Tactical analysis of direct attack from the English Premier League and Spanish La Liga.

The aim of this study was to evaluate the effect of tactical and contextual dimensions on the offensive performance, in terms of degree of penetration or creation of goal scoring opportunities (GSO), of direct attacks in the English Premier League (EPL) and Spanish La Liga. In total, 10,078 team possessions from 40 random La Liga and EPL matches were initially selected. From that, 2,384 possessions categorized as open play direct attacks were selected for analysis, including a first univariate binary regression analysis and a further construction of adjusted binary multivariate logistic regression models.

Central Nervous System Prophylaxis Utilization in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Within a Large Community Health System.

Purpose: The impact of central nervous system (CNS) prophylaxis in diffuse large B-cell lymphoma (DLBCL) is contentious. The CNS International Prognostic Index (IPI) calculator offers prognostic guidance in identifying those patients who may be at highest risk of disease progression or relapse to the CNS. However, it is unclear whether this tool has guided clinician decision-making in a real-world setting.

Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial.

Background: Morbidity and mortality in pulmonary arterial hypertension (PAH) remain high. Activation of platelet-derived growth factor receptor, colony stimulating factor 1 receptor, and mast or stem cell growth factor receptor kinases stimulates inflammatory, proliferative, and fibrotic pathways driving pulmonary vascular remodelling in PAH. Seralutinib, an inhaled kinase inhibitor, targets these pathways.

Discovery of Pyridopyrimidinones that Selectively Inhibit the H1047R PI3Kα Mutant Protein.

The H1047R mutation of is highly prevalent in breast cancers and other solid tumors. Selectively targeting PI3Kα over PI3Kα is crucial due to the role that PI3Kα plays in normal cellular processes, including glucose homeostasis. Currently, only one PI3Kα-selective inhibitor has progressed into clinical trials, while three pan mutant (H1047R, H1047L, H1047Y, E542K, and E545K) selective PI3Kα inhibitors have also reached the clinical stage.

Atypical MAP kinases - new insights and directions from amoeba.

Mitogen-activated protein kinases (MAPKs) have been the focus of many studies over the past several decades, but the understanding of one subgroup of MAPKs, orthologs of MAPK15, known as atypical MAPKs, has lagged behind others. In most organisms, specific activating signals or downstream responses of atypical MAPK signaling pathways have not yet been identified even though these MAPKs are associated with many eukaryotic processes, including cancer and embryonic development. In this Review, we discuss recent studies that are shedding new light on both the regulation and function of atypical MAPKs in different organisms.

Developing New Scales of Personal Food Security.

Background: Food insecurity is standardly measured at the household level or for groups of household members. However, food hardships may differ for individuals within households. Summary measures of people's individual experiences of food insecurity are needed.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions.

Design and Reliability of an Observational Framework to Evaluate the Individual Offensive Behavior in Youth Soccer-The INDISOC Tool.

Despite the great development of match analysis in professional soccer during the last decade, very few studies have assessed the individual technical and tactical behaviors of youth soccer players. The purpose of this paper was to design and assess the reliability of an observational instrument to evaluate the INDIvidual offensive behavior in competitive 7 and 11-a-side SOCcer (INDISOC). A total of eight experts in soccer training and analysis were included in the design of the tool by means of meetings and exploratory observations.

Design and evaluation of achiral, non-atropisomeric 4-(aminomethyl)phthalazin-1(2H)-one derivatives as novel PRMT5/MTA inhibitors.

MRTX1719 is an inhibitor of the PRMT5/MTA complex and recently entered clinical trials for the treatment of MTAP-deleted cancers. MRTX1719 is a class 3 atropisomeric compound that requires a chiral synthesis or a chiral separation step in its preparation. Here, we report the SAR and medicinal chemistry design strategy, supported by structural insights from X-ray crystallography, to discover a class 1 atropisomeric compound from the same series that does not require a chiral synthesis or a chiral separation step in its preparation.

An atypical MAPK regulates translocation of a GATA transcription factor in response to chemoattractant stimulation.

The Dictyostelium atypical mitogen-activated protein kinase (MAPK) Erk2 is required for chemotactic responses to cAMP as amoeba undergo multicellular development. In this study, Erk2 was found to be essential for the cAMP-stimulated translocation of the GATA transcription factor GtaC as indicated by the distribution of a GFP-GtaC reporter. Erk2 was also found to be essential for the translocation of GtaC in response to external folate, a foraging signal that directs the chemotaxis of amoeba to bacteria.

Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of -Deleted Cancers.

The PRMT5•MTA complex has recently emerged as a new synthetically lethal drug target for the treatment of -deleted cancers. Here, we report the discovery of development candidate . is a potent and selective binder to the PRMT5•MTA complex and selectively inhibits PRMT5 activity in -deleted cells compared to -wild-type cells.

Randomised clinical trial: a phase 1b study of GB004, an oral HIF-1α stabiliser, for treatment of ulcerative colitis.

Background: Epithelial barrier dysfunction contributes to a dysregulated intestinal immune response in ulcerative colitis (UC). GB004 is an orally administered, small molecule, gut-targeted stabiliser of hypoxia-inducible factor-1α, a transcription factor with protective roles at the epithelial layer of the inflamed gut.

Aims: To evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of GB004 in patients with active UC.

Experimental study of foam propagation and stability in highly permeable porous media under lateral water flow: Diverting groundwater for application to soil remediation.

Foam propagation and stability in highly permeable porous media, encountered in soil pollution applications, are still challenging. Here, we investigated the application of foam for blocking the aquifer to divert the flow from a contaminated zone and, therefore, ease the remediation treatments. The main aim was to better understand the critical parameters when the foam is injected into a highly permeable aquifer with high groundwater flow velocity (up to 10 m/day).

[Analgesia, sedation, neuromuscular blockade and delirium management practices in Chilean intensive care units].

Background: The appropriate use of analgesia, sedation, neuromuscular blockade and the diagnosis and prevention of delirium (ASBD) are associated with better outcomes in critically ill patients at Intensive Care Unit (ICUs).

Aim: To know the practices about analgesia, sedation, delirium, and neuromuscular blockade use among healthcare professionals working in adult ICUs in Chile.

Material And Methods: An electronic survey was sent to 812 professionals working in ICUs using a previously published instrument, which was adapted and authorized by the author.

Different Pitch Configurations Constrain the Playing Tactics and the Creation of Goal Scoring Opportunities during Small Sided Games in Youth Soccer Players.

The aim of this study was to explore the tactical effects of different pitch configurations on the collective playing tactics and the creation of goal scoring opportunities (GSO) during small sided soccer games (SSG) in youth players. A total of 22 players performed a 7 vs. 7 + 1 floater (including goalkeepers) under three different pitch configurations ("Standard", 53 × 38 m; "Long", 63 × 32 m; and "Wide", 43 × 47 m).

Measuring the impact of calorie labeling: The mechanisms behind changes in obesity.

Learning the true calorie content of fast food may induce consumers to change behavior, yet recent evidence is mixed on whether calorie labels cause consumers to order healthier meals. Especially for individuals for whom consumption of highly caloric fast-food is habitual, a rational response to calorie labeling may instead be to maintain consumption levels but increase physical activity. Using American Time Use Survey data from 2004 to 2012, we show that the 2008 New York City Calorie Labeling Mandate significantly improved several measures of physical activity, including overall metabolic equivalents of task units and minutes of sedentary activity.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation.

The KRAS Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy.

KRAS inhibitors, including MRTX849, are promising treatment options for KRAS-mutant non-small cell lung cancer (NSCLC). PD-1 inhibitors are approved in NSCLC; however, strategies to enhance checkpoint inhibitor therapy (CIT) are needed. mutations are smoking-associated transversion mutations associated with high tumor mutation burden, PD-L1 positivity, and an immunosuppressive tumor microenvironment.

Addressing the carbon footprint, healthfulness, and costs of self-selected diets in the USA: a population-based cross-sectional study.

Background: The role of diet in health is well established and, in the past decade, more attention has been given to the role of food choices in the environment. The agricultural sector produces about a quarter of the world's greenhouse gas emissions (GHGE), and meat production, especially beef, is an important contributor to global GHGE. Our study aimed to address a fundamental gap in the diet-climate literature: identifying consumers who are receptive to making dietary changes, and the effect of their potential changes on GHGE, diet healthfulness, and diet costs.

Playing tactics, contextual variables and offensive effectiveness in English Premier League soccer matches. A multilevel analysis.

The aim of this study was to investigate the combined effects of tactical and contextual indicators on achieving offensive penetration and scoring opportunities in English Premier League (EPL) soccer matches. A total of 1971 team possessions from 20 random matches were evaluated by means of multidimensional observation. The EPL matches had a great proportion of fast attacks (36.

The KRAS Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients.

Despite decades of research, efforts to directly target KRAS have been challenging. MRTX849 was identified as a potent, selective, and covalent KRAS inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRAS, and inhibits KRAS-dependent signaling. MRTX849 demonstrated pronounced tumor regression in 17 of 26 (65%) KRAS-positive cell line- and patient-derived xenograft models from multiple tumor types, and objective responses have been observed in patients with KRAS-positive lung and colon adenocarcinomas.

Effect of Match Location, Team Ranking, Match Status and Tactical Dimensions on the Offensive Performance in Spanish 'La Liga' Soccer Matches.

The aim of this paper was to study the combined effects of tactical and contextual dimensions on achieving offensive performance in open play possessions from Spanish "La Liga" soccer matches. 1860 team possessions from 20 random matches were evaluated by means of multidimensional observation. Multilevel regression models were constructed to predict the probability to achieve offensive performance according to the tactical and contextual dimensions registered in each possession.

The effect of arm-crank exercise training on power output, spirometric and cardiac function and level of autonomy in persons with tetraplegia.

Studies on the effects of exercise training in persons with cervical spinal cord injury (CSCI) are scarce. The aim of this study was to determine the effect of an 8-week stationary arm-crank exercise (ACE) training programme on the level of autonomy, exercise performance, pulmonary functional parameters and resting heart rate variability (HRV) in persons with CSCI. Quadriplegia Index of Function (QIF), arm-crank peak power output (Ppeak), spirometric variables, and HRV indices were measured before and after the training programme in a group of 11 persons with CSCI.