Stratified Medicine Paediatrics: Cell free DNA and serial tumour sequencing identifies subtype specific cancer evolution and epigenetic states.

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature.

Overcoming Challenges to Adopting Smoke-Free Multi-Unit Housing Policies in a Large U.S. Metropolitan Area: Insights and Recommendations From Affected Groups in 20 Los Angeles County Cities.

Purpose: Community members and non-academic partners ("affected groups") were asked to identify factors that can influence public support, impede adoption, and mitigate challenges related to adopting local smoke-free multi-unit housing policies.

Approach: A series of key informant interviews were conducted with affected groups from a large U.S.

Edited eukaryotic translation initiation factors confer resistance against maize lethal necrosis.

Maize lethal necrosis (MLN), which is caused by maize chlorotic mottle virus along with a potyvirus, has threatened the food security of smallholders in sub-Saharan Africa. Mutations in eukaryotic translation initiation factors (eIFs), which also facilitate virus genome translation, are known to confer variable resistance against viruses. Following phylogenetic analysis, we selected two eIF4E proteins from maize as the most likely candidates to facilitate MLN infection.

Impact of a Geriatric Pharmacy Elective on Student Knowledge, Attitudes, and Empathy Regarding Older Adults.

Objective: To evaluate the impact of a Geriatric Pharmacy elective on pharmacy students' knowledge, attitudes, and empathy regarding older adults.

Methods: Enrolled students in a 15-week Geriatric Pharmacy elective during 3 consecutive academic years were invited to complete a precourse and postcourse survey. The survey consisted of the revised Palmore facts on aging quiz, the University of California at Los Angeles geriatric attitudes scale, the Kiersma-Chen empathy scale, and demographic questions.

Subject-level spinal osteoporotic fracture prediction combining deep learning vertebral outputs and limited demographic data.

Unlabelled: Automated screening for vertebral fractures could improve outcomes. We achieved an AUC-ROC = 0.968 for the prediction of moderate to severe fracture using a GAM with age and three maximal vertebral body scores of fracture from a convolutional neural network.

Satisfaction with a new patient education program for children, adolescents, and young adults with differences of sex development (DSD) and their parents.

Objective: Evaluation of the participant satisfaction with a newly developed interdisciplinary, modular education program for children, adolescents, and young adults with differences of sex development (DSD) and their parents.

Methods: The two-day program including tailored medical information, peer consultation and psychological support aimed to improve diagnosis-specific knowledge and empowerment. Post-training satisfaction was measured using an adapted ZUF-8 questionnaire, scoring from 5 (worst) to a maximum of 26 (best) for persons aged 6-17 and from 10 to 40 points for adults, including 2 open-ended questions.

The 4.2 ka event is not remarkable in the context of Holocene climate variability.

The "4.2 ka event" is a commonly described abrupt climate excursion that occurred about 4200 years ago. However, the extent to which this event is coherent across regional and larger scales is unclear.

Implementation of self-care scenario simulations in a skills-based first year doctor of pharmacy course for student application of the Pharmacists' Patient Care Process.

Background And Purpose: The objective of this project was to assess the impact of self-care scenario simulations on first year doctor of pharmacy student performance and self-perceived confidence in applying the Pharmacists' Patient Care Process (PPCP) during self-care encounters.

Educational Activity And Settings: Self-care scenarios were developed and used during low fidelity simulations in laboratory sessions in a skills-based course. Students met individually with faculty facilitators role-playing patients to apply the PPCP in four simulations.

Precision cancer medicine platform trials: Concepts and design of AcSé-ESMART.

Precision cancer medicine brought the promise of improving outcomes for patients with cancer. High-throughput molecular profiling of tumors at treatment failure aims to direct a patient to a treatment matched to the tumor profile. In this way, improved outcome has been achieved in a small number of patients whose tumors exhibit unique targetable oncogenic drivers.

Outcomes of single- versus multi-port video-assisted thoracoscopic surgery: Data from a multicenter randomized controlled trial of video-assisted thoracoscopic surgery versus thoracotomy for lung cancer.

Objectives: Surgery through a single port may be less painful because access is supplied by 1 intercostal nerve or more painful because multiple instruments are used in 1 port. We analyzed data collected from the video-assisted thoracoscopic surgery group of a randomized controlled trial to compare differences in pain up to 1 year.

Methods: Groups were compared in a prespecified exploratory analysis using direct (regression) and indirect comparison (difference with respect to thoracotomy).

Incorporation of patient-reported outcomes in early-phase clinical trials for childhood and adolescent cancer.

Introduction: The assessment of quality of life (QoL) should be one of the main objectives in paediatric clinical trials. Even though researchers, regulators and advocates support the use of patient-reported outcomes (PROs), this has not been fully implemented. The aim of this study is to assess the measurement of QoL and the usage of PROs, palatability assessments and medication diaries in early-phase clinical trials for childhood and adolescent cancer.

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.

Possible mechanisms to improve sleep spindles via closed loop stimulation during slow wave sleep: A computational study.

Sleep spindles are one of the prominent EEG oscillatory rhythms of non-rapid eye movement sleep. In the memory consolidation, these oscillations have an important role in the processes of long-term potentiation and synaptic plasticity. Moreover, the activity (spindle density and/or sigma power) of spindles has a linear association with learning performance in different paradigms.

Mental disorders in children and adolescents with type 1 diabetes before and during the COVID-19 pandemic: results from the DPV registry.

Objectives: The COVID-19 pandemic affected the mental health of children and adolescents in the general population, yet its impact on those with chronic conditions is relatively unknown. This study aimed to compare the incidences of comorbid mental disorders and substance misuse in children and adolescents with type 1 diabetes before and during the pandemic.

Methods: A total of 42,975 patients aged 6-18 years from the multicentre DPV (Diabetes Prospective Follow-up) registry were included.

A joint model for the estimation of species distributions and environmental characteristics from point-referenced data.

Background: Predicting and explaining species occurrence using environmental characteristics is essential for nature conservation and management. Species distribution models consider species occurrence as the dependent variable and environmental conditions as the independent variables. Suitable conditions are estimated based on a sample of species observations, where one assumes that the underlying environmental conditions are known.

Contexts of care for people with differences of sex development: Diversity is still missing in the laboratory routine.

The 2006 Chicago consensus statement of management of disorders/difference of sex development (DSD) has achieved advantages in clinical care and diagnosis for patients and families affect by DSD. This article provides a brief overview of contexts of care for physicians, and points out specific challenges in clinical practice that have arisen from the transformations of the sex/gender system in recent years. We focus on the impact of diagnosis and laboratory measurements.

Stopped-flow measurement of CO hydration activity by catalytic amyloids.

With the ever-increasing rates of catalysis shown by catalytic amyloids, the use of faster characterization techniques is required for proper kinetic studies. The same is true for inherently fast chemical reactions. Carbon dioxide hydration is of significant interest to the field of enzyme design, given both carbonic anhydrases' status as a "perfect enzyme" and the central role carbonic anhydrase plays in the respiration and existence of all carbon-based life.