1 A>G SNPs was similar among controls and CRC patient groups (P>0.05). GG genotype of MUC1 SNP was more frequent in CRC patients (24.0%) than in controls (20.2%); however, this association failed to reach significance (OR-1.45, P=0.15). Overall, in the present study SNPs of PSCA (rs2294008, rs2976392), MUC1 (rs4072037) and PLCE1 (rs2274223) genes were not associated with the presence of CRC. CONCLUSIONS Gene polymorphisms of PSCA, PLCE1 and MUC1 genes are not associated with the presence of CRC in European subjects.
Hysteretic models for deteriorating inelastic structures

The modeling of deteriorating hysteretic behavior is becoming increasingly important, especially in the context of seismic analysis and design. This paper presents the development of a versatile smooth hysteretic model based on internal variables, with stiffness and strength deterioration and with pinching characteristics. The theoretical background, development, and implementation of the model are discussed. Examples are shown to illustrate the features of the model. Many inelastic constitutive models in popular use have been developed independently of each other based on different behavioral, physical, or mathematical motivations. This paper attempts to unify the concepts underlying such models. Such a holistic understanding is essential to realize limitations in application of inelastic models and to extend 1D models to 3D models featuring interaction between various stress resultants.
Hemodynamic Response to Sildenafil in Patients With Decompensated Congestive Heart Failure Can Be Predicted by Deceleration Time of Transmitral Flow

Aim: How sildenafil acutely provides hemodynamic alterations in patients with decompensated congestive heart failure remains unknown. The aim of this study was to investigate whether myocardial and/or hemodynamic conditions affect hemodynamic response to sildenafil in patients with decompensated heart failure. Methods and Results: Twenty-five consecutive patients with decompensated congestive heart failure were enrolled. The patients underwent echocardiography before and 1 hour after a single oral administration of sildenafil (20 mg). Sildenafil decreased pulmonary vascular resistance by 24% (P < 0.05), and increased left ventricular (LV) time–velocity integral by 17% (P < 0.05). Alteration of the ratio of peak velocity of early LV filling to early diastolic myocardial velocity (E/E′), an indicator of LV filling pressure, following administration of sildenafil, negatively associated with the deceleration time of early filling wave (DcT) at baseline. Patients with baseline DcT ≥200 milliseconds (n = 11) exhibited E/E′ increase, whereas patients with baseline DcT <200 milliseconds (n = 14) exhibited E/E′ decrease. Conclusions: Administration of sildenafil elevated LV filling pressure in decompensated heart failure patients with shortened deceleration time of early diastolic transmitral flow.
What Are the Long‐Term Effects of Small Classes on the Achievement Gap? Evidence from the Lasting Benefits Study

The findings on the social distribution of the immediate and lasting benefits of small classes have been mixed. We used data from Project STAR and the Lasting Benefits Study to examine the long‐term effects of small classes on the achievement gap in mathematics, reading, and science scores (Stanford Achievement Test). The results consistently indicated that all types of students benefit more in later grades from being in small classes in early grades. These positive effects are significant through grade 8. Longer periods in small classes produced higher increases in achievement in later grades for all types of students. For certain grades, in reading and science, low achievers seem to benefit more from being in small classes for longer periods. It appears that the lasting benefits of the cumulative effects of small classes may reduce the achievement gap in reading and science in some of the later grades.
An Approach for Finding Possible Presence of Water Ice Deposits on Lunar Craters Using MiniSAR Data

Investigating the feasibility of water-ice deposits on lunar surface has been a very challenging task, which requires meticulous effort. Conceptualization of MiniSAR was a breakthrough because it had capability to image the shadowed regions that may have higher possibility of water-ice. Earlier studies have found that circular polarization ratio (CPR) is greater than unity in regions having volume scattering due to dielectric mixing (or water-ice deposits). However, later experiments revealed that CPR > 1 might also occur due to surface roughness. Thus, instead of using single polarimetric parameter CPR, it is required to use textural (or roughness) behavior of lunar surface along with scattering mechanisms, for obtaining the regions having higher possibility of dielectric mixing. For this purpose, information of two different approaches namely, polarimetric approach (i.e., m - δ decomposition and m - χ decomposition) and fractal approach have been fused together. The polarimetric approaches, i.e., m - δ decomposition and m - χ decomposition, help in identifying scattering mechanisms associated with lunar surface, whereas fractal-based approach helps in characterizing lunar surface on the basis of surface roughness using a measure called fractal dimension “D. ” Finally, a decision tree algorithm has been proposed, in which decision criteria are decided on the basis of CPR, m - δ decomposition, m - χ decomposition, and fractal dimension “D. ” The proposed approach seems to resolve the vagueness caused by CPR > 1 assumption, and to segregate areas representing volume scattering in relatively smooth surfaces inside anomalous craters, where possibility of dielectric mixing (or water-ice) may be high.
Studies of in‐vitro Autohaemolysis in Blood from Newborn Infants

THE in-vitro autohaemolysis test of Dacie (1941) has been used extensively, with various modifications, for the diagnosis and study of haemolytic disorders (Selwyn and Dacie, 1954; Young, Izzo, Altman and Swisher, 1956; Crosby and Benjamin, 1957; Simon, 1963). Selwyn and Dacie (1954) also found that the in-vitro addition of glucose to blood markedly reduced the rate of autohaemolysis of normal red blood cells as well as the increased autohaemolysis occurring in hereditary spherocytosis. While extensive studies of autohaemolysis have been performed on normal and abnormal blood samples from adults, data on blood obtained from healthy newborn infants are scanty. Furthermore, the demonstration of both in-vivo haemolysis and increased in-vitro autohaemolysis in certain individuals exposed to hyperbaric oxygenation (Mengel, Kann, Lewis and Horton, 1964) warrants investigation of the effect of the sudden increase in oxygen tension attendant on the birth process on the red cells of the newborn. The present study was undertaken to establish normal values for in-vitro autohaemolysis in cord blood and in blood from healthy newborn infants and to determine the effect of the addition of glucose and of continuous oxygenation on this phenomenon. Knowledge gained from such studies could be of value in the investigation of haemolytic disorders in the newborn, and also contribute to the understanding of the physiological changes occurring during adaptation of the foetus to extra-uterine He.
Organic solvent exposure and hearing loss

Organic solvents are frequent air contaminants in industry and are found, for example, in paints, lacquers and printing inks. They are used in the production of furniture, plastics, fibres and rubber tyres. Over recent decades several studies in animals and humans have reported upon the effects of these substances on the auditory system and their interaction with noise. Potentially, this issue has significant socio-economic implications, as the chemical industry is the third largest industry in Europe, employing 1.7 million people directly and with 3 million jobs depending on it. Studies on rats suggest that several organic solvents, for example, styrene and toluene, damage the cochlea (predominantly the supporting and outer hair cells (OHCs)) resulting in mid-frequency hearing loss.1 Retrocochlear or central hearing damage, although likely, has not been demonstrated clearly so far. Styrene can increase noise damage at levels as low as 300 ppm, and toluene at 1100 ppm. These were the lowest concentrations studied in animals, but it cannot be guaranteed that even lower levels are safe. However, assuming a safety factor of 10 and extrapolating these data to humans, the lowest observed adverse effect level (LOAEL) for styrene would be 30 ppm, whereas the occupational exposure limit for styrene is set much higher than this in several countries. Synergistic effects occur in rats exposed to both noise and solvents.1 Solvents may modify the membranous structures of the OHCs, making them more fragile and vulnerable to noise. However, in combined exposures, the most important factor for inducing …
The Effect of the APOE-ε4 Allele and ACE-I/D Polymorphism on Cognition during a Two-Year Follow-Up in First-Ever Stroke Patients

Background: Cognitive impairment is commonly observed after stroke and has a negative impact on survival and rehabilitation. Some stroke patients deteriorate in cognitive functioning whereas others do not. Environmental and demographic risk factors cannot fully explain this. There is growing evidence that a genetic predisposition plays a role in the pathogenesis of post-stroke cognitive decline. Objective: To study the influence of the APOE-Ε4 allele and the ACE-I/D polymorphism on cognitive functioning after stroke. Methods: We included 194 first-ever stroke patients of whom information about APOE genotyping and ACE-I/D polymorphism was available in 92 and 129 patients, respectively. Patients were cognitively assessed at 1, 6, 12 and 24 months after the event. Linear mixed models with slope estimates were used to study the influence of the APOE-Ε4 allele and the ACE-I/D polymorphism on the MMSE score, CAMCOG, executive functioning, psychomotor speed, and verbal memory function during follow-up. Results: Patients carrying the APOE-Ε4 allele more often suffered a lacunar infarction than non-carriers. The APOE-Ε4 allele had no effect on cognitive functioning during the follow-up. ACE-DD homozygosity was associated with a worse performance in executive functioning compared to patients with neither an APOE-Ε4 allele nor the ACE-DD genotype. There was no interaction between the APOE-Ε4 allele and the ACE-DD phenotype in the prediction of cognitive decline. Conclusion: The ACE-DD genotype may be associated with post-stroke cognitive decline while the APOE-Ε4 allele is not. Further research is needed to examine the role of genetic risk factors for post-stroke cognitive decline and to determine why some patients deteriorate cognitively after stroke but others do not.
Determinants of Inhibition of Transiently Expressed Voltage-gated Calcium Channels by ω-Conotoxins GVIA and MVIIA*

The Conus magus peptide toxin ω-conotoxin MVIIA is considered an irreversible, specific blocker of N-type calcium channels, and is now in clinical trials as an intrathecal analgesic. Here, we have examined the action of MVIIA on mutant and wild type calcium channels transiently expressed in tsA-201 cells. Although we have shown previously that mutations in a putative external EF-hand motif in the domain IIIS5–H5 region alters block by both ω-conotoxin GVIA and MVIIA (Feng, Z. P., Hamid, J., Doering, C., Bosey, G. M., Snutch, T. P., and Zamponi, G. W. (2001) J. Biol. Chem. 276, 15728–15735), the introduction of five point mutations known to affect GVIA blocking (and located downstream of the EF-hand) affected MVIIA block to a smaller degree compared with GVIA. These data suggest that despite some overlap, MVIIA and GVIA block does not share identical channel structural determinants. At higher concentrations (∼3 μm), MVIIA reversibly blocked L-, P/Q-, and R-type, but not T-type channels, indicating that the overall architecture of the MVIIA site is conserved in all types of high voltage-activated calcium channels. A kinetic analysis of the MVIIA effects on the N-type channel showed that MVIIA blocked resting, open, and inactivated channels. Although the development of MVIIA block did not appear to be voltage-, nor frequency-dependent, the degree of recovery from block strongly depended on the potential applied during washout. Interestingly, the degree of washout was highly variable and appeared to weakly depend on the holding potential applied during toxin application. We propose a model in which N-type calcium channels can form both reversible and irreversible complexes with MVIIA.
Immunostimulatory Effect of Levamisole on the Immune Response of Goats to Peste des petits ruminants (PPR) Vaccination

The use of Levamisole hydrochloride as an immunostimulant has been successful in the control of certain diseases such as Derzsy’s disease in chicken as well as in increasing lymphocytes and weight gain in pigs. However, its use as immunostimulant in the prevention of Peste des petits ruminants (PPR) in goats has not been investigated. In this study, the use of Levamisole in enhancing immune response to PPR vaccination including its effects on weight gain was investigated among groups of goats (groups A, B, C and D). Virus neutralization test was used to determine the antibody profile in vaccinated goats while the total and differential leucocyte counts and body mass index (BMI) were determined using standard procedures. Goats in group A (Levamisole primed and PPR vaccinated) seroconverted to more than 3-folds of the initial pre-vaccination geometric mean titre (GMT) of neutralizing antibody beginning from second week post-vaccination and remained high throughout the period of the experiment. Similarly, there was significant increase (p 0.05) in BMI of animals in other groups throughout the period of the experiment. The results of this study further confirm the immunostimulatory effect of Levamisole when used in combination with a vaccine.