Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Variation in the Chromosome 17q23 Amplicon and Breast Cancer Risk

Background: Gene amplification leading to overexpression is a common event in breast tumors that is linked to tumor development and progression. The 17q23 region is amplified in >40% of breast tumors and contains several candidate oncogenes. Because common genetic variation in several oncogenes has been associated with cancer risk, we assessed the relevance of common variants in the 17q23 candidate oncogenes to breast cancer. Methods: We investigated 60 polymorphisms in the TUBD1, SEPT4, PRKCA, TBX2, TBX4, TEX14, TLK2, YPEL2, and PPM1E genes from this amplicon for association with breast cancer risk among 798 Caucasian breast cancer cases and 843 unaffected Caucasian controls from the Mayo Clinic. Results: Eight polymorphisms in PRKCA, TBX4, TLK2, and YPEL2 displayed significant dose-response associations with breast cancer risk (Ptrend < 0.05). Of these, PRKCA rs7342847 and TLK2 rs2245092 and rs733025 were also associated with hormone receptor–positive breast cancer: PRKCA rs7342847 (odds ratio, 0.7; 95% confidence interval, 0.6-0.9; Ptrend = 0.002) and TLK2 rs733025 and rs2245092 (both: odds ratio, 0.8; 95% confidence interval, 0.7-1.0; Ptrend = 0.03). Interactions between SEPT4 rs758377 and TEX14 rs302864 (Pinteraction = 0.0003) and between TLK2 rs733025 and YPEL2 rs16943468 (Pinteraction = 0.05) for risk of breast cancer were also observed. Conclusion: These findings suggest that single polymorphisms and combinations of polymorphisms within candidate oncogenes from the 17q23 amplicon may influence risk of breast cancer overall and possibly specific molecular subtypes of breast tumors. The findings are discussed within the context of the results from two independent data sets. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1864–8)
Smad7 protects against chronic aristolochic acid nephropathy in mice

Chronic Aristolochic Acid Nephropathy (AAN) is a progressive chronic kidney disease related to herb medicine. However, treatment for chronic AAN remains ineffective. We report here that Smad7 is protective and has therapeutic potential for chronic AAN. In a mouse model of chronic AAN, progressive renal injury was associated with a loss of renal Smad7 and disruption of Smad7 largely aggravated the severity of chronic AAN as demonstrated by a significant increase in levels of 24-hour urinary protein excretion, serum creatinine, and progressive renal ﬁbrosis and inflammation. In contrast, restored Smad7 locally in the kidneys of Smad7 knockout mice prevented the progression of chronic AAN. Further studies revealed that worsen chronic AAN in Smad7 knockout mice was associated with enhanced activation of TGF-β/Smad3 and NF-κB signaling pathways, which was reversed when renal Smad7 was restored. Importantly, we also found that overexpression of Smad7 locally in the kidneys with established chronic AAN was capable of attenuating progressive chronic AAN by inactivating TGF-β/Smad3-medated renal fibrosis and NF-κB-driven renal inflammation. In conclusion, Smad7 plays a protective role in the pathogenesis of chronic AAN and overexpression of Smad7 may represent a novel therapeutic potential for chronic AAN.
Validation of the parenting competence scale for parents with young children (PCS-YC)

ABSTRACT Parenting competences have a major influence on children’s development and well-being. The objective of this study was to validate the Parenting Competence Scale for Parents with Young Children (PCS-YC) from a preventive psycho-socio-educative approach. After performing Exploratory and Confirmatory Factor Analysis with data collected from a random sample of 1684 Spanish parents with young children, the scale includes 15 items classified into five factors explaining 42.7% of the variance: F1-Self-Regulation, F2-Self-Esteem, F3-Promotion of Children’s Self-Esteem; F4-Imposition for Conflict Resolution, and F5-Not-Assertive Communication. The selected factors are in line with the five parenting competences categories proposed by [Azar, S. T. , Lauretti, A. F. , & Loding, B. V. (1998). The evaluation of parental fitness in termination of parental rights cases: a functional-contextual perspective. Clinical Child and Family Psychology Review, 1(2), 77–100], regarding child abuse and childhood injury prevention. The reliability values and general psychometric properties of the scale, together with its length and easy application make it worth in different areas which requires an assessment of parenting competences regarding young children.
Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia

Abstract Schizophrenia has been thought of as a disorder of reduced functional and structural connectivity. Recent advances in neuroimaging techniques such as functional magnetic resonance imaging, structural magnetic resonance imaging, diffusion tensor imaging, and small animal imaging have advanced our ability to investigate this hypothesis. Moreover, the power of longitudinal designs possible with these noninvasive techniques enable the study of not just how connectivity is disrupted in schizophrenia, but when this disruption emerges during development. This article reviews genetic and neurodevelopmental influences on structural and functional connectivity in human populations with or at risk for schizophrenia and in animal models of the disorder. We conclude that the weight of evidence across these diverse lines of inquiry points to a developmental disruption of neural connectivity in schizophrenia and that this disrupted connectivity likely involves susceptibility genes that affect processes involved in establishing intra- and interregional connectivity.
Prominent Heart Organ-Level Performance Deficits in a Genetic Model of Targeted Severe and Progressive SERCA2 Deficiency

The cardiac SERCA2 Ca2+ pump is critical for maintaining normal Ca2+ handling in the heart. Reduced SERCA2a content and blunted Ca2+ reuptake are frequently observed in failing hearts and evidence implicates poor cardiac Ca2+ handling in the progression of heart failure. To gain insight into mechanism we investigated a novel genetic mouse model of inducible severe and progressive SERCA2 deficiency (inducible Serca2 knockout, SERCA2 KO). These mice eventually die from overt heart failure 7-10 weeks after knockout but as yet there have been no reports on intrinsic mechanical performance at the isolated whole heart organ level. Thus we studied whole-organ ex vivo function of hearts isolated from SERCA2 KO mice at one and four weeks post-knockout in adult animals. We found that isolated KO heart function was only modestly impaired one week post-knockout, when SERCA2a protein was 32% of normal. At four weeks post-knockout, function was severely impaired with near non-detectable levels of SERCA2. During perfusion with 10 mM caffeine, LV developed pressures were similar between 4-week KO and control hearts, and end-diastolic pressures were lower in KO. When hearts were subjected to ischemia-reperfusion injury, recovery was not different between control and KO hearts at either one or four weeks post-knockout. Our findings indicate that ex vivo function of isolated SERCA2 KO hearts is severely impaired long before symptoms appear in vivo, suggesting that physiologically relevant heart function in vivo can be sustained for weeks in the absence of robust SR Ca2+ flux.
Monitoring lensed starlight emitted close to the Galactic centre

We describe the feasibility of detecting the gravitational deflection of light emitted by stars moving around the massive object at the Galactic centre. Light reaching us from an orbiting star can pass closer to the large central mass than the star itself, so the central potential is in principle constrained to a smaller radius by lensing rather than by orbit fitting. A mass of 4.3 x 10 6 M ○. causes a 0.1-2 mas deflection in the apparent position of orbiting stars in a cone of diameter 10° as seen from the central mass. The distance to the centre of the Galaxy is uniquely constrained from such measurements because lensing deflections depend on the ratio r g /R 0 of the Schwarzschild radius to the distance to the black hole, R 0 , whereas the ratio r g /R 3 0 is obtained by fitting the shapes of the orbits. Deflection measurements are complimentary to observations of radial velocities of stars which constrain the ratio r g /R 0 in the framework of Newtonian gravity.
A Mechanistic Beta-Binomial Probability Model for mRNA Sequencing Data

A main application for mRNA sequencing (mRNAseq) is determining lists of differentially-expressed genes (DEGs) between two or more conditions. Several software packages exist to produce DEGs from mRNAseq data, but they typically yield different DEGs, sometimes markedly so. The underlying probability model used to describe mRNAseq data is central to deriving DEGs, and not surprisingly most softwares use different models and assumptions to analyze mRNAseq data. Here, we propose a mechanistic justification to model mRNAseq as a binomial process, with data from technical replicates given by a binomial distribution, and data from biological replicates well-described by a beta-binomial distribution. We demonstrate good agreement of this model with two large datasets. We show that an emergent feature of the beta-binomial distribution, given parameter regimes typical for mRNAseq experiments, is the well-known quadratic polynomial scaling of variance with the mean. The so-called dispersion parameter controls this scaling, and our analysis suggests that the dispersion parameter is a continually decreasing function of the mean, as opposed to current approaches that impose an asymptotic value to the dispersion parameter at moderate mean read counts. We show how this leads to current approaches overestimating variance for moderately to highly expressed genes, which inflates false negative rates. Describing mRNAseq data with a beta-binomial distribution thus may be preferred since its parameters are relatable to the mechanistic underpinnings of the technique and may improve the consistency of DEG analysis across softwares, particularly for moderately to highly expressed genes.
Information-Based Complexity, Feedback and Dynamics in Convex Programming

We study the intrinsic limitations of sequential convex optimization through the lens of feedback information theory. In the oracle model of optimization, an algorithm queries an oracle for noisy information about the unknown objective function and the goal is to (approximately) minimize every function in a given class using as few queries as possible. We show that, in order for a function to be optimized, the algorithm must be able to accumulate enough information about the objective. This, in turn, puts limits on the speed of optimization under specific assumptions on the oracle and the type of feedback. Our techniques are akin to the ones used in statistical literature to obtain minimax lower bounds on the risks of estimation procedures; the notable difference is that, unlike in the case of i.i. d. data, a sequential optimization algorithm can gather observations in a controlled manner, so that the amount of information at each step is allowed to change in time. In particular, we show that optimization algorithms often obey the law of diminishing returns: the signal-to-noise ratio drops as the optimization algorithm approaches the optimum. To underscore the generality of the tools, we use our approach to derive fundamental lower bounds for a certain active learning problem. Overall, the present work connects the intuitive notions of “information” in optimization, experimental design, estimation, and active learning to the quantitative notion of Shannon information.
Broadband 4×4 Butler matrix using wideband 90° hybrid couplers and crossovers for beamforming networks

The design and simulation of a wideband four-port steerable beamforming networks using a 4×4 Butler matrix for the 2.4 GHz applications is presented. The aim of this work is to develop an antenna array feeding network based on Butler matrix with a large bandwidth in order to cover the IEEE 802.11b/g/n band. In order to achieve wideband features, the matrix uses two-section branch-line couplers and four-section branch-line crossovers instead of the standard ones. The proposed circuit exhibits a high isolation and wideband 4×4 Butler matrix designed and simulated by using a single-layer FR-4 substrate, which covers the frequency band ranging from 2.1 GHz to 2.75 GHz. The return losses and the isolation are better than 28 dB and 30 dB, respectively, with its good performance is more suitable for IEEE 802.11b/g/n and ISM applications.
The Effects of Equine-Assisted Activities on the Attachment Security of Abused Women

The present study was designed to explore the impact of equine-assisted activities on attachment security among women who have experienced intimate partner violence. Attachment security was assessed at three different time points using the Experiences in Close Relationships Scale (ECR) (Brennan, Clark, & Shaver, 1998), which measures attachment on two separate scales of anxiety and avoidance. Proximity maintenance, one of the components of an attachment figure, was assessed using coded video data of the interaction between horse and participant during their first meeting and goodbye. Five women who self-reported experiencing domestic abuse were recruited for this study, of whom four were within the intended age range of 18-30 years old. Each participant was matched with a women who did not self-report any incidence of domestic abuse based on level of horse experience followed by similarity of age. Likely due to a small sample size, results from this study are not significant. However, a reduction in anxiety observed solely for the women in the abuse group suggests there may be an effect among a larger sample size; this consideration extends into the coded video data as a marginally significant effect is present with women in the abuse group spending a longer period of time meeting the horse than did the women in the matched group. Slight increases in avoidance were observed for both groups, as well as in anxiety levels of the matched group. Overall, the findings of this study hint at the potential use of equine-assisted activities for impacting attachment security in abused women but require further investigation.
MR spectroscopy in relapsing remitting MS

Hanson LG. Multi-slice echo planar spectroscopic MR imaging provides both global and local metabolite measures in multiple sclerosis (accepted for publication in Magnetic Resonance in Medicine, Appendix 1). Danish readers will find more information on the backgrounds in these papers: I wish to thank all my patients who, despite their disease, had the patience and strength to participate in this study of repeated two and a half hour MRI scans, and I wish them all the best in the future. I would also like to thank all my collaborators, including the technical and clinical staff at our department, for their help initiating the project, their continuous support and fruitful discussions and suggestions throughout the study period. In particular I wish to express my gratitude to all my supervisors: Summary The aims of this PhD thesis were to develop, validate and implement new MR (magnetic resonance) techniques with higher specificity for pathological changes seen in lesions and in normal appearing brain tissues in early relapsing remitting multiple sclerosis (RRMS). Another aim was to perform image acquisition and data-analysis of the non-conventional techniques in a relatively simple way to make these techniques usable in daily practice or clinical trials thus limiting the technical demands and the time consumption. The ultimate goal is to provide better correlations between MRI (MR imaging) and disability measures and to obtain new information on disease evolution and hence faster and more precise decisions on who, when and how to treat the patients. MR spectroscopy (MRS) can provide information about neuronal loss or dysfunction measuring decreases in N-acetyl aspartate (NAA), a metabolite widely believed to assess neuronal viability. In this thesis we have used multi-slice echo planar spectroscopic imaging (EPSI). This method was proven reproducible and to have some advantages compared to conventional non-localised or single-voxel spectroscopy. It is possible to obtain global metabolite measures and in the same session measurements of metabolites in specific brain areas, including normal appearing white matter (NAWM) and cortical grey matter (GM), which might be of great importance in MS. Cognitive dysfunction can be seen in 50% of patients with multiple sclerosis (MS), with somewhat lower incidences in the early stages of the disease. The correlations between cognitive dysfunction and conventional T 2-and T 1-weighted MRI measures (e.g. lesion load) have been moderate, and a substantial number of studies suggest that cognitive dysfunction is related to the overall disease burden of the …
Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-stimulating agents in men with chronic kidney disease.

BACKGROUND Hypogonadism or testosterone deficiency is a prevalent condition in men with chronic kidney disease (CKD). Testosterone stimulates erythropoiesis via production of haematopoietic growth factors and possible improvement of iron bioavailability. We hypothesized that testosterone deficiency predisposes to anaemia and reduced responsiveness to erythropoiesis-stimulating agents (ESAs) in CKD men. Materials and methods. We studied associations between endogenous testosterone and haemoglobin in 239 ESA-naïve nondialysed CKD Stages 1-5 male patients. Additionally, we studied associations between endogenous testosterone levels and ESA dose (U/kg/week) in 126 ESA-treated men undergoing haemodialysis (HD). RESULTS Among ESA-naïve males, patients with anaemia presented lower testosterone values. Endogenous testosterone was negatively associated with haemoglobin levels in uni- and multivariate models. Testosterone-deficient patients (total testosterone <10 nmol/L) were 5.3 (95% confidence interval 2.2-12.5) times more likely to be anaemic (Hb < 13.0 g/dL) than testosterone-sufficient patients. In ESA-treated men undergoing HD, higher ESA doses (above the median value of 121 IU/kg body weight/week) are associated with lower testosterone levels and higher percentage of hypochromic red blood cells (RBC). The inverse association between testosterone levels and ESA doses persisted after multivariate adjustment for age, sex hormone-binding globulin, comorbidities, C-reactive protein and s-albumin but was lost after further adjustment for iron medication and hypochromic RBC. CONCLUSIONS Hypogonadism may be an additional cause of anaemia and reduced ESA responsiveness in men with CKD. Our results raise the possibility that restoration of testosterone levels in hypogonadal CKD males may translate into lower prevalence of anaemia and better ESA responsiveness.
WEBT and XMM-Newton observations of 3C 454.3 during the post-outburst phase Detection of the little

Context. The quasar-type blazar 3C 454.3 was observed to undergo an unprecedented optical outburst in spring 2005, affecting the source brightness from the near-IR to the X-ray frequencies. This was first followed by a millimetric and then by a radio outburst, which peaked in February 2006. Aims. In this paper we report on follow-up observations to study the multiwavelength emission in the post-outburst phase. Methods. Radio, near-infrared, and optical monitoring was performed by the Whole Earth Blazar Telescope (WEBT) collaboration in the 2006-2007 observing season. XMM-Newton observations on July 2-3 and December 18-19, 2006 added information on the X-ray and UV states of the source. Results. The source was in a faint state. The radio flux at the higher frequencies showed a fast decreasing trend, which represents the tail of the big radio outburst. It was followed by a quiescent state, common at all radio frequencies. In contrast, moderate activity characterized the near-IR and optical light curves, with a progressive increase of the variability amplitude with increasing wavelength. We ascribe this redder-when-brighter behaviour to the presence of a ""little blue bump"" due to line emission from the broad line region, which is clearly visible in the source spectral energy distribution (SED) during faint states. Moreover, the data from the XMM- Newton Optical Monitor reveal a rise of the SED in the ultraviolet, suggesting the existence of a "" big blue bump"" due to thermal emission from the accretion disc. The X-ray spectra are well fitted with a power- law model with photoelectric absorption, possibly larger than the Galactic one. However, the comparison with previous X-ray observations would imply that the amount of absorbing matter is variable. Alternatively, the intrinsic X-ray spectrum presents a curvature, which may depend on the X-ray brightness. In this case, two scenarios are possible. i) There is no extra absorption, and the X-ray spectrum hardens at low energies, the hardening being more evident in bright states; ii) there is a constant amount of extra absorption, likely in the quasar environment, and the X-ray spectrum softens at low energies, at least in faint X-ray states. This softening might be the result of a flux contribution by the high-frequency tail of the big blue bump.
Clostridium butyricum Combined with Bifidobacterium infantis Probiotic Mixture Restores Fecal Microbiota and Attenuates Systemic Inflammation in Mice with Antibiotic-Associated Diarrhea

Antibiotic-associated diarrhea (AAD) is one of the most common complications of most types of antibiotics. Our aim was to determine the efficacy of Clostridium butyricum, Bifidobacterium infantis, and their mixture for AAD treatment in mice. AAD models were administered with single probiotic strain and probiotic mixture for short term and long term to evaluate the changes of the composition and diversity of intestinal microbiota, histopathology of the colon, and the systemic inflammation. Our data indicated that long-term probiotic therapy, but not short-term course, exerted beneficial effects on the restoration of the intestinal microbiota, the recovery of the tissue architecture, and attenuation of systemic inflammation. All predominant fecal bacteria reached normal level after the long-term probiotic mixture treatment, while IL-10, IFN-γ, and TNF-α also returned to normal level. However, the efficacy for AAD was time dependent and probiotic strain specific. Short-term administration of probiotic strains or mixture showed no apparent positive effects for AAD. In addition, the beneficial effects of C. butyricum combined with B. infantis probiotic mixture were superior to their single strain. This research showed that supplementation with C. butyricum combined with B. infantis probiotic mixture may be a simple and effective method for AAD treatment.