5,885 research outputs found

    A compendium of genetic regulatory effects across pig tissues

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    The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

    Rehabilitation protocols in unstable trochanteric fractures treated with cephalomedullary nails in elderly: current practices and outcome.

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    BACKGROUND Optimal rehabilitation treatment after surgery for fixation of unstable trochanteric fractures is challenging in elderly patients. PURPOSE The objective of this study is to analyse the existing literature on available rehabilitation protocols with regards to permitting or restricting early weight bearing following fixation of unstable trochanteric fractures treated by the use of cephalomedullary nails in patients at least 65 years of age. METHODS A systematic review was performed based on the checklist of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies published between 1948 and 2018 on elderly patients with unstable trochanteric fractures treated with cephalomedullary nails that offered information on the postoperative rehabilitation protocol have been selected. Subsequently, the results and complications have been analysed according to the protocols. RESULTS Fifteen of the 7056 initial articles have been selected for analysis. Authors who did not restrict weight bearing to their patients reported a shorter hospitalization time and a lower orthopaedic complication rate but a greater systemic complication rate, worse functional scores, and a higher reoperation and mortality rates. Those results should be taken with caution because of the heterogeneity of provided clinical information and the fact that none of the included studies considered the different rehabilitation protocols as study variables to analyse its influence on the results. CONCLUSION With evidence available to date, there is no clear agreement on the postoperative rehabilitation protocol following fixation of an unstable trochanteric fracture by cephalomedullary nail in the elderly

    Circulating Oxidized mtDNA is Associated Broadly with Cardiovascular Disease in a Longitudinal Cohort Study of Psoriasis

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    Psoriasis (PSO) is a chronic and systemic inflammatory autoimmune disease associated with atherosclerosis and myocardial infarction. Given that atherosclerosis is both inflammation and immune driven, we sought to expand on known immune and inflammatory biomarkers in a PSO cohort. In this study, we focus on oxidized mtDNA (ox-mtDNA), a product of cells undergoing pyroptosis, including keratinocytes, which was quantified in patients with PSO and individuals without PSO by ELISA. Patients with PSO had significantly higher ox-mtDNA levels than healthy subjects (mean ± SD = 9246 ± 2518 pg/ml for patients with PSO vs 7382 ± 2506 pg/ml for those without; P = .006). Importantly, ox-mtDNA was positively associated with IL-17a (β = 0.25; P = .03) and low-density granulocytes (β = 0.37; P = .005) but negatively associated with high-density lipoprotein-cholesterol (β = −0.29; P = .006). After adjusting for traditional cardiovascular risk factors, we found that ox-mtDNA was associated with noncalcified coronary burden, which was measured by coronary computed tomography angiography (β = 0.19; P = .003). Biologic-naïve patients with PSO receiving anti–IL-17a therapy had a 14% decrease in ox-mtDNA (mean ± SD: 10540 ± 614 pg/ml at baseline to 9016 ± 477 pg/ml at 1 year; P = .016) and a 10% reduction in noncalcified coronary artery burden (mean ± SD: 1.06 ± 0.45 at baseline, reducing to 0.95 ± 0.35 at 1 year; P = .0037). In summary, levels of ox-mtDNA in PSO are associated with measures of coronary plaque formation, indicating that this biomarker may be an autoimmune-driven early atherosclerotic feature

    Mechanical Cues for Triggering and Regulating Cellular Movement Selectively at the Single-Cell Level

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    Cell motility plays important roles in many biophysical and physiological processes ranging from in vitro biomechanics, wound healing, to cancer metastasis. This work introduces a new means to trigger and regulate motility individually using transient mechanical stimulus applied to designated cells. Using BV2 microglial cells, our investigations indicate that motility can be reproducibly and reliably initiated using mechanical compression of the cells. The location and magnitude of the applied force impact the movement of the cell. Based on observations from this investigation and current knowledge of BV2 cellular motility, new physical insights are revealed into the underlying mechanism of force-induced single cellular movement. The process involves high degrees of myosin activation to repair actin cortex breakages induced by the initial mechanical compression, which leads to focal adhesion degradation, lamellipodium detachment, and finally, cell polarization and movement. Modern technology enables accurate control over force magnitude and location of force delivery, thus bringing us closer to programming cellular movement at the single-cell level. This approach is of generic importance to other cell types beyond BV2 cells and has the intrinsic advantages of being transient, non-toxic, and non-destructive, thus exhibiting high translational potentials including mechano-based therapy

    Ouranosinc/xclim: v0.41.0

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    Contributors to this version: Trevor James Smith (@Zeitsperre), Pascal Bourgault (@aulemahal), Ludwig Lierhammer (@ludwiglierhammer), Éric Dupuis (@coxipi). New features and enhancements New properties xclim.sdba.properties.decorrelation_length and xclim.sdba.properties.transition_probability. (PR/1252) New indicators ensembles.change_significance now supports Mann-whitney U-test and flexible realization. (PR/1285). New indices and indicators for converting from snow water equivalent to snow depth (snw_to_snd) and snow depth to snow water equivalent (snd_to_snw) using snow density [kg / m^3]. (PR/1271). New indices and indicators for determining upwelling radiation (shortwave_upwelling_radiation_from_net_downwelling and longwave_upwelling_radiation_from_net_downwelling; CF variables rsus and rlus) from net and downwelling radiation (shortwave: rss and rsds; longwave: rls and rlds). (PR/1271). New indice and indicator {snd | snw}_season_{length | start | end} which generalize snow_cover_duration and continuous_snow_cover_{start | end} to allow using these functions with variable snw (PR/1275). New indice and indicator (dryness_index) for estimating soil humidity classifications for winegrowing regions (based on Riou et al. (1994)). (GH/355, PR/1235). Breaking changes xclim testing default behaviours have been changed (GH/1295, PR/1297): Running pytest will no longer use pytest-xdist distributed testing be default (can be set with -n auto|logical|#. Coverage is also no longer gathered/reported by default. Running tox will now set pytest-xdist to use -n logical processes (with a max of 10). Default behaviour for testing is to no longer always fetch xclim-testdata. If testdata is found in $HOME/.xclim_testing_data, files will be copied to individual processes, otherwise, will be fetched as needed. Environment variables evaluated when running pytest have been changed (GH/1295, PR/1297): For testing against specific branches of xclim-testdata: MAIN_TESTDATA_BRANCH -&gt; XCLIM_TESTDATA_BRANCH The option to skip fetching of testdata (SKIP_TEST_DATA) has been removed A new environment variable (XCLIM_PREFETCH_TESTING_DATA) is now available to gather xclim-testdata before running test ensemble (default: False). Environment variables are now passed to tox on execution. Bug fixes build_indicator_module_from_yaml now accepts a reload argument. When re-building a module that already exists, reload=True removes all previous indicator before creating the new ones. (GH/1192, PR/1284). The test for French translations of official indicators was fixed and translations for CFFWIS indices, FFDI, KDBI, DF and Jetstream metric woollings have been added or fixed. (PR/1271). use_ufunc in windowed_run_count is now supplied with argument freq to warn users that the 1d method does not support resampling after run length operations (GH/1279, PR/1291). {snd | snw}_max_doy now avoids an error due to xr.argmax when there are all-NaN slices. (PR/1277). Internal changes xclim has adopted PEP 517 and PEP 621 (pyproject.toml using the flit backend) to replace the legacy setup.py used to manage package organisation and building. Many tooling configurations that already supported the pyproject.toml standard have been migrated to this file. CI and development tooling documentation has been updated to reflect these changes. (PR/1278, suggested from PyOpenSci Software Review). Documentation source files have been moved around to remove some duplicated image files. (PR/1278). Coveralls GitHub Action removed as it did not support pyproject.toml-based configurations. (PR/1278). Add a remark about how xclim's CFFWIS is different from the original 1982 implementation. (GH/1104, PR/1284). Update CI runs to use Python3.9 when examining upstream dependencies. Replace setup-conda action with provision-with-micromamba action. (PR/1286). Update CI runs to always use tox~=4.0 and the latest virtual machine images (now ubuntu-22.04). (PR/1288, PR/1297). SBCK installation command now points to the official development repository. (PR/1288). Some references in the BibTeX were updated to point to better resources. (PR/1288). Add a GitHub CI workflow for performing dependency security review scanning. (PR/1287). Grammar and spelling corrections were applied to some docstrings. (PR/1271). Added [radiation] ([power] / [area]) to list of defined acceptable units. (PR/1271). Updated testing data used to generate the atmosds dataset to use more reproducibly-converted ERA5 data, generated with the miranda Python package. (PR/1269). Updated testing dependencies to use pytest-xdist&gt;=3.2, allowing for the new --dist=worksteal scheduler for distributing the pool of remaining tests across workers after individual workers have exhausted their own queues. (PR/1235). Adding infer context to the unit conversion in of the training of ExtremeValues. (PR/1299). Added sphinxcontrib-svg2pdfconverter for converting SVG graphics within documentation to PDF-compatible images. (PR/1296). README badges for supported Python versions and repository health have been added. (GH/1304, PR/1307). </ul

    JWST PEARLS. Prime Extragalactic Areas for Reionization and Lensing Science: Project Overview and First Results

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    We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9-4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9-4.5 μm. PEARLS is designed to be of lasting benefit to the community

    Stress, anxiety, and illness perception in patients experiencing delay in operative care due to the COVID-19 pandemic

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    Background: Amid the height of the COVID-19 pandemic in the US, the US Surgeon General ordered hospitals and healthcare systems to stop all elective surgical procedures. The aim of our study was to evaluate the additional mental health impact of surgical delay on patients awaiting surgery for benign, pre-malignant and malignant conditions within the context of the COVID-19 pandemic. Study design: All patients over the age of 18 awaiting surgery for benign, pre-malignant or malignant conditions within the gynecologic oncology, surgical oncology and colorectal services across Northwell Health were eligible for participation. Upon successful enrollment, participants completed a baseline questionnaire consisting of the Generalized Anxiety Disorder Questionnaire, the Penn State Worry Questionnaire, and Brief-Illness Patient Questionnaire. Results: The surgical delay was considered moderately to extremely concerning by 72 % of survey respondents, with one third indicating the highest (10/10) level of concern. Fifty-five percent of patients with a pre-operatively suspected/confirmed cancer or pre-malignant condition demonstrated mild to severe anxiety in their completion of the GAD-7 scale. The average time awaiting surgery was 117 days (range 8–292); and 63 % of respondents indicated that the delay had a moderate to severe impact on their daily life. Conclusions: Patients awaiting surgery for confirmed, suspected or pre-malignant conditions expressed decreased sense of control and increased levels of distress compared to patients awaiting procedures for benign conditions (p < 0.05, 95 % CI [-2.65, -0.08]). Future research will focus on the effects of COVID-19 related delays in operative care on clinical outcomes, including cancer morbidity and mortality

    xclim: xarray-based climate data analytics

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    xclim is a Python library that enables computation of climate indicators over large, hetero- geneous data sets. It is built using xarray objects and operations, can seamlessly benefit from the parallelization handling provided by dask, and relies on community conventions for data formatting and metadata attributes. xclim is meant as a tool to facilitate both climate science research and the delivery of operational climate services and products. In addition to climate indicator calculations, xclim also includes utilities for bias correction and statistical adjustment, ensemble analytics, model diagnostics, data quality assurance, and metadata standards compliance

    Evolutionary and ecological role of extracellular contractile injection systems: from threat to weapon.

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    Contractile injection systems (CISs) are phage tail-related structures that are encoded in many bacterial genomes. These devices encompass the cell-based type VI secretion systems (T6SSs) as well as extracellular CISs (eCISs). The eCISs comprise the R-tailocins produced by various bacterial species as well as related phage tail-like structures such as the antifeeding prophages (Afps) of Serratia entomophila, the Photorhabdus virulence cassettes (PVCs), and the metamorphosis-associated contractile structures (MACs) of Pseudoalteromonas luteoviolacea. These contractile structures are released into the extracellular environment upon suicidal lysis of the producer cell and play important roles in bacterial ecology and evolution. In this review, we specifically portray the eCISs with a focus on the R-tailocins, sketch the history of their discovery and provide insights into their evolution within the bacterial host, their structures and how they are assembled and released. We then highlight ecological and evolutionary roles of eCISs and conceptualize how they can influence and shape bacterial communities. Finally, we point to their potential for biotechnological applications in medicine and agriculture
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