Uncertainty reduction for precipitation prediction in North America.

Large differences in projected future annual precipitation increases in North America exists across 27 CMIP6 models under four emission scenarios. These differences partly arise from weak representations of land-atmosphere interactions. Here we demonstrate an emergent constraint relationship between annual growth rates of future precipitation and growth rates of historical temperature. The original CMIP6 projections show 0.49% (SSP126), 0.98% (SSP245), 1.45% (SSP370) and 1.92% (SSP585) increases in precipitation per decade. Combining observed warming trends, the constrained results show that the best estimates of future precipitation increases are more likely to reach 0.40-0.48%, 0.83-0.93%, 1.29-1.45% and 1.70-1.87% respectively, implying an overestimated future precipitation increases across North America. The constrained results also are narrow the corresponding uncertainties (standard deviations) by 13.8-31.1%. The overestimated precipitation growth rates also reveal an overvalued annual growth rates in temperature (6.0-13.2% or 0.12-0.37°C) and in total evaporation (4.8-14.5%) by the original models' predictions. These findings highlight the important role of temperature for accurate climate predictions, which is important as temperature from current climate models' simulations often still have systematic errors.

Method of 3D Coating Accumulation Modeling Based on Inclined Spraying.

In the process of repairing the surface of products in aviation, aerospace, and other fields by spraying, accurate 3D cumulative-coating modeling is an important research issue in spraying-process simulation. The approach to this issue is a 3D cumulative-coating model based on inclined spraying. Firstly, an oblique spraying layer cumulative model was established, which could quickly collect the coating thickness distribution data of different spray distances. Secondly, 3D cumulative-coating modeling was conducted with the distance between the measuring point and the axis of the spray gun and the spraying distance between the measuring points as the input parameters, and the coating thickness of the measuring point as the output parameter. The experimental results show that the mean relative error of the cumulative model of the oblique spraying layer is less than 4.1% in the case of a 170~290 mm spraying distance and that the model is applicable in the range of -80~80 mm, indicating that the data on the oblique spraying coating proposed in this paper is accurate and fast. The accuracy of the 3D cumulative-coating model proposed in this paper is 1.2% and 21.5% higher than that of the two similar models, respectively. Therefore, the approach of 3D cumulative-coating modeling based on inclined distance spraying is discovered, demonstrating the advantages of fast and accurate modeling and enabling accurate 3D cumulative-coating modeling for spraying process simulation.

Established and Evolving Roles of the Multifunctional Non-POU Domain-Containing Octamer-Binding Protein (NonO) and Splicing Factor Proline- and Glutamine-Rich (SFPQ).

It has been more than three decades since the discovery of multifunctional factors, the Non-POU-Domain-Containing Octamer-Binding Protein, NonO, and the Splicing Factor Proline- and Glutamine-Rich, SFPQ. Some of their functions, including their participation in transcriptional and posttranscriptional regulation as well as their contribution to paraspeckle subnuclear body organization, have been well documented. In this review, we focus on several other established roles of NonO and SFPQ, including their participation in the cell cycle, nonhomologous end-joining (NHEJ), homologous recombination (HR), telomere stability, childhood birth defects and cancer. In each of these contexts, the absence or malfunction of either or both NonO and SFPQ leads to either genome instability, tumor development or mental impairment.

A Fur-regulated type VI secretion system contributes to oxidative stress resistance and virulence in Yersinia pseudotuberculosis.

The type VI secretion system (T6SS) is a widespread protein secretion apparatus deployed by many Gram-negative bacterial species to interact with competitor bacteria, host organisms, and the environment. Yersinia pseudotuberculosis T6SS4 was recently reported to be involved in manganese acquisition; however, the underlying regulatory mechanism still remains unclear. In this study, we discovered that T6SS4 is regulated by ferric uptake regulator (Fur) in response to manganese ions (Mn2+), and this negative regulation of Fur was proceeded by specifically recognizing the promoter region of T6SS4 in Y. pseudotuberculosis. Furthermore, T6SS4 is induced by low Mn2+ and oxidative stress conditions via Fur, acting as a Mn2+-responsive transcriptional regulator to maintain intracellular manganese homeostasis, which plays important role in the transport of Mn2+ for survival under oxidative stress. Our results provide evidence that T6SS4 can enhance the oxidative stress resistance and virulence for Y. pseudotuberculosis. This study provides new insights into the regulation of T6SS4 via the Mn2+-dependent transcriptional regulator Fur, and expands our knowledge of the regulatory mechanisms and functions of T6SS from Y. pseudotuberculosis.

Enhancing H2O2 utilization efficiency for catalytic wet peroxide oxidation through the doping of La in the Fe-ZSM-5 Catalyst.

Iron-loaded zeolite (Fe-zeolite) has shown great potential as an efficient catalyst for degrading organic pollutants with high concentrations in the catalytic wet peroxide oxidation (CWPO) process under mild conditions. Here, 0.4 wt% Lanthanum (La) was added in the 1.0 wt% Fe-ZSM-5 by two-step impregnation method for an enhanced H2O2 utilization efficiency. For a systematical comparison, the CWPO process at 55 °C, where m-cresol with a high concentration of 1000 mg/L as a substrate, was studied over Fe-ZSM-5 and Fe-La-ZSM-5 catalysts. Compared with Fe-ZSM-5, Fe-La-ZSM-5 showed 15% higher H2O2 utilization efficiency with comparable total organic carbon (TOC) removal at around 40%, meanwhile with a 15% reduced metal leaching. Transmission electron microscopy (TEM) with elemental mapping (EDS), surface acidity analysis by Fourier transform infrared (FT-IR) and NH3-temperature programmed desorption (NH3-TPD), redox property analysis by Raman spectroscopy and H2-temperature-programmed reduction (H2-TPR) of both catalysts revealed, that the La doped Fe-ZSM-5 can provide an altered surface acidity, a more uniform and evenly dispersed surface Fe species with a promoted reducibility, which effectively promoted the accurate decomposition of H2O2 into the reactive •OH radicals, enhanced the H2O2 utilization efficiency, and increased the catalyst stability. Also, more than 90% conversion was maintained during the continuous experiment for more than 10 consecutive test days under 55 °C without pH adjustment, showing a promising possibility of the Fe-La-ZSM-5 for a practical wastewater treatment process.

Quantifying the morphology of eyeballs with posterior staphyloma with Zernike polynomials.

Purpose: To quantify the morphology of eyeballs with posterior staphyloma (PS) with Zernike decomposition and to explore the association between Zernike coefficients with existing PS classification. Methods: Fifty-three eyes with high myopia (HM, ≤-6.00D) and 30 with PS were included. PS was classified with traditional methods based on OCT findings. Eyeballs' morphology was obtained with 3D MRI, from which the height map of the posterior surface was extracted. Zernike decomposition was performed to derive the coefficients of the 1st-27th items, which were compared between HM and PS eyes with the Mann-Whitney-U test. Receiver operating characteristics (ROC) analysis was used to test the effectiveness of using Zernike coefficients to discriminate PS from HM. Results: Compared to HM eyeballs, PS eyeballs had significantly increased vertical and horizontal tilt, oblique astigmatism, defocus, vertical and horizontal coma, and higher order aberrations (HOA) (all Ps < 0.05). HOA was the most effective in PS classification with an area under the ROC curve (AUROC) value of 0.977. Among the 30 PS, 19 were the wide macular type with large defocus and negative spherical aberration; 4 were the narrow macular type with positive spherical aberration; 3 were inferior PS with greater vertical tilt, and 4were peripapillary PS with larger horizontal tilt. Conclusion: PS eyes have significantly increased Zernike coefficients, and HOA is the most effective parameter to differentiate PS from HM. The geometrical meaning of the Zernike components showed great accordance with PS classification.

Effect of inorganic salt on the removal of typical pollutants in wastewater by RuO2/TiO2 via catalytic wet air oxidation.

The treatment of high-salinity and high-organic wastewater is a tough task, with the removal of organic matter and the separation of salts often mutually restricting. Catalytic wet air oxidation (CWAO) coupled desalination technology (membrane distillation (MD), membrane bioreactor (MBR), ultrafiltration (UF), nanofiltration (NF), etc.) provides an effective method to simultaneously degrade the high-salinity (via desalination) and high-organic matters (via CWAO) in wastewater. In this work, five kinds of RuO2/TiO2 catalysts with different calcination temperatures were prepared for CWAO of maleic acid wastewater with a theoretical chemical oxygen demand (COD) value of 20,000 mg L-1. RuO2/TiO2 series catalysts demonstrated prominent salt resistance, with more than 80% TOC removal rates in the CWAO system containing 5 wt% Na2SO4; while RuO2/TiO2-350 showed the best degradation performance in both non-salinity and Na2SO4-containing conditions. Multiple characterization techniques, such as XRD, BET, XPS, NH3-TPD and TEM etc., verified the physicochemical structure of RuO2/TiO2 catalysts, and their influence on the degradation of pollutants. The calcination temperature was found to have a direct impact on the specific surface area, pore volume, oxygen vacancies and acid sites of catalysts, which in turn affected the ultimate catalytic activity. Furthermore, we also investigated the performance of the RuO2/TiO2-350 catalyst for the treatment of acids, alcohols and aromatic compounds with the addition of NaCl or Na2SO4, proving its good universality and excellent salt resistance in saline wastewater. Meanwhile, the relationship between the structure of three types of organic compounds and the degradation effect in the CWAO system was also explored.

T-cell activation state differentially contributes to neuropsychiatric complications in women with HIV.

Neuropsychiatric complications are common among women with HIV (WWH). The pathophysiological mechanisms underlying these complications are not fully known but likely driven in part by immune modulation. We examined associations between T-cell activation states which are required to mount an effective immune response (activation, co-stimulation/normal function, exhaustion, senescence) and neuropsychiatric complications in WWH. 369 WWH (78% HIV RNA undetectable/<20cp/mL) enrolled in the Women's Interagency HIV Study completed neuropsychological testing and measures of depression (Center for Epidemiological Studies Depression Scale-CES-D), self-reported stress levels (Perceived Stress Scale-10), and post-traumatic stress (PTSD Checklist-Civilian Scale). Multiparametric flow cytometry evaluated T-cell activation state. Partial least squares regressions were used to examine T-cell phenotypes and neuropsychiatric outcome associations after confounder adjustment. In the total sample and among virally suppressed (VS)-WWH, CD4+ T-cell exhaustion was associated with poorer learning and attention/working memory (P's < 0.05). In the total sample, CD4+ T-cell activation was associated with better attention/working memory and CD8+ T-cell co-stimulation and senescence was associated with poorer executive function (P's < 0.05). For mental health outcomes, in the total sample, CD4+ T-cell activation was associated with more perceived stress and CD4+ T-cell exhaustion was associated with less depressive symptoms (P's < 0.05). Among VS-WWH, CD4+ senescence was associated with less perceive stress and CD8+ T-cell co-stimulation and senescence was associated with higher depression (P's < 0.05). Together, results suggest the contribution of peripheral CD4+ and CD8+ T-cell activation status to neuropsychiatric complications in WWH.

Immunometabolic Reprogramming in Response to HIV Infection Is Not Fully Normalized by Suppressive Antiretroviral Therapy.

BACKGROUND: HIV infection results in immunometabolic reprogramming. While we are beginning to understand how this metabolic reprogramming regulates the immune response to HIV infection, we do not currently understand the impact of ART on immunometabolism in people with HIV (PWH). METHODS: Serum obtained from HIV-infected (n = 278) and geographically matched HIV seronegative control subjects (n = 300) from Rakai Uganda were used in this study. Serum was obtained before and ~2 years following the initiation of ART from HIV-infected individuals. We conducted metabolomics profiling of the serum and focused our analysis on metabolic substrates and pathways assocaited with immunometabolism. RESULTS: HIV infection was associated with metabolic adaptations that implicated hyperactive glycolysis, enhanced formation of lactate, increased activity of the pentose phosphate pathway (PPP), decreased ß-oxidation of long-chain fatty acids, increased utilization of medium-chain fatty acids, and enhanced amino acid catabolism. Following ART, serum levels of ketone bodies, carnitine, and amino acid metabolism were normalized, however glycolysis, PPP, lactate production, and ß-oxidation of long-chain fatty acids remained abnormal. CONCLUSION: Our findings suggest that HIV infection is associated with an increased immunometabolic demand that is satisfied through the utilization of alternative energetic substrates, including fatty acids and amino acids. ART alone was insufficient to completely restore this metabolic reprogramming to HIV infection, suggesting that a sustained impairment of immunometabolism may contribute to chronic immune activation and comorbid conditions in virally suppressed PWH.

Source analysis of heavy metal pollution in agricultural soil irrigated with sewage in Wuqing, Tianjin.

In this study, the contents of heavy metals and Cd and Pb isotope ratios of agricultural soil and potential source samples collected from farmland receiving sewage irrigation in Wuqing District, Tianjin, China were determined. Multiple methods were used for source analysis, including positive matrix factorization (PMF), correlation analysis, principal component analysis (PCA), and the Cd and Pb isotope ratio method. The results showed that agricultural soil was slightly contaminated by heavy metals in the research area, with relatively higher Cd and Pb accumulation levels compared to those of other heavy metals. Four types of pollution sources, including the soil parent material sources, industrial emission sources, agricultural practice sources, and mixed sources of sewage irrigation and transportation were apportioned and quantified by PMF, combined with the results of PCA and correlation analysis. The contribution rates quantified by the Cd and Pb isotope ratio method were similar, suggesting that no single source dominates Pb and Cd pollution. The contribution rates of Pb analyzed by the isotope ratio method were almost identical to those of the PMF model, indicating the rationality of the PMF result. Our results suggested that correlation analysis and PCA should be utilized to provide information for obtaining reasonable results and defining source categories for PMF, whereas the isotope ratio method should be applied to verify the accuracy of source contributions analyzed by PMF.

Aerobactin-Mediated Iron Acquisition Enhances Biofilm Formation, Oxidative Stress Resistance, and Virulence of Yersinia pseudotuberculosis.

Aerobactin is a citrate-hydroxamate siderophore that is critical for the virulence of pathogenic enteric bacteria. However, although the aerobactin-producing iucABCD-iutA operon is distributed widely in the genomes of Yersinia species, none of the pathogenic Yersinia spp. was found to produce aerobactin. Here, we showed that the iucABCD-iutA operon in the food-borne enteric pathogen Yersinia pseudotuberculosis YPIII is a functional siderophore system involved in iron acquisition. The expression of the operon was found to be directly repressed by the ferric uptake regulator (Fur) in an iron concentration-dependent manner. In addition, we demonstrated that the aerobactin-mediated iron acquisition contributes to bacterial growth under iron-limited conditions. Moreover, we provided evidence that aerobactin plays important roles in biofilm formation, resistance to oxidative stress, ROS removal, and virulence of Y. pseudotuberculosis. Overall, our study not only uncovered a novel strategy of iron acquisition in Y. pseudotuberculosis but also highlighted the importance of aerobactin in the pathogenesis of Y. pseudotuberculosis.

Hybrid Zeolitic Imidazolate Frameworks for Promoting Electrocatalytic Oxygen Evolution via a Dual-Site Relay Mechanism.

Developing efficient oxygen evolution reaction (OER) electrocatalysts is important for enhancing the water splitting efficiency. However, with the current catalysts containing one kind of active sites, it is challenging to achieve low overpotentials because of the four-electron transfer process. Herein is reported HZIF-2-CoMo, a new metal-organic framework with well-defined Co-Mo dual sites that can promote the OER process through an unconventional Mo6+/Co2+ dual-site relay mechanism. Theoretical calculations suggested that the Mo and Co sites stabilize the HO* and HOO* intermediates, respectively, and that the unique Co-O-Mo configuration induces the formation of a Co-O*-Mo transition intermediate, remarkably reducing the reaction free energy. As a result, HZIF-2-CoMo shows an overpotential of 277 mV at 10 mA cm-2 and a low Tafel slope of 70 mV dec-1 in alkaline solution, making it one of the best OER electrocatalysts reported to date.

Sex-specific associations between cerebrospinal fluid inflammatory marker levels and cognitive function in antiretroviral treated people living with HIV in rural Uganda.

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1ß, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies.

CoMo-bimetallic N-doped porous carbon materials embedded with highly dispersed Pt nanoparticles as pH-universal hydrogen evolution reaction electrocatalysts.

The hydrogen evolution reaction is a key half reaction for water electrolysis and is of great significance. Pt-based nanomaterials are promising candidates for HER electrocatalysts. However, the high price of platinum and poor durability impede their practical applications. Herein, a new CoMo-bimetallic hybrid zeolite imidazolate framework is employed to load Pt nanoparticles in a highly dispersed manner as a precursor to synthesize an efficient pH-universal HER electrocatalyst (PtCoMo@NC), which displays overpotentials of 26, 51, and 66 mV at a current density of 10 mA cm-2 in acidic, basic, and neutral media, respectively. The strong synergistic effect of highly dispersed multi-type catalytic species, including cobalt, molybdenum carbide, and platinum (4.7%) promotes the catalytic activity in the HER process. Meanwhile, the aggregation of Pt nanoparticles is greatly restrained by the carbon matrix so that a brilliant long-time durability of 12 hours and a negligible current decrease in the LSV curve after 10 000 CV cycles are achieved.

Two-Dimensional Mesoporous Carbon Materials Derived from Fullerene Microsheets for Energy Applications.

Porous carbon materials rich in defects are promising candidates in energy storage and conversion applications. Herein, a facile template-free approach is reported for the synthesis of a two-dimensional (2 D) mesoporous carbon material derived from fullerene (C60 ) microsheets (FMSs) through simple heat treatment. The sample obtained at 1000 °C (FMS1000) shows a large surface area of 1507.6 m2 g-1 owing to the presence of mesopores and rich defects, which promote electron and mass transfer in the electrocatalytic process of the oxygen reduction reaction (ORR), showing an excellent performance with an onset potential of 0.95 V, a half-wave potential of 0.85 V, and long-term durability of 2000 cycles, comparable to the performance of commercial Pt/C. Moreover, FMS1000 displays a remarkable supercapacitive property with a specific capacitance of 330.7 F g-1 at 0.2 A g-1 and good long-term stability with a capacitance retention of 97 % over 50 000 cycles. Thus, a practical strategy for the production of mesoporous carbon materials with different morphological structures and porous defects as high-performance energy materials is advanced.

Common genetic variants in pre-microRNAs are associated with cervical cancer susceptibility in southern Chinese women.

Cervical cancer is a commonly diagnosed cancer among females. Polymorphisms in pre-microRNAs have been demonstrated to play critical roles in cancer. However, the roles of pre-microRNA polymorphisms in the aetiology of cervical cancer have not been well documented. We genotyped eight pre-microRNA polymorphisms in 290 cervical cancer patients and 445 cancer-free female controls using quantitative polymerase chain reaction with TaqMan probes. To estimate the association between pre-microRNA polymorphisms and the risk of cervical cancer, an unconditional logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI), adjusting for age, menopause, delivery, and abortion. We found that the pre-miR-137 rs1625579 T > G polymorphism was associated with a significant decrease in cervical cancer risk (TG/GG versus TT: adjusted OR (AOR) = 0.47, 95% CI = 0.27-0.81; TG versus TT: AOR = 0.56, 95% CI = 0.34-0.91). We also observed a significant association between the pre-miR-27a rs895819 T > C polymorphism and decreased cervical cancer risk (TC/CC versus TT: AOR = 0.65, 95% CI = 0.44-0.96). Stratified analysis further demonstrated that the pre-miR-137 rs1625579 T > C and pre-miR-27a rs895819 T > C polymorphisms significantly reduced the risk of cervical cancer susceptibility in patients younger than 49 years, those who experienced fewer abortions, and clinical stage I patients. Moreover, the pre-miR-137 rs1625579 T > G polymorphism showed protective effects in premenopausal women, squamous cell carcinoma patients, and patients with unclassified types of pathologies; the pre-miR-27a rs895819 T > C polymorphism was also associated with a decreased risk in patients older than 49 years, menopausal women, and women who had experienced vaginal pregnancies. The pre-miR-137 rs1625579 T > G and pre-miR-27a rs895819 T > C polymorphisms may provide protective effects against susceptibility to cervical cancer risk.

KATP Channel Blocker Glibenclamide Prevents Radiation-Induced Lung Injury and Inhibits Radiation-Induced Apoptosis of Vascular Endothelial Cells by Increased Ca2+ Influx and Subsequent PKC Activation.

Radiation-induced lung injury (RILI) is a common and severe side effect of thoracic radiotherapy, which compromises patients' quality of life. Recent studies revealed that early vascular injury, especially microvascular damage, played a central role in the development of RILI. For this reason, early vascular protection is essential for RILI therapy. The ATP-sensitive K+ (KATP) channel is an ATP-dependent K+ channel with multiple subunits. The protective role of the KATP channel in vascular injury has been demonstrated in some published studies. In this work, we investigated the effect of KATP channel on RILI. Our findings confirmed that the KATP channel blocker glibenclamide, rather than the KATP channel opener pinacidil, remitted RILI, and in particular, provided protection against radiation-induced vascular injury. Cytology experiments verified that glibenclamide enhanced cell viability, increased the potential of proliferation after irradiation and attenuated radiation-induced apoptosis. Involved mechanisms included increased Ca2+ influx and PKC activation, which were induced by glibenclamide pretreatment. In conclusion, the KATP channel blocker glibenclamide remitted RILI and inhibited the radiation-induced apoptosis of vascular endothelial cells by increased Ca2+ influx and subsequent PKC activation.

Intravenous glucocorticoids therapy in the treatment of Graves' ophthalmopathy: a systematic review and Meta-analysis.

AIM: To evaluate the benefit and harms of high-dose intravenous glucocorticoids (IVGC) as first-line treatment for Graves' ophthalmopathy (GO). METHODS: A systematic review and Meta-analysis of randomized clinical trials (RCTs) comparing IVGC for the treatment of GO, with placebo or other treatments, were conducted. Electronic databases were searched, and standard methodological guidance of Cochrane Handbook for Systematic Reviews of Interventions was used. The primary outcome was overall response, and secondary outcomes included the improvement and change in clinical activity score (CAS), and adverse events. RESULTS: Ten RCTs were included in the Meta-analysis. Low quality evidence (one trial) showed that participants receiving IVGC achieved significantly higher response compared to participants receiving placebo [risk ratio (RR) 7.50, 95% confidence interval (CI) 1.14 to 49.26]. Moderate quality evidence (four trials) support appreciable benefit of IVGC in response compared with oral glucocorticoids (OGC), with of RR being 1.51 (95%CI 1.25 to 1.83). There was low quality evidence (one trial) compatible with appreciable benefit for IVGC plus orbital radiotherapy in response (RR 1.38, 95%CI 1.07 to 1.79), compared with OGC plus orbital radiotherapy. One IVGC versus rituximab trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using rituximab (RR 0.70, 95%CI 0.50 to 0.98). One IVGC versus mycophenolate mofetil (MMF) trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using MMF (RR 0.74, 95%CI 0.63 to 0.88). Very low quality evidence (one trial) showed that participants with dysthyroid optic neuropathy (DON) receiving IVGC were more likely to achieve response compared to participants receiving orbital decompression (RR 3.33, 95%CI 0.51 to 21.89). CONCLUSION: The current evidence is moderate quality, which is sufficient to support IVGC to be as the first-line treatment for moderate-to-severe GO, and the use of rituximab or MMF to be the second-line treatment instead of IVGC. However, the evidence is very low quality, which is insufficient to support the use of IVGC or orbital decompression as the first-line treatment of DON.

Novel Data Transformations for RNA-seq Differential Expression Analysis.

We propose eight data transformations (r, r2, rv, rv2, l, l2, lv, and lv2) for RNA-seq data analysis aiming to make the transformed sample mean to be representative of the distribution center since it is not always possible to transform count data to satisfy the normality assumption. Simulation studies showed that for data sets with small (e.g., nCases = nControls = 3) or large sample size (e.g., nCases = nControls = 100) limma based on data from the l, l2, and r2 transformations performed better than limma based on data from the voom transformation in term of accuracy, FDR, and FNR. For datasets with moderate sample size (e.g., nCases = nControls = 30 or 50), limma with the rv and rv2 transformations performed similarly to limma with the voom transformation. Real data analysis results are consistent with simulation analysis results: limma with the r, l, r2, and l2 transformation performed better than limma with the voom transformation when sample sizes are small or large; limma with the rv and rv2 transformations performed similarly to limma with the voom transformation when sample sizes are moderate. We also observed from our data analyses that for datasets with large sample size, the gene-selection via the Wilcoxon rank sum test (a non-parametric two sample test method) based on the raw data outperformed limma based on the transformed data.

New Statistical Methods for Constructing Robust Differential Correlation Networks to characterize the interactions among microRNAs.

The interplay among microRNAs (miRNAs) plays an important role in the developments of complex human diseases. Co-expression networks can characterize the interactions among miRNAs. Differential correlation network is a powerful tool to investigate the differences of co-expression networks between cases and controls. To construct a differential correlation network, the Fisher's Z-transformation test is usually used. However, the Fisher's Z-transformation test requires the normality assumption, the violation of which would result in inflated Type I error rate. Several bootstrapping-based improvements for Fisher's Z test have been proposed. However, these methods are too computationally intensive to be used to construct differential correlation networks for high-throughput genomic data. In this article, we proposed six novel robust equal-correlation tests that are computationally efficient. The systematic simulation studies and a real microRNA data analysis showed that one of the six proposed tests (ST5) overall performed better than other methods.