Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive Analysis Reveals a 4-Gene Signature in Predicting Response to Temozolomide in Low-Grade Glioma Patients

Low-grade gliomas (LGGs) are a highly heterogeneous group of slow-growing, lethal, diffusive brain tumors. Temozolomide (TMZ) is a frequently used primary chemotherapeutic agent for LGGs. Currently there is no consensus as to the optimal biomarkers to predict the efficacy of TMZ, which calls for decision-making for each patient while considering molecular profiles. Low-grade glioma data sets were retrieved from The Cancer Genome Atlas. Cox regression and survival analyses were applied to identify clinical features significantly associated with survival. Subsequently, Ordinal logistic regression, co-expression, and Cox regression analyses were applied to identify genes that correlate significantly with response rate, disease-free survival, and overall survival of patients receiving TMZ as primary therapy. Finally, gene expression and methylation analyses were exploited to explain the mechanism between these gene expression and TMZ efficacy in LGG patients. Overall survival was significantly correlated with age, Karnofsky Performance Status score, and histological grade, but not with IDH1 mutation status. Using 3 distinct efficacy end points, regression and co-expression analyses further identified a novel 4-gene signature of ASPM, CCNB1, EXO1, and KIF23 which negatively correlated with response to TMZ therapy. In addition, expression of the 4-gene signature was associated with those of genes involved in homologous recombination. Finally, expression and methylation profiling identified a largely unknown olfactory receptor OR51F2 as potential mediator of the roles of the 4-gene signature in reducing TMZ efficacy. Taken together, these findings propose the 4-gene signature as a novel panel of efficacy predictors of TMZ therapy, as well as potential downstream mechanisms, including homologous recombination, OR51F2, and DNA methylation independent of MGMT.
Response of maize biomass and soil water fluxes on elevated CO2 and drought—From field experiments to process‐based simulations

The rising concentration of atmospheric carbon dioxide (CO2) is known to increase the total aboveground biomass of several C3 crops, whereas C4 crops are reported to be hardly affected when water supply is sufficient. However, a free‐air carbon enrichment (FACE) experiment in Braunschweig, Germany, in 2007 and 2008 resulted in a 25% increased biomass of the C4 crop maize under restricted water conditions and elevated CO2 (550 ppm). To project future yields of maize under climate change, an accurate representation of the effects of eCO2 and drought on biomass and soil water conditions is essential. Current crop growth models reveal limitations in simulations of maize biomass under eCO2 and limited water supply. We use the coupled process‐based hydrological‐plant growth model Catchment Modeling Framework‐Plant growth Modeling Framework to overcome this limitation. We apply the coupled model to the maize‐based FACE experiment in Braunschweig that provides robust data for the investigation of combined CO2 and drought effects. We approve hypothesis I that CO2 enrichment has a small direct‐fertilizing effect with regard to the total aboveground biomass of maize and hypothesis II that CO2 enrichment decreases water stress and leads to higher yields of maize under restricted water conditions. Hypothesis III could partly be approved showing that CO2 enrichment decreases the transpiration of maize, but does not raise soil moisture, while increasing evaporation. We emphasize the importance of plant‐specific CO2 response factors derived by use of comprehensive FACE data. By now, only one FACE experiment on maize is accomplished applying different water levels. For the rigorous testing of plant growth models and their applicability in climate change studies, we call for datasets that go beyond single criteria (only yield response) and single effects (only elevated CO2).
Smoking and school absenteeism among 15- to 16-year-old adolescents: a cross-section analysis on 36 European countries

Abstract Background Schools have a crucial role to play in preventing youth smoking. However, the well-known long-term health consequences of youth smoking may be insufficient to convince education stakeholders to devote efforts to implement school-based programmes. However, if youth smoking were to have short-term consequences, this evidence could prompt education stakeholders’ action. In this article, we investigate the link between smoking and school absenteeism. Methods We used data from the 2011 wave of the European School Survey Project on Alcohol and Other Drugs, on adolescents aged 15–16. We applied logistic models to assess the risk of more than 3 missed school days, by cause, as function of smoking intensity, adjusting for age, sex, socioeconomic status, academic performance, parental involvement and other risk behaviours (alcohol and cannabis consumption). Consistency was assessed by replicating the analyses for each sex and age group and further adjusting for depression and self-esteem. Results Smoking more than five cigarettes per day was significantly linked to school absenteeism, with a 55% excess risk of missing more than 3 school days per month due to illness (OR = 1.55, 95% CI 1.46–1.64), and a more than two times excess risk due to skipping (OR = 2.29; 95% CI 2.16–2.43). These findings were consistent across age and sex groups. Conclusion We observed an association between smoking intensity and absenteeism among youth in Europe. This implies that, to the extent that this association is causal, school tobacco control policies may reduce the short-term consequences of smoking on adolescents’ education and health.
Regulation of gene expression in trypanosomatids: living with polycistronic transcription

In trypanosomes, RNA polymerase II transcription is polycistronic and individual mRNAs are excised by trans-splicing and polyadenylation. The lack of individual gene transcription control is compensated by control of mRNA processing, translation and degradation. Although the basic mechanisms of mRNA decay and translation are evolutionarily conserved, there are also unique aspects, such as the existence of six cap-binding translation initiation factor homologues, a novel decapping enzyme and an mRNA stabilizing complex that is recruited by RNA-binding proteins. High-throughput analyses have identified nearly a hundred regulatory mRNA-binding proteins, making trypanosomes valuable as a model system to investigate post-transcriptional regulation.
Individuals’ expected genetic contributions to future generations, reproductive value, and short‐term metrics of fitness in free‐living song sparrows (Melospiza melodia)

Appropriately defining and enumerating ‘fitness’ is fundamental to explaining and predicting evolutionary dynamics. Yet theoretical concepts of fitness are often hard to translate into quantities that can be quantified in wild populations experiencing complex environmental, demographic, genetic and selective variation. While the ‘fittest’ entities might be widely understood to be those that ultimately leave most descendants at some future time, such long-term legacies are hard to measure, impeding evaluation of how well more tractable short-term metrics of individual fitness directly predict longer-term outcomes. One opportunity for conceptual and empirical convergence stems from the principle of individual reproductive value (Vi), defined as the number of copies of each of an individual’s alleles that is expected to be present in future generations given the individual’s realised pedigree of descendants. Since Vi tightly predicts an individual’s longer-term genetic contribution, quantifying Vi provides a tractable route to quantifying what, to date, has been an abstract fitness concept. We used complete pedigree data from free-living song sparrows (Melospiza melodia) to demonstrate that individuals’ expected genetic contributions stabilise within an observed 20-year time period, allowing individual Vi to be evaluated. Considerable among-individual variation in Vi was evident in both sexes. However, standard short-term metrics of individual fitness, comprising lifespan, lifetime reproductive success and projected growth rate, typically explained less than half the variation. Given these results, we discuss what evolutionary inferences can and cannot be directly drawn from short-term versus longer-term fitness metrics observed on individuals, and highlight that analyses of pedigree structure may provide useful complementary insights into evolutionary processes and outcomes.
Social Determinants of Racial Disparities in Cognitive Functioning in Later Life in Canada

Objective: The objectives of this study were (a) to assess the nature and extent of racial disparities in cognitive functioning among older adults in Canada, and (b) to assess the role of socioeconomic factors and patterned health behaviors as social determinants of racial disparities in cognitive functioning. Method: Data were drawn from the 2009-2010 Canadian Community Health Survey. The study sample included 20,646 people aged 60 years or older. Ordered logistic regression analyses were carried out to test hypotheses linking race, socioeconomic factors, and patterned health behaviors, and cognitive functioning. Results: Our findings revealed a racial gap in cognitive functioning among older adults in Canada. This gap was, in part, mediated by socioeconomic inequalities (in income and food security) and socially patterned behaviors (i.e., drinking, physical activity levels). However, socioeconomic status (SES) and behavioral factors appeared to operate independently of one another. Discussion: The findings suggest a need to focus on the direct effects of race as well as its indirect effects, through socioeconomic factors and patterned health behaviors, for an understanding of racial disparities in cognitive functioning.
Indole Signaling at the Host-Microbiota-Pathogen Interface

Pathogens sense and respond to several small molecules within the GI tract to modulate expression of their virulence repertoire. Indole is a signaling molecule produced by the gut microbiota. Here we show that indole concentrations are higher in the lumen, where the microbiota is present, than in the intestinal tissue. The enteric pathogens EHEC and C. rodentium sense indole to downregulate expression of their virulence genes, as a read-out of the luminal compartment. We also identified the bacterial membrane-bound HK CpxA as an indole sensor. This regulation ensures that EHEC and C. rodentium express their virulence genes only at the epithelial lining, which is the niche they colonize. ABSTRACT Microbial establishment within the gastrointestinal (GI) tract requires surveillance of the gut biogeography. The gut microbiota coordinates behaviors by sensing host- or microbiota-derived signals. Here we show for the first time that microbiota-derived indole is highly prevalent in the lumen compared to the intestinal tissue. This difference in indole concentration plays a key role in modulating virulence gene expression of the enteric pathogens enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium. Indole decreases expression of genes within the locus of enterocyte effacement (LEE) pathogenicity island, which is essential for these pathogens to form attaching and effacing (AE) lesions on enterocytes. We synthetically altered the concentration of indole in the GI tracts of mice by employing mice treated with antibiotics to deplete the microbiota and reconstituted with indole-producing commensal Bacteroides thetaiotaomicron (B. theta) or a B. theta ΔtnaA mutant (does not produce indole) or by engineering an indole-producing C. rodentium strain. This allowed us to assess the role of self-produced versus microbiota-produced indole, and the results show that decreased indole concentrations promote bacterial pathogenesis, while increased levels of indole decrease bacterial virulence gene expression. Moreover, we identified the bacterial membrane-bound histidine sensor kinase (HK) CpxA as an indole sensor. Enteric pathogens sense a gradient of indole concentrations in the gut to probe different niches and successfully establish an infection. IMPORTANCE Pathogens sense and respond to several small molecules within the GI tract to modulate expression of their virulence repertoire. Indole is a signaling molecule produced by the gut microbiota. Here we show that indole concentrations are higher in the lumen, where the microbiota is present, than in the intestinal tissue. The enteric pathogens EHEC and C. rodentium sense indole to downregulate expression of their virulence genes, as a read-out of the luminal compartment. We also identified the bacterial membrane-bound HK CpxA as an indole sensor. This regulation ensures that EHEC and C. rodentium express their virulence genes only at the epithelial lining, which is the niche they colonize.
Association between continuity of provider-adjusted regularity of general practitioner contact and unplanned diabetes-related hospitalisation: a data linkage study in New South Wales, Australia, using the 45 and Up Study cohort

Objective To assess the association between continuity of provider-adjusted regularity of general practitioner (GP) contact and unplanned diabetes-related hospitalisation or emergency department (ED) presentation. Design Cross-sectional study. Setting Individual-level linked self-report and administrative health service data from New South Wales, Australia. Participants 27 409 survey respondents aged ≥45 years with a prior history of diabetes and at least three GP contacts between 1 July 2009 and 30 June 2015. Main outcome measures Unplanned diabetes-related hospitalisations or ED presentations, associated costs and bed days. Results Twenty-one per cent of respondents had an unplanned diabetes-related hospitalisation or ED presentation. Increasing regularity of GP contact was associated with a lower probability of hospitalisation or ED presentation (19.9% for highest quintile, 23.5% for the lowest quintile). Conditional on having an event, there was a small decrease in the number of hospitalisations or ED presentations for the low (−6%) and moderate regularity quintiles (−8%), a reduction in bed days (ranging from −30 to −44%) and a reduction in average cost of between −23% and −41%, all relative to the lowest quintile. When probability of diabetes-related hospitalisation or ED presentation was included, only the inverse association with cost remained significant (mean of $A3798 to $A6350 less per individual, compared with the lowest regularity quintile). Importantly, continuity of provider did not significantly modify the effect of GP regularity for any outcome. Conclusions Higher regularity of GP contact—that is more evenly dispersed, not necessarily more frequent care—has the potential to reduce secondary healthcare costs and, conditional on having an event, the time spent in hospital, irrespective of continuity of provider. These findings argue for the advocacy of regular care, as distinct from solely continuity of provider, when designing policy and financial incentives for GP-led primary care.
The Effects of Leucine-Enriched Branched-Chain Amino Acid Supplementation on Recovery After High-Intensity Resistance Exercise.

Context: Of the 3 branched-chain amino acids (BCAA), leucine has arguably received the most attribution for the role of BCAA supplementation in alleviating symptoms of exercise-induced muscle damage and facilitation of acute performance recovery. Purpose: To examine whether enrichment of a standard BCAA supplement with additional leucine or a standalone leucine (LEU) supplement differentially affects exercise-induced muscle damage and performance recovery compared with a standard BCAA supplement. Methods: A total of 22 recreationally active male and female subjects were recruited and assigned to consume a BCAA, leucine-enriched BCAA (LBCAA), or LEU supplement for 11 d. On the eighth day, subjects performed eccentric-based resistance exercise (ECRE). Lower-body mean average and peak power, plasma creatine kinase, soreness, and pain threshold were measured before and 24, 48, and 72 h after ECRE. Results: LEU showed decreased mean average power (P = .02) and mean peak power (P = .01) from baseline to 48 h post-ECRE, whereas LBCAA and BCAA only trended toward a reduction at 24 hours post-ECRE. At 48 h post-ECRE, BCAA showed greater recovery of mean peak power than LEU (P = .04). At 24 h post-ECRE, LEU demonstrated a greater increase in plasma creatine kinase from baseline than BCAA (P = .04). Area under the curve for creatine kinase was greater in LEU than BCAA (P = .02), whereas BCAA and LBCAA did not differ. Only LEU demonstrated increased soreness during rest and under muscular tension at 24 and 48 h post-ECRE (P < .05). Conclusions: LBCAA failed to afford any advantages over a standard BCAA supplement for postexercise muscle recovery, whereas a LEU supplement was comparatively ineffective.
Optimal Adaptive Quantization Based on Temporal Distortion Propagation Model for HEVC

Optimal adaptive quantization is one of the key points to optimize the coding efficiency of video encoders. The latest block-based video compression standards, such as high-efficiency video coding (HEVC), extensively use predictive coding techniques that create dependencies between blocks and increase the complexity of optimal block quantizers search. Specifically, the motion compensation is responsible for a dependency network connecting all blocks of the same GOP together. In this paper, this dependency network is estimated by a temporal distortion propagation model and an accurate estimation of Inter and Skip modes probabilities. Optimal quantizers are then designed per block in order to achieve global optimization in terms of rate-distortion efficiency. By implementing the algorithm into the HEVC reference model (HM), we report −16.51% PSNR-based and −26.26% SSIM-based average bitrate savings compared to no adaptive quantization. The proposed algorithm outperforms several related methods from the state-of-the-art. Moreover, along with the demonstration of an optimal quantizer solution, we propose an in-depth analysis of the algorithm behavior. This analysis includes, among others, the relative distribution of rates between frames and the control of quantizers dynamic range.
Coreceptor Competition for Association with CD4 May Change the Susceptibility of Human Cells to Infection with T-Tropic and Macrophagetropic Isolates of Human Immunodeficiency Virus Type 1

ABSTRACT The chemokine receptors CCR5 and CXCR4 were found to function in vivo as the principal coreceptors for M-tropic and T-tropic human immunodeficiency virus (HIV) strains, respectively. Since many primary cells express multiple chemokine receptors, it was important to determine if the efficiency of virus-cell fusion is influenced not only by the presence of the appropriate coreceptor (CXCR4 or CCR5) but also by the levels of other coreceptors expressed by the same target cells. We found that in cells with low to medium surface CD4 density, coexpression of CCR5 and CXCR4 resulted in a significant reduction in the fusion with CXCR4 domain (X4) envelope-expressing cells and in their susceptibility to infection with X4 viruses. The inhibition could be reversed either by increasing the density of surface CD4 or by antibodies against the N terminus and second extracellular domains of CCR5. In addition, treatment of macrophages with a combination of anti-CCR5 antibodies or β-chemokines increased their fusion with X4 envelope-expressing cells. Conversely, overexpression of CXCR4 compared with CCR5 inhibited CCR5-dependent HIV-dependent fusion in 3T3.CD4. 401 cells. Thus, coreceptor competition for association with CD4 may occur in vivo and is likely to have important implications for the course of HIV type 1 infection, as well as for the outcome of coreceptor-targeted therapies.
Medicaid Acceptance by Psychiatrists Before and After Medicaid Expansion.

Medicaid Acceptance by Psychiatrists Before and After Medicaid Expansion Medicaid is the principal payer of behavioral health services in the United States and has been expected to play an increasing role in financing behavioral health services after states’ implementation of Medicaid expansions.1,2 Little is known about recent trends in psychiatrists’ acceptance of Medicaid, including before and after 2014, when most Medicaid expansions under the Affordable Care Act went into effect. Without adequate participation in Medicaid among psychiatrists, Medicaid enrollees with behavioral health needs may be unable to find a local psychiatrist who accepts new patients with Medicaid or have to wait a long time for an intake appointment.3,4
GenoType NTM-DR Performance Evaluation for Identification of Mycobacterium avium Complex and Mycobacterium abscessus and Determination of Clarithromycin and Amikacin Resistance

We evaluated the GenoType NTM-DR (NTM-DR) line probe assay for identifying Mycobacterium avium complex (MAC) species and Mycobacterium abscessus subspecies and for determining clarithromycin and amikacin resistance. Thirty-eight reference strains and 145 clinical isolates (58 MAC and 87 M. abscessus isolates), including 54 clarithromycin- and/or amikacin-resistant strains, were involved. ABSTRACT We evaluated the GenoType NTM-DR (NTM-DR) line probe assay for identifying Mycobacterium avium complex (MAC) species and Mycobacterium abscessus subspecies and for determining clarithromycin and amikacin resistance. Thirty-eight reference strains and 145 clinical isolates (58 MAC and 87 M. abscessus isolates), including 54 clarithromycin- and/or amikacin-resistant strains, were involved. The performance of the NTM-DR assay in rapid identification was evaluated by comparison with results of multigene sequence-based typing, whereas performance in rapid detection of clarithromycin and amikacin resistance was evaluated by comparison with sequencing of the erm(41), rrl, and rrs genes and drug susceptibility testing (DST). The accuracies of MAC and M. abscessus (sub)species identification were 92.1% (35/38) and 100% (145/145) for the 38 reference strains and 145 clinical isolates, respectively. Three MAC strains other than M. intracellulare were found to cross-react with the M. intracellulare probe in the assay. Regarding clarithromycin resistance, NTM-DR detected rrl mutations in 52 isolates and yielded 99.3% (144/145) and 98.6% (143/145) concordant results with sequencing and DST, respectively. NTM-DR sensitivity and specificity in the detection of clarithromycin resistance were 96.3% (52/54) and 100% (91/91), respectively. The NTM-DR yielded accurate erm(41) genotype results for all 87 M. abscessus isolates. Regarding amikacin resistance, NTM-DR detected rrs mutations in five isolates and yielded 99.3% (144/145) and 97.9% (142/145) concordant results with sequencing and DST, respectively. Our results indicate that the NTM-DR assay is a straightforward and accurate approach for discriminating MAC and M. abscessus (sub)species and for detecting clarithromycin and amikacin resistance mutations and that it is a useful tool in the clinical setting.