Association between external training loads and injury incidence during 44 weeks of military training.

Military training is physically arduous and associated with high injury incidence. Unlike in high-performance sport, the interaction between training load and injury has not been extensively researched in military personnel. Sixty-three (43 men, 20 women; age 24 ± 2 years; stature 1.

Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis.

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients with TP53 germline pathogenic variants. We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy.

The clinical utility of integrative genomics in childhood cancer extends beyond targetable mutations.

We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset.

Knowledge overconfidence is associated with anti-consensus views on controversial scientific issues.

Public attitudes that are in opposition to scientific consensus can be disastrous and include rejection of vaccines and opposition to climate change mitigation policies. Five studies examine the interrelationships between opposition to expert consensus on controversial scientific issues, how much people actually know about these issues, and how much they think they know. Across seven critical issues that enjoy substantial scientific consensus, as well as attitudes toward COVID-19 vaccines and mitigation measures like mask wearing and social distancing, results indicate that those with the highest levels of opposition have the lowest levels of objective knowledge but the highest levels of subjective knowledge.

Signatures of copy number alterations in human cancer.

Gains and losses of DNA are prevalent in cancer and emerge as a consequence of inter-related processes of replication stress, mitotic errors, spindle multipolarity and breakage-fusion-bridge cycles, among others, which may lead to chromosomal instability and aneuploidy. These copy number alterations contribute to cancer initiation, progression and therapeutic resistance. Here we present a conceptual framework to examine the patterns of copy number alterations in human cancer that is widely applicable to diverse data types, including whole-genome sequencing, whole-exome sequencing, reduced representation bisulfite sequencing, single-cell DNA sequencing and SNP6 microarray data.

Rapid Spike in Hip Adduction Strength in Early Adolescent Footballers: A Study of 125 Elite Male Players From Youth to Senior.

Purpose: To investigate the differences in hip adductor and abductor muscle strength in elite male footballers from youth to senior level.

Methods: We tested 125 players from the under-13-years (U'13) to senior squads of a Danish male professional football club in this cross-sectional design study. Hip adductor and abductor force (in newtons), torque (in newton meters), normalized torque (in newton meters per body mass), and adduction-to-abduction ratio were measured using handheld dynamometry.

3D Analysis of maxillary incisor root inclinations in cases of unilateral maxillary canine impaction.

Objectives: To evaluate the association between maxillary incisor root inclinations and unilateral canine impaction.

Methods: A retrospective cross-sectional study of 59 pre-treatment CBCT scans (23 palatal impactions, 10 buccal impactions, and 26 comparison patients). Using Dolphin 3-D Imaging software (Chatsworth, CA), relative incisor angulations to a 3D palatal plane and the shortest distance between the canine crown and the root of the closest lateral incisor were calculated.

Lineage-defined leiomyosarcoma subtypes emerge years before diagnosis and determine patient survival.

Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown.

Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma.

Unlabelled: Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts.

Materials And Methods: Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA.

Injuries in youth football and the relationship to player maturation: An analysis of time-loss injuries during four seasons in an English elite male football academy.

A better insight into injuries in elite-youth football may inform prevention strategies. The purpose of this prospective cohort study was to investigate the frequency, incidence, and pattern of time-loss injuries in an elite male football academy, exploring injuries in relation to age and maturation status. Across four consecutive playing seasons, playing exposure and injuries to all academy players (U'9 to U'21) were recorded by club medical staff.

Extreme opponents of genetically modified foods know the least but think they know the most.

There is widespread agreement among scientists that genetically modified foods are safe to consume and have the potential to provide substantial benefits to humankind. However, many people still harbour concerns about them or oppose their use. In a nationally representative sample of US adults, we find that as extremity of opposition to and concern about genetically modified foods increases, objective knowledge about science and genetics decreases, but perceived understanding of genetically modified foods increases.

Myc and Loss of p53 Cooperate to Drive Formation of Choroid Plexus Carcinoma.

Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the oncogene and deleting the tumor suppressor gene in murine neural stem cells or progenitors.

Ewing-like sarcoma: An emerging family of round cell sarcomas.

Ewing-like sarcomas are an emerging subgroup of small round blue cell sarcomas that share various degrees of morphological, immunohistochemical, molecular, and clinical similarity with Ewing sarcoma. Despite these similarities, Ewing-like sarcomas lack the pathognomonic molecular hallmark of Ewing sarcoma: A translocation between a gene of the RNA-binding TET family (EWSR1 or FUS) with a gene of the ETS-transcription family ( FLI1, ERG, ETV1, ETV4, or FEV). Recently, increased use of modern molecular methods based on next-generation sequencing have enabled the identification of distinct subgroups within this previously uncharacterized group of Ewing-like sarcomas based on the discovery of novel molecular driving events.

The effect of acute match play loading on hip adductor strength and flexibility in soccer players.

Background: Deficits in adductor strength and flexibility are considered risk factors for soccer hip/groin injury, yet little is known about the acute effects of soccer match play on these physical features. The aim of this study was to examine the changes in adductor strength and flexibility before; during and immediately after soccer match play.

Methods: Twenty male university soccer players (mean age 22.

Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair.

Tumors defective for DNA polymerase (Pol) ε proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol ε proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered to have defects in Pol ε proofreading and mismatch repair.

Comprehensive Analysis of Hypermutation in Human Cancer.

We present an extensive assessment of mutation burden through sequencing analysis of >81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor.

The precision and torque production of common hip adductor squeeze tests used in elite football.

Objectives: Decreased hip adductor strength is a known risk factor for groin injury in footballers, with clinicians testing adductor strength in various positions and using different protocols. Understanding how reliable and how much torque different adductor squeeze tests produce will facilitate choosing the most appropriate method for future testing. In this study, the reliability and torque production of three common adductor squeeze tests were investigated.

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.

Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types.

Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.

Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays.

Development of a composite resin disclosing agent based on the understanding of tooth staining mechanisms.

Objectives: To characterize the surface composition of dental enamel and composite resin, assess the ability of dyes with different affinities to stain these surfaces, and use this information to develop a disclosing agent that stains composite resin more than dental enamel.

Methods: One hundred and ten sound extracted teeth were collected and 60 discs of composite resin, 9 mm diameter and 3 mm thick, were prepared. X-ray photoelectron spectroscopy (XPS) was employed to determine the elemental composition on the different surfaces.

Analysis of expressed SNPs identifies variable extents of expression from the human inactive X chromosome.

Background: X-chromosome inactivation (XCI) results in the silencing of most genes on one X chromosome, yielding mono-allelic expression in individual cells. However, random XCI results in expression of both alleles in most females. Allelic imbalances have been used genome-wide to detect mono-allelically expressed genes.

Human genetics in full resolution.

A report on the 12th International Congress of Human Genetics, joint with the 61st annual American Society of Human Genetics conference, Montreal, Quebec, 11-15 October 2011.