Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study

BackgroundObservational studies have suggested the association between atopic dermatitis (AD) and the risks of autoimmune diseases. It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded.ObjectivesOur study seeks to assess the possibility of AD as a cause of autoimmune diseases, and to estimate the magnitude of the causal effect.MethodsTwo-sample mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) summary-level statistics. Specifically, bidirectional MR analyses were conducted to examine the direction of association of AD with autoimmune diseases; multivariable MR analyses (MVMR1) were used to test the independence of causal association of AD with autoimmune diseases after controlling other atopic disorders (asthma and allergic rhinitis), while MVMR2 analyses were conducted to account for potential confounding factors such as smoking, drinking, and obesity. Genetic instruments for AD (Ncases=22 474) were from the latest GWAS meta-analysis. The GWAS summary data for asthma and allergic rhinitis were obtained from UK Biobank. The GWAS summary data for smoking, alcohol consumption, obesity and autoimmune diseases (alopecia areata, vitiligo, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, and type 1 diabetes) were selected from the largest GWASs available. Causal estimates were derived by the inverse-variance weighted method and verified through a series of sensitivity analyses.ResultsGenetically predicted AD linked to higher risks of rheumatoid arthritis (OR, 1.28; P=0.0068) (ORMVMR1, 1.65; P=0.0020) (ORMVMR2, 1.36; P<0.001), type 1 diabetes (OR, 1.37; P=0.0084) (ORMVMR1, 1.42; P=0.0155) (ORMVMR2, 1.45; P=0.002), and alopecia areata (OR, 1.98; P=0.0059) (ORMVMR1, 2.55; P<0.001) (ORMVMR2, 1.99; P=0.003) in both univariable and multivariable MR. These causal relationships were supported by sensitivity analyses. No causal effect of AD was identified in relation to systemic lupus erythematosus, vitiligo, and ankylosing spondylitis. Concerning the reverse directions, no significant association was noted.ConclusionThe results of this MR study provide evidence to support the idea that AD causes a greater risk of rheumatoid arthritis, type 1 diabetes and alopecia areata. Further replication in larger samples is needed to validate our findings, and experimental studies are needed to explore the underlying mechanisms of these causal effects

Safe Offline Reinforcement Learning with Real-Time Budget Constraints

Aiming at promoting the safe real-world deployment of Reinforcement Learning (RL), research on safe RL has made significant progress in recent years. However, most existing works in the literature still focus on the online setting where risky violations of the safety budget are likely to be incurred during training. Besides, in many real-world applications, the learned policy is required to respond to dynamically determined safety budgets (i.e., constraint threshold) in real time. In this paper, we target at the above real-time budget constraint problem under the offline setting, and propose Trajectory-based REal-time Budget Inference (TREBI) as a novel solution that approaches this problem from the perspective of trajectory distribution. Theoretically, we prove an error bound of the estimation on the episodic reward and cost under the offline setting and thus provide a performance guarantee for TREBI. Empirical results on a wide range of simulation tasks and a real-world large-scale advertising application demonstrate the capability of TREBI in solving real-time budget constraint problems under offline settings.Comment: We propose a method to handle the constraint problem with dynamically determined safety budgets under the offline settin

Identification of hub genes associated with hepatitis B virus-related hepatocellular cancer using weighted gene co-expression network analysis and protein-protein interaction network analysis

Background. Chronic hepatitis B virus (HBV) infection is the main pathogen of hepatocellular carcinoma. However, the mechanisms of HBV-related hepatocellular carcinoma (HCC) progression are practically unknown. Materials and Methods. The results of RNA-sequence and clinical data for GSE121248 and GSE17548 were accessed from the Gene Expression Omnibus data library. We screened Sangerbox 3.0 for differentially expressed genes (DEGs). The weighted gene co-expression network analysis (WGCNA) was employed to select core modules and hub genes, and protein-protein interaction network module analysis also played a significant part in it. Validation was performed using RNA-sequence data of cancer and normal tissues of HBV-related HCC patients in the cancer genome atlas-liver hepatocellular cancer database (TCGA-LIHC). Results. 787 DEGs were identified from GSE121248 and 772 DEGs were identified from GSE17548. WGCNA analysis indicated that black modules (99 genes) and grey modules (105 genes) were significantly associated with HBV-related HCC. Gene ontology analysis found that there is a direct correlation between DEGs and the regulation of cell movement and adhesion; the internal components and external packaging structure of plasma membrane; signaling receptor binding, calcium ion binding, etc. Kyoto Encyclopedia of Genes and Genomes pathway analysis found out the association between cytokine receptors, cytokine-cytokine receptor interactions, and viral protein interactions with cytokines were important and HBV-related HCC. Finally, we further validated 6 key genes including C7, EGR1, EGR3, FOS, FOSB, and prostaglandin-endoperoxide synthase 2 by using the TCGALIHC. Conclusions. We identified 6 hub genes as candidate biomarkers for HBV-related HCC. These hub genes may act as an essential part of HBV-related HCC progression

Photochemical runaway in exoplanet atmospheres: implications for biosignatures

About 2.5 billion years ago, microbes learned to harness plentiful solar energy to reduce CO2 with H2O, extracting energy and producing O2 as waste. O2 production from this metabolic process was so vigorous that it saturated its photochemical sinks, permitting it to reach "runaway" conditions and rapidly accumulate in the atmosphere despite its reactivity. Here we argue that O2 may not be unique: diverse gases produced by life may experience a "runaway" effect similar to O2. This runaway occurs because the ability of an atmosphere to photochemically cleanse itself of trace gases is generally finite. If produced at rates exceeding this finite limit, even reactive gases can rapidly accumulate to high concentrations and become potentially detectable. Planets orbiting smaller, cooler stars, such as the M dwarfs that are the prime targets for the James Webb Space Telescope (JWST), are especially favorable for runaway, due to their lower UV emission compared to higher-mass stars. As an illustrative case study, we show that on a habitable exoplanet with an H2–N2 atmosphere and net surface production of NH3 orbiting an M dwarf (the "Cold Haber World" scenario), the reactive biogenic gas NH3 can enter runaway, whereupon an increase in the surface production flux of one order of magnitude can increase NH3 concentrations by three orders of magnitude and render it detectable by JWST in just two transits. Our work on this and other gases suggests that diverse signs of life on exoplanets may be readily detectable at biochemically plausible production rates

The role of tripartite motif-containing 28 in cancer progression and its therapeutic potentials

Tripartite motif-containing 28 (TRIM28) belongs to tripartite motif (TRIM) family. TRIM28 not only binds and degrades its downstream target, but also acts as a transcription co-factor to inhibit gene expression. More and more studies have shown that TRIM28 plays a vital role in tumor genesis and progression. Here, we reviewed the role of TRIM28 in tumor proliferation, migration, invasion and cell death. Moreover, we also summarized the important role of TRIM28 in tumor stemness sustainability and immune regulation. Because of the importance of TRIM28 in tumors, TIRM28 may be a candidate target for anti-tumor therapy and play an important role in tumor diagnosis and treatment in the future

JWST-TST DREAMS: Quartz Clouds in the Atmosphere of WASP-17b

Clouds are prevalent in many of the exoplanet atmospheres that have been observed to date. For transiting exoplanets, we know if clouds are present because they mute spectral features and cause wavelength-dependent scattering. While the exact composition of these clouds is largely unknown, this information is vital to understanding the chemistry and energy budget of planetary atmospheres. In this work, we observe one transit of the hot Jupiter WASP-17b with JWST's MIRI LRS and generate a transmission spectrum from 5-12 $\rm{\mu}$m. These wavelengths allow us to probe absorption due to the vibrational modes of various predicted cloud species. Our transmission spectrum shows additional opacity centered at 8.6 $\rm{\mu}$m, and detailed atmospheric modeling and retrievals identify this feature as SiO$_2$(s) (quartz) clouds. The SiO$_2$(s) clouds model is preferred at 3.5-4.2$\sigma$ versus a cloud-free model and at 2.6$\sigma$ versus a generic aerosol prescription. We find the SiO$_2$(s) clouds are comprised of small ${\sim}0.01$ $\rm{\mu}$m particles, which extend to high altitudes in the atmosphere. The atmosphere also shows a depletion of H$_2$O, a finding consistent with the formation of high-temperature aerosols from oxygen-rich species. This work is part of a series of studies by our JWST Telescope Scientist Team (JWST-TST), in which we will use Guaranteed Time Observations to perform Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy (DREAMS).Comment: 19 pages, 7 figures, accepted for publication in ApJ

How Do Different Parental Beliefs and Parenting Behaviors Affect Students' College Academic Performance

I examine the differences between Asian Americans and Caucasian Americans with respect to parental beliefs, parenting behaviors, and college academic achievement. The results suggest that 1) there is a strong causal effect of study time on college performance, 2) parental strictness and emphasis on education distinguish Asian American students from Caucasian American students in their choice of a major, study effort, and self-motivation, all of which determine college GPA, and 3) an expanded list of parental control measures and self-motivation measures should be introduced in future research to effectively explain the ethnicity effect on study effort and college academic outcomes.Honors Thesi

Passenger Flow Scale Prediction of Urban Rail Transit Stations Based on Multilayer Perceptron (MLP)

Accurately predicting passenger flow at rail stations is an effective way to reduce operation and maintenance costs, improve the quality of passenger travel while meeting future passenger travel demand. The improvement of data acquisition capability allows fine-grained and large-scale built environment data to be extracted. Therefore, this paper focuses on investigating the relationship between the built environment around the station and the station passenger flow and discusses whether the built environment data can be applied to the station passenger flow prediction. Firstly, the evaluation system of station passenger flow influencing factors is built based on multisource data. The inner relationship between built environment factors and station passenger flow is investigated using the Pearson correlation analysis. Based on this, a multilayer perceptron (MLP)-based passenger flow prediction model was developed to predict the passenger flow at key stations. The study results show that the built environment factors impact station passenger flow, and the MLP prediction model has better prediction accuracy and applicability. The results of the study can be applied to predict the passenger flow scale of rail stations without historical passenger flow data and thus are also applicable to new rail stations

H₂-dominated Atmosphere as an Indicator of Second-generation Rocky White Dwarf Exoplanets

Following the discovery of the first exoplanet candidate transiting a white dwarf (WD), a "white dwarf opportunity" for characterizing the atmospheres of terrestrial exoplanets around WDs is emerging. Large planet-to-star size ratios and hence large transit depths make transiting WD exoplanets favorable targets for transmission spectroscopy - conclusive detection of spectral features on an Earth-like planet transiting a close-by WD can be achieved within a medium James Webb Space Telescope (JWST) program. Despite the apparently promising opportunity, however, the post-main sequence (MS) evolutionary history of a first-generation WD exoplanet has never been incorporated in atmospheric modeling. Furthermore, second-generation planets formed in WD debris disks have never been studied from a photochemical perspective. We demonstrate that transmission spectroscopy can identify a second-generation rocky WD exoplanet with a thick ($\sim1$ bar) H$_2$-dominated atmosphere. In addition, we can infer outgassing activities of a WD exoplanet based on its transmission spectra and test photochemical runaway by studying CH$_4$ buildup.Comment: 25 pages, 10 figures, 3 tables, accepted for publication in ApJ Letter