Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Cytomegalovirus Induces Multiple Means To Combat Reactive Oxygen Species

ABSTRACT Reactive oxygen species (ROS) are generated as by-products of many cellular processes and can modulate cellular signaling pathways. However, high ROS levels are toxic; thus, intracellular ROS need to be tightly controlled. Therefore, cells use a group of antioxidant molecules and detoxifying enzymes that remove or detoxify reactive species. We found that the level of the antioxidant glutathione is greatly increased in human cytomegalovirus (HCMV)-infected cells due to activation of glutathione synthetic enzymes. In addition, our data suggest that virus-specific mechanisms are used to induce the expression of target antioxidant and detoxifying enzymes critical for the success of the infection. As a result of this virus-induced anti-ROS environment, key signaling kinases, such as the mammalian target of rapamycin (mTOR) kinase in mTOR complex 1 (mTORC1), are protected from inhibition by exogenous hydrogen peroxide (H2O2). In this regard, we found that phosphorylation of mTOR kinase at serine 2448 (suggested to be activating) was maintained during infection even under ROS stress conditions that inhibited it in uninfected cells. We also show that AMP-dependent kinase (AMPK)-mediated phosphorylation of serine 792 of raptor, the specificity subunit of mTORC1, increases in infected cells after H2O2 treatment. This phosphorylation is normally inhibitory for mTORC1. However, in infected cells this did not result in inhibition of mTORC1 activity, suggesting that inhibitory effects of raptor phosphorylation are circumvented. Overall, our data suggest that HCMV utilizes virus-specific mechanisms to activate a variety of means to protect the cell and mTORC1 from the effects of ROS.
Performance of Different Scan Protocols of Fetal Echocardiography in the Diagnosis of Fetal Congenital Heart Disease: A Systematic Review and Meta-Analysis

Objective The rapid progress in fetal echocardiography has lead to early detection of congenital heart diseases. Increasing evidences have shown that prenatal diagnosis could be life saving in certain cases. However, there is no agreement on which protocol is most adaptive diagnostic one. Thus, we use meta-analysis to conduct a pooled performance test on 5 diagnostic protocols. Methods We searched PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials and WHO clinical trails registry center to identify relevant studies up to August, 2012. We performed meta-analysis in a fixed/random-effect model using Meta-disc 1.4. We used STATA 11.0 to estimate the publication bias and SPSS 17.0 to evaluate variance. Results We use results from 81 studies in 63 articles to analyze the pooled accuracy. The overall performance of pooled sensitivities of spatiotemporal image correlation (STIC), extend cardiac echography examination (ECEE) and 4 chambers view + outflow tract view + 3 vessels and trachea view (4 CV+OTV+3 VTV) were around 0.90, which was significant higher than that of 4 chambers view + outflow tract view or 3 vessels and trachea view (4 CV+OTV/3 VTV) and 4 chambers view (4 CV). Unfortunately the pooled specificity of STIC was 0.92, which was significant lower than that of other 4 protocols which reached at 1.00. The area under the summary receiver operating characteristic curves value of STIC, ECEE, 4 CV+OTV+3 VTV, 4 CV+OTV/3 VTV and 4 CV were 0.9700, 0.9971, 0.9983, 0.9929 and 0.9928 respectively. Conclusion These results suggest a great diagnostic potential for fetal echocardiography detection as a reliable method of fetal congenital heart disease. But at least 3 sections view (4 CV, OTV and 3 VTV) should be included in scan protocol, while the STIC can be used to provide more information for local details of defects, and can not be used to make a definite diagnosis alone with its low specificity.
Flexible functional regression methods for estimating individualized treatment rules

A major focus of personalized medicine is on the development of individualized treatment rules that depend upon baseline measures. Good decision rules have the potential to significantly advance patient care and reduce the burden of a host of diseases. Statistical methods for developing such rules are progressing rapidly, but few methods have considered the use of pretreatment functional data to guide decision‐making. Furthermore, those methods that do allow for the incorporation of functional pretreatment covariates typically make strong assumptions about the relationships between the functional covariates and the response of interest. We propose two approaches for using functional data to select an optimal treatment that address some of the shortcomings of previously developed methods. Specifically, we combine the flexibility of functional additive regression models with Q‐learning or A‐learning in order to obtain treatment decision rules. Properties of the corresponding estimators are discussed. Our approaches are evaluated in several realistic settings using synthetic data and are applied to data arising from a clinical trial comparing two treatments for major depressive disorder in which baseline imaging data are available for subjects who are subsequently treated. Copyright © 2016 John Wiley & Sons, Ltd.
Comparative Proteomics of Activated THP-1 Cells Infected with Mycobacterium tuberculosis Identifies Putative Clearance Biomarkers for Tuberculosis Treatment

Biomarkers for determining clearance of Mycobacterium tuberculosis (Mtb) infection during anti-tuberculosis therapy or following exposure could facilitate enhanced monitoring and treatment. We screened for biomarkers indicating clearance of Mtb infection in vitro. A comparative proteomic analysis was performed using GeLC MSI/MS. Intracellular and secreted proteomes from activated THP-1 cells infected with the Mtb H37Rv strain (MOI = 1) and treated with isoniazid and rifampicin for 1 day (infection stage) and 5 days (clearance stage) were analyzed. Host proteins associated with early infection (n = 82), clearance (n = 121), sustained in both conditions (n = 34) and suppressed by infection (n = 46) were elucidated. Of the potential clearance markers, SSFA2 and CAECAM18 showed the highest and lowest protein intensities, respectively. A western blot of CAECAM18 validated the LC MS/MS result. For three clearance markers (SSFA2, PARP14 and PSME4), in vivo clinical validation was concordantly reported in previous patient cohorts. A network analysis revealed that clearance markers were enriched amongst four protein interaction networks centered on: (i) CD44/CCND1, (ii) IFN-β1/NF-κB, (iii) TP53/TGF-β and (iv) IFN-γ/CCL2. After infection, proteins associated with proliferation, and recruitment of immune cells appeared to be enriched possibly reflecting recruitment of defense mechanisms. Counteracting proteins (CASP3 vs. Akt and NF-κB vs. TP53) associated with apoptosis regulation and its networks were enriched among the early and sustained infection biomarkers, indicating host-pathogen competition. The BRCA1/2 network was suppressed during infection, suggesting that cell proliferation suppression is a feature of Mtb survival. Our study provides insights into the mechanisms of host-Mtb interaction by comparing the stages of infection clearance. The identified clearance biomarkers may be useful in monitoring tuberculosis treatment.
An optimal load shedding approach for distribution networks with DGs considering capacity deficiency modelling of bulked power supply

This paper discusses a genetic algorithm (GA) based optimal load shedding that can apply for electrical distribution networks with and without dispersed generators (DG). Also, the proposed method has the ability for considering constant and variable capacity deficiency caused by unscheduled outages in the bulked generation and transmission system of bulked power supply. The genetic algorithm (GA) is employed to search for the optimal load shedding strategy in distribution networks considering DGs in two cases of constant and variable modelling of bulked power supply of distribution networks. Electrical power distribution systems have a radial network and unidirectional power flows. With the advent of dispersed generations, the electrical distribution system has a locally looped network and bidirectional power flows. Therefore, installed DG in the electrical distribution systems can cause operational problems and impact on existing operational schemes. Introduction of DGs in electrical distribution systems has introduced many new issues in operational and planning level. Load shedding as one of operational issue has no exempt. The objective is to minimize the sum of curtailed load and also system losses within the frame-work of system operational and security constraints. The proposed method is tested on a radial distribution system with 33 load points for more practical applications.
Injuries among male and female World Cup alpine skiers

Background: Limited knowledge exists on injuries among professional alpine skiers. Objective: To describe the risk of injury and the injury pattern among competitive World Cup alpine skiers during the competitive season. Methods: Retrospective interviews were performed with all World Cup athletes from 10 nations at the end of the 2006–7 and 2007–8 winter seasons, and all acute injuries occurring during the 4.5-month competitive season were recorded. If the athlete was not present, their coaches or medical personnel were interviewed. Results: A total of 191 acute injuries were recorded among 521 World Cup alpine skiers. As many as 86 injuries (45%) occurred during World Cup/World Ski Championship competitions, corresponding to an injury rate of 9.8 injuries per 1000 runs (95% CI 7.8 to 11.9). The injury rate was found to increase with increasing speed (slalom 4.9 injuries per 1000 runs, 95% CI 2.5 to 7.4—giant slalom 9.2, 5.1 to 13.3—super-G 11.0, 5.2 to 16.8—downhill 17.2, 11.6 to 22.7). The most frequently injured body part was the knee, with 68 injuries (36%), and 37 of these were severe. The overall injury rate was higher in males than in females, but not for knee injuries. Conclusions : The risk of injury among World Cup athletes in alpine skiing is even higher than previously reported. The knee is the most commonly injured body part and with many severe injuries. Injury rate increased with a higher speed and was higher among males than in females.
Transient Induction of ENC-1, a Kelch-related Actin-binding Protein, Is Required for Adipocyte Differentiation*

In an attempt to study molecules that play a regulatory role early in adipocyte differentiation, we identified by differential display ENC-1, a Drosophila kelch-related protein. ENC-1 colocalizes with actin filaments. ENC-1 is expressed in adipose tissue, specifically in the adipose-derived stroma-vascular fraction. ENC-1 mRNA levels are transiently increased 8–12-fold early in in vitro adipocyte differentiation of primary cells of the adipose-derived stroma-vascular fraction and of 3T3-L1 cells. Treatment with the adipogenic inducers dexamethasone and methylisobutylxanthine causes an increase in ENC-1 mRNA levels specifically in preadipocytes, and methylisobutylxanthine is the main effector of ENC-1 expression. The induction of ENC-1 precedes expression of the transcription factors, peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein (C/EBPα), and other adipocyte markers including adipocyte fatty acid-binding protein. The ENC-1 induction correlates with the subsequent differentiation of primary stroma-vascular cells into adipocytes. Furthermore, decreasing the endogenous ENC-1 levels by stable antisense transfection, thereby preventing the transient induction, effectively inhibits 3T3-L1 adipocyte differentiation. Overall, these studies indicate that ENC-1, an actin-binding protein, plays a regulatory role early in adipocyte differentiation when cytoskeletal reorganization and cell shape change from fibroblastic preadipocytes to spherical adipocytes occur.
Variations in Stress Sensitivity and Genomic Expression in Diverse S. cerevisiae Isolates

Interactions between an organism and its environment can significantly influence phenotypic evolution. A first step toward understanding this process is to characterize phenotypic diversity within and between populations. We explored the phenotypic variation in stress sensitivity and genomic expression in a large panel of Saccharomyces strains collected from diverse environments. We measured the sensitivity of 52 strains to 14 environmental conditions, compared genomic expression in 18 strains, and identified gene copy-number variations in six of these isolates. Our results demonstrate a large degree of phenotypic variation in stress sensitivity and gene expression. Analysis of these datasets reveals relationships between strains from similar niches, suggests common and unique features of yeast habitats, and implicates genes whose variable expression is linked to stress resistance. Using a simple metric to suggest cases of selection, we found that strains collected from oak exudates are phenotypically more similar than expected based on their genetic diversity, while sake and vineyard isolates display more diverse phenotypes than expected under a neutral model. We also show that the laboratory strain S288c is phenotypically distinct from all of the other strains studied here, in terms of stress sensitivity, gene expression, Ty copy number, mitochondrial content, and gene-dosage control. These results highlight the value of understanding the genetic basis of phenotypic variation and raise caution about using laboratory strains for comparative genomics.
Molecular Evidence of a New Strain of Ehrlichia canis from South America

ABSTRACT Blood samples from dogs with clinical signs compatible with ehrlichiosis were examined for infection of Ehrlichia canis using PCR, multiplex real-time PCR, and DNA sequencing analysis. Eleven of 25 samples were positive for a new strain of E. canis. This is the first molecular identification of E. canis infection in dogs from Peru.
Scattered radiation from a tissue-equivalent phantom for x rays from 50 to 300 kVp.

Data have been taken showing the ratio of scatter-to-incident exposure over a kilovoltage range of 50 to 150 kVp for radiographic conditions wherein the field was centered on the scatterer and wherein the field is at the edge of the scatterer, using a phantom that has a shape similar to that of the trunk of the human body. Similar data were taken for conditions used in therapy for the voltage range of 50 to 300 kVp. The data presented here will be useful to those setting up recommended methods for calculating secondary protective barriers.
Effect of eccentricity on binary neutron star searches in advanced LIGO

Binary neutron stars (BNSs) are the primary source of gravitational waves for the Laser Interferometer Gravitational-Wave Observatory (LIGO) and its international partners Virgo and KAGRA. Current BNS searches target field binaries whose orbits will have circularized by radiation reaction before their gravitational waves enter the advanced LIGO sensitive band at 15 Hz. It has been suggested that a population of BNSs may form by n-body interactions near supermassive black holes or in globular clusters and that these systems may have non-negligible eccentricity in the advanced LIGO band. We show that for BNS systems with total mass of 2. 4M_⊙ (6M_⊙), the effect of eccentricity e≲0.02 (0.05) is negligible and a circular search is effectual for these binaries. For eccentricities up to e = 0.4, we investigate the selection bias caused by neglecting eccentricity in BNS searches. If such high eccentricity systems exist, searches that specifically target eccentric binaries will be needed in advanced LIGO and Virgo.
Physical Activity Socialization: Peer Interactions and Affective Responses among a Sample of Sixth Grade Girls

Premised on an interactive socialization as construction and internalization approach, physical activity socialization experiences related to peer interactions and associated affective responses in physical activity settings were explored among eight 11- to 12-year-old girls. Three possible physical activity choices (formal sport, informal physical activity, and exercise) were considered. Three methods of data collection were employed: observation, sociometric evaluation, and interview. Physical activity socialization experiences were found to be context specific both in terms of activity type (formal sport, informal physical activity, and exercise) and social situation (home and school). Boys in physical education classes appeared to be the major source of negative peer treatment, primarily by criticizing girls’ physical skill performances and constructing them as subordinate to those of the boys. Positive or negative affective responses to peer treatment were reported to lead to the seeking or avoidance.
Gut feelings about smoking and coffee in Parkinson's disease

Strong epidemiologic evidence suggests that smokers and coffee drinkers have a lower risk of Parkinson's disease (PD). The explanation for this finding is still unknown, and the discussion has focused on two main hypotheses. The first suggests that PD patients have premorbid personality traits associated with dislike for coffee‐drinking and smoking. The second posits that caffeine and nicotine are neuroprotective. We propose an alternative third hypothesis, in which both cigarette and coffee consumption change the composition of the microbiota in the gut in a way that mitigates intestinal inflammation. This, in turn, would lead to less misfolding of the protein alpha‐synuclein in enteric nerves, reducing the risk of PD by minimizing propagation of the protein aggregates to the central nervous system, where they otherwise can induce neurodegeneration. © 2014 International Parkinson and Movement Disorder Society
Pancreas transplantation for type 2 diabetes mellitus.

PURPOSE OF REVIEW This review will provide evidence that selected patients with type 2 diabetes mellitus (T2DM) may benefit from vascularized pancreas transplantation (PTX). RECENT FINDINGS Initial experience with simultaneous pancreas-kidney transplantation (SPKT) in patients with T2DM and end-stage renal disease (ESRD) suggested that augmentation of endogenous insulin production by PTX in patients with C-peptide-positive, insulin-requiring diabetes resulted in insulin independence, improved glucose counter-regulation, and enhanced quality of life. A number of single-center retrospective studies have documented equivalent outcomes in patients with either type 1 diabetes mellitus (T1DM) or T2DM undergoing predominantly SPKT, although clearly a selection bias exists for patients in the latter category. Selection criteria for SPKT in T2DM include patients less than 55-60 years of age with a BMI less than 30-32 kg/m², insulin-requiring for a minimum of 5 years with a total daily insulin requirement less than 1 u/kg/day, a fasting C-peptide level less than 10 ng/ml, absence of severe vascular disease or tobacco abuse, adequate cardiac function, and presence of 'complicated' diabetes. Data from the International Pancreas Transplant Registry show that up to 7% of SPKT recipients are classified as having T2DM and that outcomes in these patients are comparable to those undergoing SPKT and classified as having T1DM. SUMMARY Consequently, characterization of the 'type' of diabetes may be irrelevant and insulin-requiring diabetic patients with ESRD should be evaluated for PTX based exclusively on their predicted ability to tolerate the surgical procedure and requisite immunosuppression as well as comply with a stringent posttransplant follow-up regimen.
No Evidence for Race and Socioeconomic Status as Independent Predictors of 30-Day Readmission Rates Following Orthopedic Surgery

The Centers for Medicare & Medicaid Services considers readmissions within 30 days of discharge to be a quality indicator. Hospitals’ and eventually physicians’ readmission rates will be used to determine payment for services. It is imperative that health care providers understand which patients are at risk for readmission so that they can apply the appropriate preventive interventions. The research team analyzed all orthopedic admissions and readmissions at their institution from September 2008 to April 2011 in this study. Preparing for the next stage in health care reform, identifying any preoperative factors that may place certain patients into a “high-risk” category for readmission following an orthopedic procedure is of paramount importance. This data analysis of more than 13 000 patients noted that race-based and income-based risk factors did not translate into significant risk factors or predictors of 30-day readmission following orthopedic admission.
The mTOR Pathway Controls Cell Proliferation by Regulating the FoxO3a Transcription Factor via SGK1 Kinase

The mechanistic target of rapamycin (mTOR) functions as a component of two large complexes, mTORC1 and mTORC2, which play crucial roles in regulating cell growth and homeostasis. However, the molecular mechanisms by which mTOR controls cell proliferation remain elusive. Here we show that the FoxO3a transcription factor is coordinately regulated by mTORC1 and mTORC2, and plays a crucial role in controlling cell proliferation. To dissect mTOR signaling, mTORC1 was specifically inactivated by depleting p18, an essential anchor of mTORC1 on lysosomes. mTORC1 inactivation caused a marked retardation of cell proliferation, which was associated with upregulation of cyclin-dependent kinase inhibitors (CDKIs). Although Akt was activated by mTORC1 inactivation, FoxO3a was upregulated via an epigenetic mechanism and hypophosphorylated at Ser314, which resulted in its nuclear accumulation. Consistently, mTORC1 inactivation induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), the kinase responsible for Ser314 phosphorylation. Expression of FoxO3a mutated at Ser314 suppressed cell proliferation by inducing CDKI expression. SGK1 overexpression suppressed CDKI expression in p18-deficient cells, whereas SGK1 knockdown induced CDKI expression in wild-type cells, resulting in the suppression of cell proliferation. These results suggest that mTORC1, in coordination with mTORC2, controls cell proliferation by regulating FoxO3a gene expression and SGK1-mediated phosphorylation of FoxO3a at Ser314.
Validating the Use of Vignettes for Subjective Threshold Scales

Comparing self-assessed indicators of subjective outcomes such as health, work disability, political efficacy, job satisfaction, etc. across countries or socio-economic groups is often hampered by the fact that different groups use systematically different response scales. Anchoring vignettes have been introduced as an effective tool to correct for such differences. This paper develops an integrated framework in which objective measurements are used to validate the vignette-based corrections. The framework is applied to vignettes and objective and subjective self-assessments of drinking behavior by students in Ireland. Model comparisons using the Akaike information criterion favor a specification with response consistency and vignette corrected response scales. Put differently, vignette based corrections appear quite effective in bringing objective and subjective measures closer together.