Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of Herpes Zoster in Individuals on Biologics, Disease-Modifying Antirheumatic Drugs, and/or Corticosteroids for Autoimmune Diseases: A Systematic Review and Meta-Analysis

Background. Studies examining the risk of herpes zoster (HZ) associated with immunosuppressants, such as biologics, nonbiological disease-modifying antirheumatic drugs (nbDMARDs), or corticosteroids, have generated conflicting results. Methods. We conducted a systematic literature search from January 1946 to February 2016. Search terms related to HZ, rheumatoid arthritis, psoriasis, psoriatic arthritis, systemic lupus erythematous, or inflammatory bowel disease, biologics, nbDMARDS, and corticosteroids were used. We included randomized controlled trials (RCTs) and observational studies reporting associations between immunosuppressants and HZ outcomes in adults. For RCTs, we used the Mantel-Haenszel fixed-effects model to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for HZ risk. For observational studies, adjusted ORs were pooled separately using random-effects inverse variance models. Results. Data were pooled from 40 eligible RCTs (20136 patients) and 19 observational studies (810939 patients). Biologics were associated with a greater risk of HZ than control (RCTs: OR = 1.71, 95% CI = 1.11–2.64; observational studies: OR = 1.58, 95% CI = 1.39–1.81). In RCTs, the OR of non-tumor necrosis factor (TNF) blockers was 2.19 (95% CI 1.20–4.02), but that of TNF blockers was not significantly different from control. Increased risks of HZ with nbDMARDs (OR = 1.21; 95% CI = 1.15–1.28) and corticosteroids (OR = 1.73; 95% CI = 1.57–1.89) were observed in observational studies, but few RCTs examined these comparisons. Conclusions. Immunocompromised patients receiving biologics were associated with an increased risk of HZ. The risk is also increased with corticosteroids and nbDMARDs. These findings raise the issue of prophylaxis with zoster vaccine in patients initiating immunosuppressive therapy for autoimmune diseases.
IFN‐γ‐mediated inhibition of lung cancer correlates with PD‐L1 expression and is regulated by PI3K‐AKT signaling

IFN‐γ plays a crucial role in anti‐tumor responses and also induces expression of PD‐L1, a well‐established inhibitor of anti‐tumor immune function. Understanding how molecular signaling regulates the function of IFN‐γ might improve its anti‐tumor efficacy. Here, we show that the tumor expression of IFN‐γ expression alone has no significant prognostic value in patients with locally advanced lung adenocarcinoma. Surprisingly, patients with tumors expressing both IFN‐γ and PD‐L1 have the best prognosis compared to those with tumors expressing IFN‐γ or PD‐L1 alone. Transcriptome analysis demonstrated that tumor tissues expressing IFN‐γ display gene expression associated with suppressed cell cycle progression and expansion. Unexpectedly this profile was observed in PD‐L1+ but not PD‐L1− tumors. The current concept is that PD‐L1 functions as a shield protecting tumor cells from cytolytic T cell (CTL)‐mediated anti‐tumor progression. However, our data indicate that PD‐L1 expression in the presence of IFN‐γ might serve as biomarker for the sensitivity of tumors to the inhibitory effect of IFN‐γ. Mechanistic analysis revealed that in lung adenocarcinoma cells IFN‐γ‐induced activation of JAK2‐STAT1 and PI3K‐AKT pathways. The activation of JAK2‐STAT1 is responsible for the anti‐proliferative effect of IFN‐γ. Inhibition of PI3K downregulated PD‐L1 expression and enhanced the anti‐proliferative effect of IFN‐γ, suggesting that blockade of PI3K might maximize the IFN‐γ‐mediated anti‐tumor effect. Our findings provide evidence for crosstalk between JAK2‐STAT1 and PI3K‐AKT pathways in response to IFN‐γ in lung adenocarcinoma and have implications for the design of combinatorial targeted therapy and immunotherapy for the treatment of lung adenocarcinoma.
The effect of dietary supplementation with Aurantiochytrium limacinum on lactating dairy cows in terms of animal health, productivity and milk composition

The aim of this study was to investigate the effect of dietary supplementation with the docosahexaenoic acid (DHA)-rich microalgae, Aurantiochytrium limacinum (AURA), on a variety of health and productivity parameters in lactating cows. Twenty-four cows were blocked by parity and number of days in milk and then randomly assigned to a control (CON; n = 12) group with no algal supplementation, or a treatment group (AURA; n = 12) provided with 100 g AURA cow-1 day-1 or 16 g DHA cow-1 day-1 . A variety of health and productivity measurements were taken, and results indicated that supplementation had no negative effects on animal health in terms of somatic cell count, haematological and biochemical blood parameters, while body condition was marginally improved by algal supplementation. No differences were found for the various production parameters measured; however, a tendency towards increased milk production was observed for the AURA group during the final stage of the study (+4.5 kg cow-1 day-1 , day 78-84). The fatty acid profile of milk was improved by supplementation, with significantly lower saturated fatty acids, significantly higher omega-3 fatty acids and an improved omega-3/omega-6 ratio observed when compared to the control group. The amount of DHA in the milk of cows provided 105 g AURA head-1 day-1 was 4.7 mg/100 g milk with a peak transfer efficiency from feed to milk at day 49 of 8.3%. These results indicate that supplementation with 105 g AURA head-1 day-1 resulted in the successful enrichment of milk with DHA without negatively impacting the health or productivity of the animals.
Parental perception of child weight and its association with weight-related parenting behaviours and child behaviours: a Chinese national study

Abstract Objective Parents commonly fail to correctly recognize the weight status of their child. Whether parental perception of child weight is associated with weight-related parenting behaviours and child behaviours is unclear. The present study aimed to investigate the distribution of parental perception of child weight and its associations with weight-related parenting behaviours and child behaviours in China. Design Cross-sectional study. Setting Seven provinces in China. Subjects A total of 47 417 children aged 6–17 years and their parents were included from a national survey in 2013. Parental perception of child weight, weight-related parenting behaviours and child behaviours were self-reported. Child’s weight and height were objectively measured. Results A total of 30·5 % of parents underestimated and 8·7 % overestimated the child’s weight. Parental underestimation was more common among younger children, boys and children with a lower BMI Z-score. Parents who perceived that their child had a healthy weight (accurately or inaccurately) were more likely to prepare breakfast for the child, exercise with him/her, set apart his/her exercise time, restrict his/her screen time, and were less likely to store soft drinks for the child. Children perceived to have a healthy weight, regardless of their actual weight status, behaved healthier on dietary intake, physical activity and homework time. Conclusions Parental underestimation of their child’s weight was prominent in China, especially among younger children, boys and children with a lower BMI Z-score. Parental recognition of their child being overweight did not appear to translate into healthy changes in weight-related parenting behaviours or child behaviours.
Linear Networks Based Speaker Adaptation for Speech Synthesis

Speaker adaptation methods aim to create fair quality synthesis speech voice font for target speakers while only limited resources available. Recently, as deep neural networks based statistical parametric speech synthesis (SPSS) methods become dominant in SPSS TTS back-end modeling, speaker adaptation under the neural network based SPSS framework has also became an important task. In this paper, linear networks (LN) is inserted in multiple neural network layers and fine-tuned together with output layer for best speaker adaptation performance. When adaptation data is extremely small, the low-rank plus diagonal(LRPD) decomposition for LN is employed to make the adapted voice more stable. Speaker adaptation experiments are conducted under a range of adaptation utterances numbers. Moreover, speaker adaptation from 1) female to female, 2) male to female and 3) female to male are investigated. Objective measurement and subjective tests show that LN with LRPD decomposition performs most stable when adaptation data is extremely limited, and our best speaker adaptation (SA) model with only 200 adaptation utterances achieves comparable quality with speaker dependent (SD) model trained with 1000 utterances, in both naturalness and similarity to target speaker.
Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Associated With Decreased Incidence of Atrial Fibrillation

Background Atrial fibrillation (AF) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (TT) levels were associated with a higher incidence of AF. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF. To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy (TRT) in patients with low testosterone. Methods and Results Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT), group 2 had TRT without normalization of TT levels (nonnormalized TRT), and group 3 did not receive TRT (no TRT). Propensity score–weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post‐TRT levels of TT and the incidence of AF. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81–0.99, P=0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70–0.89, P=0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78– 1.0009, P=0.0675) in incidence of AF. Conclusions These novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF.
Exposure to Inhalable Dust, Endotoxin, and Total Volatile Organic Carbons on Dairy Farms Using Manual and Automated Feeding Systems

Introduction Agricultural workers tend to have high exposures to organic dusts which may induce or exacerbate respiratory disorders. Studies investigating the effect of work tasks and farm characteristics on organic dust exposures among farm workers suggest that handling of animal feed is an important exposure determinant; however, the effect of the animal feeding system has not been explored in any detail. Objectives To measure the exposure of Irish dairy farmers to inhalable dust, endotoxin, and total volatile organic compounds (TVOCs) during parlour work and to explore whether levels of exposure to these agents depend on the applied feeding system in the farms. Methods Thirty-eight personal exposure measurements were collected from farmers across seven dairy farms. The farms used manual, loft, or semi-automated feeding systems. Information on worker tasks and farm characteristics was collected during the surveys. Associations between exposure concentrations and feeding systems, worker tasks, and other farm characteristics were explored in linear mixed-effect regression models with farmer identity treated as a random effect. Results Exposure concentrations were variable and had a geometric mean (GM; geometric standard deviation) of 1.5 mg m-3 (1.8) for inhalable dust and 128 EU m-3 (2.5) for endotoxin. More than 50% of the exposure measurements for endotoxin, and organic dust exceeded recommended health-based occupational exposure limits. Endotoxin levels were somewhat lower in farms using semi-automatic feeding systems when compared to those using manual feeding systems but in multivariate regression analysis associations were not statistically significant (β = -0.54, P = 0.4). Performance of activities related to handling and spreading of hay or straw was the strongest determinant for both inhalable dust and endotoxin exposure (β = 0.78, P ≤ 0.001; β = 0.72, P = 0.02, respectively). The level of dust exposure increased also as a consequence of a lower outdoor temperature, and higher ratio of distributed feed per cow (P = 0.01). Stationary measurements of TVOC and CO2 concentrations inside the dairy parlours had a GM of 180 ppb (1.9) and 589 ppb (1.3), respectively. The use of cow teat disinfectants and building ventilation were both strong predictors of TVOC concentrations within parlours. Conclusions Dairy farm workers can be exposed to high and variable levels of inhalable dust and endotoxin and may be at risk of respiratory disease. Results from this study suggest that exposure control strategies for organic dusts and TVOCs exposures should consider building ventilation and work tasks such as spreading of bedding material, using spray disinfectants and animal feeding. Until effective permanent engineering controls are established farm workers should be encouraged to wear respiratory protective equipment during these tasks.
Optimizing precision overhead for x86 processors

It is a major challenge for a Java JIT compiler to perform single‐precision floating‐point operations efficiently for the x86 processors. In previous research, the double‐precision mode is set as the default precision mode when methods are invoked. Sophisticated approaches then use heuristic approaches to optimization by considering the trade‐offs between roundings and mode switches. However, this convention introduces redundant mode switches across method boundaries. Furthermore, methods that include both single‐ and double‐precision operations cannot switch the mode, even if single‐precision operations are dominant. We propose a new approach to these problems. We eliminate redundant mode switches by ignoring the default precision mode and calling a method in the same precision mode as the caller. For methods that include both single‐ and double‐precision methods, we reduce the overhead of rounding by isolating code segments of a given method that should be executed in the single‐precision mode. We implemented our approach in IBM's Just‐in‐Time compiler, and obtained experimental results demonstrating that, in SPECjvm98, it consistently shows the best performance in any configuration of benchmark programs, inline policies, and processor architectures compared with previous research approaches. Copyright © 2004 John Wiley & Sons, Ltd.
Arthritis Among Veterans — United States, 2011–2013

Arthritis is among the most common chronic conditions among veterans and is more prevalent among veterans than nonveterans. Contemporary population-based estimates of arthritis prevalence among veterans are needed because previous population-based studies predate the Persian Gulf War, were small, or studied men only despite the fact that women comprise an increasing proportion of military personnel and typically have a higher prevalence of arthritis than men. To address this knowledge gap, CDC analyzed combined 2011, 2012, and 2013 Behavioral Risk Factor Surveillance System (BRFSS) data among all adults aged ≥18 years, by veteran status, to estimate the total and sex-specific prevalence of doctor-diagnosed arthritis overall and by sociodemographic categories, and the state-specific prevalence (overall and sex-specific) of doctor-diagnosed arthritis. This report summarizes the results of these analyses, which found that one in four veterans reported that they had arthritis (25.6%) and that prevalence was higher among veterans than nonveterans across most sociodemographic categories, including sex (prevalence among male and female veterans was 25.0% and 31.3%, respectively). State-specific, age-standardized arthritis prevalence among veterans ranged from 18.8% in Hawaii to 32.7% in West Virginia. Veterans comprise a large and important target group for reducing the growing burden of arthritis. Those interested in veterans' health can help to improve the quality of life of veterans by ensuring that they have access to affordable, evidence-based, physical activity and self-management education classes that reduce the adverse effects of arthritis (e.g., pain and depression) and its common comorbidities (e.g., heart disease and diabetes).
DNA topoisomerase II can drive changes in higher order chromosome architecture without enzymatically modifying DNA

Topoisomerase II has been suggested to play a major role in chromosome organization based on its DNA decatenating activity and its ability to mediate direct binding interactions between DNA and nuclear matrix. However, this latter point remains controversial. Here we address the question of whether the chromatin binding activity of Topoisomerase II is sufficient to modify chromosome form using whole mammalian chromosomes in vitro. Intact chromosomes were microsurgically removed from living cells and disassembled by treatment with protease or heparin. When these disassembled chromosomes were incubated with recombinant human Topoisomerase II, the enzyme became incorporated into chromatin and reassembly resulted, leading to almost complete restoration of pre‐existing chromosome shape and position within minutes. Chromosome reconstituition by Topoisomerase II was dose‐dependent, saturable, and appeared to be controlled stoichiometrically, rather than enzymatically. Similar reassembly was observed in the absence of ATP and when a catalytically inactive thermosensitive Topoisomerase II mutant was used at the restrictive temperature. Chromosome recondensation also could be induced after the strand‐passing activity of Topoisomerase II was blocked by treatment with an inhibitor of its catalytic activity, amsacrine. When a non‐hydrolyzable β,γ‐imido analog of ATP (AMP‐PNP) was used to physiologically fix bound Topoisomerase II enzyme in a closed form around DNA, subsequent chromosome disassembly was prevented in the presence of high salt. These data suggest that Topoisomerase II may control higher order chromatin architecture through direct binding interactions, independently of its well‐known catalytic activity. J. Cell. Biochem. 69:127–142, 1998. © 1998 Wiley‐Liss, Inc.
Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia

Background Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhibited by hyperthermia, thereby inducing synthetic lethal conditions in every tumor type. Since cisplatin is successfully used combined with hyperthermia (thermochemotherapy), we investigated the effectiveness of combining PARP1-i with thermochemotherapy. Results The in vitro data demonstrate a decreased in cell survival after addition of PARP1-i to thermochemotherapy, which can be explained by increased DNA damage induction and less DSB repair. These in vitro findings are in line with in vivo model, in which a decreased tumor growth is observed upon addition of PARP1-i. Materials and Methods Survival of three HR-proficient cell lines after cisplatin, hyperthermia and/or PARP1-i was studied. Cell cycle analyses, quantification of γ-H2AX foci and apoptotic assays were performed to understand these survival data. The effects of treatments were further evaluated by monitoring tumor responses in an in vivo rat model. Conclusions Our results in HR-proficient cell lines suggest that PARP1-i combined with thermochemotherapy can be a promising clinical approach for all tumors independent of HR status.
Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast

Cells react to extracellular perturbations with complex and intertwined responses. Systematic identification of the regulatory mechanisms that control these responses is still a challenge and requires tailored analyses integrating different types of molecular data. Here we acquired time-resolved metabolomics measurements in yeast under salt and pheromone stimulation and developed a machine learning approach to explore regulatory associations between metabolism and signal transduction. Existing phosphoproteomics measurements under the same conditions and kinase-substrate regulatory interactions were used to estimate the enzymatic activity of signalling kinases. Our approach identified informative associations between kinases and metabolic enzymes capable of predicting metabolic changes. We extended our analysis to two studies containing transcriptomics, phosphoproteomics and metabolomics measurements across a comprehensive panel of kinases/phosphatases knockouts and time-resolved perturbations to the nitrogen metabolism, conveying a total of 143 unique conditions. Our approach accurately estimated the change in activity of transcription factors, kinases and phosphatases and these were capable of building predictive models to infer the metabolic adaptations of previously unseen conditions across different dynamic experiments. Time-resolved experiments were significantly more informative than genetic perturbations to infer metabolic adaptation. This difference may be due to the indirect nature of the associations and of general cellular states that can hinder the identification of causal relationships. This work provides a novel genome-scale integrative analysis to propose putative transcriptional and post-translational regulatory mechanisms of metabolic processes.
The cysteine protease dipeptidyl aminopeptidase 3 does not contribute to egress of Plasmodium falciparum from host red blood cells

The ability of Plasmodium parasites to egress from their host red blood cell is critical for the amplification of these parasites in the blood. Previous forward chemical genetic approaches have implicated the subtilisin-like protease (SUB1) and the cysteine protease dipeptidyl aminopeptidase 3 (DPAP3) as key players in egress, with the final step of SUB1 maturation thought to be due to the activity of DPAP3. In this study, we have utilized a reverse genetics approach to engineer transgenic Plasmodium falciparum parasites in which dpap3 expression can be conditionally regulated using the glmS ribozyme based RNA-degrading system. We show that DPAP3, which is expressed in schizont stages and merozoites and localizes to organelles distinct from the micronemes, rhoptries and dense granules, is not required for the trafficking of apical proteins or processing of SUB1 substrates, nor for parasite maturation and egress from red blood cells. Thus, our findings argue against a role for DPAP3 in parasite egress and indicate that the phenotypes observed with DPAP3 inhibitors are due to off-target effects.