Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution.

Osteosarcoma is the most common primary cancer of the bone, with a peak incidence in children and young adults. Using multi-region whole-genome sequencing, we find that chromothripsis is an ongoing mutational process, occurring subclonally in 74% of osteosarcomas. Chromothripsis generates highly unstable derivative chromosomes, the ongoing evolution of which drives the acquisition of oncogenic mutations, clonal diversification, and intra-tumor heterogeneity across diverse sarcomas and carcinomas.

Is the timing of eating relevant for weight loss?

The potential influence of the timing of eating on body weight regulation in humans has attracted substantial research interest. This review aims to critically evaluate the evidence on timed eating for weight loss, considering energetic and behavioural components of the timing of eating in humans. It has been hypothesised that timed eating interventions may alter energy balance in favour of weight loss by enhancing energy expenditure, specifically the thermic effect of food.

A deep learning framework deploying segment anything to detect pan-cancer mitotic figures from haematoxylin and eosin-stained slides.

Mitotic activity is an important feature for grading several cancer types. However, counting mitotic figures (cells in division) is a time-consuming and laborious task prone to inter-observer variation. Inaccurate recognition of MFs can lead to incorrect grading and hence potential suboptimal treatment.

"It's like it's the old boys club"-the age-related experiences of diverse older women living with HIV: A scoping review and consultative exercise.

Objectives: HIV is often under-recognized in older individuals, particularly women, despite a significant number of new cases being diagnosed in those aged >50 years. This review aimed to understand the age-related experiences and challenges faced by women aged ≥50 years living with HIV through an intersectional perspective.

Methods: We conducted a systematic scoping review using the framework by Arksey and O'Malley, refined by Levac, Colquhoun, and Peters, and informed by a Sex- and Gender-Based Analysis Plus (SGBA+) approach.

Exploring the Perspectives of Older Adults Living With HIV on Virtual Care: Qualitative Study.

Background: As the population of individuals with HIV ages rapidly due to advancements in antiretroviral therapy, virtual care has become an increasingly vital component in managing their complex health needs. However, little is known about perceptions of virtual care among older adults living with HIV.

Objective: This study aimed to understand the perceptions of older adults living with HIV regarding virtual care.

Short-term changes in human metabolism following a 5-h delay of the light-dark and behavioral cycle.

Experimental inversion of circadian and behavioral rhythms by 12 h adversely affects markers of metabolic health. We investigated the effects of a more modest 5-h delay in behavioral cycles. Fourteen participants completed an 8-day in-patient laboratory protocol, with controlled sleep-wake opportunities, light-dark cycles, and diet.

HOX gene expression in the developing human spine.

Positional coding along the anterior-posterior axis is regulated by HOX genes, whose 3' to 5' expression correlates with location along this axis. The precise utilisation of HOX genes in different human cell types is not fully understood. Here, we use single-cell and spatial-transcriptomics, along with in-situ sequencing, to create a developmental atlas of the human fetal spine.

Origins and impact of extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.

Starting From Scratch: Husbandry Techniques to Establish the First Population of 'Akikiki (Oreomystis bairdi) in Human Care Using Wild-Collected Eggs.

Conservation breeding programs can save species from extinction by establishing assurance populations that provide individuals for achieving species recovery goals in the wild. However, keeping animals in human care can result in the selection of phenotypes that may be suboptimal for post-release survival and reproduction. It is therefore essential that conservation breeding programs provide animals with naturalistic conditions that facilitate the performance of species-typical behaviors, an endeavor that is also a vital aspect of animal welfare.

Nest quality predicts the probability of egg loss in the critically endangered 'Alalā (Corvus hawaiiensis).

Conservation breeding programs for endangered species face challenges, notably in the development of husbandry techniques, complicated by the impracticality of conducting controlled experiments. To reduce uncertainty regarding what works in conservation breeding programs, it is essential to capture data. In avian breeding programs, the construction of quality nests and appropriate incubation and handling of eggs by the parents are essential prerequisites to the successful production of offspring.

Design and rationale for a randomized clinical trial testing the efficacy of a lifestyle physical activity intervention for people with HIV and engaged in unhealthy drinking.

Background: Among people living with HIV (PLWH), unhealthy drinking presents an increased risk for negative outcomes. Physical inactivity and sedentariness raise additional health risks. Despite evidence that physical activity (PA) is associated with improved physical and mental functioning and reduced alcohol cravings, there have been no PA studies conducted with PLWH engaged in unhealthy drinking.

A Prospective Observational Cohort Study for Newly Diagnosed Osteosarcoma Patients in the UK: ICONIC Study Initial Results.

There has been little change to the standard treatment for osteosarcoma (OS) over the last 25 years and there is an unmet need to identify new biomarkers and novel therapeutic approaches if outcomes are to improve. Furthermore, there is limited evidence on the impact of OS treatment on patient-reported outcomes (PROs). ICONIC (Improving Outcomes through Collaboration in Osteosarcoma; NCT04132895) is a prospective observational cohort study recruiting newly diagnosed OS patients across the United Kingdom (UK) with matched longitudinal collection of clinical, biological, and PRO data.

The History of Chromosomal Instability in Genome-Doubled Tumors.

Tumors frequently display high chromosomal instability and contain multiple copies of genomic regions. Here, we describe Gain Route Identification and Timing In Cancer (GRITIC), a generic method for timing genomic gains leading to complex copy number states, using single-sample bulk whole-genome sequencing data. By applying GRITIC to 6,091 tumors, we found that non-parsimonious evolution is frequent in the formation of complex copy number states in genome-doubled tumors.

Epigenetic age acceleration is a distinctive trait of epithelioid sarcoma with potential therapeutic implications.

Recently, DNA methylation clocks have been proven to be precise age predictors, and the application of these clocks in cancer tissue has revealed a global age acceleration in a majority of cancer subtypes when compared to normal tissue from the same individual. The polycomb repressor complex 2 plays a pivotal role in the aging process, and its targets have been shown to be enriched in CpG sites that gain methylation with age. This complex is further regulated by the chromatin remodeling complex SWItch/Sucrose Non-Fermentable and its core subunit, notably the tumor suppressor gene SMARCB1, which under physiological conditions inhibits the activity of the polycomb repressor complex 2.

The Effect of Knee Height Asymmetry on Gait Biomechanics.

Background: Though the primary goal for limb length discrepancy (LLD) management is to equalize the leg lengths, symmetry between corresponding long bones is usually not achieved, leading to knee height asymmetry (KHA). To date, there is minimal information on what effect KHA has on gait biomechanics and joint loading. Thus, the purpose of this study is to determine the impact of KHA on gait biomechanics.

Need for a nutrition-specific scientific paradigm for research quality improvement.

Nutrition science has been criticised for its methodology, apparently contradictory findings and generating controversy rather than consensus. However, while certain critiques of the field are valid and informative for developing a more cogent science, there are also unique considerations for the study of diet and nutrition that are either overlooked or omitted in these discourses. The ongoing critical discourse on the utility of nutrition sciences occurs at a time when the burden of non-communicable cardiometabolic disease continues to rise in the population.

(B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer.

Identification of mutations in histones in a number of human neoplasms and developmental syndromes represents the most compelling evidence to date for a causal role of epigenetic perturbations in human disease. In most cases, these mutations have gain of function properties that cause deviation from normal developmental processes leading to embryo defects and/or neoplastic transformation. These exciting discoveries represent a step-change in our understanding of the role of chromatin (dys)regulation in development and disease.

A Comparative Analysis of Data Synthesis Techniques to Improve Classification Accuracy of Raman Spectroscopy Data.

Raman spectra are examples of high dimensional data that can often be limited in the number of samples. This is a primary concern when Deep Learning frameworks are developed for tasks such as chemical species identification, quantification, and diagnostics. Open-source data are difficult to obtain and often sparse; furthermore, the collecting and curating of new spectra require expertise and resources.

Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma.

Introduction: Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma.

Methods: Using genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs).

Complete loss of and is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma.

Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for patients with PRMS, and little is known about the molecular drivers of this disease. To better characterize PRMS, we performed a broad array of genomic and immunostaining analyses on 25 patient samples.

Adapting conservation breeding techniques using a data-driven approach to restore the 'Alalā (Hawaiian crow, Corvus hawaiiensis).

For some critically endangered species, conservation breeding is a vital steppingstone toward re-establishing wild populations. The 'Alalā (Hawaiian crow, Corvus hawaiiensis), currently extinct in the wild, exists today only in a conservation breeding program, which, for many years, utilized successful hands-on husbandry approaches such as separating and resocializing pairs, providing partially manmade nests, artificially incubating eggs, and puppet rearing nestlings. Yet, a top priority of any conservation breeding program is to retain natural behaviors essential to postrelease survival and reproduction, to achieve successful reintroduction and restoration to the wild.

Positive mindset and exercise capacity in school-aged children and adolescents with congenital heart disease.

Introduction: Patients with congenital heart disease (CHD) have variable degrees of peak oxygen consumption (VO) that can be improved with supervised fitness training. The ability to exercise is affected by anatomy, hemodynamics, and motivation. Motivation is in part related to mindset, or personal attitudes and beliefs, and a more positive mindset around exercise has been associated with better outcomes.