Paediatric strategy forum for medicinal product development of PI3-K, mTOR, AKT and GSK3β inhibitors in children and adolescents with cancer.

Phosphatidylinositol 3-kinase (PI3-K) signalling pathway is a crucial path in cancer for cell survival and thus represents an intriguing target for new paediatric anti-cancer drugs. However, the unique clinical toxicities of targeting this pathway (resulting in hyperglycaemia) difficulties combining with chemotherapy, rarity of mutations in childhood tumours and concomitant mutations have resulted in major barriers to clinical translation of these inhibitors in treating both adults and children. Mutations in PIK3CA predict response to PI3-K inhibitors in adult cancers.

Initiation patterns of anticoagulants for atrial fibrillation among older UK adults with and without chronic kidney disease, 2010-2020.

Background: There is a paucity of data on the initiation patterns of anticoagulants among older atrial fibrillation patients with and without chronic kidney disease (CKD).

Setting And Methods: We used the UK Clinical Practice Research Datalink (2010-2020) to conduct a retrospective cohort study to evaluate anticoagulant initiation patterns for older adults (≥65 years) with CKD (N=18 421) and without CKD (N=41 901), categorised by severity of CKD: stages 3a, 3b and 4, and initiation dose by respective direct oral anticoagulant (DOAC).

Results: Over the study period, warfarin initiations sharply declined and were replaced by DOACs regardless of CKD status or stage.

Pelvic Incidence as a Predictor of Proximal Junctional Failure in Patients Undergoing Anterior Column Realignment with Anterior Longitudinal Ligament Release to Restore Lordosis in Adult Spinal Deformity: A Retrospective Cohort Study.

Objective: To identify variables that may contribute to the development of proximal junctional failure (PJF) in patients with long lumbo-sacral and thoraco-lumbo-pelvic constructs undergoing anterior column realignment (ACR) with anterior longitudinal ligament release (ALLR).

Methods: Data of patients with adult spinal deformity who underwent ACR with ALLR at L3-4 were collected retrospectively from medical records and a prospectively maintained spine research database between 2016 and 2022.

Results: Eleven (41%) developed PJF at a mean of 24 ± 21 months from the index surgery.

Highly Tough and Reliable Poly(Amic Acid) with Ballistic Impact-Resistance through Modulation of Hydrogen Bonding Interactions.

Poly(amic acid) (PAA) materials as the precursor of polyimide generally show remarkably poor mechanical properties, thus limiting their application as the engineering plastics. In this study, it is demonstrated that the mechanical properties of PAA materials can be improved significantly for tens of folds with breaking strength >50 MPa, Young's modulus >400 MPa, and elongation at break >300% by incorporation of 20% (mol%) poly(propylene glycol) (PPO) soft segments. The optimization for suitable hard-soft composition with 20% PPO and the existence of various hydrogen bonds with different binding energies can dissipate energies efficiently, which simultaneously improve the material strength and toughness.