Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Thiazide-Type and Thiazide-Like Diuretics on Cardiovascular Events and Mortality: Systematic Review and Meta-Analysis

Thiazide diuretics are recommended as first-line therapy for hypertension and are among the most commonly prescribed drugs worldwide. According to their molecular structure, thiazide diuretics can be divided in thiazide-type (TT) and thiazide-like (TL) diuretics. TL diuretics have a longer elimination half-life compared with TT diuretics and have been shown to exert additional pharmacological effects, which may differently affect cardiovascular risk. In this meta-analysis, we compared the effects of TT and TL diuretics on cardiovascular events and mortality. Randomized, controlled studies in adult hypertensive patients that compared TT or TL diuretics with placebo or antihypertensive drugs and had ≥1 year follow-up were included. Primary outcome was cardiovascular events; secondary outcomes included coronary events, heart failure, cerebrovascular events, and all-cause mortality. Meta-regression analysis was used to identify confounders and correct for the achieved blood pressure reductions. Twenty-one studies with >480 000 patient-years were included. Outcomes were not affected by heterogeneity in age, sex, and ethnicity among included studies, whereas larger blood pressure reductions were significantly associated with increased risk reductions for all outcomes (P<0.001). Corrected for differences in office blood pressure reductions among trials, TL diuretics resulted in a 12% additional risk reduction for cardiovascular events (P=0.049) and a 21% additional risk reduction for heart failure (P=0.023) when compared with TT diuretics. The incidence of adverse events was comparable among TT, TL diuretics, and other antihypertensive therapy. Our data suggest that the best available evidence seems to favor TL diuretics as the drug of choice when thiazide treatment is considered for hypertension.
A new genome scan for primary nonsyndromic vesicoureteric reflux emphasizes high genetic heterogeneity and shows linkage and association with various genes already implicated in urinary tract development

Primary vesicoureteric reflux (VUR), the retrograde flow of urine from the bladder toward the kidneys, results from a developmental anomaly of the vesicoureteric valve mechanism, and is often associated with other urinary tract anomalies. It is the most common urological problem in children, with an estimated prevalence of 1–2%, and is a major cause of hypertension in childhood and of renal failure in childhood or adult life. We present the results of a genetic linkage and association scan using 900,000 markers. Our linkage results show a large number of suggestive linkage peaks, with different results in two groups of families, suggesting that VUR is even more genetically heterogeneous than previously imagined. The only marker achieving P < 0.02 for linkage in both groups of families is 270 kb from EMX2. In three sibships, we found recessive linkage to KHDRBS3, previously reported in a Somali family. In another family we discovered sex‐reversal associated with VUR, implicating PRKX, for which there was weak support for dominant linkage in the overall data set. Several other candidate genes are suggested by our linkage or association results, and four of our linkage peaks are within copy‐number variants recently found to be associated with renal hypodysplasia. Undoubtedly there are many genes related to VUR. Our study gives support to some loci suggested by earlier studies as well as suggesting new ones, and provides numerous indications for further investigations.
Morphological Inflection Generation with Hard Monotonic Attention

We present a neural model for morphological inflection generation which employs a hard attention mechanism, inspired by the nearly-monotonic alignment commonly found between the characters in a word and the characters in its inflection. We evaluate the model on three previously studied morphological inflection generation datasets and show that it provides state of the art results in various setups compared to previous neural and non-neural approaches. Finally we present an analysis of the continuous representations learned by both the hard and soft (Bahdanau, 2014) attention models for the task, shedding some light on the features such models extract.
Antibodies to adalimumab are associated with future inflammation in Crohn's patients receiving maintenance adalimumab therapy: a post hoc analysis of the Karmiris trial

Introduction Data on immunogenicity to adalimumab (ADL) therapy in patients with IBD is limited. We performed additional analyses on the Karmiris cohort using the homogeneous mobility shift assay (HMSA) focusing on the inter-relationship of serum ADL concentration, antibodies-to-adalimumab (ATA), inflammatory markers and sustained response. Methods 536 prospectively collected serum samples were available for analysis of ADL concentration and ATA using HMSA. We studied the role of week 4 serum ADL concentration and immunomodulator (IMM) use on ATA formation with a Cox proportional hazards model. Mixed model repeated measures analysis was performed to assess the independent effects of serum ADL concentration and ATA on C-reactive protein (CRP) and response. Results ATA was detected in 20% of patients after a median of 34 (12.4–60.5) weeks. ATA-positive samples correlated with lower serum ADL concentration (p<0.001). Cox regression modelling showed that week 4 ADL concentration of <5 µg/mL significantly increased the future risk of ATA formation (HR=25.1; 95% CI 5.6 to 111.9; p=0.0002) and that IMM co-treatment prevented ATA formation (HR=0.23; 95% CI 0.06 to 0.86; p=0.0293). Regression modelling showed a negative correlation between CRP and ADL concentration (p=0.0001) and a positive one with ATA (p=0.0186). The model revealed that both lower serum ADL concentration and ATA were independently associated with future CRP (p=0.0213 and p=0.0013 respectively). ATA positivity was associated with discontinuation of ADL because of loss or response (OR=3.04; 95% CI 1.039 to 9.093; p=0.034). Conclusions ATA were detected in 20% of patients. Risk of ATA formation increased with lower early serum ADL concentration and in patients not on IMM. ATA and ADL were strongly associated with higher future CRP level and discontinuation of ADL.
Biomarkers in Contrast-Induced Acute Kidney Injury: Towards A New Perspective

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional “gold standard” biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.
High-Dispersion Optical Spectra of Nearby Stars Younger Than the Sun

We present high-dispersion (R ∼ 16,000) optical (3900-8700 Å) spectra of 390 stars obtained with the Palomar 60 inch telescope. The majority of stars observed are part of the Spitzer Legacy Science Program "The Formation and Evolution of Planetary Systems. " Through detailed analysis we determine stellar properties for this sample, including radial and rotational velocities, Li I λ6708 and Hα equivalent widths, the chromospheric activity index R, and temperature- and gravity-sensitive line ratios. Several spectroscopic binaries are also identified. From our tabulations, we illustrate basic age- and rotation-related correlations among measured indices. One novel result is that Ca II chromospheric emission appears to saturate at v sin i values above ∼30 km s-1, similar to the well-established saturation of X-rays that originate in the spatially separate coronal region.
Origin of Long-Lived Coherences in Light-Harvesting Complexes

A vibronic exciton model is applied to explain the long-lived oscillatory features in the two-dimensional (2D) electronic spectra of the Fenna–Matthews–Olson (FMO) complex. Using experimentally determined parameters and uncorrelated site energy fluctuations, the model predicts oscillations with dephasing times of 1.3 ps at 77 K, which is in a good agreement with the experimental results. These long-lived oscillations originate from the coherent superposition of vibronic exciton states with dominant contributions from vibrational excitations on the same pigment. The oscillations obtain a large amplitude due to excitonic intensity borrowing, which gives transitions with strong vibronic character a significant intensity despite the small Huang–Rhys factor. Purely electronic coherences are found to decay on a 200 fs time scale.
Multiphase integrated on-board battery chargers for electrical vehicles

The paper considers on-board battery charging of electrical vehicles (EVs) using a multiphase voltage source and a multiphase propulsion motor. The multiphase inverter and the multiphase machine are fully integrated into the charging process. The proposed integrated on-board battery charger has an advantage of unity power factor operation with no torque production in the machine during the charging mode. The principle of the charging mode operation is based on the additional degrees of freedom that exist in multiphase machines. It is shown that they can be conveniently utilised to achieve charging through the machine's stator winding with zero electromagnetic torque. Detailed theoretical analysis is reported for a five-phase system, with a subsequent generalization to other multiphase systems with other higher odd numbers of phases. A mathematical model of a multiphase voltage source rectifier (VSR) is developed, its control in the charging mode is discussed, and the concept is validated by simulation.
Convergence Analysis of a Multigrid Method for a Convection-Dominated Model Problem

The paper presents a convergence analysis of a multigrid solver for a system of linear algebraic equations resulting from the discretization of a convection-diffusion problem using a finite element method. We consider piecewise linear finite elements in combination with a streamline diffusion stabilization. We analyze a multigrid method that is based on canonical intergrid transfer operators, a "direct discretization" approach for the coarse-grid operators and a smoother of line-Jacobi type. A robust (diffusion and h-independent) bound for the contraction number of the two-grid method and the multigrid W-cycle are proved for a special class of convection-diffusion problems, namely with Neumann conditions on the outflow boundary, Dirichlet conditions on the rest of the boundary, and a flow direction that is constant and aligned with gridlines. Our convergence analysis is based on modified smoothing and approximation properties. The arithmetic complexity of one multigrid iteration is optimal up to a logarithmic term.
Distinct interaction modes of an AKAP bound to two regulatory subunit isoforms of protein kinase A revealed by amide hydrogen/deuterium exchange

The structure of an AKAP docked to the dimerization/docking (D/D) domain of the type II (RIIα) isoform of protein kinase A (PKA) has been well characterized, but there currently is no detailed structural information of an AKAP docked to the type I (RIα) isoform. Dual‐specific AKAP2 (D‐AKAP2) binds in the nanomolar range to both isoforms and provided us with an opportunity to characterize the isoform‐selective nature of AKAP binding using a common docked ligand. Hydrogen/deuterium (H/D) exchange combined with mass spectrometry (DXMS) was used to probe backbone structural changes of an α‐helical A‐kinase binding (AKB) motif from D‐AKAP2 docked to both RIα and RIIα D/D domains. The region of protection upon complex formation and the magnitude of protection from H/D exchange were determined for both interacting partners in each complex. The backbone of the AKB ligand was more protected when bound to RIα compared to RIIα, suggesting an increased helical stabilization of the docked AKB ligand. This combined with a broader region of backbone protection induced by the AKAP on the docking surface of RIα indicated that there were more binding constraints for the AKB ligand when bound to RIα. This was in contrast to RIIα, which has a preformed, localized binding surface. These distinct modes of AKAP binding may contribute to the more discriminating nature of the RIα AKAP‐docking surface. DXMS provides valuable structural information for understanding binding specificity in the absence of a high‐resolution structure, and can readily be applied to other protein–ligand and protein–protein interactions.
Time course and distribution of neuronal degeneration in the dentate gyrus of rat after adrenalectomy: A silver impregnation study

Recently, Sloviter et al. reported that adrenalectomy (ADX) of young adult rats after 3 months led to a selective loss of granule neurons in the dentate gyrus (DG) and that this loss could be prevented by low doses of corticosterone. In the present study, the ADX‐induced neuronal degeneration was investigated in Wistar rats, using a silver impregnation method for degenerating neurons. To examine the time course and distribution of the ADX‐induced degeneration, young adult male rats were allowed to survive 2, 3, and 5 days and 1, 2, and 3 weeks after ADX. Argyrophilic neurons were present in the dentate granule cell layer on the second day following ADX. Three days after ADX, the number of argyrophilic granule neurons was much more abundant, and it increased gradually with longer post‐ADX survival times. Argyrophilia was specifically confined to dentate granule cells and was accompanied by the occurrence of pyknotic nuclei as observed in adjacent cresyl violet‐stained section. There were significant differences between individual rats in quantity of argyrophilia. About one fifth of the ADX rats showed sporadic or no argyrophilia, in spite of plasma corticosterone levels below the detection limit (10 ng/mL). Sham‐operated rats and ADX rats receiving corticosterone (10 mg/L) or dexamethasone (15 mg/L) in their drinking water did not display any argyrophilic neurons in the dentate gyrus. The distribution of the argyrophilia within the DG was highly characteristic with the highest number of degenerating cells in the hidden blade of the middle and the temporal thirds of the DG. There was a strong crest‐to‐tip and deep (hilar)‐to‐superficial increase in density of degenerating neurons. Along the entire septotemporal axis of the free blade and at the septal pole of the hidden blade, the number of argyrophilic cells was low. Wistar rats of different sex and aged 1–6 months all showed dentate granule cell degeneration 1 week following ADX. The distribution of the degeneration was identical to that of the young adult male group.
The genetics of symptom-based phenotypes: toward a molecular classification of schizophrenia.

OBJECTIVE Genetic linkage studies in schizophrenia (SZ) have primarily focused on the phenotype of disease susceptibility. A limited number of studies, however, have reported suggestive linkage to specific SZ symptom domains including regions on chromosomes 6, 8, and 20. We examined these chromosomal regions for association to positive, negative, and disorganized symptom clusters, using a dense set of single-nucleotide polymorphisms (SNPs). METHODS We ascertained 178 Caucasian patients with SZ for lifetime severity of clinical symptomatology using a structured diagnostic interview. The cohort was genotyped with the Affymetrix 500K microarray, from which we selected, a priori, 4833 intragenic SNPs located within chromosomal regions previously linked to specific SZ symptom clusters. Parametric tests, corrected for multiple testing, were used to compare the effects of allelic variation within these SNPs to the lifetime severity of the specific symptom domain that had been implicated by prior linkage studies. RESULTS We were able to extend previous reports of linkage between chromosome 6q and both positive and disorganized symptoms. Lifetime severity of positive symptoms was significantly (P = 2.50 x 10(-5)) associated with a SNP within the origin recognition complex subunit 3-like (ORC3L) gene, a gene implicated in synaptic plasticity. Level of disorganized symptoms was significantly (P < 6.00 x 10(-5)) associated 2 SNPs within the brain-specific angiogenesis inhibitor 3 (BAI3) gene, which is highly expressed in brain during development. CONCLUSIONS These data point toward specific candidate genes located within previously implicated linkage peaks for clinical symptomatology. Identification of functional variants within these regions and a characterization of the effect of these risk genotypes on the treatment of specific clinical symptoms are needed.
Hitchin integrable systems, deformations of spectral curves, and KP-type equations

An effective family of spectral curves appearing in Hitchin fibrations is determined. Using this family the moduli spaces of stable Higgs bundles on an algebraic curve are embedded into the Sato Grassmannian. We show that the Hitchin integrable system, the natural algebraically completely integrable Hamiltonian system defined on the Higgs moduli space, coincides with the KP equations. It is shown that the Serre duality on these moduli spaces corresponds to the formal adjoint of pseudo-differential operators acting on the Grassmannian. From this fact we then identify the Hitchin integrable system on the moduli space of Sp(2m)-Higgs bundles in terms of a reduction of the KP equations. We also show that the dual Abelian fibration (the SYZ mirror dual) to the Sp(2m)-Higgs moduli space is constructed by taking the symplectic quotient of a Lie algebra action on the moduli space of GL-Higgs bundles.
A survey about ASR for children

This paper is intended to survey the state of the art of automatic speech recognition (ASR) for children’s speech. Investigating ASR for children is a current trend in research. Therefore databases of children’s speech are needed for training and testing of ASR systems. In the ﬁrst part of this paper the most relevant databases of children’s speech are described. There are less speech data of children available than of adults and speech of preschool children is even more rarely available. In the second part of this paper the common techniques for recognizing children’s speech are summarized. Most investigations about children’s ASR focus on the acoustic model. The common methods are described and approaches regarding the lexical and speech model are mentioned subsequently. In an extensive literature research we collected papers investigating ASR for children. Several studies have been carried out investigating children’s ASR. Due to the lack of data from preschool children only a few investigations for this age group have been accomplished. This is illustrated by presenting a statistic on the age of the children in past studies.
Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis

Cell proliferation is strictly controlled during differentiation. In T cell development, the cell cycle is normally arrested at the CD4+CD8+ stage, but the mechanism underlying such differentiation-specific exit from the cell cycle has been unclear. Fbxw7 (also known as Fbw7, Sel-10, hCdc4, or hAgo), an F-box protein subunit of an SCF-type ubiquitin ligase complex, induces the degradation of positive regulators of the cell cycle, such as c-Myc, c-Jun, cyclin E, and Notch. FBXW7 is often mutated in a subset of human cancers. We have now achieved conditional inactivation of Fbxw7 in the T cell lineage of mice and found that the cell cycle is not arrested at the CD4+CD8+ stage in the homozygous mutant animals. The mutant mice manifested thymic hyperplasia as a result of c-Myc accumulation and eventually developed thymic lymphoma. In contrast, mature T cells of the mutant mice failed to proliferate in response to mitogenic stimulation and underwent apoptosis in association with accumulation of c-Myc and p53. These latter abnormalities were corrected by deletion of p53. Our results suggest that Fbxw7 regulates the cell cycle in a differentiation-dependent manner, with its loss resulting in c-Myc accumulation that leads to hyperproliferation in immature T cells but to p53-dependent cell-cycle arrest and apoptosis in mature T cells.
Different Sense Granularities for Different Applications

This paper describes an hierarchical approach to WordNet sense distinctions that provides different types of automatic Word Sense Disambiguation (WSD) systems, which perform at varying levels of accuracy. For tasks where fine-grained sense distinctions may not be essential, an accurate coarse-grained WSD system may be sufficient. The paper discusses the criteria behind the three different levels of sense granularity, as well as the machine learning approach used by the WSD system.
Distributed feedback surface-emitting laser with air/semiconductor gratings embedded by mass-transport assisted wafer fusion technique

We report on a distributed feedback InGaAsP MQW laser with air/semiconductor gratings embedded by wafer-fusion technique with the assistance of mass-transport phenomenon for the first time. The air/semiconductor gratings with 0.4-/spl mu/m period and 0.2-/spl mu/m depth are successfully fabricated inside the device, and a single longitudinal mode oscillation at about 1.28 /spl mu/m is demonstrated under pulsed condition at room temperature. The threshold current density is estimated to be about 1.4 kA/cm/sup 2/. It is also shown that the device has a surface-emitting function since it has a low loss multiquantum-well waveguide with grating output coupler.