Efficacy of Physical Activity Promoting Interventions in Physical Therapy and Exercise Therapy for Persons with Noncommunicable Diseases: An Overview of Systematic Reviews.

OBJECTIVE: The objective of this study was to synthesize the evidence from systematic reviews on the efficacy of physical therapy and exercise therapy including interventional elements explicitly aiming at physical activity promotion (PAP) in patients with noncommunicable diseases (NCDs). METHODS: PubMed, Scopus, PsycINFO, and Cochrane Database of Systematic Reviews were searched from inception to February 28, 2023. Two independent reviewers screened the literature to identify systematic reviews that evaluated the effect of physical therapy and exercise therapy including PAP interventions. Patient-reported and device-based measures of physical activity outcomes were included. Qualitative and quantitative data from systematic reviews were extracted by 2 independent reviewers. Assessment of the methodological quality of included systematic reviews was performed using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews). We assessed primary study overlap by calculating the corrected covered area and conducted the evidence synthesis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Fourteen systematic reviews were included in the present overview, including patients with a variety of NCDs. Most included systematic reviews had critically low (n = 5) to low (n = 7) methodological quality. Most meta-analysis (67%; 8/12) provided evidence supporting the short- and long-term efficacy of PAP interventions but not all pooled estimates were clinically relevant. Only 3 of the systematic reviews with meta-analysis included an assessment of the certainty of evidence. The evidence from systematic reviews without meta-analysis was inconclusive. CONCLUSIONS: The results of the present overview suggest that PAP interventions in physical therapy or exercise therapy may be effective to improve physical activity for patients with NCDs in the short term and long term. The results should be interpreted with caution due to the limited certainty of evidence and critically low to low methodological quality of included systematic reviews. Both high quality primary studies and systematic reviews are required to confirm these results. IMPACT: There is limited evidence that PAP interventions in physical therapy and exercise therapy may be effective to improve physical activity for patients with NCDs.

Panel-based RNA fusion sequencing improves diagnostics of pediatric acute myeloid leukemia.

New methods like panel-based RNA fusion sequencing (RNA-FS) promise improved diagnostics in various malignancies. We here analyzed the impact of RNA-FS on the initial diagnostics of 241 cases with pediatric acute myeloid leukemia (AML). We show that, compared to classical cytogenetics (CCG), RNA-FS reliably detected risk-relevant fusion genes in pediatric AML. In addition, RNA-FS strongly improved the detection of cryptic fusion genes like NUP98::NSD1, KMT2A::MLLT10 and CBFA2T3::GLIS2 and thereby resulted in an improved risk stratification in 25 patients (10.4%). Validation of additionally detected non-risk-relevant high confidence fusion calls identified PIM3::BRD1, C22orf34::BRD1, PSPC1::ZMYM2 and ARHGAP26::NR3C1 as common genetic variants and MYB::GATA1 as recurrent aberration, which we here describe in AML subtypes M0 and M7 for the first time. However, it failed to detect rare cytogenetically confirmed fusion events like MNX1::ETV6 and other chromosome 12p-abnormalities. As add-on benefit, the proportion of patients for whom measurable residual disease (MRD) monitoring became possible was increased by RNA-FS from 44.4 to 75.5% as the information on the fusion transcripts' sequence allowed the design of new MRD assays.

Service access experiences of immigrant and refugee caregivers of autistic children in Canada: A scoping review.

Primary caregivers are the main mediators of care for children with an autism diagnosis in Canada, and the navigation process to gain access to autism-related services is known to be a major burden. These challenges to service access are compounded for newcomers to Canada, which include immigrants and refugees. The purpose of this scoping review is to describe the available research on Canadian newcomer caregiver experiences navigating and accessing autism-related services. After a systematic search and screening process, 28 studies were included. Data were extracted regarding the populations, study aims, and themes reported. Included studies characterized barriers and facilitators to service access and navigation specific to immigrants, while limited information was available for refugees. Based on the existing literature, the authors provide recommendations for possible research approaches, populations to include, and themes to examine in future research to promote health equity in Canadian autism service access.

Counseling and support services for healthcare workers in German university hospitals during the pandemic-descriptive results of a Germany-wide cross-sectional survey.

Background: Due to the SARS-CoV-2 pandemic, healthcare workers (HCWs) are experiencing tremendous levels of emotional and physical stress. Hospitals are trying to help personnel cope with work-related pressure. The aim of this study was to assess HCWs' awareness and utilization of counseling and support services during the pandemic, HCWs' unmet counseling and support needs, and the type and content of these services. Methods: A cross-sectional online survey was conducted from January to June 2021 through the German national research organization Network University Medicine (NUM). All participating hospitals (6 in total) were asked to inform their employees about the study. Results: A total of 1,495 HCWs were included in the analysis. Of these, 42.8% (n = 637) were frontline HCWs (who had contact with COVID-19 patients), 23.1% (n = 344) were second-line HCWs (who only had contact with non-COVID-19 patients) and 34.1% (n = 508) had no contact with any patients. Participating hospitals offer various counseling and support services for their staff. The percentage of respondents who were unaware of available counseling and support services ranged from 5.0 to 42.0%. Depending on the type of counseling and support services, 23.0-53.6% of the respondents indicated that counseling and support services were provided but not used, while 1.7-11.6% indicated that, despite the need for them, such services were not available. HCWs' overall satisfaction with the provided counseling and support services and their unmet support needs differed by patient contact: Frontline HCWs reported more unmet needs for counseling and support than second-line HCWs, while second-line HCWs reported more unmet needs than HCWs without patient contact. Conclusion: The results indicate that hospitals should make more efforts to inform HCWs about available counseling and support services. Hospitals could also create networks where HCWs could share information about the type and content of services and their experiences with various counseling and support services. These steps would enable hospitals to respond more quickly and effectively to the problems facing HCWs during pandemics.

Understanding WT1 Alterations and Expression Profiles in Hematological Malignancies.

WT1 is a true chameleon, both acting as an oncogene and tumor suppressor. As its exact role in leukemogenesis is still ambiguous, research with model systems representing natural conditions surrounding the genetic alterations in WT1 is necessary. In a cohort of 59 leukemia/lymphoma cell lines, we showed aberrant expression for WT1 mRNA, which does not always translate into protein levels. We also analyzed the expression pattern of the four major WT1 protein isoforms in the cell lines and primary AML blasts with/without WT1 mutations and demonstrated that the presence of mutations does not influence these patterns. By introduction of key intronic and exonic sequences of WT1 into a lentiviral expression vector, we developed a unique tool that can stably overexpress the four WT1 isoforms at their naturally occurring tissue-dependent ratio. To develop better cellular model systems for WT1, we sequenced large parts of its gene locus and also other important myeloid risk factor genes and revealed previously unknown alterations. Functionally, inhibition of the nonsense-mediated mRNA decay machinery revealed that under natural conditions, the mutated WT1 alleles go through a robust degradation. These results offer new insights and model systems regarding the characteristics of WT1 in leukemia and lymphoma.

Firing of Replication Origins Is Disturbed by a CDK4/6 Inhibitor in a pRb-Independent Manner.

Over the last decade, CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have emerged as promising anticancer drugs. Numerous studies have demonstrated that CDK4/6 inhibitors efficiently block the pRb-E2F pathway and induce cell cycle arrest in pRb-proficient cells. Based on these studies, the inhibitors have been approved by the FDA for treatment of advanced hormonal receptor (HR) positive breast cancers in combination with hormonal therapy. However, some evidence has recently shown unexpected effects of the inhibitors, underlining a need to characterize the effects of CDK4/6 inhibitors beyond pRb. Our study demonstrates how palbociclib impairs origin firing in the DNA replication process in pRb-deficient cell lines. Strikingly, despite the absence of pRb, cells treated with palbociclib synthesize less DNA while showing no cell cycle arrest. Furthermore, this CDK4/6 inhibitor treatment disturbs the temporal program of DNA replication and reduces the density of replication forks. Cells treated with palbociclib show a defect in the loading of the Pre-initiation complex (Pre-IC) proteins on chromatin, indicating a reduced initiation of DNA replication. Our findings highlight hidden effects of palbociclib on the dynamics of DNA replication and of its cytotoxic consequences on cell viability in the absence of pRb. This study provides a potential therapeutic application of palbociclib in combination with other drugs to target genomic instability in pRB-deficient cancers.

RUNX1 mutation has no prognostic significance in paediatric AML: a retrospective study of the AML-BFM study group.

In acute myeloid leukaemia (AML) RUNX1 mutation is characterised by certain clinicopathological features with poor prognosis and adverse risk by the European LeukemiaNet recommendation. Though initially considered as provisional category, the recent World Health Organisation (WHO) classification of 2022 removed RUNX1-mutated AML from the unique entity. However, the significance of RUNX1 mutation in paediatric AML remains unclear. We retrospectively analysed a German cohort of 488 paediatric patients with de novo AML, enroled in the AMLR12 or AMLR17 registry of the AML-BFM Study Group (Essen, Germany). A total of 23 paediatric AML patients (4.7%) harboured RUNX1 mutations, 18 of which (78%) had RUNX1 mutation at initial diagnosis. RUNX1 mutations were associated with older age, male gender, number of coexisting alterations and presence of FLT3-ITD but mutually exclusive of KRAS, KIT and NPM1 mutation. RUNX1 mutations did not prognostically impact overall or event-free survival. Response rates did not differ between patients with and without RUNX1 mutations. This comprehensive study, comprising the largest analysis of RUNX1 mutation in a paediatric cohort to date, reveals distinct but not unique clinicopathologic features, with no prognostic significance of RUNX1-mutated paediatric AML. These results broaden the perspective on the relevance of RUNX1 alterations in leukaemogenesis in AML.

Supporting brain health in multiple sclerosis: exploring the potential of neuroeducation combined with practical mindfulness exercises in the management of neuropsychological symptoms.

OBJECTIVE: We aimed at examining the effects of a known metacognitive training in MS (MaTiMS) and its modification with an additional neuroeducational module and mindfulness-based exercises (MaTiMS-modified) on neuropsychiatric and cognitive outcomes in people with progressive multiple sclerosis (pwpMS). Exploratively, we investigated whether the modification may show an additional benefit. METHODS: Both interventions were administered in small groups of ambulatory patients. Neuropsychological testing before and after the 3- to 4-week intervention phase comprised patient reported outcomes and cognitive tests. After 3, 6 and 12 months, participants completed online surveys. Analysis of change scores (between baseline and retest) with t-tests (Mann-Whitney U and Wilcoxon tests, respectively) and mixed ANCOVAs with repeated measures for comparison of both interventions were conducted. RESULTS: A total of 65 pwpMS turned to a final sample of 50 (n = 15 excluded due to drop-outs, occurrence of relapse or steroid treatment). Change scores within MaTiMS revealed no significant effect on the PDQ-20 total score and only a significant effect on the subscale retrospective memory lasting 3 months with a moderate effect size. In contrast, MaTiMS-modified revealed a highly significant change in PDQ-20 total compared to baseline and significant improvements with small to moderate effect sizes on all PDQ-20 subscales (lasting until 3 months), in self-efficacy, stress, visuo-spatial working memory (moderate effect sizes), and fatigue (small effect size). While no interaction effect between time and group could be revealed, a significant main effect for time was found in PDQ-20 total. CONCLUSION: Both MaTiMS and MaTiMS-modified positively affected perceived cognitive deficits. However, our data speak in favor of additional benefits by adding neuroeducational and mindfulness-based exercises thus being valuable methods to support brain health including self-efficacy, perceived stress, and fatigue, even in patients with a chronic and progressive brain disease.

The correlation of honesty-humility and learning goals with academic cheating.

Academic cheating is a problem that affects many educational institutions and has become increasingly significant with the new challenges of online education. Recent studies have found that learning goals are correlated with cheating behavior among students. In this study, we investigated whether learning goals are still a predictor of cheating behavior when controlling for students' Honesty-Humility (emanated from the HEXACO model of personality) within a sample of 311 German university students. Regrading students' learning goals, we assessed their learning approach, performance approach, performance avoidance, and work avoidance. The result shows an intermediate negative and highly significant association between Honesty-Humility and academic cheating. Learning goals did not explain any incremental variance in academic cheating that goes beyond the Honesty-Humility factor. As the only exception, the work avoidance goal was found to also predict cheating behavior, but this positive association seems to be not as strong as the negative correlation between Honesty-Humility and academic cheating. We discuss the theoretical and practical implications of these results and make recommendations for future research.

Fostering study crafting to increase engagement and reduce exhaustion among higher education students: A randomized controlled trial of the STUDYCoach online intervention.

The study demands-resources framework states that study demands increase exhaustion and study resources increase engagement. Study crafting describes a student's proactive adaption to demands and resources. To date, no intervention in the higher education context has aimed to foster study crafting. Accordingly, this study developed and evaluated the STUDYCoach online intervention, which aimed to increase engagement and reduce exhaustion by promoting study crafting. The study was a randomized controlled trial with a waiting-list control group. All participants (N = 209) completed a questionnaire before (T1) and after (T2) the intervention and at a 20-week follow-up (T3). Participants in the intervention group (n = 149) used the STUDYCoach over three consecutive weeks. Results showed that overall study crafting, decreasing hindering demands, and engagement significantly increased in the intervention group compared to the control group after the intervention. All effects remained stable at follow-up. Notably, exhaustion decreased significantly in the intervention group from T1 to T3 and T2 to T3. Study crafting mediated the intervention's effect on engagement and exhaustion. Our study extends the study demands-resources framework and the literature on job crafting by confirming that study crafting interventions can be effective in higher education.

[Willingness to get vaccinated among hospital staff in Germany: What is the role of COVID-19 conspiracy assumptions?] / Impfbereitschaft von Krankenhauspersonal in Deutschland: Welche Rolle spielen Verschwörungsannahmen zu COVID-19?

BACKGROUND: A critical factor in achieving widespread immunity against COVID-19 is the willingness of previously unvaccinated individuals to get vaccinated. Medical staff play a key role in this, as they ensure healthcare during the pandemic and for many serve as a source of information about vaccinations. Among the factors that negatively influence the general willingness to get vaccinated are conspiracy assumptions and the spread of misinformation. OBJECTIVE: The willingness of hospital staff in Germany to get vaccinated and various influencing variables were examined to obtain indicators that could help increase the general willingness to get vaccinated. METHODS: Between January and June 2021, a voluntary and anonymous online survey conducted as part of the egePan joint project of the national network for university medicine (funded by the Federal Ministry of Education and Research) was used to assess the willingness to be vaccinated, individual social characteristics, the belief in conspiracy assumptions, and communication items in German hospitals. RESULTS: In comparison with the general population, physicians and scientific staff in particular indicated an increased willingness to get vaccinated. Conspiracy assumptions were not very widespread but most frequent among administrative and nursing staff. Conspiracy assumptions were negatively associated with the willingness to get vaccinated. Predictors for a higher willingness to get vaccinated were the perceived safety and effectiveness of vaccinations and a higher age. DISCUSSION: Since the perceived safety and effectiveness of vaccinations have a positive effect on the willingness to get vaccinated, educational work and transparent information transfer could counteract the spread of conspiracy assumptions and increase vaccination rates among hospital staff.

Crystal structure of the Na+/H+ antiporter NhaA at active pH reveals the mechanistic basis for pH sensing.

The strict exchange of protons for sodium ions across cell membranes by Na+/H+ exchangers is a fundamental mechanism for cell homeostasis. At active pH, Na+/H+ exchange can be modelled as competition between H+ and Na+ to an ion-binding site, harbouring either one or two aspartic-acid residues. Nevertheless, extensive analysis on the model Na+/H+ antiporter NhaA from Escherichia coli, has shown that residues on the cytoplasmic surface, termed the pH sensor, shifts the pH at which NhaA becomes active. It was unclear how to incorporate the pH senor model into an alternating-access mechanism based on the NhaA structure at inactive pH 4. Here, we report the crystal structure of NhaA at active pH 6.5, and to an improved resolution of 2.2 Å. We show that at pH 6.5, residues in the pH sensor rearrange to form new salt-bridge interactions involving key histidine residues that widen the inward-facing cavity. What we now refer to as a pH gate, triggers a conformational change that enables water and Na+ to access the ion-binding site, as supported by molecular dynamics (MD) simulations. Our work highlights a unique, channel-like switch prior to substrate translocation in a secondary-active transporter.

Effects of SativexⓇ on cognitive function in patients with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Cognitive impairment is a common manifestation of multiple sclerosis (MS). OBJECTIVE: To assess by systematic review and meta-analysis available evidence regarding the impact of nabiximols oromucosal spray on cognition in patients with MS. METHODS: A systematic literature search of clinical studies (all types, any comparator) that measured cognitive function in patients with MS spasticity treated with nabiximols. Meta-analysis for cognitive endpoints was not possible due to heterogenous measurement instruments and outcomes. Meta-analysis was performed for adverse events (AEs) of special interest (cognition disorders) reported in randomized controlled trials (RCTs) of nabiximols versus placebo in patients with MS (with or without spasticity). Certainty of evidence and risk of bias were assessed. RESULTS: Seven clinical studies (three RCTs) directly assessing cognitive function were included in the qualitative analysis. There was no consistent evidence to suggest that nabiximols causes cognitive impairment as assessed by a range of specific psychometric instruments across cognitive domains. Thirteen double-blind, placebo-controlled RCTs (nabiximols, n = 964; placebo, n = 904) were included in the meta-analysis of cognitive AEs. Most cognitive AEs (30 of 32 events, 93.8%) reported with nabiximols in MS patients occurred with not in-label use, i.e., dosage >12 sprays per day and/or not administered primarily for treatment of spasticity. CONCLUSIONS: Within the limitations of the review, we can conclude that no detrimental effects of nabiximols on cognitive function were observed in patients with MS spasticity during up to 12 months follow-up and that cognitive AEs were rare and occurred only when nabiximols was not used according to its approved label.

Electrophysiological Safety Profile of Antiestrogenic Therapies in the Isolated Rabbit Heart.

INTRODUCTION: Hormone-mediated therapies are on the rise and are key therapies in the treatment of some of the most common cancer entities. Proarrhythmic effects have been described in patients treated with SERMs while little to none is known about the electrophysiological effects of the potentially less arrhythmogenic selective estrogen receptor degraders. METHODS: Twenty hearts of female New Zealand White rabbits were excised and retrogradely perfused employing a Langendorff setup. An electrophysiology study was performed to obtain CL-dependent action potential duration at 90% of repolarization (APD90), QT interval, effective refractory period (ERP), and post-repolarization refractoriness (PRR = ERP-APD90). After generating baseline data, the hearts were assigned to two groups and perfused with (n = 10) increasing doses of fulvestrant (1 µM and 5 µM; n = 10) or tamoxifen (2.5 µM and 7.5 µM; n = 10), and the protocol was repeated again. RESULTS: Fulvestrant led to a decrease in APD90 and QT interval and an increased PRR. The inducibility of ventricular tachycardia (VT) episodes was unaltered. Tamoxifen showed similar effects, resulting in a shortened APD90 and QT interval and no increased VT incidence in the setting of a prolonged PRR. CONCLUSION: The present study shows no acute proarrhythmic effect of tamoxifen and fulvestrant in an established whole heart model when employing clinically relevant concentrations.

Pig models for Duchenne muscular dystrophy - from disease mechanisms to validation of new diagnostic and therapeutic concepts.

Duchenne muscular dystrophy (DMD) is a fatal X-linked disease caused by mutations in the DMD gene, leading to complete absence of dystrophin and progressive degeneration of skeletal muscles and heart. Animal models are essential for preclinical evaluation of novel diagnostic procedures and treatment strategies. Gene targeting/editing offers the possibility of developing tailored pig models for monogenic diseases. The first porcine DMD model was generated by deletion of DMD exon 52 (DMDΔ52) in cultured kidney cells, which were used for somatic cell nuclear transfer to produce DMDΔ52 offspring. The animals resembled clinical, biochemical, and pathological hallmarks of DMD, but died before sexual maturity, thus preventing their propagation by breeding. This limitation was overcome by the generation of female heterozygous DMDΔ52 carrier pigs, which allowed the establishment of a large breeding colony. In this overview, we summarize how porcine DMD models have been used for dissecting disease mechanisms, for validating multispectral optoacoustic tomography as an imaging modality for monitoring fibrosis, and for preclinical testing of a CRISPR/Cas9 based approach to restore an intact DMD reading frame. Particular advantages of porcine DMD models include their targeted design and the rapid disease progression with early cardiac involvement, facilitating translational studies in reasonable time frames.

Distinct Patterns of University Students Study Crafting and the Relationships to Exhaustion, Well-Being, and Engagement.

Job crafting has been established as a bottom-up work design instrument for promoting health and well-being in the workplace. In recent years, the concepts of job crafting have been applied to the university student context, proving to be positively related to student well-being. Building on person-centered analyses from the employment context, we assessed approach study crafting strategy combinations and the relationships to students' exhaustion, study engagement, and general well-being. Data from 2,882 German university students were examined, collected online during the summer term in 2020. Using latent profile analysis, we found five distinct crafting groups, which showed discriminate validity with regard to emotional exhaustion, engagement, and well-being. The results underscore the positive role of study crafting for students' health and well-being. They further indicate a less important role of increasing social resources for emotional exhaustion when combined with a moderate increase in structural resources and a moderate increase in challenging demands. Our findings imply that interventions to promote study crafting should be considered to promote student health and well-being.

Genomic Epidemiology of SARS-CoV-2 in Seychelles, 2020-2021

Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge of SARS-CoV-2 cases was observed on the islands. Here, we investigated the potential drivers of the surge by genomic analysis 1,056 SARS-CoV-2 positive samples collected in Seychelles between 14th March 2020 and 31st December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1,042 of which fell within four variants of concern i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (European origin) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using ancestral state reconstruction approach, we estimated at least 78 independent SARS-CoV-2 introduction events into Seychelles during the study period. Majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands.

A scalable, clinically severe pig model for Duchenne muscular dystrophy.

Large-animal models for Duchenne muscular dystrophy (DMD) are crucial for the evaluation of diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMDΔ52) exhibit molecular, clinical and pathological hallmarks of DMD, but die before sexual maturity and cannot be propagated by breeding. Therefore, we generated female DMD+/- carriers. A single founder animal had 11 litters with 29 DMDY/-, 34 DMD+/- as well as 36 male and 29 female wild-type offspring. Breeding with F1 and F2 DMD+/- carriers resulted in an additional 114 DMDY/- piglets. With intensive neonatal management, the majority survived for 3-4 months, providing statistically relevant cohorts for experimental studies. Pathological investigations and proteome studies of skeletal muscles and myocardium confirmed the resemblance to human disease mechanisms. Importantly, DMDY/- pigs displayed progressive myocardial fibrosis and increased expression of connexin-43, associated with significantly reduced left ventricular ejection fraction, at 3 months. Furthermore, behavioral tests provided evidence for impaired cognitive ability. Our breeding cohort of DMDΔ52 pigs and standardized tissue repositories provide important resources for studying DMD disease mechanisms and for testing novel treatment strategies.

Impact of KMT2A Rearrangement and CSPG4 Expression in Pediatric Acute Myeloid Leukemia.

KMT2A rearrangements (KMT2A-r) are among the most common structural aberrations in pediatric acute myeloid leukemia (AML) and are very important for the risk group stratification of patients. Here, we report the outcome of 967 pediatric AML patients with a known KMT2A-r status. The large cohort was characterized by morphology, multicolor flow cytometry, classical cytogenetics and mutation analysis via panel sequencing. In total, the blasts of 241 patients (24.9%) showed KMT2A-r. KMT2A-r is associated with FAB M5, a high white blood cell count and younger age at diagnosis. When subgroups were combined, KMT2A-r had no impact on event-free survival (EFS) and overall survival (OS); however, various subgroups showed a different prognosis, ranging from a <50% OS for KMT2A/AFDN (n = 11) to a 100% chance of survival for patients harboring the rare translocation KMT2A/SEPTIN9 (n = 3, follow up of 3.7 to 9.6 years). A positive correlation of KMT2A-r with KRAS mutations (p < 0.001) existed, albeit without any prognostic impact. In addition, FLT3-ITDs were detected less frequently in AML with KMT2A-r (p < 0.001). Furthermore, KMT2A-r were mutually exclusive, with mutations in NPM1 (p = 0.002), KIT (p = 0.036), WT1 (p < 0.001) and CEBPA (p = 0.006), and translocations NUP98/NSD1 (p = 0.009), RUNX1/RUNX1T1 (p = 0.003) and CBFB/MYH11 (p = 0.006). In the 346 patients tested for CSPG4 expression, a correlation between CSPG4 expression and KMT2A-r was confirmed. However, CSPG4 expression also occurred in patients without KMT2A-r and had no significant prognostic impact on EFS and OS.

Antecedents and Moderation Effects of Maladaptive Coping Behaviors Among German University Students.

Prolonging working hours and presenteeism have been conceptualized as self-endangering coping behaviors in employees, which are related to health impairment. Drawing upon the self-regulation of behavior model, the goal achievement process, and Warr's vitamin model, we examined the antecedents and moderation effects regarding quantitative demands, autonomy, emotion regulation, and self-motivation competence of university students' self-endangering coping behaviors (showing prolonging working hours and presenteeism). Results from a cross-sectional survey of 3,546 German university students indicate that quantitative demands are positively related and autonomy has a u-shape connection with self-endangering coping. Emotion regulation was shown to be a protective factor for prolonging working hours. Moreover, self-motivation moderated the relationship between quantitative demands and prolonging of working hours, but not in the assumed direction. Self-motivation showed a systematic positive relationship with prolonging of working hours, but no relationship with presenteeism. Autonomy moderated the relationship of quantitative demands with both self-endangering behaviors. We found no moderating effects for emotion regulation of quantitative demands or autonomy and self-endangering behaviors. Besides further practical implications, the results suggest that lecturers should design their courses accordingly with less time pressure and university students should be trained in the use of autonomy.