Teaching high quality paediatric basic life support to laypeople: The development and evaluation of a virtual simulation game.

Background: Self-directed training has been recognized as a reasonable alternative to traditional instructor-led formats to teach laypeople Basic Life Support (BLS). Virtual tools can facilitate high-quality self-directed resuscitation education; however, their role in teaching paediatric BLS remains unclear due to limited empiric evaluation and suboptimal design of existing tools.

Aim: We describe the development and evaluation of a virtual simulation game (VSG) designed to teach high-quality paediatric BLS using a self-directed, online format with integrated deliberate practice and feedback.

Discovery of PF-07265028, A Selective Small Molecule Inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) for the Treatment of Cancer.

Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights of the drug discovery campaign within the lactam/azalactam series of inhibitors that yielded a small molecule (, PF-07265028), which was advanced to a phase 1 clinical trial (NCT05233436). Key components of the discovery effort included optimization of potency through mitigation of ligand strain as guided by the use of cocrystal structures, mitigation of ADME liabilities (plasma instability and fraction metabolism by CYP2D6), and optimization of kinase selectivity, particularly over immune-modulating kinases with high homology to HPK1.

Synthesis of Fused Bicyclic [1,2,4]-Triazoles from Amino Acids.

A 3-step modular procedure combining carboxylic acids with acyl hydrazines provides access to medicinally relevant [1,2,4]-fused triazoles. Good to excellent yields are achieved with tolerance of aliphatic and aryl substituents as well as 5-, 6-, and 7-membered rings for the fused ring. Conditions that can avoid column chromatography and be applicable for both small scale discovery efforts as well as large scale development processes are demonstrated within.

Transcriptional chronology reveals conserved genes involved in pennate diatom sexual reproduction.

Sexual reproduction is a major driver of adaptation and speciation in eukaryotes. In diatoms, siliceous microalgae with a unique cell size reduction-restitution life cycle and among the world's most prolific primary producers, sex also acts as the main mechanism for cell size restoration through the formation of an expanding auxospore. However, the molecular regulators of the different stages of sexual reproduction and size restoration are poorly explored.

Leaf growth - complex regulation of a seemingly simple process.

Understanding the underlying mechanisms of plant development is crucial to successfully steer or manipulate plant growth in a targeted manner. Leaves, the primary sites of photosynthesis, are vital organs for many plant species, and leaf growth is controlled by a tight temporal and spatial regulatory network. In this review, we focus on the genetic networks governing leaf cell proliferation, one major contributor to final leaf size.

Spatial transcriptomics of a lycophyte root sheds light on root evolution.

Plant roots originated independently in lycophytes and euphyllophytes, whereas early vascular plants were rootless. The organization of the root apical meristem in euphyllophytes is well documented, especially in the model plant Arabidopsis. However, little is known about lycophyte roots and their molecular innovations during evolution.

Design and Synthesis of Functionally Active 5-Amino-6-Aryl Pyrrolopyrimidine Inhibitors of Hematopoietic Progenitor Kinase 1.

Immune activating agents represent a valuable class of therapeutics for the treatment of cancer. An area of active research is expanding the types of these therapeutics that are available to patients via targeting new biological mechanisms. Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of immune signaling and a target of high interest for the treatment of cancer.

Criteria Used to Determine Unrestricted Return to Activity After ACL Reconstruction in Pediatric and Adolescent Patients: A Systematic Review.

Background: The rates of anterior cruciate ligament (ACL) graft failure or contralateral ACL rupture range from 17% to 30% in pediatric patients after ACL reconstruction (ACLR). A contributing factor to the high reinjury rate in this population may be the limited evidence regarding appropriate criteria for allowing unrestricted return to activity (RTA) postoperatively.

Purpose: To review the literature and identify the most commonly used criteria when determining unrestricted RTA after ACLR in pediatric patients.

Barriers and Facilitators of Research in Pediatric Sports Medicine Practitioners: A Survey of the PRiSM Society.

Background: Barriers and facilitators to research in sports medicine (SM) by physicians and allied health (AH) professions such as physical therapists and athletic trainers are understudied. The purpose of this research was to examine and compare research barriers, facilitators, and other research related facets including interests, comfort, knowledge, and resources among SM physicians and AH practitioners.

Study Design: Cross-sectional survey.

Chromosome-scale assembly and annotation of the perennial ryegrass genome.

Background: The availability of chromosome-scale genome assemblies is fundamentally important to advance genetics and breeding in crops, as well as for evolutionary and comparative genomics. The improvement of long-read sequencing technologies and the advent of optical mapping and chromosome conformation capture technologies in the last few years, significantly promoted the development of chromosome-scale genome assemblies of model plants and crop species. In grasses, chromosome-scale genome assemblies recently became available for cultivated and wild species of the Triticeae subfamily.

Protocol for the systematic review of return-to-activity criteria in adolescent patients following an anterior cruciate ligament reconstruction.

Background: Anterior cruciate ligament (ACL) rupture is a debilitating knee injury associated with sequela such as joint instability and progressive degeneration. Unfortunately, following surgical ACL reconstruction in adolescents, the rates of ACL graft failure range from 17 to 19%. A contributing factor to the high reinjury rate in this population may be the limited evidence regarding appropriate criteria for allowing unrestricted return-to-activities (RTA) postoperatively.

PCR performance in the SARS-CoV-2 Omicron variant of concern?

The new SARS-CoV-2 Omicron variant (B.1.1.

PLAZA 5.0: extending the scope and power of comparative and functional genomics in plants.

PLAZA is a platform for comparative, evolutionary, and functional plant genomics. It makes a broad set of genomes, data types and analysis tools available to researchers through a user-friendly website, an API, and bulk downloads. In this latest release of the PLAZA platform, we are integrating a record number of 134 high-quality plant genomes, split up over two instances: PLAZA Dicots 5.

Sex differences in muscle activation patterns associated with anterior cruciate ligament injury during landing and cutting tasks: A systematic review.

Neuromuscular control is critical for maintaining dynamic joint stability and mitigating the risk of anterior cruciate ligament (ACL) injury. Given the increased risk of ACL injury in females, sex-based differential muscle activation strategies are often associated with this risk. For example, the quadriceps-dominant muscle activation strategy sometimes observed in females has been discussed as a cause of their increased risk of ACL injury.

1,2-Difunctionalized bicyclo[1.1.1]pentanes: Long-sought-after mimetics for /-substituted arenes.

The development of a versatile platform for the synthesis of 1,2-difunctionalized bicyclo[1.1.1]pentanes to potentially mimic /-substituted arenes is described.

TRAPID 2.0: a web application for taxonomic and functional analysis of de novo transcriptomes.

Advances in high-throughput sequencing have resulted in a massive increase of RNA-Seq transcriptome data. However, the promise of rapid gene expression profiling in a specific tissue, condition, unicellular organism or microbial community comes with new computational challenges. Owing to the limited availability of well-resolved reference genomes, de novo assembled (meta)transcriptomes have emerged as popular tools for investigating the gene repertoire of previously uncharacterized organisms.

Integrative inference of transcriptional networks in Arabidopsis yields novel ROS signalling regulators.

Gene regulation is a dynamic process in which transcription factors (TFs) play an important role in controlling spatiotemporal gene expression. To enhance our global understanding of regulatory interactions in Arabidopsis thaliana, different regulatory input networks capturing complementary information about DNA motifs, open chromatin, TF-binding and expression-based regulatory interactions were combined using a supervised learning approach, resulting in an integrated gene regulatory network (iGRN) covering 1,491 TFs and 31,393 target genes (1.7 million interactions).

SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021-Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing.

The rapid spread of the SARS-CoV-2 lineages B.1.1.

The Arabidopsis condensin CAP-D subunits arrange interphase chromatin.

Condensins are best known for their role in shaping chromosomes. Other functions such as organizing interphase chromatin and transcriptional control have been reported in yeasts and animals, but little is known about their function in plants. To elucidate the specific composition of condensin complexes and the expression of CAP-D2 (condensin I) and CAP-D3 (condensin II), we performed biochemical analyses in Arabidopsis.

Sex-specific landing biomechanics and energy absorption during unanticipated single-leg drop-jumps in adolescents: implications for knee injury mechanics.

Females aged between 13 and 17 years old possess the highest non-contact ACL injury incidence of any sex-age strata. Considering that energy absorption strategies have been associated with a reduced risk for sustaining an ACL injury, evaluating landing performance in youth athletes requires investigations beyond the kinematic level. The purpose of this study was to identify sex-specific energy absorption strategies in adolescent males and females, including the relationship between strength and the observed strategies.