Miracle-dz/UniFAR-FTUs huggingface dataset:
Prostate cancer surveillance by occupation and industry: the Canadian Census Health and Environment Cohort (CanCHEC)

As there are no well‐established modifiable risk factors for prostate cancer, further evidence is needed on possible factors such as occupation. Our study uses one of the largest Canadian worker cohorts to examine occupation, industry, and prostate cancer and to assess patterns of prostate cancer rates. The Canadian Census Health and Environment Cohort (CanCHEC) was established by linking the 1991 Canadian Census Cohort to the Canadian Cancer Database (1969–2010), Canadian Mortality Database (1991–2011), and Tax Summary Files (1981–2011). A total of 37,695 prostate cancer cases were identified in men aged 25–74 based on age at diagnosis. Cox proportional hazards models were used to estimate hazards ratios and 95% confidence intervals. In men aged 25–74 years, elevated risks were observed in the following occupations: senior management (HR = 1.12, 95% CI: 1.04–1.20); office and administration (HR = 1.19, 95% CI: 1.11–1.27); finance services (HR = 1.09, 95% CI: 1.04–1.14); education (HR = 1.05, 95% CI: 1.00–1.11); agriculture and farm management (HR = 1.12, 95% CI: 1.06–1.17); farm work (HR = 1.11, 95% CI: 1.01–1.21); construction managers (HR = 1.07, 95% CI: 1.01–1.14); firefighting (HR = 1.17, 95% CI: 1.01–1.36); and police work (HR = 1.22, 95% CI: 1.09–1.36). Decreased risks were observed across other construction and transportation occupations. Results by industry were consistent with occupation results. Associations were identified for white‐collar, agriculture, protective services, construction, and transportation occupations. These findings emphasize the need for further study of job‐related exposures and the potential influence of nonoccupational factors such as screening practices.
First Genome-Wide Association Study in an Australian Aboriginal Population Provides Insights into Genetic Risk Factors for Body Mass Index and Type 2 Diabetes

A body mass index (BMI) >22kg/m2 is a risk factor for type 2 diabetes (T2D) in Aboriginal Australians. To identify loci associated with BMI and T2D we undertook a genome-wide association study using 1,075,436 quality-controlled single nucleotide polymorphisms (SNPs) genotyped (Illumina 2.5M Duo Beadchip) in 402 individuals in extended pedigrees from a Western Australian Aboriginal community. Imputation using the thousand genomes (1000G) reference panel extended the analysis to 6,724,284 post quality-control autosomal SNPs. No associations achieved genome-wide significance, commonly accepted as P<5x10-8. Nevertheless, genes/pathways in common with other ethnicities were identified despite the arrival of Aboriginal people in Australia >45,000 years ago. The top hit (rs10868204 P genotyped = 1.50x10-6; rs11140653 Pimputed_1000G = 2.90x10-7) for BMI lies 5’ of NTRK2, the type 2 neurotrophic tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF) that regulates energy balance downstream of melanocortin-4 receptor (MC4R). PIK3C2G (rs12816270 Pgenotyped = 8.06x10-6; rs10841048 Pimputed_1000G = 6.28x10-7) was associated with BMI, but not with T2D as reported elsewhere. BMI also associated with CNTNAP2 (rs6960319 Pgenotyped = 4.65x10-5; rs13225016 Pimputed_1000G = 6.57x10-5), previously identified as the strongest gene-by-environment interaction for BMI in African-Americans. The top hit (rs11240074 Pgenotyped = 5.59x10-6, Pimputed_1000G = 5.73x10-6) for T2D lies 5’ of BCL9 that, along with TCF7L2, promotes beta-catenin’s transcriptional activity in the WNT signaling pathway. Additional hits occurred in genes affecting pancreatic (KCNJ6, KCNA1) and/or GABA (GABRR1, KCNA1) functions. Notable associations observed for genes previously identified at genome-wide significance in other populations included MC4R (Pgenotyped = 4.49x10-4) for BMI and IGF2BP2 Pimputed_1000G = 2.55x10-6) for T2D. Our results may provide novel functional leads in understanding disease pathogenesis in this Australian Aboriginal population.
26Al/10Be Burial Dating of Xujiayao-Houjiayao Site in Nihewan Basin, Northern China

The Xujiayao-Houjiayao site in Nihewan Basin is among the most important Paleolithic sites in China for having provided a rich collection of hominin and mammalian fossils and lithic artifacts. Based on biostratigraphical correlation and exploratory results from a variety of dating methods, the site has been widely accepted as early Upper Pleistocene in time. However, more recent paleomagnetic analyses assigned a much older age of ∼500 ka (thousand years). This paper reports the application of 26Al/10Be burial dating as an independent check. Two quartz samples from a lower cultural horizon give a weighted mean age of 0.24 ± 0.05 Ma (million years, 1σ). The site is thus younger than 340 ka at 95% confidence, which is at variance with the previous paleomagnetic results. On the other hand, our result suggests an age of older than 140 ka for the site’s lower cultural deposits, which is consistent with recent post-infrared infrared stimulated luminescence (pIR-IRSL) dating at 160–220 ka.
Composite Shaft Rotordynamic Analysis Using the Finite Element Method

This work is concerned with the study of the vibratory behaviour of rotating composite shafts. A finite element models based on Equivalent Single Layer Theory and Modified Equivalent Single Layer Theory are developed to model the rotating composite shafts using Timoshenko beam theory. Moreover, a new multi-layer finite element for rotating laminated shaft based on Layerwise and shaft theories is formulated and implemented to dispose of a more realistic description of the displacement field through the laminated shaft thickness. Those formulations are introduced to consider the effects of fiber orientation, stacking sequence and shear-normal coupling. Furthermore, a Euler-Bernoulli shaft finite element formulation based on Equivalent Single Layer Theory including hysteretic internal damping and transverse shear effects is introduced and then used to evaluate the influence of various parameters on natural frequencies, critical speeds and instability thresholds. The close agreement in the obtained results shows that the developed theories can be effectively used for composite rotor dynamic analysis and that rotor stability is sensitive to laminate parameters and bearing properties.
Interindividual Variability in Functional Connectivity as Long-Term Correlate of Temporal Discounting

During intertemporal choice (IT) future outcomes are usually devaluated as a function of the delay, a phenomenon known as temporal discounting (TD). Based on task-evoked activity, previous neuroimaging studies have described several networks associated with TD. However, given its relevance for several disorders, a critical challenge is to define a specific neural marker able to predict TD independently of task execution. To this aim, we used resting-state functional connectivity MRI (fcMRI) and measured TD during economic choices several months apart in 25 human subjects. We further explored the relationship between TD, impulsivity and decision uncertainty by collecting standard questionnaires on individual trait/state differences. Our findings indicate that fcMRI within and between critical nodes of task-evoked neural networks associated with TD correlates with discounting behavior measured a long time afterwards, independently of impulsivity. Importantly, the nodes form an intrinsic circuit that might support all the mechanisms underlying TD, from the representation of subjective value to choice selection through modulatory effects of cognitive control and episodic prospection.
Atomic and electronic structure of self-organized defects in epitaxial films of functional perovskite-type oxides

vii Resum (in catalan). ix Abbreviation list . xi Chapter 1 Thesis rationale . 1 1.1. Outline of the thesis . 2 Chapter 2 General concepts of epitaxial thin films of functional perovskite-type oxides . 5 2.1. Physical properties of transition metal perovskite-type oxides . 5 2.1.1. Perovskite crystalline structure . 5 2.1. 2. Electronic structure . 8 2.1. 3. Magnetism in transition metal oxides . 9 2.1. 4. Lanthanum manganites perovskites . 9 2.2. Thin film heterostructures: strain engineering . 11 2.2.1. Nucleation and growth mechanisms . 11 2.2.2. Epitaxial strain and relaxation mechanism . 13 2.2. 3. Interfacial effects . 15 2.2. 4. Self-organized defects . 18 Chapter 3 Methodologies and methods . 21
Space-Time Coding for MIMO Radar Detection and Ranging

Space-time coding (STC) has been shown to play a key role in the design of MIMO radars with widely spaced antennas: In particular, rank-one coding amounts to using the multiple transmit antennas as power multiplexers, while full-rank coding maximizes the transmit diversity, compromises between the two being possible through rank-deficient coding. In detecting a target at known distance and Doppler frequency, no uniformly optimum transmit policy exists, and diversity maximization turns out to be the way to go only in a (still unspecified) large signal-to-noise ratio region. The aim of this paper is to shed some light on the optimum transmit policy as the radar is to detect a target at an unknown location: To this end, at first the Cramér-Rao bounds as a function of the STC matrix are computed, and then waveform design is stated as a constrained optimization problem, where now the constraint concerns also the accuracy in target ranging, encapsulated in the Fisher Information on the range estimate. Results indicate that such accuracy constraints may visibly modify the required transmit policy and lead to rank-deficient STC also in regions where pure detection would require pursuing full transmit diversity.
A Role for Tn6029 in the Evolution of the Complex Antibiotic Resistance Gene Loci in Genomic Island 3 in Enteroaggregative Hemorrhagic Escherichia coli O104:H4

In enteroaggregative hemorrhagic Escherichia coli (EAHEC) O104 the complex antibiotic resistance gene loci (CRL) found in the region of divergence 1 (RD1) within E. coli genomic island 3 (GI3) contains bla TEM-1, strAB, sul2, tet(A)A, and dfrA7 genes encoding resistance to ampicillin, streptomycin, sulfamethoxazole, tetracycline and trimethoprim respectively. The precise arrangement of antibiotic resistance genes and the role of mobile elements that drove the evolutionary events and created the CRL have not been investigated. We used a combination of bioinformatics and iterative BLASTn searches to determine the micro-evolutionary events that likely led to the formation of the CRL in GI3 using the closed genome sequences of EAHEC O104:H4 strains 2011C-3493 and 2009EL-2050 and high quality draft genomes of EAHEC E. coli O104:H4 isolates from sporadic cases not associated with the initial outbreak. Our analyses indicate that the CRL in GI3 evolved from a progenitor structure that contained an In2-derived class 1 integron in a Tn21/Tn1721 hybrid backbone. Within the hybrid backbone, a Tn6029-family transposon, identified here as Tn6029C abuts the sul1 gene in the 3´-Conserved Segment (-CS) of a class 1 integron generating a unique molecular signature that has only previously been observed in pASL01a, a small plasmid found in commensal E. coli in West Africa. From this common progenitor, independent IS26-mediated events created two novel transposons identified here as Tn6029D and Tn6222 in 2011C-3493 and 2009EL-2050 respectively. Analysis of RD1 within GI3 reveals IS26 has played a crucial role in the assembly of regions within the CRL.
Inhibiting EGFR Dimerization Using Triazolyl-Bridged Dimerization Arm Mimics

The epidermal growth factor receptor (EGFR) is overexpressed in multiple carcinomas and is the focus of a variety of targeted therapies. Here we report the design of peptide-based compounds that mimic the EGFR dimerization arm and inhibit allosteric activation of EGFR. These peptides are modified to contain a triazolyl bridge between the peptide strands to constrain the EGFR dimerization arm β-loop. In this study, we demonstrate that these peptides have significantly improved proteolytic stability over the non-modified peptide sequence, and their inhibitory effects are dependent on the number of the methylene units and orientation of the introduced triazolyl bridge. We identified a peptide, EDA2, which downregulates receptor phosphorylation and dimerization and reduces cell viability. This is the first example of a biologically active triazolyl-bridged peptide targeting the EGFR dimerization interface that effectively downregulates EGFR activation.
AUDIT, AUDIT-C, and AUDIT-3: Drinking Patterns and Screening for Harmful, Hazardous and Dependent Drinking in Katutura, Namibia

Objectives To describe alcohol drinking patterns among participants in Katutura, Namibia, and to evaluate brief versions of the AUDIT against the full AUDIT to determine their effectiveness in detecting harmful drinking. Methods A cross-sectional survey was conducted in four constituencies and 639 participants, 18 years or older, completed a sociodemographic survey and the AUDIT. The effectiveness of the AUDIT-C (first three questions) and the AUDIT-3 (third question) was compared to the full AUDIT. Results Approximately 40% were identified as harmful, hazardous or likely dependent drinkers, with men having a higher likelihood than women (57.2% vs. 31.0%, p<.0001). Approximately 32% reported making and/or selling alcohol from home. The AUDIT-C performed best at a cutoff ≥ 3, better in men (sensitivity: 99.3%, specificity: 77.8%) than women (sensitivity: 91.7%, specificity: 77.4%). The AUDIT-3 performed poorly (maximum sensitivity: < 90%, maximum specificity: <51%). According to AUROC, the AUDIT-C performed better than the AUDIT-3. Conclusions A large proportion of participants met criteria for alcohol misuse, indicating a need for screening and referral for further evaluation and intervention. The AUDIT-C was almost as effective as the full AUDIT and may be easier to implement in clinical settings as a routine screening tool in resource-limited settings because of its brevity.
Discovery of Novel Adenosine Receptor Antagonists through a Combined Structure- and Ligand-Based Approach Followed by Molecular Dynamics Investigation of Ligand Binding Mode

An intense effort is made by pharmaceutical and academic research laboratories to identify and develop selective antagonists for each adenosine receptor (AR) subtype as potential clinical candidates for "soft" treatment of various diseases. Crystal structures of subtypes A2A and A1ARs offer exciting opportunities for structure-based drug design. In the first part of the present work, Maybridge HitFinder library of 14400 compounds was utilized to apply a combination of structure-based against the crystal structure of A2AAR and ligand-based methodologies. The docking poses were rescored by CHARMM energy minimization and calculation of the desolvation energy using Poisson-Boltzmann equation electrostatics. Out of the eight selected and tested compounds, five were found positive hits (63% success). Although the project was initially focused on targeting A2AAR, the identified antagonists exhibited low micromolar or micromolar affinity against A2A/A3, ARs, or A3AR, respectively. Based on these results, 19 compounds characterized by novel chemotypes were purchased and tested. Sixteen of them were identified as AR antagonists with affinity toward combinations of the AR family isoforms (A2A/A3, A1/A3, A1/A2A/A3, and A3). The second part of this work involves the performance of hundreds of molecular dynamics (MD) simulations of complexes between the ARs and a total of 27 ligands to resolve the binding interactions of the active compounds, which were not achieved by docking calculations alone. This computational work allowed the prediction of stable and unstable complexes which agree with the experimental results of potent and inactive compounds, respectively. Of particular interest is that the 2-amino-thiophene-3-carboxamides, 3-acylamino-5-aryl-thiophene-2-carboxamides, and carbonyloxycarboximidamide derivatives were found to be selective and possess a micromolar to low micromolar affinity for the A3 receptor.
Sedation for magnetic resonance imaging using propofol with or without ketamine at induction in pediatrics—A prospective randomized double‐blinded study

Deep sedation using propofol has become a standard technique in children. This double‐blinded randomized clinical trial aims to compare the clinical effects of propofol‐mono‐sedation vs a combination of propofol and ketamine at induction and a reduced propofol infusion rate for maintenance in children undergoing diagnostic magnetic resonance imaging.
Wound Edge Protectors in Open Abdominal Surgery to Reduce Surgical Site Infections: A Systematic Review and Meta-Analysis

Importance Surgical site infections remain one of the most frequent complications following abdominal surgery and cause substantial costs, morbidity and mortality. Objective To assess the effectiveness of wound edge protectors in open abdominal surgery in reducing surgical site infections. Evidence Review A systematic literature search was conducted according to a prespecified review protocol in a variety of data-bases combined with hand-searches for randomized controlled trials on wound edge protectors in patients undergoing laparotomy. A qualitative and quantitative analysis of included trials was conducted. Findings We identified 16 randomized controlled trials including 3695 patients investigating wound edge protectors published between 1972 and 2014. Critical appraisal uncovered a number of methodological flaws, predominantly in the older trials. Wound edge protectors significantly reduced the rate of surgical site infections (risk ratio 0.65; 95%CI, 0.51–0.83; p = 0.0007; I2 = 52%). The results were robust in a number of sensitivity analyses. A similar effect size was found in the subgroup of patients undergoing colorectal surgery (risk ratio 0.65; 95%CI, 0.44–0.97; p = 0.04; I2 = 56%). Of the two common types of wound protectors double ring devices were found to exhibit a greater protective effect (risk ratio 0.29; 95%CI, 0.15–0.55) than single-ring devices (risk ratio 0.71; 95%CI, 0.54–0.92), but this might largely be due to the lower quality of available data for double-ring devices. Exploratory subgroup analyses for the degree of contamination showed a larger protective effect in contaminated cases (0.44; 95%CI, 0.28–0.67; p = 0.0002, I2 = 23%) than in clean-contaminated surgeries (0.72, 95%CI, 0.57–0.91; p = 0.005; I2 = 46%) and a strong effect on the reduction of superficial surgical site infections (risk ratio 0.45; 95%CI, 0.24–0.82; p = 0.001; I2 = 72%). Conclusions and Relevance Wound edge protectors significantly reduce the rate of surgical site infections in open abdominal surgery. Further trials are needed to explore their effectiveness in different risk constellations.
Differing mechanisms of surviving phagosomal stress among group B Streptococcus strains of varying genotypes

ABSTRACT Group B Streptococcus (GBS), a leading cause of neonatal sepsis and meningitis, asymptomatically colonizes up to 30% of women and can persistently colonize even after antibiotic treatment. Previous studies have shown that GBS resides inside macrophages, but the mechanism by which it survives remains unknown. Here, we examined the ability of 4 GBS strains to survive inside macrophages and then focused on 2 strains belonging to sequence type (ST)-17 and ST-12, to examine persistence in the presence of antibiotics. A multiple stress medium was also developed using several stressors found in the phagosome to assess the ability of 30 GBS strains to withstand phagosomal stress. The ST-17 strain was more readily phagocytosed and survived intracellularly longer than the ST-12 strain, but the ST-12 strain was tolerant to ampicillin unlike the ST-17 strain. Exposure to sub-inhibitory concentrations of ampicillin and erythromycin increased the level of phagocytosis of the ST-17 strain, but had no effect on the ST-12 strain. In addition, blocking acidification of the phagosome decreased the survival of the ST-17 strain indicating a pH-dependent survival mechanism for the ST-17 strain. Congruent with the macrophage experiments, the ST-17 strain had a higher survival rate in the multiple stress medium than the ST-12 strain, and overall, serotype III isolates survived significantly better than other serotypes. These results indicate that diverse GBS strains may use differing mechanisms to persist and that serotype III strains are better able to survive specific stressors inside the phagosome relative to other serotypes.
Mesenchymal stem cell mechanics on osteoinductive peptide nanofibers

MESENCHYMAL STEM CELL MECHANICS ON OSTEOINDUCTIVE PEPTIDE NANOFIBERS Ahmet Emin Topal Ph.D. in Materials Science and Nanotechnology Advisor: Aykutlu Dâna July 2017 In this thesis, changes in Young's modulus of mesenchymal stem cells (MSCs) were investigated during their osteogenic differentiation on bioactive peptide nanofibers that bear triple glutamic acid sequence (EEE), a non-collagenous protein sequence of some extracellular matrix (ECM) proteins (e.g. bone sialoprotein) found in bone tissue. MSCs formed spherical cell aggregates on the osteoinductive peptide nanofibers, here also called osteospheroids, of which their cells made intensive cell-cell contacts and showed osteoblast-like cell morphology. Mechanical characterization of the osteospheroids on the peptide nanofiber hydrogel was performed using atomic force microscope (AFM) where AFM probes modified with a thin film coating of octafluorocyclobutane (C4F8) were used to measure force maps of the cells at days 3, 7 and 14 of osteogenic differentiation. Hertz Cone model, same as Sneddon, was applied to approach curves of 12 force curves per cell to calculate the Young's modulus values. As a result, an increasing pattern was observed in the average Young's modulus of rMSCs on the peptide nanofibers throughout the osteogenic differentiation. Mineral deposition by the cells on the peptide nanofibers was checked by Alizarin red staining and a large amount of mineral deposition by the osteospheroids was observed, proving that an efficient osteogenic differentiation of the rMSCs happens on the osteoinductive peptide nanofibers. In the literature, a gradual decrease is shown in AFM measured average Young's modulus values of adhered MSCs throughout their osteogenic differentiation. When gelatin-coated glass was used as substrate instead of the peptide nanofibers, rMSCs showed a decreasing pattern in their Young's moduli, similarly to the literature, due to osteogenic differentiation. However, there was no significant calcium mineral deposition on the gelatin group, even until day 14 of osteogenic differentiation, indicating that a limited or a slower progression of osteogenic differentiation of rMSCs is present on the gelatin compared to rMSCs on the osteoinductive peptide nanofibers. A correlation between the observed increase in average Young's moduli of osteospheroid rMSCs and