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The CD1 and MR1 protein families present lipid antigens and small molecules to T cells, complementing well-studied major histocompatibility complex–peptide mechanisms. The CD1a subtype is highly and continuously expressed within the skin, most notably on Langerhans cells, and has been demonstrated to present self and foreign lipids to T cells, highlighting its cutaneous sentinel role. Alteration of CD1a-dependent T-cell responses has recently been discovered to contribute to the pathogenesis of several inflammatory skin diseases. In this review, we overview the structure and role of CD1a and outline the current evidence implicating CD1a in the development of psoriasis, atopic dermatitis and allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

The exploratory nature of phase II trials makes it quite common to include heterogeneous patient subgroups with different prognoses in the same trial. Incorporating such patient heterogeneity or stratification into statistical calculation for sample size can improve efficiency and reduce sample sizes in single-arm phase II trials with binary outcomes. However, such consideration is lacking in randomized phase II trials. In this paper, we propose methods that can utilize some natural order constraints that may exist in stratified population to gain statistical efficiency for randomized phase II designs. For thoroughness and simplicity, we focus on the randomized phase II selection designs in this paper, although our method can be easily generalized to the randomized phase II screening designs. We consider both binary and time-to-event outcomes in our development. Compared with methods that do not use order constraints, our method is shown to improve the probabilities of correct selection or reduce sample size in our simulation and real examples. [ABSTRACT FROM AUTHOR]

The Himalayan marmot Marmota himalayana is widely distributed across the Qinghai–Tibetan Plateau and lives in social groups, yet the mating system of this highly social marmot species is unknown. In this study, the genetic mating system of Himalayan marmots was investigated using microsatellite markers to determine which mating strategies individuals employ. Results revealed that both monogamous and polygamous mating relationships occur in our study population, indicating that the genetic mating system of this marmot species is promiscuity. This study presents the first genetic evidence on the mating system for Himalayan marmots, yet indicates that further studies employing both a genetic and behavioral framework are needed to better understand the social structure and reproductive biology of this marmot species. [ABSTRACT FROM AUTHOR]

In Crypto'19, Gohr proposed the first deep learning-based key recovery attack on 11-round Speck32/64, which opens the direction of neural-aided cryptanalysis. Until now, neural-aided cryptanalysis still faces two problems: (i) the attack complexity estimations rely purely on practical experiments; (ii) it does not work when there are not enough neutral bits. To the best of our knowledge, we are the first to solve these two problems. In this paper, we propose a Neural-Aided Statistical Attack (NASA) that has the following advantages: (i) NASA supports estimating the theoretical complexity. (ii) NASA does not rely on any special properties including neutral bits. Moreover, we propose three methods for reducing the complexity of NASA. One of the methods, which is based on a newly proposed concept named Informative Bit that reveals an important phenomenon, makes NASA applicable to large-size ciphers. We have performed a series of experiments on round reduced Speck32/64, DES, and Speck96/96. These experiments do not only verify the correctness of NASA, but also further highlight the advantage and potential of NASA. Our work arguably raises a new direction for neural-aided cryptanalysis. [ABSTRACT FROM AUTHOR]

The propagation of active galactic nucleus jets depends both on the environment into which they propagate and on their internal structure. To test the impact that different magnetic topologies have on the observable properties of radio galaxies on kpc scales, we conducted a series of magnetohydrodynamic simulations of jets injected with different magnetic field configurations propagating into a gaseous atmosphere modelled on the Perseus cluster. The simulations show that the structure of the field affects the collimation and propagation of the jets on cluster scales and thus the morphology of the radio lobes inflated by the jets, due to both magnetic collimation and the development of dynamical instabilities in jets with different magnetic topologies. In all cases, the simulations show a distinct reversal of the synchrotron spectral age gradient in the radio lobes about a dynamical time after the jets turn off due to large-scale circulation inside the radio lobe, driven primarily by buoyancy, which could provide a way to constrain the age of radio sources in cluster environments without the need for detailed spectral modelling and thus constrain the radio-mode feedback efficiency. We suggest a robust diagnostic to search for such age gradients in multifrequency radio data. [ABSTRACT FROM AUTHOR]

Accretion discs around supermassive black holes not only power active galactic nuclei (AGNs), but also host single and binary embedded stellar-mass black holes (EBHs) that grow rapidly from gas accretion. The merger of these EBHs provides a promising mechanism for the excitation of some gravitational wave events observed by LIGO–Virgo, especially those with source masses considerably larger than isolated stellar-mass black hole binaries. In addition to their mass and mass-ratio distribution, their hitherto enigmatic small spin parameters (χeff) carry important clues and stringent constraints on their formation channels and evolutionary pathways. Here, we show that, between each coalescence, the typical rapid spin of the merged EBHs is suppressed by their subsequent accretion of gas from a turbulent environment, due to its ability to randomize the flow's spin orientation with respect to that of the EBHs on an eddy-turnover time-scale. This theory provides supporting evidence for the prolificacy of EBH mergers and suggests that their mass growth may be dominated by gas accretion rather than their coalescence in AGN discs. [ABSTRACT FROM AUTHOR]

Neural-aided cryptanalysis is a challenging topic, in which the neural distinguisher (⁠|$\mathcal{ND}$|⁠) is a core module. In this paper, we propose a new |$\mathcal{ND}$| considering multiple ciphertext pairs simultaneously. Besides, multiple ciphertext pairs are constructed from different keys. The motivation is that the distinguishing accuracy can be improved by exploiting features derived from multiple ciphertext pairs. To verify this motivation, we have applied this new |$\mathcal{ND}$| to five different ciphers. Experiments show that taking multiple ciphertext pairs as input indeed brings accuracy improvement. Then, we prove that our new |$\mathcal{ND}$| applies to two different neural-aided key recovery attacks. Moreover, the accuracy improvement is helpful for reducing the data complexity of the neural-aided statistic attack. The code is available at https://github.com/AI-Lab-Y/ND_mc. [ABSTRACT FROM AUTHOR]

Background Empyema thoracis is a serious infectious disease and is associated with high morbidity and mortality. The perioperative outcomes between culture-positive and culture-negative empyema after thoracoscopic decortication remained controversial, especially since there were no studies that reported the survival outcomes between culture-positive and culture-negative empyema. Methods This single-institute study involved a retrospective analysis. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. Patients were grouped into a culture-positive group and a culture-negative group according to culture results obtained no later than 2 weeks after surgery. Results A total of 1087 patients with empyema received surgery, and 824 were enrolled after exclusion. Among these, 366 patients showed positive culture results and 458 patients showed negative results. Longer intensive care unit stays (11.69 vs 5.64 days, P <.001), longer ventilator usage (24.70 vs 14.01 days, P =.002), and longer postoperative hospital stays (40.83 vs 28.37 days, P <.001) were observed in the culture-positive group. However, there was no significant difference in 30-day mortality between the 2 groups (5.2% in culture negative vs 5.0% in culture positive, P =.913). The 2-year survival was not significantly different between the 2 groups (P =.236). Conclusions Patients with culture-positive or culture-negative empyema who underwent thoracoscopic decortication showed similar short-term and long-term survival outcomes. A higher risk of death was associated with advanced age, a higher Charlson Comorbidity Index score, phase III empyema, and a cause other than pneumonia. [ABSTRACT FROM AUTHOR]

Thrips hawaiiensis (Morgan) (Thysanoptera: Thripidae) is a sap-sucking pest that seriously damages several crops and reduces their economic value. Exposure to low concentrations of insecticides may have a sublethal effect on surviving insects. In order to provide a reference for the rational application of emamectin benzoate, its sublethal effects on the development and reproduction of T. hawaiiensis were evaluated. Pupal development time was significantly shorter in T. hawaiiensis treated with sublethal concentrations of emamectin benzoate (LC10 and LC20) than in control. Female adult longevity and female total longevity were significantly longer following LC20 treatment than in the control and LC10 treatment groups. Nevertheless, male adult longevity and male total longevity were significantly shorter in the LC10 treatment group than in the control and LC20 treatment groups. The sublethal concentration of emamectin benzoate (LC20) significantly shortened the preadult stages and the mean generation. Meanwhile, it significantly increased the finite rate of increase, intrinsic rate of increase, and net reproductive rate. The fecundity was significantly higher after LC20 treatment than after LC10 and control treatments. Compared with the control group, the LC10 and LC20 groups of T. hawaiiensis adults showed a significantly higher expression of the vitellogenin (Vg) and vitellogenin receptor (VgR) genes, which played a key role in increasing their fecundity. These findings suggest that short-term exposure to sublethal concentrations of emamectin benzoate may lead to a resurgence and secondary outbreak of T. hawaiiensis infestation. The results have practical applications for the management of this important and noxious pest. [ABSTRACT FROM AUTHOR]

Continental deep subduction after the closure of large oceanic basins is commonly ascribed to the gravitational pull of the subducting oceanic slab. However, it is not clear how continental lithosphere adjacent to small oceanic basins was subducted to mantle depths. The Sesia Zone in the Western Alps provides an excellent target for exploration of subduction dynamics in such a tectonic setting. Here we report the first finding of coesite in a jadeite-bearing orthogneiss from the Sesia Zone, providing the first evidence for deep subduction of the continental crust to mantle depths for ultrahigh-pressure (UHP) metamorphism in this zone. Three coesite inclusions were identified by laser Raman spectroscopy in two garnet grains. Based on zircon U-Pb dating and trace element analysis, the UHP metamorphic age was constrained to be 76.0 ± 1.0 Ma. The phase equilibrium modeling yields peak metamorphic pressures of 2.8–3.3 GPa, demonstrating the continental deep subduction to mantle depths of >80 km. The subducted continental crust was a rifted hyperextended continental margin, which was converted to the passive continental margin during seafloor spreading and then deeply subducted during the oblique convergence between the Adria microplate and Eurasian plate in the Late Cretaceous. Because the slab pull could only play a limited role in closing small oceanic basins for continental collision, the distal push of either continental breakup or seafloor spreading is suggested as the major driving force for the deep subduction of continental crust in the Western Alps. Therefore, deep subduction of the continental crust bordering small oceanic basins would have been induced by the far-field stress of compression, whereas that bordering large oceanic basins was spontaneous due to the oceanic slab pull. This provides a new insight into the geodynamic mechanism of continental deep subduction. The ultrahigh-pressure metamorphism in the Sesia zone of Western Alps is firstly reported, demonstrating the deep subduction of continental crust to mantle depths of >80 km. The continental deep subduction is driven by the distal push of either continental breakup or seafloor spreading, rather than by the proximal pull of the subducting oceanic slab. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common neoplasm in the world among women. The age-specific incidences and onset ages vary widely between Asian and Western countries/regions. Invasive breast cancer cases among women from 1997 to 2011 were abstracted from the International Agency for Research on Cancer and the Taiwan Cancer Registry. Age-period-cohort analysis was performed to examine the trends. The cohort effect was prominent in South Korea, Taiwan, Japan, and Thailand, possibly related to the timing of westernization. The risk of breast cancer initially rose with the birth cohorts in Hong Kong and India (both former British colonies), peaked, and then declined in recent birth cohorts. Unlike other Asian countries/regions, virtually no birth cohort effect was identified in the Philippines (a Spanish colony in 1565 and the first Asian country to adopt Western cultural aspects). Moreover, an at-most negligible birth cohort effect was identified for all ethnic groups (including Asian immigrants) in the United States. This global study identified birth cohort effects in most Asian countries/regions but virtually no impact in Western countries/regions. The timing of westernization was associated with the birth cohort effect. [ABSTRACT FROM AUTHOR]

This article discusses a case of disseminated amoebic infection with orbital compartment syndrome in an 81-year-old female patient. The patient presented with poor appetite, generalized weakness, and swelling and redness of the right eyelid. A physical examination revealed increased intraocular pressure and complete ophthalmoplegia, indicating orbital compartment syndrome. The patient underwent diagnostic laparoscopy and emergent lateral canthotomy, and treatment with intravenous metronidazole resulted in improvement. This case is the first reported instance of orbital compartment syndrome related to free-living amoebae infection. The article emphasizes the importance of early diagnosis and the potential use of a simple swab as a diagnostic tool for periorbital or cutaneous free-living amoebae infection. [Extracted from the article]

Objectives: There is an urgent need for novel drugs that target unique cellular pathways to combat infections caused by Mycobacterium tuberculosis. CRISPR interference (CRISPRi)-mediated transcriptional repression has recently been developed for use in mycobacteria as a genetic tool for identifying and validating essential genes as novel drug targets. Whilst CRISPRi has been applied to extracellular bacteria, no studies to date have determined whether CRISPRi can be used in M. tuberculosis infection models.Methods: Using the human monocytic macrophage-like THP-1 cell line as a model for M. tuberculosis infection we investigated if CRISPRi can be activated within intracellular M. tuberculosis.Results: The transcriptional repression of two candidate M. tuberculosis genes, i.e. mmpL3 and qcrB, leads to a reduction in viable M. tuberculosis within infected THP-1 cells. The reduction in viable colonies is dependent on both the level of CRISPRi-mediated repression and the duration of repression.Conclusions: These results highlight the utility of CRISPRi in exploring mycobacterial gene function and essentiality under a variety of conditions pertinent to host infection. [ABSTRACT FROM AUTHOR]

The authors comment on the study "Association Between Clostridium innocuum and Antibiotic-Associated Diarrhea in Adults and Children: A Cross-Sectional Study and Comparative Genomics Analysis," by K. E. Cherny, E. B. Muscat and A. Balaji which appeared in the 2022 issue. Topics covered include the issue with the colonization rate in gastrointestinal tract of healthy populations, the carriage rate of Clostridium innocuum in children and adults and the pathogenicity of Clostridium innocuum.

Motivation Transcriptomics is a common approach to identify changes in gene expression induced by a disease state. Standard transcriptomic analyses consider differentially expressed genes (DEGs) as indicative of disease states so only a few genes would be treated as signals when the effect size is small, such as in brain tissue. For tissue with small effect sizes, if the DEGs do not belong to a pathway known to be involved in the disease, there would be little left in the transcriptome for researchers to follow up with. Results We developed RNA Solutions: Synthesizing Information to Support Transcriptomics (RNASSIST), a new approach to identify hidden signals in transcriptomic data by linking differential expression and co-expression networks using machine learning. We applied our approach to RNA-seq data of post-mortem brains that compared the Alcohol Use Disorder (AUD) group with the control group. Many of the candidate genes are not differentially expressed so would likely be ignored by standard transcriptomic analysis pipelines. Through multiple validation strategies, we concluded that these RNASSIST-identified genes likely play a significant role in AUD. Availability and implementation The RNASSIST algorithm is available at https://github.com/netrias/rnassist and both the software and the data used in RNASSIST are available at https://figshare.com/articles/software/RNAssist%5fSoftware%5fand%5fData/16617250. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Bacterial membrane vesicles (MVs) have been reported to kill other bacteria. In the case of Pseudomonas aeruginosa the bactericidal activity has been attributed to an unidentified 26 kDa peptidoglycan (PG) hydrolase that is associated with MVs and gives rise to a lytic band on zymograms using murein sacculi as substrate. In this study, we employed a proteomics approach to show that this PG hydrolase is the AmphD3 amidase. The analysis of an amphD3 mutant as well as of an AmphD3 overexpression derivative revealed that this enzyme is not required for the bactericidal activity of P. aeruginosa MVs but is involved in cell wall recycling and thus protects the cell against PG damage. Another 23 kDa PG hydrolase, which we observed on zymograms of SOS-induced MVs, was identified as the endolysin Lys, which triggers explosive cell lysis but is shown to be dispensable for MV-mediated killing. We conclude that the lytic activities observed on zymograms do not correlate with the bactericidal potential of MVs. We demonstrate that P. aeruginosa MVs are enriched for several autolysins, suggesting that the predatory activity of MVs depends on the combined action of different murein hydrolases. Peptidoglycan hydrolytic activities on zymograms do not correlate with the bacteriocidal potential of membrane vesicles. [ABSTRACT FROM AUTHOR]

Summary We introduce the newest version of TargetMine, which includes the addition of new visualization options; integration of previously disaggregated functionality; and the migration of the front-end to the newly available Bluegenes service. Availability and Implementation TargeteMine is accessible online at https://targetmine.mizuguchilab.org/bluegenes. Users do not need to register to use the software. Source code for the different components listed in the article is available from TargetMine's organizational account at http://github.com/targetmine. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Jets launched by the supermassive black holes in the centres of cool-core clusters are the most likely heat source to solve the cooling flow problem. One way for this heating to occur is through generation of a turbulent cascade by jet-inflated bubbles. Measurements of the X-ray intensity power spectra show evidence of this cascade in different regions of the cluster, constraining the role of driving mechanisms. We analyse feedback simulations of the Perseus cluster to constrain the effect of the jet activity on the intensity fluctuations and kinematics of the cluster atmosphere. We find that, within the inner 60 kpc, the power spectra of the predicted surface brightness fluctuations are broadly consistent with those measured by Chandra and that even a single episode of jet activity can generate a long-lasting imprint on the intensity fluctuations in the innermost region of the cluster. Active galactic nucleus (AGN)-driven motions within the same region approach the values reported by Hitomi during and right after the AGN episode. However, the line-of-sight velocity dispersion excited by the jet in simulations underpredicts the Hitomi measurement. This indicates that driving a volume-filling sustained level of turbulence requires several episodes of jet activity, and/or additional processes drive turbulence outside the 60-kpc sphere. This also suggests that sharp edges of the bubbles in the innermost region of the cluster contribute substantially to the intensity of fluctuations, consistent with the Perseus observations in the inner 30-kpc region. We discuss new diagnostics to decompose annular power spectra to constrain past episodes of jet activity. [ABSTRACT FROM AUTHOR]

Motivation In high-dimensional genetic/genomic data, the identification of genes related to clinical survival trait is a challenging and important issue. In particular, right-censored survival outcomes and contaminated biomarker data make the relevant feature screening difficult. Several independence screening methods have been developed, but they fail to account for gene–gene dependency information, and may be sensitive to outlying feature data. Results We improve the inverse probability-of-censoring weighted (IPCW) Kendall's tau statistic by using Google's PageRank Markov matrix to incorporate feature dependency network information. Also, to tackle outlying feature data, the nonparanormal approach transforming the feature data to multivariate normal variates are utilized in the graphical lasso procedure to estimate the network structure in feature data. Simulation studies under various scenarios show that the proposed network-adjusted weighted Kendall's tau approach leads to more accurate feature selection and survival prediction than the methods without accounting for feature dependency network information and outlying feature data. The applications on the clinical survival outcome data of diffuse large B-cell lymphoma and of The Cancer Genome Atlas lung adenocarcinoma patients demonstrate clearly the advantages of the new proposal over the alternative methods. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Objectives Perceiving simultaneity of a visual and an auditory signal is critical for humans to integrate these multisensory inputs effectively and respond properly. We examined age-related changes in audiovisual simultaneity perception, and the relationships between this perception and working memory performances with aging. Methods Audiovisual simultaneity perception of young, middle-aged, and older adults was measured using a simultaneity judgment (SJ) task, in which a flash and a beep were presented at 1 of 11 stimulus-onset asynchronies (SOAs). Participants judged whether these two stimuli were perceived simultaneously. Precision of simultaneity perception, the SOA corresponding to the point of subjective simultaneity (PSS), and response errors at each SOA were estimated using model fitting. The precision and PSS are associated with multisensory perception per se, whereas the response error reflects executive ability when performing the SJ task. Visual working memory of the same middle-aged and older adults was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB) beforehand. Results Compared to young adults' performances, middle-aged and older adults showed a decreased precision, a shift of PSS toward the visual-leading SOAs, and increased response errors at the visual-leading SOAs. Among these changes, only the increased response errors correlated with worse spatial recognition memory in middle-aged and older adults. Discussion Age-related decrements in audiovisual simultaneity perception start from middle age and are manifested in both perceptual and executive parameters. Furthermore, higher-order executive ability is plausibly a common cause for age-related degenerations in the audiovisual simultaneity perception and visual working memory. [ABSTRACT FROM AUTHOR]

Objectives This study provides the first comparison of trends in dementia prevalence in the U.S. population using 3 different dementia ascertainments/data sources: neuropsychological assessment, cognitive tests, and diagnosis codes from Medicare claims. Methods We used data from the nationally representative Health and Retirement Study and Aging, Demographics, and Memory Study, and a 20% random sample of Medicare beneficiaries. We compared dementia prevalence across the 3 sources by race, gender, and age. We estimated trends in dementia prevalence from 2006 to 2013 based on cognitive tests and diagnosis codes utilizing logistic regression. Results Dementia prevalence among older adults aged 70 and older in 2004 was 16.6% (neuropsychological assessment), 15.8% (cognitive tests), and 12.2% (diagnosis codes). The difference between dementia prevalence based on cognitive tests and diagnosis codes diminished in 2012 (12.4% and 12.9%, respectively), driven by decreasing rates of cognitive test-based and increasing diagnosis codes-based dementia prevalence. This difference in dementia prevalence between the 2 sources by sex and for age groups 75–79 and 90 and older vanished over time. However, there remained substantial differences across measures in dementia prevalence among blacks and Hispanics (10.9 and 9.8 percentage points, respectively) in 2012. Discussion Our results imply that ascertainment of dementia through diagnosis may be improving over time, but gaps across measures among racial/ethnic minorities highlight the need for improved measurement of dementia prevalence in these populations. [ABSTRACT FROM AUTHOR]

Traditional machine learning methods used to detect the side effects of drugs pose significant challenges as feature engineering processes are labor-intensive, expert-dependent, time-consuming and cost-ineffective. Moreover, these methods only focus on detecting the association between drugs and their side effects or classifying drug–drug interaction. Motivated by technological advancements and the availability of big data, we provide a review on the detection and classification of side effects using deep learning approaches. It is shown that the effective integration of heterogeneous, multidimensional drug data sources, together with the innovative deployment of deep learning approaches, helps reduce or prevent the occurrence of adverse drug reactions (ADRs). Deep learning approaches can also be exploited to find replacements for drugs which have side effects or help to diversify the utilization of drugs through drug repurposing. [ABSTRACT FROM AUTHOR]

Background Virtual reality (VR) is a frequently used intervention for the rehabilitation of individuals with neurological disorders. Purpose The aims of this review were to identify the short-term effect of VR on balance and to compare it with the effect of active interventions in individuals with Parkinson disease (PD). Data Sources Searches for relevant articles available in English were conducted using the MEDLINE (via PubMed), EMBASE, CENTRAL, CINAHL, PsycINFO, and Physiotherapy Evidence Database databases from inception until March 2019. Study Selection All randomized controlled trials comparing the effect of training with VR and the effect of training without VR on balance in individuals with PD were included. Data Extraction Two authors independently extracted data, assessed the methodological quality, and evaluated the evidence quality of the studies. Data Synthesis Fourteen randomized controlled trials including 574 individuals were eligible for qualitative analyses, and 12 of the studies involving 481 individuals were identified as being eligible for meta-analyses. Compared with active interventions, the use of VR improved the Berg Balance Scale score (mean difference = 1.23; 95% CI = 0.15 to 2.31; I2 = 56%). The Dynamic Gait Index and Functional Gait Assessment results were also significant after the sensitivity analyses (mean difference = 0.69; 95% CI = 0.12 to 1.26; I2 = 0%). Both provided moderate statistical evidence. However, the Timed "Up & Go" Test and the Activities-Specific Balance Confidence Scale did not differ significantly. Limitations Publication bias and diversity in the interventions were the main limitations. Conclusions Existing moderate evidence of the effectiveness of VR with the Berg Balance Scale, Dynamic Gait Index, and Functional Gait Assessment for individuals with PD was promising. Although the differences did not reach the clinically important change threshold, VR was comparable to active interventions and could be considered an adjuvant therapy for balance rehabilitation in individuals with PD. [ABSTRACT FROM AUTHOR]

Motivation In gene expression and genome-wide association studies, the identification of interaction effects is an important and challenging issue owing to its ultrahigh-dimensional nature. In particular, contaminated data and right-censored survival outcome make the associated feature screening even challenging. Results In this article, we propose an inverse probability-of-censoring weighted Kendall's tau statistic to measure association of a survival trait with biomarkers, as well as a Kendall's partial correlation statistic to measure the relationship of a survival trait with an interaction variable conditional on the main effects. The Kendall's partial correlation is then used to conduct interaction screening. Simulation studies under various scenarios are performed to compare the performance of our proposal with some commonly available methods. In the real data application, we utilize our proposed method to identify epistasis associated with the clinical survival outcomes of non-small-cell lung cancer, diffuse large B-cell lymphoma and lung adenocarcinoma patients. Both simulation and real data studies demonstrate that our method performs well and outperforms existing methods in identifying main and interaction biomarkers. Availability and implementation R-package 'IPCWK' is available to implement this method, together with a reference manual describing how to perform the 'IPCWK' package. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Aims The myocardial ischaemia/reperfusion (I/R) injury is almost inevitable since reperfusion is the only established treatment for acute myocardial infarction (AMI). To date there is no effective strategy available for reducing the I/R injury. Our aim was to elucidate the mechanisms underlying myocardial I/R injury and to develop a new strategy for attenuating the damage it causes. Methods and results Using a mouse model established by ligation of left anterior descending artery, we found an increase in activity of protein tyrosine phosphatases (PTPs) in myocardium during I/R. Treating the I/R-mice with a pan-PTP inhibitor phenyl vinyl sulfone attenuated I/R damage, suggesting PTP activation to be harmful in I/R. Through analysing RNAseq data, we showed PTPs being abundantly expressed in mouse myocardium. By exposing primary cardiomyocytes ablated with specific endogenous PTPs by RNAi to hypoxia/reoxygenation (H/R), we found a role that PTP-PEST (PTPN12) plays to promote cell death under H/R stress. Auranofin, a drug being used in clinical practice for treating rheumatoid arthritis, may target PTP-PEST thus suppressing its activity. We elucidated the molecular basis for Auranofin-induced inactivation of PTP-PEST by structural studies, and then examined its effect on myocardial I/R injury. In the mice receiving Auranofin before reperfusion, myocardial PTP activity was suppressed, leading to restored phosphorylation of PTP-PEST substrates, including ErbB-2 that maintains the survival signalling of the heart. In line with the inhibition of PTP-PEST activity, the Auranofin-treated I/R-mice had smaller infarct size and better cardiac function. Conclusions PTP-PEST contributes to part of the damages resulting from myocardial I/R. The drug Auranofin, potentially acting through the PTP-PEST-ErbB-2 signalling axis, reduces myocardial I/R injury. Based on this finding, Auranofin could be used in the development of new treatments that manage I/R injury in patients with AMI. [ABSTRACT FROM AUTHOR]

In recent times, the reduced cost of DNA sequencing has resulted in a plethora of genomic data that is being used to advance biomedical research and improve clinical procedures and healthcare delivery. These advances are revolutionizing areas in genome-wide association studies (GWASs), diagnostic testing, personalized medicine and drug discovery. This, however, comes with security and privacy challenges as the human genome is sensitive in nature and uniquely identifies an individual. In this article, we discuss the genome privacy problem and review relevant privacy attacks, classified into identity tracing, attribute disclosure and completion attacks, which have been used to breach the privacy of an individual. We then classify state-of-the-art genomic privacy-preserving solutions based on their application and computational domains (genomic aggregation, GWASs and statistical analysis, sequence comparison and genetic testing) that have been proposed to mitigate these attacks and compare them in terms of their underlining cryptographic primitives, security goals and complexities—computation and transmission overheads. Finally, we identify and discuss the open issues, research challenges and future directions in the field of genomic privacy. We believe this article will provide researchers with the current trends and insights on the importance and challenges of privacy and security issues in the area of genomics. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing techniques find applications in many fields, such as molecular biology, cancer biology, and disease modeling. In contrast to the knock-out procedure, a key step of CRISPR knock-in experiments is the homology-directed repair process that requires donor constructs as repair templates. Therefore, it is desirable to generate a series of donor templates efficiently and cost-effectively. In this study, we developed a new strategy that combines (i) Gibson assembly reaction, (ii) a linker pair composed of eight in silico screened restriction enzyme sites, and (iii) a hierarchical framework, to remarkably improve the efficiency of producing donor constructs for common genes as well as for the genes containing unbalanced guanine-cytosine content and requiring a selectable marker. Furthermore, the approach provides the ability of inserting additional elements into the donor templates, such as single guide RNA recognition sites that have been reported to enhance the efficiency of homology-directed repair. Conclusively, our modularized process is simple, fast, and cost-effective for making donor constructs and benefits the application of CRISPR knock-in methods. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapy (cART) has improved the life expectancy of HIV patients, thus increasing the number of people living with HIV (PLWH). However, cardiovascular diseases (CVD) are now one of the most prevalent causes of death among PLWH. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of cART, and the emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) coformulation is commonly used. In prior studies, acute NRTI treatment-induced endothelial dysfunction, increased reactive oxygen species production, and mitophagic activity, suggesting that mitochondrial dysfunction may be critical to NRTI-induced endothelial dysfunction. Mitochondrial dysfunction plays a causal role in endothelial senescence, whereas premature endothelial senescence can promote the development of CVD. We hypothesize that for chronic NRTI treatment, a disruption in mitochondrial homeostasis leads to premature endothelial senescence and predisposes PLWH to CVD. We used human aortic endothelial cells (HAEC) and HIV-1 transgenic (Tg26) mice to test the interrelationship between mitochondrial and vascular dysfunction after chronic NRTI treatment in vitro and in vivo. Mitochondrial DNA copy number was decreased in late-passage HAEC treated with NRTIs, and senescence-associated β-galactosidase accumulation was elevated. In late-passage HAEC, NRTIs decreased the activity of Parkin-mediated mitophagy. In Tg26 mice treated with FTC, plasma nitrite levels were decreased. Endothelium-dependent vasodilation in NRTI-treated Tg26 mice was also reduced. Our work suggests that long-term use of NRTI may disrupt mitochondrial homeostasis, induce premature endothelial senescence, and impair vascular function. [ABSTRACT FROM AUTHOR]

Electronic cigarette(s) (EC) becoming a preferred replacement for nicotine delivery among many smokers in recent years. However, the effect of EC on human health is inconclusive due to a lack of empirical research investigating EC-induced health hazard or benefit. In this study, we examine the effect of vapor produced by EC on exercise performance and health-related profiles in a mouse model. Female ICR mice were divided into five groups (n = 6 per group) and exposed for 14 days. Our results indicate that EC exposure leads to dose-dependent decrease in the grip strength and swimming time of the mice. The EC-treated groups also showed a dose-dependent decrease in liver and muscle glycogen storage. In addition, EC treatment had no negative effect on levels of biochemical indices. We also did not detect any adverse effect or gross abnormalities on the morphology of the major organs. EC exposure leads to dose-dependent decrease in exercise performance (endurance and explosiveness) and glycogen storage capacity of the mice. [ABSTRACT FROM AUTHOR]

Feedback from active galactic nucleus (AGN) jets has been proposed to counteract the catastrophic cooling in many galaxy clusters. However, it is still unclear which physical processes are acting to couple the energy from the bi-directional jets to the intra-cluster medium (ICM). We study the long-term evolution of rising bubbles that were inflated by AGN jets using magnetohydrodynamic simulations. In the wake of the rising bubbles, a significant amount of low-entropy gas is brought into contact with the hot cluster gas. We assess the energy budget of the uplifted gas and find it comparable to the total energy injected by the jets. Although our simulation does not include explicit thermal conduction, we find that, for reasonable assumptions about the conduction coefficient, the rate is fast enough that much of the uplifted gas may be thermalized before it sinks back to the core. Thus, we propose that the AGN can act like a geothermal heat pump to move low-entropy gas from the cluster core to the heat reservoir and will be able to heat the inner cluster more efficiently than would be possible by direct energy transfer from jets alone. We show that the maximum efficiency of this mechanism, i.e. the ratio between the conductive thermal energy and the work needed to lift the gas, ξmax, can exceed 100 per cent. While ξ < ξmax in realistic scenarios, AGN-induced thermal conduction has the potential to significantly increase the efficiency with which AGN can heat cool-core clusters and transform the bursty AGN activities into a smoother and enduring heating process. [ABSTRACT FROM AUTHOR]

Purpose We previously reported an interaction with warfarin anticoagulation when initiating treatment with direct-acting antiviral agents for hepatitis C infection. A decreased warfarin sensitivity led to subtherapeutic anticoagulation. To study this interaction further, we expanded our research to include patients treated with the combination of elbasvir and grazoprevir concurrent with warfarin anticoagulation and investigated changes in warfarin sensitivity during and after treatment. Methods Using electronic health records of the Veterans Health Administration, patients starting treatment with elbasvir–grazoprevir for hepatitis C infection concurrent with warfarin anticoagulation were identified. Inclusion required stable warfarin anticoagulation prior to 12 weeks of treatment with elbasvir–grazoprevir. A warfarin sensitivity index (WSI) was calculated at the start of treatment, after 12 weeks after treatment, and at the end of treatment. The primary endpoint was the difference in WSI from pre- to end-treatment. The secondary endpoint was the WSI difference from before treatment to Changes in International Normalized Ratio, warfarin doses, and time in therapeutic range were measured. Results In the final sample of 43 patients, the mean WSI decreased during treatment from 0.53 to 0.40, or 25.2%. After treatment, the mean WSI rose to 0.51. Although the mean weekly warfarin dose increased from 40.3 to 44.6 mg during treatment, the mean International Normalized Ratio decreased from 2.40 to 1.96, recovering to 2.59 after treatment. The time spent in therapeutic range decreased from 74.1% before treatment to 39.8% during treatment and back to 64.9% 12 weeks posttreatment. Conclusion When elbasvir–grazoprevir was added to stable warfarin anticoagulation, warfarin sensitivity decreased significantly during treatment and returned to baseline after treatment. [ABSTRACT FROM AUTHOR]

Extensins (EXTs), a class of hydroxyproline-rich glycoprotein with multiple Ser-Pro3–5 motifs, are known to play roles in cell wall reinforcement and environmental responses. EXTs with repetitive Tyr-X-Tyr (YXY) motifs for crosslinking are referred as crosslinking EXTs. Our comprehensive study spanned 194 algal and plant species, categorizing EXTs into seven subfamilies: classical extensins (EXT I and II), arabinogalactan-protein extensins (AGP-EXTs), proline-rich extensin-like receptor kinases (PERKs), leucine-rich repeat extensins (LRX I and II), formin homology (FH) domain-containing extensins (FH-EXTs), proline-rich, arabinogalactan proteins, conserved cysteines (PAC) domain-containing extensins (PAC I and II), and eight-cysteine motif (8CM)-containing extensins (8CM-EXTs). In the examined dataset, EXTs were detected ubiquitously in plants but infrequently in algae, except for one Coccomyxa and four Chlamydomonadales species. No crosslinking EXTs were found in Poales or certain Zingiberales species. Notably, the previously uncharacterized EXT II, PAC II, and liverwort-specific 8CM-EXTs were found to be crosslinking EXTs. EXT II, featuring repetitive YY motifs instead of the conventional YXY motif, was exclusively identified in Solanaceae. Furthermore, tandem genes encoding distinctive 8CM-EXTs specifically expressed in the germinating spores of Marchantia polymorpha. This updated classification of EXT types allows us to propose a plausible evolutionary history of EXT genes during the course of plant evolution. [ABSTRACT FROM AUTHOR]

Background Evidence indicates the health care system disproportionately misses dementia in African American compared to White individuals. In preliminary data, we examined factors related to dementia identification by the health care system among African Americans. Methods We leveraged linked Medicare fee-for-service claims and detailed annual cohort evaluations in African Americans from 4 cohorts at Rush Alzheimer's Disease Center. Results Among 88 African Americans with cognitive impairment (mean = 10 years follow-up), Medicare claims identified dementia <2 years from cohort diagnosis in 55%; 27% were identified 2–9.9 years after cohort diagnosis, and in 18% there was either no claims diagnosis during the study period, or claims identified dementia 10+ years after cohort diagnosis. Claims identification of dementia was related to older age at cohort diagnosis (eg, <2 years between cohort and claims: mean = 82 years; 10+ years/no diagnosis: mean = 77 years, p  = .04), lower Mini-Mental State Examination (MMSE) score (<2 years: mean = 24; 10+ years/no diagnosis: mean = 26, p  = .04), more depressive symptoms (<2 years: mean = 2.1 symptoms; 10+ years/no diagnosis: mean = 1.2, p  = .04), and more comorbidity (<2 years: mean = 5.6 comorbidities; 10+ years/no diagnosis, mean = 3.0, p  = .02). Conclusions Among African Americans, preliminary data indicate the health care system most rapidly identifies dementia in older individuals, with worse cognitive and physical health. The health care system may miss opportunities for early support of African Americans with dementia, and caregivers. [ABSTRACT FROM AUTHOR]

Rice is a major dietary source of inorganic arsenic (As), a nonthreshold carcinogen. Reducing As accumulation in rice grain is of critical importance for food safety. In the present study, we investigated the role of a member of the rice C-type ATP-binding cassette (ABC) transporter (OsABCC) family, OsABCC7, in arsenite [As(III)] accumulation in rice. Quantitative real-time RT-PCR showed that OsABCC7 was expressed intensively in the roots and the expression was strongly suppressed by As(III) exposure. Transgenic rice plants expressing OsABCC7 Promoter-GUS (β -glucuronidase) suggest that the gene was predominantly expressed in the xylem parenchyma cells in the stele region of the primary and lateral roots. Transient expression of OsABCC7: GFP fusion protein in Nicotiana benthamiana leaf cells showed that the protein was localized at the plasma membrane. When expressed in Xenopus laevis oocytes, OsABCC7 showed an efflux activity for As(III)-phytochelatin and As(III)-glutathione complexes, but not for As(III). Knockout of OsABCC7 in rice significantly decreased As concentration in the xylem sap and As concentration in the shoots, but had little effect on root As concentration. Taken together, our results indicate that OsABCC7 is involved in the root-to-shoot translocation of As(III). [ABSTRACT FROM AUTHOR]

The integration of context-aware ubiquitous learning (CAUL) into English for Specific Purposes (ESP) learning has become increasingly widespread due to the enhanced interaction between learners and situated contexts. Using an authentic learning site on environmental protection and its related discourse-specific English as target knowledge, this study analyzed the learning needs for developing ESP knowledge and skills through the use of smartphones and QR codes. Different need choices of the four language skills, requirements of CAUL system design, and effective audio–visual materials for social interaction are discussed. Based on previous reviewed arguments and current empirical arguments, the quantitative results reveal significant findings in ESP material design, content knowledge, and effective methods for CAUL. Further, qualitative interview results are classified into technological viewpoints and practical infield viewpoints. Consequently, identified themes and contradictions among three target groups—experts, students, and guides—are explained in terms of different pursuits of context-specific English learning needs. [ABSTRACT FROM AUTHOR]

Summary: We develop a joint analysis approach for recurrent and nonrecurrent event processes subject to case I interval censorship, which are also known in literature as current count and current status data, respectively. We use a shared frailty to link the recurrent and nonrecurrent event processes, while leaving the distribution of the frailty fully unspecified. Conditional on the frailty, the recurrent event is assumed to follow a nonhomogeneous Poisson process, and the mean function of the recurrent event and the survival function of the nonrecurrent event are assumed to follow some general form of semiparametric transformation models. Estimation of the models is based on the pseudo‐likelihood and the conditional score techniques. The resulting estimators for the regression parameters and the unspecified baseline functions are shown to be consistent with rates of square and cubic roots of the sample size, respectively. Asymptotic normality with closed‐form asymptotic variance is derived for the estimator of the regression parameters. We apply the proposed method to a fracture‐osteoporosis survey data to identify risk factors jointly for fracture and osteoporosis in elders, while accounting for association between the two events within a subject. [ABSTRACT FROM AUTHOR]

Summary: We propose a model selection criterion for semiparametric marginal mean regression based on generalized estimating equations. The work is motivated by a longitudinal study on the physical frailty outcome in the elderly, where the cluster size, that is, the number of the observed outcomes in each subject, is “informative” in the sense that it is related to the frailty outcome itself. The new proposal, called Resampling Cluster Information Criterion (RCIC), is based on the resampling idea utilized in the within‐cluster resampling method (Hoffman, Sen, and Weinberg, 2001, Biometrika 88, 1121–1134) and accommodates informative cluster size. The implementation of RCIC, however, is free of performing actual resampling of the data and hence is computationally convenient. Compared with the existing model selection methods for marginal mean regression, the RCIC method incorporates an additional component accounting for variability of the model over within‐cluster subsampling, and leads to remarkable improvements in selecting the correct model, regardless of whether the cluster size is informative or not. Applying the RCIC method to the longitudinal frailty study, we identify being female, old age, low income and life satisfaction, and chronic health conditions as significant risk factors for physical frailty in the elderly. [ABSTRACT FROM AUTHOR]

Polyhydroxyalkanoates (PHAs) are biopolyesters produced by microorganisms that are environmentally friendly. PHAs can be used to replace traditional plastic to reduce environmental pollution in various fields. PHA production costs are high because PHA must be produced from a carbon substrate. The purpose of this study was to find the strain that can used the BDF by-product as the sole carbon source to produce high amounts of medium-chain-length PHA. Three isolates were evaluated for potential PHA production by using biodiesel-derived crude glycerol as the sole carbon source. Among them, Pseudomonas mosselii TO7 yielded high PHA content. The PHA produced from P. mosselii TO7 were medium-chain-length-PHAs. The PHA content of 48% cell dry weight in 48 h with a maximum PHA productivity of 13.16 mg PHAs L−1 h−1. The narrow polydispersity index value of 1.3 reflected the homogeneity of the polymer chain, which was conducive to industrial applications. [ABSTRACT FROM AUTHOR]

Background: Mechanisms by which spontaneous clearance of acute hepatitis C occurs are unclear. A critical role for the innate immune system and IFNL4 polymorphisms has been proposed. This study investigates whether Toll-like receptor (TLR) expression and signaling during acute hepatitis C correlates with clinical outcomes.Methods: Participants identified from the Australian Trial in Acute Hepatitis C and the Networks study were followed longitudinally from the time of diagnosis of acute hepatitis C. Peripheral blood mononuclear cells (PBMCs) and plasma were collected at and 2 time points after diagnosis. At each time point, TLR2, TLR4, and CD86 expression on peripheral blood monocytes, natural killer (NK) cells, and NK T cells was measured, as well as the response of PBMCs to stimulation with TLR ligands. Cytokine and chemokine levels were measured in stimulated PBMCs and plasma.Results: We identified 20 participants with acute hepatitis C (10 with hepatitis C virus [HCV] monoinfection and 10 with HCV and human immunodeficiency virus coinfection). Eleven participants (55%) spontaneously cleared HCV. Acute hepatitis C and spontaneous clearance was associated with lower TLR4 expression on monocytes (P = .009) and NK cells (P = .029). Acute hepatitis C and spontaneous clearance was also associated with a reduced interferon γ response to TLR4 (P = .038) and TLR7/8 stimulation (P = .035), a reduced interleukin 6 response to TLR7/8 stimulation (P = .037), and reduced IFN-γ-inducible protein 10 (IP-10) response to TLR2 stimulation (P = .042). Lower plasma IP-10 levels were associated with spontaneous clearance (P = .001).Conclusions: These findings implicate TLR4 signaling as playing a critical role in the outcome of acute hepatitis C. [ABSTRACT FROM AUTHOR]

Objectives: Hepatitis B surface antigen (HBsAg) reduction during nucleos(t)ide analogue therapy is related to ALT level. ALT reflects hepatocytolysis while α-fetoprotein (AFP) ≥100 ng/mL during hepatitis flare reflects more extensive hepatocytolysis (bridging hepatic necrosis). The impact of AFP levels on early HBsAg kinetics during entecavir therapy was investigated.Methods: HBsAg level was measured at baseline and months 6 and 12 of entecavir therapy in 149 chronic hepatitis B patients with hepatitis flare, defined as ALT ≥5× upper limit of normal (ULN), and 58 patients with ALT <5× ULN.Results: There was a significantly greater HBsAg reduction in an ALT (<5, 5-10, 10-20 and ≥20× ULN, P = 0.001) and AFP (<20, 20-99 and ≥100 ng/mL, P = 0.000) level-dependent manner. In hepatitis flares with a peak AFP level ≥20 ng/mL, the differences in HBsAg reduction across all ALT levels became non-significant. HBsAg reduction was greater in genotype B- than genotype C-infected patients with baseline ALT ≥20× ULN, but the difference became non-significant in those with peak AFP ≥100 ng/mL. Multivariate linear regression analysis showed that AFP level ≥100 ng/mL, baseline HBsAg level and genotype B were independent significant factors for greater HBsAg decline at month 6 of entecavir therapy.Conclusions: During entecavir therapy, early HBsAg reduction increased in an AFP and ALT level-dependent manner, suggesting the impact of hepatocytolysis rather than nucleos(t)ide analogue per se. Notably, a higher AFP level during hepatitis flare, reflecting more extensive hepatic necrosis, was a more powerful factor than ALT and genotype for greater HBsAg decline. [ABSTRACT FROM AUTHOR]

Inspired by the debate about character between situationism and virtue ethics, I argue that John Doris's idea, 'local trait', offers a fresh insight into contemporary character education. Its positive variant, 'local virtue', signals an inescapable relay station of the gradual development of virtue, and serves as a promising point of departure for advanced growth. The idea of converting local virtues to more global ones is accordingly proposed to represent an empirically more realistic way of conceiving how to approach the ethical ideal of global virtues. It helps to direct our gaze to the great intermediate developmental stages of virtue, which mark out a whole spectrum of virtues of varying degrees that fall short of full virtue. This new notion works together with the traditional Aristotelian account to provide a full account of how to effectively undertake the age-old educational business of the inculcation of virtues. [ABSTRACT FROM AUTHOR]

Drug resistance is increasingly among the main issues affecting human health and threatening agriculture and food security. In particular, developing approaches to overcome target mutation-induced drug resistance has long been an essential part of biological research. During the past decade, many bioinformatics tools have been developed to explore this type of drug resistance, and they have become popular for elucidating drug resistance mechanisms in a low cost, fast and effective way. However, these resources are scattered and underutilized, and their strengths and limitations have not been systematically analyzed and compared. Here, we systematically surveyed 59 freely available bioinformatics tools for exploring target mutation-induced drug resistance. We analyzed and summarized these resources based on their functionality, data volume, data source, operating principle, performance, etc. And we concisely discussed the strengths, limitations and application examples of these tools. Specifically, we tested some predictive tools and offered some thoughts from the clinician's perspective. Hopefully, this work will provide a useful toolbox for researchers working in the biomedical, pesticide, bioinformatics and pharmaceutical engineering fields, and a good platform for non-specialists to quickly understand drug resistance prediction. [ABSTRACT FROM AUTHOR]

Bias caused by missing or incomplete information on confounding factors constitutes an important challenge in observational studies. The incorporation of external data on more detailed confounding information into the main study data may help remove confounding bias. This work was motivated by a study of the association between chronic obstructive pulmonary disease and herpes zoster. Analyses were based on administrative databases in which information on important confounders—cigarette smoking and alcohol consumption—was lacking. We consider adjusting for the confounding bias arising from missing confounders by incorporating a validation sample with data on smoking and alcohol consumption obtained from a small-scale National Health Interview Survey study. We propose a 2-stage calibration (TSC) method, which summarizes the confounding information through propensity scores and combines the analysis results from the main and the validation study samples, where the propensity score adjustment from the main sample is crude and that from the validation sample is more precise. Unlike the existing methods, the validity of the TSC approach does not rely on any specific measurement error model. When applying the TSC method to the motivating study above, the odds ratio of herpes zoster associated with chronic obstructive pulmonary disease is 1.91 (95% confidence interval: 1.62, 2.26) after adjustment for cumulative smoking and alcohol consumption. [ABSTRACT FROM PUBLISHER]

The Galactic disc is one of the main components of the Milky Way, which contributes most of the luminosity. Its structure is essential for understanding the formation and evolution of the Milky Way. Using 174 443 K-type dwarf stars observed by both Large Sky Area Multi-Object Fiber Spectroscopic Telescope and Gaia Data Release 3, we study the disc density profile in the local volume within 1200 pc. In the azimuthal dimension, we find strong asymmetric signal of the thin disc. The surface density and the scale height of the southern disc significantly change versus the azimuthal angle at the same Galactocentric distance R. Meanwhile, in the vertical dimension, the scale height of the northern disc has quite different trend than that of the southern one. The scale height of the southern disc shows a decreasing trend with ϕ ∼ −2.5°, and change to an increasing one with ϕ ∼ 5.0°. Meanwhile, the scale height of the northern disc has a consistently smaller increase. Finally, we divide the entire sample into three subsamples based on metallicity and all three subsamples show significant non-axisymmetric and north–south asymmetric signals in the Galactic disc. Furthermore, we find that the scale height of the metal-poor ([Fe/H] < −0.4 dex) subsample in the northern disc is greater than that of the metal-rich ([Fe/H] > −0.1 dex) subsample. However, in the southern disc, the scale height exhibits varying relationships across different metallicity slices. [ABSTRACT FROM AUTHOR]

Objectives To compare the risk of PsA in psoriasis (PsO) patients treated with acitretin vs DMARDs. Methods This retrospective study used Taiwan's National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan–Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of NSAIDs and comorbidities. Results The study included 1948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P  = 0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P  = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65–1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment. Conclusion Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients. [ABSTRACT FROM AUTHOR]

Many insects have evolved the ability to manipulate plant growth to generate extraordinary structures called galls, in which insect larva can develop while being sheltered and feeding on the plant. In particular, cynipid (Hymenoptera: Cynipidae) wasps have evolved to form morphologically complex galls and generate an astonishing array of gall shapes, colors, and sizes. However, the biochemical basis underlying these remarkable cellular and developmental transformations remains poorly understood. A key determinant in plant cellular development is cell wall deposition that dictates the physical form and physiological function of newly developing cells, tissues, and organs. However, it is unclear to what degree cell walls are restructured to initiate and support the formation of new gall tissue. Here, we characterize the molecular alterations underlying gall development using a combination of metabolomic, histological, and biochemical techniques to elucidate how valley oak (Quercus lobata) leaf cells are reprogrammed to form galls. Strikingly, gall development involves an exceptionally coordinated spatial deposition of lignin and xylan to form de novo gall vasculature. Our results highlight how cynipid wasps can radically change the metabolite profile and restructure the cell wall to enable the formation of galls, providing insights into the mechanism of gall induction and the extent to which plants can be entirely reprogrammed to form unique structures and organs. Cynipid wasps radically change the metabolite profile and restructure the cell wall to enable the formation of galls. [ABSTRACT FROM AUTHOR]

Deep learning-based multi-omics data integration methods have the capability to reveal the mechanisms of cancer development, discover cancer biomarkers and identify pathogenic targets. However, current methods ignore the potential correlations between samples in integrating multi-omics data. In addition, providing accurate biological explanations still poses significant challenges due to the complexity of deep learning models. Therefore, there is an urgent need for a deep learning-based multi-omics integration method to explore the potential correlations between samples and provide model interpretability. Herein, we propose a novel interpretable multi-omics data integration method (DeepKEGG) for cancer recurrence prediction and biomarker discovery. In DeepKEGG, a biological hierarchical module is designed for local connections of neuron nodes and model interpretability based on the biological relationship between genes/miRNAs and pathways. In addition, a pathway self-attention module is constructed to explore the correlation between different samples and generate the potential pathway feature representation for enhancing the prediction performance of the model. Lastly, an attribution-based feature importance calculation method is utilized to discover biomarkers related to cancer recurrence and provide a biological interpretation of the model. Experimental results demonstrate that DeepKEGG outperforms other state-of-the-art methods in 5-fold cross validation. Furthermore, case studies also indicate that DeepKEGG serves as an effective tool for biomarker discovery. The code is available at https://github.com/lanbiolab/DeepKEGG. [ABSTRACT FROM AUTHOR]

Background Everyday discrimination—experiences of being treated unfairly based on background characteristics like race—is linked to poor physical and mental health throughout the lifespan. Whether more experiences of discrimination are associated with higher odds of being hospitalized in older African Americans has not been explored. Methods Community-dwelling participants from 3 longitudinal cohort studies (N  = 446, age 65+ years) with discrimination scores and ≥12 months of linked Medicare claims were included. Hospitalizations were identified using Medicare fee-for-service claims, available for an average of 6.2 (SD : 3.7) years of follow-up after baseline. Results In mixed-effects ordinal logistic regression models (outcomes of 0, 1, or 2+ hospitalizations per year) adjusted for age, sex, education, and income, higher discrimination was associated with higher odds of total annual hospitalizations (odds ratio [OR] per point higher = 1.09, 95% confidence intervals [95% CI]: 1.02–1.17). Results were similar when accounting for depressive symptoms. Conclusions Higher exposure to everyday discrimination is associated with higher odds of hospitalization among older African Americans. Mechanisms underlying associations should be explored further to understand how hospitalizations may be reduced in older African Americans. [ABSTRACT FROM AUTHOR]

Background In the era of biologic therapy, phototherapy and methotrexate (MTX) are still commonly used for treatment in patients with moderate-to-severe psoriasis. However, the skin cancer risk following a combination of MTX and narrowband ultraviolet B (NB-UVB) has rarely been explored. Objectives To investigate whether MTX plus NB-UVB increases skin cancer risk in patients with psoriasis. Methods We conducted a retrospective cohort study of data in the Taiwan National Health Insurance Research Database from 1997 to 2013. Cumulative incidences and multivariate analysis were investigated using a competing risk regression model, comparing skin cancer risk between cohorts of people having combination therapy and those using NB-UVB alone, matched for relative confounders. We further conducted a sensitivity analysis for those receiving a higher MTX dose. Standardized incidence ratios (SIRs) were calculated for skin cancer risk. Results We enrolled 3203 participants in each cohort. No significant differences in skin cancers were noted between the two cohorts for the cumulative incidences (log-rank test, P = 0.28) and for the hazard ratio (HRs) [adjusted HR 0.50, 95% confidence interval (CI) 0.15–1.63, P = 0.247] in the competing risk regression model. There were also no significant differences between those receiving higher-dose MTX and UVB alone in the cumulative incidences of skin cancers (P = 0.23) and the HR (adjusted HR = 0.29, 95% CI 0.04–2.21, P = 0.23) in the multivariate analysis. There was no significant difference in the SIR between the two cohorts compared with the general population. Conclusions In the Taiwanese population, MTX does not increase skin cancer risk in patients with moderate-to-severe psoriasis receiving NB-UVB. [ABSTRACT FROM AUTHOR]