A pre-performance routine (PPR) refers to a set of task-relevant thoughts and actions an athlete systematically engages in prior to performance execution. The aim of this meta-analysis was to ...determine the effectiveness of the PPR intervention to facilitate sport performance. The meta-analysis included 112 effect sizes from pre-post and experimental designs in low-pressure and pressurised conditions. Extensive PPRs with several preparatory elements as well as specific stand-alone PPRs, such as left-hand dynamic handgrip and quiet eye, were analysed. Three-level random-effects models were used for analysis, utilising Knapp-Hartung adjustments and restricted maximum likelihood estimation. Results showed a significant but small effect of PPRs on sport performance in pre-post designs (SMC = 0.31, 95% CI 0.18, 0.44) and moderate-to-large effects in experimental designs, both under low-pressure (Hedges' g = 0.64, 95% CI 0.45, 0.83) and pressurised conditions (Hedges' g = 0.70, 95% CI 0.24, 1.16). These effects were not moderated by the type of PPR, age, gender, skill level, or intervention characteristics. Overall, the meta-analytic results support the benefits of the PPR intervention in practice regardless of the type of routine. Both extensive and stand-alone PPRs are effective in optimising sport performance.
MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). The exact amplicon structure ...has not been described thus far and the functional relevance of its rearrangements is unknown. Here, we analyze the MYCN amplicon structure using short-read and Nanopore sequencing and its chromatin landscape using ChIP-seq, ATAC-seq and Hi-C. This reveals two distinct classes of amplicons which explain the regulatory requirements for MYCN overexpression. The first class always co-amplifies a proximal enhancer driven by the noradrenergic core regulatory circuit (CRC). The second class of MYCN amplicons is characterized by high structural complexity, lacks key local enhancers, and instead contains distal chromosomal fragments harboring CRC-driven enhancers. Thus, ectopic enhancer hijacking can compensate for the loss of local gene regulatory elements and explains a large component of the structural diversity observed in MYCN amplification.
Neuroblastoma is a malignancy of the developing sympathetic nervous system that is often lethal when relapse occurs. We here used whole-exome sequencing, mRNA expression profiling, array CGH and DNA ...methylation analysis to characterize 16 paired samples at diagnosis and relapse from individuals with neuroblastoma. The mutational burden significantly increased in relapsing tumors, accompanied by altered mutational signatures and reduced subclonal heterogeneity. Global allele frequencies at relapse indicated clonal mutation selection during disease progression. Promoter methylation patterns were consistent over disease course and were patient specific. Recurrent alterations at relapse included mutations in the putative CHD5 neuroblastoma tumor suppressor, chromosome 9p losses, DOCK8 mutations, inactivating mutations in PTPN14 and a relapse-specific activity pattern for the PTPN14 target YAP. Recurrent new mutations in HRAS, KRAS and genes mediating cell-cell interaction in 13 of 16 relapse tumors indicate disturbances in signaling pathways mediating mesenchymal transition. Our data shed light on genetic alteration frequency, identity and evolution in neuroblastoma.
Knowledge of within-patient dynamics of resistance plasmids during outbreaks is important for understanding the persistence and transmission of plasmid-mediated antimicrobial resistance. During an ...outbreak of a Klebsiella pneumoniae carbapenemase-producing (KPC) K. pneumoniae, the plasmid and chromosomal dynamics of K. pneumoniae within-patients were investigated.
During the outbreak, all K. pneumoniae isolates of colonized or infected patients were collected, regardless of their susceptibility pattern. A selection of isolates was short-read and long-read sequenced. A hybrid assembly of the short-and long-read sequence data was performed. Plasmid contigs were extracted from the hybrid assembly, annotated, and within patient plasmid comparisons were performed.
Fifteen K. pneumoniae isolates of six patients were short-read whole-genome sequenced. Whole-genome multi-locus sequence typing revealed a maximum of 4 allele differences between the sequenced isolates. Within patients 1 and 2 the resistance gene- and plasmid replicon-content did differ between the isolates sequenced. Long-read sequencing and hybrid assembly of 4 isolates revealed loss of the entire KPC-gene containing plasmid in the isolates of patient 2 and a recombination event between the plasmids in the isolates of patient 1. This resulted in two different KPC-gene containing plasmids being simultaneously present during the outbreak.
During a hospital outbreak of a KPC-producing K. pneumoniae isolate, plasmid loss of the KPC-gene carrying plasmid and plasmid recombination was detected within the isolates from two patients. When investigating outbreaks, one should be aware that plasmid transmission can occur and the possibility of within- and between-patient plasmid variation needs to be considered.
Existing research shows that high achievement boredom is correlated with a range of undesirable behavioral and personality variables and that the main antecedents of boredom are being over- or ...under-challenged. However, merely knowing that students are highly bored, without taking their achievement level into account, might be insufficient for drawing conclusions about students' behavior and personality. We, therefore, investigated if low- vs. high-achieving students who experience strong mathematics boredom show different behaviors and personality traits. The sample consisted of 1,404 German secondary school students (fifth to 10th grade, mean age 12.83 years, 52% female). We used self-report instruments to assess boredom in mathematics, behavioral (social and emotional problems, positive/negative affect, cognitive reappraisal, and expressive suppression), and personality variables (neuroticism and conscientiousness). In comparing highly bored students (more than one SD above M, n = 258) who were low vs. high achievers (as indicated by the math grade, n = 125 / n = 119), results showed that there were no mean level differences across those groups for all variables. In conclusion, our results suggest that high boredom can occur in both low- and high-achieving students and that bored low- and high-achievers show similar behaviors and personality profiles.
Extrachromosomal DNA amplifications in cancer Yi, Eunhee; Chamorro González, Rocío; Henssen, Anton G ...
Nature reviews. Genetics,
12/2022, Letnik:
23, Številka:
12
Journal Article
Recenzirano
Extrachromosomal DNA (ecDNA) amplification is an important driver alteration in cancer. It has been observed in most cancer types and is associated with worse patient outcome. The functional impact ...of ecDNA has been linked to its unique properties, such as its circular structure that is associated with altered chromatinization and epigenetic regulatory landscape, as well as its ability to randomly segregate during cell division, which fuels intercellular copy number heterogeneity. Recent investigations suggest that ecDNA is structurally more complex than previously anticipated and that it localizes to specialized nuclear bodies (hubs) and can act in trans as an enhancer for genes on other ecDNAs or chromosomes. In this Review, we synthesize what is currently known about how ecDNA is generated and how its genetic and epigenetic architecture affects proto-oncogene deregulation in cancer. We discuss how recently identified ecDNA functions may impact oncogenesis but also serve as new therapeutic vulnerabilities in cancer.
Calcific aortic valve disease (CAVD), previously thought to represent a passive degeneration of the valvular extracellular matrix (VECM), is now regarded as an intricate multistage disorder with ...sequential yet intertangled and interacting underlying processes. Endothelial dysfunction and injury, initiated by disturbed blood flow and metabolic disorders, lead to the deposition of low-density lipoprotein cholesterol in the VECM further provoking macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines. Such changes in the valvular homeostasis induce differentiation of normally quiescent valvular interstitial cells (VICs) into synthetically active myofibroblasts producing excessive quantities of the VECM and proteins responsible for its remodeling. As a result of constantly ongoing degradation and re-deposition, VECM becomes disorganised and rigid, additionally potentiating myofibroblastic differentiation of VICs and worsening adaptation of the valve to the blood flow. Moreover, disrupted and excessively vascularised VECM is susceptible to the dystrophic calcification caused by calcium and phosphate precipitating on damaged collagen fibers and concurrently accompanied by osteogenic differentiation of VICs. Being combined, passive calcification and biomineralisation synergistically induce ossification of the aortic valve ultimately resulting in its mechanical incompetence requiring surgical replacement. Unfortunately, multiple attempts have failed to find an efficient conservative treatment of CAVD; however, therapeutic regimens and clinical settings have also been far from the optimal. In this review, we focused on interactions and transitions between aforementioned mechanisms demarcating ascending stages of CAVD, suggesting a predisposing condition (bicuspid aortic valve) and drug combination (lipid-lowering drugs combined with angiotensin II antagonists and cytokine inhibitors) for the further testing in both preclinical and clinical trials.
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•Calcific aortic valve disease is a multi-step disorder leading to the heart failure•Endothelial dysfunction followed by lipid deposition and inflammation triggers CAVD.•Myofibroblastic differentiation of valvular interstitial cells causes AV fibrosis•Dystrophic calcification and biomineralisation result in mechanically incompetent AV.•Lipid-lowering drugs, ACEIs/ARBs, and cytokine inhibitors may be tested in patients with bicuspid AV in relation to CAVD.
Improving the outcomes in gastric cancer surgery Tegels, Juul J W; De Maat, Michiel F G; Hulsewé, Karel W E ...
World journal of gastroenterology : WJG,
10/2014, Letnik:
20, Številka:
38
Journal Article
Odprti dostop
Gastric cancer remains a significant health problem worldwide and surgery is currently the only potentially curative treatment option. Gastric cancer surgery is generally considered to be high risk ...surgery and fiveyear survival rates are poor,therefore a continuous strive to improve outcomes for these patients is warranted. Fortunately,in the last decades several potential advances have been introduced that intervene at various stages of the treatment process. This review provides an overview of methods implemented in pre-,intra- and postoperative stage of gastric cancer surgery to improve outcome. Better preoperative risk assessment using comorbidity index(e.g.,Charlson comorbidity index),assessment of nutritional status(e.g.,short nutritional assessment questionnaire,nutritional risk screening- 2002) and frailty assessment(Groningen frailty indicator,Edmonton frail scale,Hopkins frailty) was introduced. Also preoperative optimization of patients using prehabilitation has future potential.Implementation of fast-track or enhanced recovery after surgery programs is showing promising results,although future studies have to determine what the exact optimal strategy is.Introduction of laparoscopic surgery has shown improvement of results as well as optimization of lymph node dissection.Hyperthermic intraperitoneal chemotherapy has not shown to be beneficial in peritoneal metastatic disease thus far.Advances in postoperative care include optimal timing of oral diet,which has been shown to reduce hospital stay.In general,hospital volume,i.e.,centralization,and clinical audits might further improve the outcome in gastric cancer surgery.In conclusion,progress has been made in improving the surgical treatment of gastric cancer.However,gastric cancer treatment is high risk surgery and many areas for future research remain.
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