Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (OR = 46.5, p = 1.74 × 10). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway

Lung adenocarcinoma promotion by air pollutants

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Open Data from the Third Observing Run of LIGO, Virgo, KAGRA, and GEO

Calibration of the LIGO strain data was performed with a GstLAL-based calibration software pipeline (Viets et al. 2018). Calibration of the Virgo strain data was performed with C-based software (Acernese et al. 2022b). Data quality products and event-validation results were computed using the DMT (https://labcit.ligo.caltech.edu/~jzweizig/DMT-Project. html), DQR (https://docs.ligo.org/detchar/data-quality-report/), DQSEGDB (Fisher et al. 2021), gwdetchar (Macloed et al. 2021a), hveto (Smith et al. 2011), iDQ (Essick et al. 2020), and Omicron (Robinet et al. 2020) software packages and contribut- ing software tools. Analyses relied upon the LALSuite software library (LIGO Scientific Collaboration 2018). PESummary was used to postprocess and collate parameter estimation results (Hoy & Raymond 2021). For an exhaustive list of the software used for searching the GW signals and characterizing their source, see Abbott et al. (2021c). Plots were prepared with Matplotlib (Hunter 2007), seaborn (Waskom 2021), GWSumm (Macleod et al. 2021b), and GWpy (Macleod et al. 2021c). NumPy (Harris et al. 2020) and SciPy (Virtanen et al. 2020) were used in the preparation of the manuscript. This material is based upon work supported by NSF’s LIGO Laboratory which is a major facility fully funded by the National Science Foundation. The authors also gratefully acknowledge the support of the Science and Technology Facilities Council (STFC) of the United Kingdom, the Max- Planck-Society (MPS), and the State of Niedersachsen/ Germany for support of the construction of Advanced LIGO and construction and operation of the GEO 600 detector. Additional support for Advanced LIGO was provided by the Australian Research Council. The authors gratefully acknowl- edge the Italian Istituto Nazionale di Fisica Nucleare (INFN), the French Centre National de la Recherche Scientifique (CNRS), and the Netherlands Organization for Scientific Research (NWO) for the construction and operation of the Virgo detector and the creation and support of the EGO consortium. The authors also gratefully acknowledge research support from these agencies as well as by the Council of Scientific and Industrial Research of India, the Department of Science and Technology, India, the Science & Engineering Research Board (SERB), India, the Ministry of Human Resource Development, India, the Spanish Agencia Estatal de Investigación (AEI), the Spanish Ministerio de Ciencia e Innovación and Ministerio de Universidades, the Conselleria de Fons Europeus, Universitat i Cultura and the Direcció General de Política Universitaria i Recerca del Govern de les Illes Balears, the Conselleria d'Innovació, Universitats, Ciència i Societat Digital de la Generalitat Valenciana and the CERCA Programme Generalitat de Catalunya, Spain, the National Science Centre of Poland and the European Union – European Regional Development Fund; Foundation for Polish Science (FNP), the Swiss National Science Foundation (SNSF), the Russian Foundation for Basic Research, the Russian Science Foundation, the European Commission, the European Social Funds (ESF), the European Regional Development Funds (ERDF), the Royal Society, the Scottish Funding Council, the Scottish Universities Physics Alliance, the Hungarian Scientific Research Fund (OTKA), the French Lyon Institute of Origins (LIO), the Belgian Fonds de la Recherche Scientifique (FRS- FNRS), Actions de Recherche Concertées (ARC) and Fonds Wetenschappelijk Onderzoek – Vlaanderen (FWO), Belgium, the Paris Île-de-France Region, the National Research, Development and Innovation Office Hungary (NKFIH), the National Research Foundation of Korea, the Natural Science and Engineering Research Council Canada, Canadian Founda- tion for Innovation (CFI), the Brazilian Ministry of Science, Technology, and Innovations, the International Center for Theoretical Physics South American Institute for Fundamental Research (ICTP-SAIFR), the Research Grants Council of Hong Kong, the National Natural Science Foundation of China (NSFC), the Leverhulme Trust, the Research Corporation, the Ministry of Science and Technology (MOST), Taiwan, the United States Department of Energy, and the Kavli Foundation. The authors gratefully acknowledge the support of the NSF, STFC, INFN, and CNRS for provision of computational resources. This work was supported by MEXT, JSPS Leading-edge Research Infrastructure Program, JSPS Grant-in-Aid for Specially Promoted Research 26000005, JSPS Grant-in-Aid for Scientific Research on Innovative Areas 2905: JP17H06358, JP17H06361 and JP17H06364, JSPS Core-to- Core Program A, Advanced Research Networks, JSPS Grant- in-Aid for Scientific Research (S) 17H06133 and 20H05639, JSPS Grant-in-Aid for Transformative Research Areas (A) 20A203: JP20H05854, the joint research program of the Institute for Cosmic Ray Research, University of Tokyo, National Research Foundation (NRF), Computing Infrastruc- ture Project of Global Science experimental Data hub Center (GSDC) at KISTI, Korea Astronomy and Space Science Institute (KASI), and Ministry of Science and ICT (MSIT) in Korea, Academia Sinica (AS), AS Grid Center (ASGC) and the National Science and Technology Council (NSTC) in Taiwan under grants including the Rising Star Program and Science Vanguard Research Program, Advanced Technology Center (ATC) of NAOJ, and Mechanical Engineering Center of KEK.Peer reviewe

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of binary black hole coalescences confidently observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include the effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that have already been identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total source-frame mass M > 70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz emitted gravitational-wave frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place a conservative upper limit for the merger rate density of high-mass binaries with eccentricities 0 < e ≤ 0.3 at 16.9 Gpc−3 yr−1 at the 90% confidence level

Measurement of the VH,H → ττ process with the ATLAS detector at 13 TeV

A measurement of the Standard Model Higgs boson produced in association with a W or Z boson and decaying into a pair of τ-leptons is presented. This search is based on proton-proton collision data collected at √s = 13 TeV by the ATLAS experiment at the LHC corresponding to an integrated luminosity of 140 fb−1. For the Higgs boson candidate, only final states with at least one τ-lepton decaying hadronically (τ →hadrons + vτ ) are considered. For the vector bosons, only leptonic decay channels are considered: Z → ℓℓ and W → ℓvℓ, with ℓ = e, μ. An excess of events over the expected background is found with an observed (expected) significance of 4.2 (3.6) standard deviations, providing evidence of the Higgs boson produced in association with a vector boson and decaying into a pair of τ-leptons. The ratio of the measured cross-section to the Standard Model prediction is μττ VH = 1.28 +0.30 −0.29 (stat.) +0.25 −0.21 (syst.). This result represents the most accurate measurement of the VH(ττ) process achieved to date