Miracle-dz/UniFAR-FTUs huggingface dataset:
Course and predictors of work productivity in gout — results from the NOR-Gout longitudinal 2-year treat-to-target study

Abstract Objectives In patients with gout there is a lack of longitudinal studies on the course of work productivity. We explored longitudinal changes in and predictors of work productivity over 2 years. Methods Patients in the NOR-Gout observational study with a recent gout flare and serum urate (sUA) >360 µmol/l attended tight-control visits during escalating urate lowering therapy according to a treat-to-target strategy. From the Work Productivity and Activity Impairment (WPAI) questionnaire, scores for work productivity and activity impairment were assessed over 2 years together with the Beliefs about Medicines Questionnaire and a variety of demographic and clinical variables. Results At baseline patients had a mean age of 56.4 years and 95% were males. WPAI scores at baseline were 5.0% work missed (absenteeism), 19.1% work impairment (presenteeism), 21.4% overall work impairment and 32.1% activity impairment. Work productivity and activity impairment improved during the first months, and remained stable at 1 and 2 years. Comorbidities were not cross-sectionally associated with WPAI scores at baseline, but predicted worse work impairment and activity impairment at year 1. The Beliefs about Medicines Questionnaire subscale with concerns about medicines at baseline independently predicted worse overall work impairment and worse activity impairment at year 1. Conclusions In patients with gout who were intensively treated to the sUA target, work productivity and activity impairment were largely unchanged and at 1 year predicted by comorbidities and patient concerns about medication.
Segmentation and interpretation using multiple physical hypotheses of image formation

One of the first, and most important tasks in single image analysis is segmentation: finding groups of pixels in an image that "belong" together. Physics-based segmentation algorithms are based upon identifying coherent regions of an image according to a model of object appearance. This work challenges considers multiple physical hypotheses for simple image regions. For each initial region, the framework proposes a set of hypotheses, each of which specifically models the illumination, reflectance, and shape of the 3-D patch which caused that region. Each hypothesis represents a distinct, plausible explanation for the color and intensity variation of that patch. The framework proposes comparing hypotheses of adjacent patches for similarity and merging them when appropriate, resulting in more global hypotheses which group elementary regions that are part of the same surface. A physical analysis of the hypotheses reveals strong constraints on hypothesis compatibility which significantly reduces the space of possible image interpretations and specifies which hypothesis pairs should be tested for compatibility. A consequence of this framework is a new approach to segmenting complex scenes into regions corresponding to coherent surfaces rather than merely regions of similar color. The second part of this work presents an implementation of this new approach and example segmentations of scenes containing multi-colored piece-wise uniform objects. The algorithm contains four phases. The first phase segments an image based upon normalized color. The algorithm then attaches a list of potential explanations, or hypotheses to each initial region. The second phase examines adjacent hypotheses for compatibility. This work explores two methods of compatibility testing. The first is direct comparison, which estimates the shape, illumination, and material properties of each region and directly compares their compatibility. The second method uses weak tests of compatibility, which compare physical characteristics that must be compatible if two hypotheses are part of the same surface, but which are not necessarily incompatible between different objects. By using a number of these necessary, but not sufficient tests the algorithm rules out most incompatible hypothesis pairs. The third phase builds a hypothesis graph from the results of the analysis. Each hypothesis is a node in the graph, and edges contain information about the cost of merging adjacent hypotheses. The fourth phase then extracts segmentations from the hypothesis graph and rank-orders them. Each segmentation contains exactly one hypothesis from each region and provides a potential physical interpretation of the scene. This work explores the issue of preferring certain hypotheses over others depending on their compatibility with the image data. It also shows how the algorithm can expand to handle scenes of greater complexity by expanding the initial list of hypotheses and developing new tests of hypothesis compatibility. (Abstract shortened by UMI.)
Disk diffusion‐based method aids in the detection of vanM‐positive Enterococcus faecium with low vancomycin minimum inhibitory concentrations

We first reported the vanM vancomycin resistance gene in enterococci in Shanghai, China in 2006 and later found it to be the predominant van gene in vancomycin‐resistant enterococci (VRE). In this study, we successively collected 1292 Enterococcus faecium and Enterococcus faecalis strains from in‐ and outpatients at Huashan Hospital, Fudan University and found that nearly all of the isolates (1290/1292) were vancomycin‐sensitive determined by the VITEK 2 system. However, using a modified macromethod‐based disk diffusion test, 10 E. faecium isolates that were previously determined to be vancomycin‐sensitive by the VITEK 2 system were found to have colonies in the vancomycin disk inhibition zone. Pulse‐field gel electrophoresis results showed that each randomly selected colony in the inhibition zone belonged to the same clone as the original strain. All 10 isolates were later found to be vanM‐positive. The disk diffusion‐based method may aid in the detection of vanM‐positive E. faecium with low vancomycin minimum inhibitory concentrations and prevent missing the detection of vancomycin sensitivity‐variable enterococci.
A blinking rotlet model for chaotic advection

The Stokes flow due to a rotlet in a circle is determined. The solution shows that for a certain position of the rotlet, the flow has a second stagnation point symmetrically placed inside the circle. Thus, a ‘‘blinking rotlet’’ model can be constructed in which the rotlet that is ‘‘off’’ does not disturb the flow. This model seems preferable to the ‘‘blinking vortex’’ flow when discussing chaotic advection by a Stokes flow, and is useful for comparisons with recent experimental and computational investigations of this phenomenon in a cylindrical tank with two rotating cylinders.
The Effects of Relativistic Corrections on Cosmological Parameter Estimations from Sunyaev-Zeldovich Effect Cluster Surveys

Sunyaev-Zeldovich effect (SZE) cluster surveys are anticipated to yield tight constraints on cosmological parameters, such as the equation of state of dark energy. In this paper, we study the effect of relativistic corrections of the thermal SZE on the cluster number counts expected from a cosmological model and thus, assuming that other cosmological parameters are known to high accuracies, on the determination of the w-parameter and σ8 from an SZE cluster survey, where w = p/ρ (with p the pressure and ρ the density of dark energy) and σ8 is the rms of the extrapolated linear density fluctuation smoothed over 8 Mpc h-1. For the purpose of illustrating the effects of relativistic corrections, our analyses mainly focus on ν = 353 GHz and Slim = 30 mJy, where ν and Slim are the observing frequency and the flux limit of a survey, respectively. These observing parameters are relevant to the Planck survey. It is found that from two measurable quantities, the total number of SZE clusters and the number of clusters with redshift z ≥ 0.5, σ8 and w can be determined to a level of ±1% and ±8%, respectively, with 1 σ uncertainties from a survey of 10,000 deg2. Relativistic effects are important in determining the central values of σ8 and w. If we choose the two quantities calculated relativistically from the flat cosmological model with σ8 = 0.8284 and w = -0.75 as input, the derived σ8 and w would be 0.819 and -0.81, respectively, if relativistic effects are wrongly neglected. The location of the resulting σ8 and w in the σ8-w plane is outside the 3 σ region around the real central σ8 and w.
A CROSSED MOLECULAR BEAM, LOW-TEMPERATURE KINETICS, AND THEORETICAL INVESTIGATION OF THE REACTION OF THE CYANO RADICAL (CN) WITH 1,3-BUTADIENE (C4H6). A ROUTE TO COMPLEX NITROGEN-BEARING MOLECULES IN LOW-TEMPERATURE EXTRATERRESTRIAL ENVIRONMENTS

We present a joint crossed molecular beam and kinetics investigation combined with electronic structure and statistical calculations on the reaction of the ground-state cyano radical, CN(X2Σ+), with the 1,3-butadiene molecule, H2CCHCHCH2(X1Ag), and its partially deuterated counterparts, H2CCDCDCH2(X1Ag) and D2CCHCHCD2(X1Ag). The crossed beam studies indicate that the reaction proceeds via a long-lived C5H6N complex, yielding C5H5N isomer(s) plus atomic hydrogen under single collision conditions as the nascent product(s). Experiments with the partially deuterated 1,3-butadienes indicate that the atomic hydrogen loss originates from one of the terminal carbon atoms of 1,3-butadiene. A combination of the experimental data with electronic structure calculations suggests that the thermodynamically less favorable 1-cyano-1,3-butadiene isomer represents the dominant reaction product; possible minor contributions of less than a few percent from the aromatic pyridine molecule might be feasible. Low-temperature kinetics studies demonstrate that the overall reaction is very fast from room temperature down to 23 K with rate coefficients close to the gas kinetic limit. This finding, combined with theoretical calculations, indicates that the reaction proceeds on an entrance barrier-less potential energy surface (PES). This combined experimental and theoretical approach represents an important step toward a systematic understanding of the formation of complex, nitrogen-bearing molecules—here on the C5H6N PES—in low-temperature extraterrestrial environments. These results are compared to the reaction dynamics of D1-ethynyl radicals (C2D; X2Σ+) with 1,3-butadiene accessing the isoelectronic C6H7 surface as tackled earlier in our laboratories.
Expression of Homing Receptors in IgM+IgD+CD27+ B Cells and Their Frequencies in Appendectomized and/or Tonsillectomized Individuals

ABSTRACT Background In humans, blood circulating IgM+IgD+CD27+ B cells are considered analogous to those described in the marginal zone of the spleen and are involved in important immunological processes. The homing receptors they express, and the organs involved in their development (for example, intestinal organs in rabbits) are only partially known. We recently reported that this population is heterogeneous and composed of at least two subsets: one expressing high levels of IgM – IgMhi B cells – and another low levels – IgMlo B cells. Objectives To evaluate the expression of homing receptors on IgD+CD27+ IgMhi and IgMlo B cells and quantify their frequencies in blood of control and appendectomized and/or tonsillectomized volunteers. Materials and Methods Using spectral flow cytometry, the simultaneous expression of 12 previously reported markers that differentiate IgMhi B cells and IgMlo B cells and of α4β7, CCR9, CD22 and CCR10 were evaluated in blood circulating B cells of control and appendectomized and/or tonsillectomized volunteers. Results The existence of phenotypically defined IgMlo and IgMhi B cell subsets was confirmed. They differentially expressed intestinal homing receptors, and the expression of α4β7 and CCR9 seems to determine new IgM subpopulations. IgMlo and IgMhi B cells were detected at lower frequencies in the appendectomized and/or tonsillectomized volunteers relative to controls. Conclusions Human blood circulating IgD+CD27+ IgMlo and IgMhi B cell subsets differentially express homing receptors, and it is necessary to investigate if mucosal organs are important in their development.
Ergodic optimization of super-continuous functions on shift spaces

Abstract Ergodic optimization is the process of finding invariant probability measures that maximize the integral of a given function. It has been conjectured that ‘most’ functions are optimized by measures supported on a periodic orbit, and it has been proved in several separable spaces that an open and dense subset of functions is optimized by measures supported on a periodic orbit. All known positive results have been for separable spaces. We give in this paper the first positive result for a non-separable space, the space of super-continuous functions on the full shift, where the set of functions optimized by periodic orbit measures contains an open dense subset.
Ataxia-Telangiectasia Mutated Is Involved in Autolysosome Formation

Ataxia-telangiectasia mutated (ATM), a master kinase of the DNA damage response (DDR), phosphorylates a multitude of substrates to activate signaling pathways after DNA double-strand breaks (DSBs). ATM inhibitors have been evaluated as anticancer drugs to potentiate the cytotoxicity of DNA damage-based cancer therapy. ATM is also involved in autophagy, a conserved cellular process that maintains homeostasis by degrading unnecessary proteins and dysfunctional organelles. In this study, we report that ATM inhibitors (KU-55933 and KU-60019) provoked accumulation of autophagosomes and p62 and restrained autolysosome formation. Under autophagy-inducing conditions, the ATM inhibitors caused excessive autophagosome accumulation and cell death. This new function of ATM in autophagy was also observed in numerous cell lines. Repression of ATM expression using an siRNA inhibited autophagic flux at the autolysosome formation step and induced cell death under autophagy-inducing conditions. Taken together, our results suggest that ATM is involved in autolysosome formation and that the use of ATM inhibitors in cancer therapy may be expanded.
pH regulates hematopoietic stem cell potential via polyamines

Upon ex vivo culture, hematopoietic stem cells (HSCs) quickly lose potential and differentiate into progenitors. The identification of culture conditions that maintain the potential of HSCs ex vivo is therefore of high clinical interest. Here, we demonstrate that the potential of murine and human HSCs is maintained when cultivated for 2 days ex vivo at a pH of 6.9, in contrast to cultivation at the commonly used pH of 7.4. When cultivated at a pH of 6.9, HSCs remain smaller, less metabolically active, less proliferative and show enhanced reconstitution ability upon transplantation compared to HSC cultivated at pH 7.4. HSCs kept at pH 6.9 show an attenuated polyamine pathway. Pharmacological inhibition of the polyamine pathway in HSCs cultivated at pH 7.4 with DFMO mimics phenotypes and potential of HSCs cultivated at pH 6.9. Ex vivo exposure to a pH of 6.9 is therefore a positive regulator of HSC function by reducing polyamines. These findings might improve HSC short‐term cultivation protocols for transplantation and gene therapy interventions.
LMI approach of constrained optimization in generalized predictive control

The addition of equality and inequality constraints in generalized predictive control (GPC) strategies switches the classical problem of quadratic cost function minimization into a nonlinear optimization. Some approaches have already been developed, which consider the Lagrange multipliers and gradient optimization. This paper presents the reformulation of GPC under constraints into an adequate form for linear matrix inequalities (LMI) solvers. The optimization of the reformulated problem is performed by linear convex programming. Moreover, it is shown that this new presentation of constrained GPC provides an original flexibility for adding further constraints to the problem. Finally, some simulation results are given and compared to previous approaches of this structure.
Stability and Stabilization of Networked Control Systems Under Limited Communication Capacity and Variable Sampling

This paper investigates the problem of quantized feedback control for networked control systems (NCSs) with time‐varying delays and time‐varying sampling intervals, wherein the physical plant is a continuous‐time, and the control input is a discrete‐time signal. By using an input delay approach and a sector bound method, the network induced delays, the signal quantization and sampling intervals are presented in one framework in the case of the state and the control input by quantization in a logarithmic form. We exploit a novel Lyapunov functional with discontinuity, taking full advantage of the NCS characteristic information including the bounds of delays, the bounds of sampling intervals and quantization parameters. In addition, it has been shown that the Lyapunov functional is decreased at the jump instants. Furthermore, we use the Leibniz‐Newton formula and free‐weighting matrix method to obtain the stability analysis and stabilization conditions which are dependent on the NCS characteristic information. The proposed stability analysis and stabilizing controller design conditions can be presented in term of linear matrix inequalities, which have less conservativeness and less computational complexity. Four examples demonstrate the effectiveness of the proposed methods.
Diagnostic test accuracy meta‐analysis of PRAME in distinguishing primary cutaneous melanomas from benign melanocytic lesions

PRAME is a novel immunohistochemical marker that aids the diagnosis of melanocytic lesions. Diffuse PRAME positivity suggests melanoma, whereas benign naevi are negative or only weakly positive. However, the factual diagnostic accuracy of PRAME is not well established. Moreover, some studies have suggested that the threshold of 3+/50% positive cells may be more useful in practice than the most widely used cut‐off (4+/75% of positive cells). Hence, we performed a systematic review and diagnostic accuracy meta‐analysis to evaluate sensitivity, specificity, likelihood ratios and optimal threshold for PRAME in distinguishing benign melanocytic proliferations from melanomas. Twenty‐six studies were enrolled into the meta‐analysis. A total of 2915 melanocytic lesions were analysed. The optimal threshold for PRAME positivity was estimated at 3.11, which translates into 3+ in practice. Sensitivity and specificity calculated from SROC at the 3+ threshold were 0.735 (0.631–0.818) and 0.915 (0.834–0.958), respectively, compared to 0.679 (0.559–0.957) and 0.957 (0.908–0.981) at the 4+ cut‐off. In subgroup analysis, the spitzoid subgroup was characterised by the lowest sensitivity and diagnostic odds ratio of PRAME. Our findings indicate that PRAME immunohistochemistry may serve as an ancillary marker to support the diagnosis of melanoma. Nevertheless, the accuracy of PRAME may be lower in spitzoid neoplasms. Our meta‐analysis suggests that the 3+/50% threshold might be more useful in practice than the 4+/75% cut‐off, as it shows higher sensitivity with retained satisfactory specificity.
Quality of Social Relationships with Parents and Peers in Adolescents Born Extremely Preterm

This article has supplementary material on the web site: www.jdbp. org. ABSTRACT: Objective: Adolescents born extremely preterm (EPT, gestational age [GA] <28 weeks) are at higher risk for problems in peer socialization than those born full-term (FT, GA >36 weeks). This study was designed to examine the possibility that adolescents born EPT may also have difficulty in transitioning from parents to peers for socialization, a process referred to as “social reorienting. ” A secondary aim was to investigate associations of social reorienting with other neurodevelopmental characteristics. Methods: The Network of Relationships Inventory, Relationship Quality Version was administered to 24 adolescents (ages 11–16 years) born EPT and 29 born FT to obtain self-ratings of closeness and discord with parents and peers. Measures of other neurodevelopmental characteristics included tests of cognitive and social skills, adolescent self-ratings of adjustment and victimization, and parent ratings of youth behavior and adaptive skills. Mixed model analyses controlling for sex, socioeconomic status, and race were conducted to examine group differences in measures of relationship quality and their associations with other neurodevelopmental characteristics. Results: The EPT group had higher ratings of closeness with parents than the FT group. For adolescents from lower socioeconomic backgrounds, those born EPT had lower closeness with peers. Higher closeness with parents was associated with lower test scores. Lower closeness and more discord with peers were associated with more behavior problems. Conclusion: Findings suggest that adolescents born EPT have difficulties in social reorientation toward peers and identify factors related to these difficulties. Results imply a need for interventions to improve peer socialization in youth born EPT.
Delineating the impact of pathogenic mutations on the conformational dynamics of HDL’s vital protein ApoA1: a combined computational and molecular dynamic simulation approach

Abstract Apolipoprotein A1 (ApoA1), is the important component of high‐density lipoproteins (HDL), that has key role in HDL biogenesis, cholesterol trafficking, and reverse cholesterol transport (RCT). Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in ApoA1 have been linked to cardiovascular diseases and amyloidosis as they alter the protein’s native structure and function. Therefore in this study, we attempted to understand the molecular pathogenicity profile of nsSNPs of ApoA1 using various computational approaches. We used state-of-the-art computational methods to thoroughly investigate the 295 ApoA1 nsSNPs at sequence and structural levels. Seven nsSNPs (L13R, L84R, L84P, L99P, R173P, L187P, and L238P) out of 295 were classified as the most deleterious and destabilizing. In order to estimate the effect of such destabilizing mutations on the protein conformation, all-atom molecular dynamics simulations (MDS) of ApoA1 wild-type (WT), L99P and R173P for 100 ns, was carried out using GROMACS 5.0. 1 package. The MD simulation investigation revealed significant structural alterations in L99P and R173P. In addition, they had changed principal component analysis and electrostatic surface potential, decreased structural compactness, and intramolecular hydrogen bonds, which supported the rationale underpinning ApoA1 dysfunction with such mutations. This work sheds light on ApoA1 dysfunction due to single amino acid alterations, and offers new insight into the molecular basis of ApoA1-related diseases progression. Communicated by Ramaswamy H. Sarma HIGHLIGHTS ApoA1 is a key HDL protein involved in RCT and HDL synthesis. Mutations in the ApoA1 protein can lead to defects in RCT and HDL biogenesis. In total 295nsSNPS of ApoA1 protein were studied using various computational approaches. Seven highly pathogenic and destabilizing mutations were found (L13R, L84R, L84P, L99P, R173P, L187P, and L238P). Further MD results showed L99P and R173P mutations in ApoA1 are highly destabilizing.