saseR: Juggling offsets unlocks RNA-seq tools for fast and Scalable differential usage, Aberrant Splicing and Expression Retrieval.

RNA-seq data analysis relies on many different tools, each tailored to specific applications and coming with unique assumptions and restrictions. Indeed, tools for differential transcript usage, or diagnosing patients with rare diseases through splicing and expression outliers, either lack in performance, discard information, or do not scale to massive data compendia. Here, we show that replacing the normalisation offsets unlocks bulk RNA-seq workflows for scalable differential usage, aberrant splicing and expression analyses.

An update for (Stål, 1855) (Hemiptera, Pentatomidae) distribution in Belgium.

The brown marmorated stink bug, , represents an important insect pest and subsequently an important agricultural threat due to its polyphagous feeding habits and adaptability to diverse climates. Native from East Asia, its recent establishment in various regions, including North America and Europe, has led to substantial yield losses and economic impacts, which highlight the need for comprehensive research efforts, based on data occurrence by combining those from expert entomologists and citizen scientists. We reported here 14 new occurrences of this insect pest in the three regions of Belgium.

Mode of action of in the intestinal dialogue: role of extracellular proteins, metabolites and cell envelope components.

is a promising next-generation beneficial microbe due to its natural presence in the mucus layer of the gut, its symbiotic ability to degrade mucus, and its capacity to improve the intestinal barrier function. is able to counteract weight gain and immuno-metabolic disturbances in several animal models. Many of these disorders, including obesity and auto-immune diseases, have been associated with decreased gut barrier function and consequent increased inflammation.

Observational constraints reduce model spread but not uncertainty in global wetland methane emission estimates.

The recent rise in atmospheric methane (CH ) concentrations accelerates climate change and offsets mitigation efforts. Although wetlands are the largest natural CH source, estimates of global wetland CH emissions vary widely among approaches taken by bottom-up (BU) process-based biogeochemical models and top-down (TD) atmospheric inversion methods. Here, we integrate in situ measurements, multi-model ensembles, and a machine learning upscaling product into the International Land Model Benchmarking system to examine the relationship between wetland CH emission estimates and model performance.

Inhibition of thrombin-activatable fibrinolysis inhibitor via DS-1040 to accelerate clot lysis in patients with acute pulmonary embolism: a randomized phase 1b study.

Background: The optimal treatment of intermediate-risk pulmonary embolism (PE) in hemodynamically stable patients remains unknown. Fibrinolytics reduce the risk of hemodynamic deterioration but increase bleeding risk. DS-1040, an inhibitor of thrombin-activatable fibrinolysis inhibitor, enhanced endogenous fibrinolytic activity without increasing bleeding risk in preclinical studies.

Impacts of Semiochemical Traps Designed for Boheman 1833 (Coleoptera: Chrysomelidae) on Nontarget Beneficial Entomofauna in Field Bean Crops.

Broad bean weevils (BBWs-Coleoptera: Chrysomelidae) are serious pests of field bean seeds that hamper the promotion of this crop in the diversification of European cropping systems. Recent research has identified different semiochemical lures and trap devices for the development of semiochemical-based control strategies of BBWs. In this study, two field trials were carried out in order to provide necessary information supporting the implementation of sustainable field use of semiochemical traps against BBWs.

Screening for hazardous alcohol use in the Emergency Department: Comparison of phosphatidylethanol with the Alcohol Use Disorders Identification Test and the Timeline Follow-back.

Background: Up to 15% of all visits to the Emergency Department (ED) are alcohol related. Identification of problematic alcohol use is important in this setting because it allows for intervention and prevention efforts. This study investigated the correlation between the objective phosphatidylethanol (PEth) marker and the subjective Alcohol Use Disorders Identification Test (AUDIT) and Timeline Followback Questionnaire (TLFB) as screening methods for hazardous alcohol use in the general ED population.

Chronic jetlag reprograms gene expression in the colonic smooth muscle layer inducing diurnal rhythmicity in the effect of bile acids on colonic contractility.

Background: Secondary bile acids entrain peripheral circadian clocks and inhibit colonic motility via the bile acid receptor GPBAR1. We aimed to investigate whether chronodisruption affected the rhythm in serum bile acid levels and whether this was associated with alterations in clock gene and Gpbar1 mRNA expression in the colonic smooth muscle layer. We hypothesized that this in turn may affect the rhythm in the inhibitory effect of secondary bile acids on colonic contractility.

Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity.

Bitter taste receptors (taste 2 receptors, TAS2Rs) serve as warning sensors in the lingual system against the ingestion of potentially poisonous food. Here, we investigated the functional role of TAS2Rs in the human gut and focused on their potential to trigger an additional host defense pathway in the intestine. Human jejunal crypts, especially those from individuals with obesity, responded to bitter agonists by inducing the release of antimicrobial peptides (α-defensin 5 and regenerating islet-derived protein 3 α [REG3A]) but also regulated the expression of other innate immune factors (mucins, chemokines) that affected E.

Milvexian for the Prevention of Venous Thromboembolism.

Background: Factor XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism may be more effective and result in less bleeding than conventional anticoagulants. Additional data are needed regarding the efficacy and safety of milvexian, an oral factor XIa inhibitor.

Methods: In this parallel-group, phase 2 trial, we randomly assigned 1242 patients undergoing knee arthroplasty to receive one of seven postoperative regimens of milvexian (25 mg, 50 mg, 100 mg, or 200 mg twice daily or 25 mg, 50 mg, or 200 mg once daily) or enoxaparin (40 mg once daily).

Regional trends and drivers of the global methane budget.

The ongoing development of the Global Carbon Project (GCP) global methane (CH ) budget shows a continuation of increasing CH emissions and CH accumulation in the atmosphere during 2000-2017. Here, we decompose the global budget into 19 regions (18 land and 1 oceanic) and five key source sectors to spatially attribute the observed global trends. A comparison of top-down (TD) (atmospheric and transport model-based) and bottom-up (BU) (inventory- and process model-based) CH emission estimates demonstrates robust temporal trends with CH emissions increasing in 16 of the 19 regions.

Risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer using edoxaban.

Background: In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients.

Abelacimab for Prevention of Venous Thromboembolism.

Background: The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.

Methods: In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily.

Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice.

Aim: Chronodisruption desynchronizes peripheral clocks and leads to metabolic diseases. Feeding cues are important synchronizers of peripheral clocks and influence rhythmic oscillations in intestinal microbiota and their metabolites. We investigated whether chronic jetlag, mimicking frequent time zone travelling, affected the diurnal fluctuations in faecal short-chain fatty acid (SCFA) levels, that feed back to the gut clock to regulate rhythmicity in gut function.

Circadian clocks in the digestive system.

Many molecular, physiological and behavioural processes display distinct 24-hour rhythms that are directed by the circadian system. The master clock, located in the suprachiasmatic nucleus region of the hypothalamus, is synchronized or entrained by the light-dark cycle and, in turn, synchronizes clocks present in peripheral tissues and organs. Other environmental cues, most importantly feeding time, also synchronize peripheral clocks.

Sources of particulate-matter air pollution and its oxidative potential in Europe.

Particulate matter is a component of ambient air pollution that has been linked to millions of annual premature deaths globally. Assessments of the chronic and acute effects of particulate matter on human health tend to be based on mass concentration, with particle size and composition also thought to play a part. Oxidative potential has been suggested to be one of the many possible drivers of the acute health effects of particulate matter, but the link remains uncertain.

Involvement of the GHSR in the developmental programming and metabolic disturbances induced by maternal undernutrition.

The mismatch between maternal undernutrition and adequate nutrition after birth increases the risk of developing metabolic diseases. We aimed to investigate whether the hyperghrelinemia during maternal undernourishment rewires the hypothalamic development of the offspring and contributes to the conversion to an obese phenotype when fed a high-fat diet (HFD). Pregnant C57BL/6 J, wild type (WT) and ghrelin receptor (GHSR) mice were assigned to either a normal nourished (NN) group, or an undernutrition (UN) (30% food restricted) group.

Definition of pulmonary embolism-related death and classification of the cause of death in venous thromboembolism studies: Communication from the SSC of the ISTH.

Pulmonary embolism (PE)-related death is often a component of the primary outcome in venous thromboembolism (VTE) clinical studies. Definitions for PE-related death vary widely, which may lead to biased risk estimates of clinical outcomes, thereby affecting both internal and external validity of study results. We here provide a standardized definition of PE-related death and propose guidance for classification and reporting of the cause of death for clinical studies in VTE.

Development of a standardized definition of pulmonary embolism-related death: A cross-sectional survey of international thrombosis experts.

Introduction: Pulmonary embolism (PE)-related death is often part of the primary outcome in venous thromboembolism (VTE) studies. The Scientific and Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis developed a definition for PE-related death and classification of the cause of death. The present survey evaluated a preliminary version of this definition and classification.

Night-time feeding of Bmal1-/- mice restores SCFA rhythms and their effect on ghrelin.

The known crosstalk between short-chain fatty acids (SCFAs) and the circadian clock is tightly intertwined with feeding time. We aimed to investigate the role of the core clock gene Bmal1 and feeding time in the diurnal rhythms in plasma and caecal SCFA levels and in their effect on the release of the hunger hormone ghrelin in the stomach and colon. WT, Bmal1-/- (ad libitum fed) and night-time-restricted-fed (RF)-Bmal1-/- littermates were killed at zeitgeber time (ZT) 4 and 16.

Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: Results from the Hokusai VTE Cancer study.

Background: The safety and efficacy of edoxaban and dalteparin is unclear for several cancer groups.

Methods: We evaluated the occurrence of the primary outcome in large cancer groups. The primary outcome was the composite of recurrent VTE or major bleeding over 12 months.

Clinical implications of incidental venous thromboembolism in cancer patients.

Introduction: In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed to evaluate anticoagulant therapy in cancer patients with incidental and symptomatic VTE.

Methods: The Hokusai VTE Cancer Study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE.

Randomized phase 2 trial comparing JNJ-9375, a thrombin-directed antibody, with apixaban for prevention of venous thrombosis.

Background: JNJ-9375 is an antibody against exosite 1 on thrombin, inhibits substrate binding but not catalytic activity.

Objective: To examine the possibility that JNJ-9375 attenuates thrombosis without affecting hemostasis, we compared the efficacy and safety of JNJ-9375 and apixaban.

Methods: In this double-blind, double-dummy phase 2 trial, 308 patients undergoing knee arthroplasty were randomized to receive either a single postoperative intravenous infusion of JNJ-9375 in doses ranging from 0.