Analysis of clinically relevant variants from ancestrally diverse Asian genomes

Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.</p

Technology roadmap for flexible sensors

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.Agency for Science, Technology and Research (A*STAR)National Research Foundation (NRF)Submitted/Accepted versionY.L., Z.L., M.Z., and X.C. acknowledge the National Research Foundation, Singapore (NRF) under NRF’s Medium Sized Centre: Singapore Hybrid-Integrated Next-Generation μElectronics (SHINE) Centre funding programme, and AME programming funding scheme of Cyber Physiochemical Interface (CPI) project (no. A18A1b0045). Y.L. acknowledges National Natural Science Foundation of China (62201243). C.J. acknowledges funding support from the National Key R&D Program of China (no. 2019YFA0706100), the National Natural Science Foundation of China (82151305), Lingang Laboratory (LG-QS-202202-09). T.Q.T. and N.E.L. acknowledge support by the Basic Science Research Program (no. 2020R1A2C3013480) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT. A.F. acknowledges the AFOSR (grant FA9550-22-1-0423). Y.L. and Y.Z. would like to acknowledge the NSF (award no. 2134664) and NIH (award no. R01HD108473) for financial support. X.F. acknowledges the support from the National Natural Science Foundation of China (grant no. U20A6001). L.Y. would like to thank the A*STAR Central Research Fund (CRF) and the AME Programmatic A18A1b0045 (Cyber Physiochemical Interfaces) for funding support. C.F.G. acknowledges the National Natural Science Foundation of China (no. T2225017). T.Q.T. acknowledges the Brain Pool Program (No. 2020H1D3A2A02111068) through the National Research Foundation (NRF) funded by the Ministry of Science. Z.L. acknowledges the support from RIE2020 AME Programmatic Grant funded by A*STAR-SERC, Singapore (Grant No. A18A1b0045). X.G. acknowledges funding support through the Shanghai Science and Technology Commission (grant no. 19JC1412400), the National Science Fund for Excellent Young Scholars (grant no. 61922057). C.D. acknowledges National Science Foundation CAREER: Conformable Piezoelectrics for Soft Tissue Imaging (grant no. 2044688) and MIT Media Lab Consortium funding. D.K. and O.G.S. acknowledge Leibniz Association and the German Research Foundation DFG (Gottfried Wilhelm Leibniz Program SCHM 1298/22-1, KA5051/1-1 and KA 5051/3-1), as well as the Leibniz association (Leibniz Transfer Program T62/2019). C.W. acknowledges the National Key Research and Development Program of China (grant no. 2021YFA1202600), National Natural Science Foundation of China (grant no. 62174082). A.V.-Y.T., E.Z., Y.Z., X.Z., and J.P. acknowledge the National Research Foundation, Singapore (NRF) under NRF’s Medium Sized Centre: Singapore Hybrid-Integrated Next-Generation μElectronics (SHINE) Centre funding programme, and AME programming funding scheme of Cyber Physiochemical Interface (CPI) project (no. A18A1b0045). R.Z. acknowledges National Natural Science Foundation of China (grant no. 51735007) and Beijing Natural Science Foundation (grant no. 3191001). N.M. acknowledges the support by JST PRESTO Grant Number JPMJPR20B7 and JST Adaptable and Seamless Technology transfer Program through Target-driven R&D (ASTEP) grant number JPMJTM22BK. C.P. acknowledges the Korean government (Ministry of Science and ICT, MSIT) (2022R1A4A3032923). M.W. acknowledges the National Key R&D Program of China under Grant (2021YFB3601200). X.Z. acknowledges National Natural Science Foundation of China (no. 62074029). S.X. acknowledges the 3M nontenured faculty award. T.-W.L. and D.-G.S. acknowledge the Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (grant no. NRF-2022M3C1A3081211). C.T.L. would like to acknowledge support from the Institute for Health Innovation and Technology (iHealthtech), the MechanoBioEngineering Laboratory at the Department of Biomedical Engineering and the Institute for Functional Intelligent Materials (I-FIM) at the National University of Singapore (NUS). C.T.L. also acknowledges support from the National Research Foundation and A*STAR, under its RIE2020 Industry Alignment Fund − Industry Collaboration Projects (IAF-ICP) (grant no. I2001E0059) − SIA-NUS Digital Aviation Corp Lab and the NUS ARTIC Research (grant no. HFM-RP1). X.Y. acknowledges funding support by City University of Hong Kong (grant no. 9667221). T.X. and X.Z. acknowledge National Natural Science Foundation of China (22234006). B.C.K.T. acknowledges Cyber-Physiochemical Interfaces CPI, A*STAR A18A1b0045. H.G. acknowledges a research start-up grant (002479-00001) from Nanyang Technological University and the Agency for Science, Technology and Research (A*STAR) in Singapore. W.G. acknowledges National Science Foundation grant 2145802. D.J.L. acknowledges support from the US National Science Foundation grant number CBET-2223566. G.Y. acknowledges support from The Welch Foundation award F-1861, and Camille Dreyfus Teacher-Scholar Award. M.D.D. acknowledges funding support from NSF (grant no. EEC1160483). J.-H.A acknowledges the National Research Foundation of Korea (NRF-2015R1A3A2066337). J.C. acknowledges the Henry Samueli School of Engineering & Applied Science and the Department of Bioengineering at the University of California, Los Angeles for startup support and a Brain & Behavior Research Foundation Young Investigator Grant. K.T. acknowledges JST AIP Accelerated Program (no. JPMJCR21U1) and JSPS KAKENHI (grant no. JP22H00594). P.S.W. acknowledges the National Science Foundation (CMMI1636136) for support. A.M.A., M.C.H., and P.S.W. thank the National Institute on Drug Abuse (DA045550) for support. S.M. and X.C. appreciated the support from the Smart Grippers for Soft Robotics (SGSR) Programme under the National Research Foundation, Prime Minister’s Office, Singapore under its Campus of Research Excellence and Technological Enterprise (CREATE) programme

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to &lt; 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of &amp; GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P &lt; 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo