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Digital bioethics: introducing fresh options for the research into bioethical concerns.
Epithelial-mesenchymal transition (EMT) is an important biological process through which epithelial cells undergo phenotypic transitions to mesenchymal cells by losing cell-cell adhesion and gaining migratory properties that cells use in embryogenesis, wound healing, and cancer metastasis. An important research topic is to identify the underlying gene regulatory networks (GRNs) governing the decision making of EMT and develop predictive models based on the GRNs. The advent of recent genomic technology, such as single-cell RNA sequencing, has opened new opportunities to improve our understanding about the dynamical controls of EMT. In this article, we review three major types of computational and mathematical approaches and methods for inferring and modeling GRNs driving EMT. We emphasize (1) the bottom-up approaches, where GRNs are constructed through literature search; (2) the top-down approaches, where GRNs are derived from genome-wide sequencing data; (3) the combined top-down and bottom-up approaches, where EMT GRNs are constructed and simulated by integrating bioinformatics and mathematical modeling. We discuss the methodologies and applications of each approach and the available resources for these studies.Mutational signatures are imprints of pathophysiological processes arising through tumorigenesis. We generated isogenic CRISPR-Cas9 knockouts (Δ) of 43 genes in human induced pluripotent stem cells, cultured them in the absence of added DNA damage, and performed whole-genome sequencing of 173 subclones. ΔOGG1, ΔUNG, ΔEXO1, ΔRNF168, ΔMLH1, ΔMSH2, ΔMSH6, ΔPMS1, and ΔPMS2 produced marked mutational signatures indicative of being critical mitigators of endogenous DNA modifications. Detailed analyses revealed mutational mechanistic insights, including how 8-oxo-dG elimination is sequence-context-specific while uracil clearance is sequence-context-independent. Mismatch repair (MMR) deficiency signatures are engendered by oxidative damage (C>A transversions), differential misincorporation by replicative polymerases (T>C and C>T transitions), and we propose a 'reverse template slippage' model for T>A transversions. ΔMLH1, ΔMSH6, and ΔMSH2 signatures were similar to each other but distinct from ΔPMS2. Finally, we developed a classifier, MMRDetect, where application to 7,695 WGS cancers showed enhanced detection of MMR-deficient tumors, with implications for responsiveness to immunotherapies.Clonal hematopoiesis predisposes to hematological malignancies. However, clonal hematopoiesis is understudied in classical Hodgkin lymphoma (cHL), a mature B-cell neoplasm exhibiting the most abundant microenvironment. We analyzed clonal hematopoiesis in 40 cHL cases by sequencing microdissected tumor cells and matched normal cells from blood and/or lymph nodes. Five patients had blood and/or tissue clonal hematopoiesis. In three of five patients (all failing first-line therapy), clonal hematopoiesis spread through the tissue microenvironment extensively, and featured mutant DNMT3AR882H , KRASG60D and DNMT3AR882H +TET2Q1274 * in 33%, 92% and 60% of non-neoplastic cells, respectively. In the latter case, DNMT3A/TET2-mutant clonal hematopoiesis seeded the neoplastic clone, which was infected by the Epstein-Barr virus and showed almost no other somatic mutations exome-wide. In the former case, DNMT3A-mutant clonal hematopoiesis did not originate the neoplastic clone despite dominating the blood and B-cell lineage (~94% leukocytes; ~96% mature blood B cells), yet led to NPM1-mutated acute myeloid leukemia 6 years after therapy for cHL. Our results expand to cHL the spectrum of hematologic malignancies associated with clonal hematopoiesis.With the rise in cancer burden, need for palliative care services has increased simultaneously and majority of people requiring services are from low- and middle-income countries where palliative care is in primitive stage. Nepal is also facing similar challenges of dealing with cancer care and end-of-life care. From its initiation in the early 1990s, there has been gradual progress in the development of palliative care with joint effort of government as well as non-governmental organizations. Morphine, a major milestone for pain management, is being manufactured in the country for nearly a decade, yet morphine equivalence mg per capita is far below the global average. Currently, Nepal has been placed under 'Category 3a' with isolated care provision and there are a lot of challenges to overcome to improve the existing services. Majority of hospice and palliative care centres are located in the capital city and only a few in the periphery. Scarcity of treatment centres and expertise, limited finances, lack of awareness among patients and health care workers, and difficult terrain are major barriers for optimal care. Proper implementation of national guidelines, human resource development and integration of palliative care to primary healthcare level would be crucial steps for further improvement.
The public's view of palliative care often involves its potential to improve of quality-of-life as well as its use as a last resource prior to death.

To obtain an idea of the image of palliative care held by the public in the German-speaking part of Switzerland, the authors sought to understand (1) the perceptions of palliative care and the (2) elements important when thinking about their own end of life.

A qualitative design with an inductive reasoning approach based on Mayring (2014) was chosen. Visitors at an exhibition about palliative care in six locations provided hand-written answers on provided cards to two statements (1) if I hear the term 'Palliative Care' I think of … and (2) when thinking about my own end of life, the following is important to me ….

Answers of 199 visitors (mean age 52, mostly in a good/very good health status) were analysed. In response to hearing the term palliative care, six areas were categorized (1) the main focus; (2) ways of providing palliative care; (3) the best t persisting stigma that palliative care is mainly limited to end-of-life care. The results may help healthcare professionals to better understand how the public view palliative care.Sleep spindles of non-REM sleep are transient, waxing-and-waning 10-16 Hz EEG oscillations, whose cortical synchronization depends on the engagement of thalamo-cortical loops. However, previous studies in animal models lacking the corpus callosum due to agenesis or total callosotomy and in humans with agenesis of the corpus callosum suggested that cortico-cortical connections may also have a relevant role in cortical (inter-hemispheric) spindle synchronization. Yet, most of these works did not provide direct quantitative analyses to support their observations. By studying a rare sample of callosotomized, split-brain patients, we recently demonstrated that the total resection of the corpus callosum is associated with a significant reduction in the inter-hemispheric propagation of non-REM slow waves. Interestingly, sleep spindles are often temporally and spatially grouped around slow waves (0.5-4 Hz), and this coordination is thought to have an important role in sleep-dependent learning and memory consolidationle duration, which could represent the result of a faster desynchronization of spindle activity across cortical areas of the two hemispheres. In contrast with our previous findings regarding sleep slow waves, we failed to detect in callosotomized patients any clear, systematic change in the inter-hemispheric synchronization of sleep spindles. In line with this, callosotomized patients were characterized by a reduced extension of the spatial association between temporally coupled spindles and slow waves. Our findings are consistent with a dependence of spindles on thalamo-cortical rather than cortico-cortical connections in humans, but also revealed that, despite their temporal association, slow waves and spindles are independently regulated in terms of topographic expression.There is a growing debate, both in the academic and sporting worlds, about the most appropriate pathway for high potential young players in sport. In this regard, there has been a considerable focus on the age of selection into structured talent development pathways and the nature of the experience once players have been recruited. Given the economic and reputational currency associated with developing professional footballers in particular, it is unsurprising that professional football clubs continue to invest significant financial resources into their academy structures. Understandably, this recruitment policy has attracted substantial attention within the media and research community, with ethical concerns arising surrounding the impact early selection may have on the welfare and the experiences of the young players within the pathway. The aim of this perspective article was to critically consider the research underpinning the early engagement practises of football clubs and the extent to which, and how, the pathway can provide players with the most appropriate starting point for their development. This evidence points to the need to look beyond the prevalent 'early specialisation vs. BMS-536924 chemical structure diversification' debate in youth sport towards a consideration of an early engagement perspective that reflects the biopsychosocial influences on talent development and the socio-political environment that influences decisions. We provide practical recommendations focused on the quality of the early engagement experience.The primary purpose of this study was to examine how the type and magnitude of changes in running behavior, as a consequence of COVID-19 pandemic restrictions, influence running-related injuries. Secondarily, we aimed to examine how lifestyle and psychosocial well-being measures may influence running behavior change. An online survey was advertised to individuals over the age of 18 that currently run or have previously participated in running for exercise. The survey questions examined injury history and new injuries sustained during COVID-19 restrictions, as well as changes related to training behavior changes, training environment changes, social behaviors, and psychosocial well-being. Changes reflected differences in running behaviors prior to COVID-19 restrictions (1 month prior to COVID-19 restrictions being imposed) and during COVID-19 restrictions (May 5 to June 10, 2020). A total of 1,035 runners were included in the analysis. Current injuries sustained during COVID-19 occurred in 9.5% of the runners. Injured runners made a greater number of total changes (p = 0.031) as well as training-related (p = 0.042) and environment-related (p = 0.017) changes compared with uninjured runners. A significant relationship was found between injury and those that reported less time to exercise to changes in work environment (p = 0017). This study highlights the multi-dimensional nature of running-related injuries and the need to consider the interaction of multiple changes in running behavior, rather than isolating single factors. Greater understanding of the underlying causes of running-related injuries can help reduce the risk of future injury.In 2020, the world was affected by the COVID-19 pandemic, which remains a major challenge for most countries today. In Brazil, football clubs' youth academies have faced a disruption of their regular activities. In order to study how the learning cultures of a Brazilian professional football club youth academy have been changed, and the alternatives created by the club's staff within this context, this perspective article aims to analyze how they have structured the Under-15 (U15) team learning culture during social isolation due to the COVID-19 pandemic. Through document and thematic analysis on a Brazilian professional football club's youth academy program, we promoted a dialogue between the process of adaptation to remote theoretical-tactical teaching with the learning theory proposed by Hodkinson and collaborators. The main theme of analysis of this study was the remote structure of the theoretical-tactical learning and physical training. Challenged with the need to transpose face-to-face activities into a learning culture based on remote communication, the U15 team coaching staff created a process to prescribe physical training, and to teach and discuss football tactical issues with young players during the period of social isolation.
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