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In applying a hierarchical mixed model to genome-wide association analysis (GWAS) of longitudinal data, dimensionality reduction through modeling repeated measurements improves both computational efficiency and statistical power. Legendre polynomials can flexibly fit population growth trajectories, but higher orders substantially increase computational complexity. Instead of using Legendre polynomials, we first estimated fewer individual-specific parameters using biologically meaningful non-linear models and then associated these phenotypic regressions with genetic markers using a multivariate linear mixed model (mvLMM). After performing a canonical transformation of the regressions based on the pre-estimated covariance matrices under the null genomic mvLMM, we decomposed the mvLMM into mutually independent univariate models and incorporated EMMAX to enable rapid genome-wide mixed-model associations for each transformed phenotype. Simulations for longitudinal association analysis in maize and GWAS for the growth trajectories of body weights in mice demonstrated the advantages of hierarchical non-linear mixed models in computing efficiency and statistical power for detecting quantitative trait loci (QTL), compared with mvLMM for multiple growth points and the hierarchical random regression model using Legendre polynomials as sub-models.

Key messageIn extension of Single-RunKing to analyze multiple correlated traits, mvRunKing not only enlarged number of the analyzed phenotypes with canonical transformation, but also improved statistical power to detect pleiotropic QTNs through joint association analysis.Based on genomic variance–covariance matrices, we simplified multivariate mixed model association analysis to multiple univariate ones by using canonical transformation, and then individually implemented univariate association tests in the Single-RunKing. which enlarged number of the analyzed phenotypes. With canonical transformation back to the original scale, the association results would be biologically interpretable. Especially, we rapidly estimated genomic variance–covariance matrices with multivariate GEMMA and optimized separately the polygenic variances (or heritabilities) for only the markers that had large effects or higher significance levels in univariate mixed models, greatly improving computing efficiency for multiple univariate association tests. Beyond one test at once, joint association analysis for quantitative trait nucleotide (QTN) candidates can significantly increase statistical powers to detect QTNs. A user-friendly mvRunKing software was developed to efficiently implement multivariate mixed model association analyses.

The emergence of flash drought has attracted widespread attention due to its rapid onset. However, little is known about the recent evolution of flash droughts in terms of the speed of onset and the causes of such a rapid onset phase of flash droughts. Here, we present a comprehensive assessment of the onset development of flash droughts and the underlying mechanisms on a global scale. We find that 33.64−46.18% of flash droughts with 5-day onset of drying, and there is a significant increasing trend in the proportion of flash droughts with the 1-pentad onset time globally during the period 2000−2020. Flash droughts do not appear to be occurring more frequently in most global regions, just coming on faster. In addition, atmospheric aridity is likely to create a flash drought-prone environment, and the joint influence of soil moisture depletion and atmospheric aridity further accelerates the rapid onset of flash droughts. The occurrence of flash droughts has attracted widespread attention due to their rapid onset. Here, the authors find that the joint influence of soil moisture depletion and atmospheric aridity further accelerates the rapid onset of flash droughts.

Dynamical downscaling is an important approach to obtaining fine-scale weather and climate information. However, dynamical downscaling simulations are often degraded by biases in the large-scale forcing itself. We constructed a bias-corrected global dataset based on 18 models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) and the European Centre for Medium-Range Weather Forecasts Reanalysis 5 (ERA5) dataset. The bias-corrected data have an ERA5-based mean climate and interannual variance, but with a non-linear trend from the ensemble mean of the 18 CMIP6 models. The dataset spans the historical time period 1979–2014 and future scenarios (SSP245 and SSP585) for 2015–2100 with a horizontal grid spacing of (1.25° × 1.25°) at six-hourly intervals. Our evaluation suggests that the bias-corrected data are of better quality than the individual CMIP6 models in terms of the climatological mean, interannual variance and extreme events. This dataset will be useful for dynamical downscaling projections of the Earth’s future climate, atmospheric environment, hydrology, agriculture, wind power, etc. Measurement(s) temperature of air • atmospheric wind • humidity • geopotential height • temperature of sea surface • surface pressure • sea level pressure Technology Type(s) climate model • meteorological reanalysis Factor Type(s) zonal wind • meridional wind • temporal interval • geographic location Sample Characteristic - Environment climate system • climate change Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16802326

Groundwater provides critical freshwater supply, particularly in dry regions where surface water availability is limited. Climate change impacts on GWS (groundwater storage) could affect the sustainability of freshwater resources. Here, we used a fully-coupled climate model to investigate GWS changes over seven critical aquifers identified as significantly distressed by satellite observations. We assessed the potential climate-driven impacts on GWS changes throughout the 21 st century under the business-as-usual scenario (RCP8.5). Results show that the climate-driven impacts on GWS changes do not necessarily reflect the long-term trend in precipitation; instead, the trend may result from enhancement of evapotranspiration, and reduction in snowmelt, which collectively lead to divergent responses of GWS changes across different aquifers. Finally, we compare the climate-driven and anthropogenic pumping impacts. The reduction in GWS is mainly due to the combined impacts of over-pumping and climate effects; however, the contribution of pumping could easily far exceed the natural replenishment. Climate change may impact groundwater storage and thus the availability of freshwater resources. Here the authors use climate models to examine seven aquifers and find that storage changes are primarily the result of enhancement of evapotranspiration, reduction in snowmelt, and over-pumping rather than long-term precipitation changes.

Annual precipitation anomalies over eastern China are characterized by a north–south dipole pattern, referred to as the “southern flooding and northern drought” pattern (SF/ND), fluctuating on decadal time scales. Previous research has suggested possible links with oceanic forcing, but the underlying physical mechanisms by which sea surface temperature (SST) variability impacts the dipole pattern remains unclear. Idealized atmospheric general circulation model experiments conducted by the U.S. CLIVAR Drought Working Group are used to investigate the role of historical SST anomalies associated with Pacific El Niño–Southern Oscillation (ENSO)-like and the Atlantic multidecadal oscillation (AMO) patterns in this dipole pattern. The results show that the Pacific SST pattern plays a dominant role in driving the decadal variability of this dipole pattern and the associated atmospheric circulation anomalies, whereas the Atlantic SST pattern contributes to a much lesser degree. The direct atmospheric response to the Pacific SST pattern is a large-scale cyclonic or anticyclonic circulation anomaly in the lower troposphere occupying the entire northern North Pacific. During the warm phase of the Pacific SST pattern, it is cyclonic with northwesterly wind anomalies over northern China pushing the monsoon front to the south and consequently SF/ND. During the cold phase of the Pacific SST pattern, the circulation anomaly reverses with southeasterly winds over northern China allowing the monsoon front and the associated rainband to migrate northward, resulting in southern drought and northern flooding. The Atlantic SST pattern plays a supplementary role, enhancing the dipole pattern when the Pacific SST and Atlantic SST patterns are in opposite phases and weakening it when the phases are the same.

Over the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field.

We performed a meta-analysis to determine safety and efficacy of corticosteroids in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. We searched PubMed, Web of Science, Medline, WanFang Chinese database, and ZhiWang Chinese database using Boolean operators and search terms covering SARS-CoV-2, SARS-CoV, OR MERS-CoV AND corticosteroids to find appropriate studies. Review Manager 5.3 was used to analyze results of meta-analysis. Observational studies were analyzed for quality using the modified Newcastle–Ottawa scale and randomized clinical trials, using the Jadad scale. Subjects were divided into those with severe-only and other (severe and not severe) cohorts based on published criteria. Efficacy endpoints studied included mortality, hospitalization duration, rates of intensive care unit (ICU) admission, use of mechanical ventilation, and a composite endpoint (death, ICU admission, or mechanical ventilation). We included 11 reports including 10 cohort studies and 1 randomized clinical trial involving 5249 subjects (2003–2020). Two discussed the association of corticosteroids and virus clearing and 10 explored how corticosteroids impacted mortality, hospitalization duration, use of mechanical ventilation, and a composite endpoint. Corticosteroid use was associated with delayed virus clearing with a mean difference (MD) = 3.78 days (95% confidence Interval [CI] = 1.16, 6.41 days; I2 = 0%). There was no significant reduction in deaths with relative Risk Ratio (RR) = 1.07 (90% CI = 0.81; 1.42; I2 = 80%). Hospitalization duration was prolonged and use of mechanical ventilation increased. In conclusion, corticosteroid use in subjects with SARS-CoV-2, SARS-CoV, and MERS-CoV infections delayed virus clearing and did not convincingly improve survival, reduce hospitalization duration or ICU admission rate and/or use of mechanical ventilation. There were several adverse effects. Because of a preponderance of observational studies in the dataset and selection and publication biases our conclusions, especially regarding SARS-CoV-2, need confirmation in a randomized clinical trial. In the interim we suggest caution using corticosteroids in persons with COVID-19.

Natural killer/T-cell lymphoma (NKTL) is a sub-type of Epstein–Barr virus (EBV)-related non-Hodgkin lymphomas common in Asia and Latin America but rare elsewhere. Its pathogenesis is complex and incompletely understood. Lymphoma cells are transformed from NK- or T-cells, sometimes both. EBV-infection and subsequent genetic alterations in infected cells are central to NKTL development. Hemophagocytic syndrome is a common complication. Accurate staging is important to predict outcomes but there is controversy which system is best. More than two-thirds of NKTL lympohmas are localized at diagnosis, are frequently treated with radiation therapy only and have 5-year survival of about 70 percent. Persons with advanced NKTLs receive radiation therapy synchronously or metachronously with diverse multi-drug chemotherapy typically including l -asparginase with 5-year survival of about 40 percent. Some persons with widespread NKTL receive chemotherapy only. There are few data on safety and efficacy of high-dose therapy and a haematopoietic cell autotransplant. Immune therapies, histone deacetylase (HDAC)-inhibitors and other drugs are in early clinical trials. There are few randomized controlled clinical trials in NKTLs and no therapy strategy is clearly best ; more effective therapy(ies) are needed. Some consensus recommendations are not convincingly evidence-based. Mechanisms of multi-drug resistance are considered. We discuss these issues including recent advances in our understanding of and therapy of NKTLs.

Metal-free and controlled synthesis of sulfur-containing polymer is still a big challenge in polymer chemistry. Here, we report a metal-free, living copolymerization of carbonyl sulfide (COS) with epoxides via the cooperative catalysis of organic Lewis pairs including bases (e.g.: phosphazene, amidine, and guanidine) and thioureas as hydrogen-bond donors, afford well-defined poly(monothiocarbonate)s with 100% alternating degree, >99% tail-to-head content, controlled molecular weights (up to 98.4 kg/mol), and narrow molecular weight distributions (1.13–1.23). The effect of the types of Lewis pairs on the copolymerization of COS with several epoxides is investigated. The turnover frequencies (TOFs) of these Lewis pairs are as high as 112 h −1 at 25 °C. Kinetic and mechanistic results suggest that the supramolecular specific recognition of thiourea to epoxide and base to COS promote the copolymerization cooperatively. This strategy provides commercially available Lewis pairs for metal-free synthesis of sulfur-containing polymers with precise structure. Sulfur-containing polymers are useful commodities, but there is still a big challenge to produce such polymers in a controlled fashion. Here the authors show a metal-free living copolymerization between carbonyl sulfide and epoxides via cooperative catalysis.