Olympic distance duathlon and cardiac performance in highly-trained triathletes.

The effects of triathlon exercise on cardiac function are well documented. While Olympic triathlon (swim-bike-run) remains the standard format, increasing concerns about water quality in natural waterways present ongoing challenges for open-water swimming events, highlighting the potential need to consider alternative formats such as duathlon (run-bike-run) in some circumstances. An additional run may increase the overall metabolic and cardiovascular demand compared with the swim in triathlon, leading to reduced future performance.

Characterising the activity, lifestyle behaviours and health outcomes of UK university students: an observational cohort study with a focus on gender and ethnicity.

Background: Health-related outcomes and behaviours in university students are known to be poor relative to the general population. The substantial contextual shifts related to the COVID-19 pandemic, combined with increased numbers of students from minoritised ethnicity backgrounds and presenting as trans and gender diverse (TGD), means that up-to-date information is unavailable. The primary aim of this study was therefore to characterise the current movement, dietary and lifestyle behaviours, mental health, and Body Mass Index (BMI) of UK university students and assess differences between genders and ethnic groups.

Investigating the Influence of a Tooth Absence on Facial Bone Growth Using a Porcine Model.

With the current state of knowledge regarding disorders of facial bone development, including anodontia, the development of a suitable animal model for preclinical studies is essential. The agenesis of dental buds occurs in about 25% of the human population. Prospects for treatment include the use of growth factors, stem cells, and bioengineering.

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.