Notes

DDX21 is a p38-MAPK-sensitive nucleolar protein required for computer mouse preimplantation embryo growth and cell-fate spec.
Advances in paediatric care have contributed to an increasing survival of children with complex heart disease. Yet, life-saving management demands prolonged inpatient admissions, which contribute to emotional and psychological distress for parents and other caregivers in a role of main custody.

The purpose of this study was to identify, appraise and synthesise qualitative studies exploring caregivers' experiences of paediatric inpatient cardiac services, generating an understanding of their needs in hospital and informing priorities for change in healthcare delivery.

Searches were conducted in Medline, Allied and Complimentary Medicine Database, Cumulative Index of Nursing and Allied Health Literature, EMCARE, Scopus, PsychINFO, Proquest, OpenGrey and ETHOs from 2008-2019, reflecting recent advances in cardiac healthcare. Articles were selected using predetermined eligibility criteria dictating qualitative inquiry into caregiver perspectives whilst their child received hospital-based interventions for hnal challenges that caregivers face and practicalities of undertaking a caregiver role, whilst looking after their child with heart disease in hospital. The results widen the context of the caregiver role, encompassing the whole family unit beyond the hospital environment. This review exposes the impact of these challenges on caregiver competence, wellbeing and attachment to their unwell child, informing priorities for development of family-centred paediatric inpatient cardiac services.
A more accurate and simpler scoring systems for early risk stratification of acute myocardial infarction at admission can accelerate and improve decision-making.

To develop and validate a simple physiological prognostic scoring system for early risk stratification in patients with acute myocardial infarction.

Easily accessible physiological vital signs and demographic characteristics of patients with acute myocardial infarction at the time of presentation in the multicentre Retrospective Evaluation of Acute Chest Pain study were used to develop a multivariate logistic regression model predicting 12 and 24-month mortality. The study population consisted of 2619 patients from seven hospitals and was divided into a 70% sample for model derivation and a 30% sample for model validation. A nomogram was created to enable prospective risk stratification for clinical care.

The simple physiological prognostic scoring system consisted of age, heart rate, body mass index and Killip class. The area under the receiver operating characteristic curve of the simple physiological prognostic scoring system was superior to that of several risk scoring systems in clinical use. Net reclassification improvement, integrated discrimination improvement and decision curve analysis of the derivation set also revealed superior performance to the Global Registry of Acute Coronary Events score, and the Hosmer-Lemeshow test indicated good calibration for predicting mortality in patient with acute myocardial infarction in the validation set (P = 0.612).

This simple physiological prognostic scoring system may be a useful risk stratification tool for early assessment of patients with acute myocardial infarction.
This simple physiological prognostic scoring system may be a useful risk stratification tool for early assessment of patients with acute myocardial infarction.
To quantify the provision of standard cardiac rehabilitation to Danish survivors of cardiac arrest at a programme level, and to analyse whether organizational factors influenced the provision.

We mapped the provision of cardiac rehabilitation core components to survivors of cardiac arrest and compared this with a reference group of patients after acute myocardial infarction using data from a cross-sectional programme-level survey among all hospitals (n = 34) and municipalities (n = 98) in Denmark. Organizational factors of potential importance to service provision were considered health care region, size of catchment area/population, type of department/municipality and socioeconomic index.

Response rates for the provision of each core component of cardiac rehabilitation ranged from 64% to 98%. All hospitals and municipalities provided some aspect of cardiac rehabilitation to survivors of cardiac arrest. Across hospitals, provision of four core components of cardiac rehabilitation to survivors of cardiac arrest was lower compared with post acute myocardial infarction patients patient education (relative risk (RR) = 0.45 (95% confidence interval (CI) 0.27 to 0.75)), exercise training (RR = 0.69 (95% CI 0.49 to 0.98)), screening for anxiety and depression (RR = 0.64 (95% CI 0.46 to 0.90) and nutritional counselling RR = 0.76 (95% CI 0.62 to 0.93)). No difference was found in the provision of core components across municipalities. Overall, the provision of cardiac rehabilitation to survivors of cardiac arrest was not affected by organizational factors.

This study indicates a need for future research to inform the development, adoption and implementation of equal access to all components of cardiac rehabilitation for survivors of cardiac arrest in Denmark.
This study indicates a need for future research to inform the development, adoption and implementation of equal access to all components of cardiac rehabilitation for survivors of cardiac arrest in Denmark.Because the time between study conception and dissemination of findings generally takes long, efforts to reduce this lag are important. A solution to accelerate the research process can be found in flash mob research. This is a method to study clinically relevant questions on a large scale in a very short course of time. The research question and the set-up of the study should be exciting. Doing so, it attracts a large 'mob' of people who collect the data. Consequently, the generalizability of flash mob studies may be higher than that of traditional research studies.Cyclobutane pyrimidine dimers (CPDs) are the major products of DNA produced by direct absorption of UV light, and result in C to T mutations linked to human skin cancers. Most recently a new pathway to CPDs in melanocytes has been discovered that has been proposed to arise from a chemisensitized pathway involving a triplet sensitizer that increases mutagenesis by increasing the percentage of C-containing CPDs. To investigate how triplet sensitization may differ from direct UV irradiation, CPD formation was quantified in a 129-mer DNA designed to contain all 64 possible NYYN sequences. CPD formation with UVB light varied about 2-fold between dipyrimidines and 12-fold with flanking sequence and was most frequent at YYYR and least frequent for GYYN sites in accord with a charge transfer quenching mechanism. In contrast, photosensitized CPD formation greatly favored TT over C-containing sites, more so for norfloxacin (NFX) than acetone, in accord with their differing triplet energies. While the sequence dependence for photosensitized TT CPD formation was similar to UVB light, there were significant differences, especially between NFX and acetone that could be largely explained by the ability of NFX to intercalate into DNA.Technical challenges remain in the sequencing of RNA viruses due to their high intra-host diversity. This bottleneck is particularly pronounced when interrogating long-range co-evolved genetic interactions given the read-length limitations of next-generation sequencing platforms. This has hampered the direct observation of these genetic interactions that code for protein-protein interfaces with relevance in both drug and vaccine development. Here we overcome these technical limitations by developing a nanopore-based long-range viral sequencing pipeline that yields accurate single molecule sequences of circulating virions from clinical samples. We demonstrate its utility in observing the evolution of individual HIV Gag-Pol genomes in response to antiviral pressure. Our pipeline, called Multi-read Hairpin Mediated Error-correction Reaction (MrHAMER), yields >1000s of viral genomes per sample at 99.9% accuracy, maintains the original proportion of sequenced virions present in a complex mixture, and allows the detection of rare viral genomes with their associated mutations present at less then 1% frequency. This method facilitates scalable investigation of genetic correlates of resistance to both antiviral therapy and immune pressure and enables the identification of novel host-viral and viral-viral interfaces that can be modulated for therapeutic benefit.The eukaryotic replisome is comprised of three family-B DNA polymerases (Polα, δ and ϵ). Polα forms a stable complex with primase to synthesize short RNA-DNA primers, which are subsequently elongated by Polδ and Polϵ in concert with proliferating cell nuclear antigen (PCNA). In some species of archaea, family-D DNA polymerase (PolD) is the only DNA polymerase essential for cell viability, raising the question of how it alone conducts the bulk of DNA synthesis. We used a hyperthermophilic archaeon, Thermococcus kodakarensis, to demonstrate that PolD connects primase to the archaeal replisome before interacting with PCNA. Whereas PolD stably connects primase to GINS, a component of CMG helicase, cryo-EM analysis indicated a highly flexible PolD-primase complex. A conserved hydrophobic motif at the C-terminus of the DP2 subunit of PolD, a PIP (PCNA-Interacting Peptide) motif, was critical for the interaction with primase. The dissociation of primase was induced by DNA-dependent binding of PCNA to PolD. Point mutations in the alternative PIP-motif of DP2 abrogated the molecular switching that converts the archaeal replicase from de novo to processive synthesis mode.The SIB Swiss Institute of Bioinformatics (https//www.sib.swiss) creates, maintains and disseminates a portfolio of reliable and state-of-the-art bioinformatics services and resources for the storage, analysis and interpretation of biological data. selleck compound Through Expasy (https//www.expasy.org), the Swiss Bioinformatics Resource Portal, the scientific community worldwide, freely accesses more than 160 SIB resources supporting a wide range of life science and biomedical research areas. In 2020, Expasy was redesigned through a user-centric approach, known as User-Centred Design (UCD), whose aim is to create user interfaces that are easy-to-use, efficient and targeting the intended community. This approach, widely used in other fields such as marketing, e-commerce, and design of mobile applications, is still scarcely explored in bioinformatics. In total, around 50 people were actively involved, including internal stakeholders and end-users. In addition to an optimised interface that meets users' needs and expectations, the new version of Expasy provides an up-to-date and accurate description of high-quality resources based on a standardised ontology, allowing to connect functionally-related resources.Associative toehold is a powerful concept enabling efficient combinatorial computation in DNA circuit. A longer association length boosts circuit kinetics and equilibrium signal but results in higher leak rate. We reconcile this trade-off by using a hairpin lock design to dynamically elongate the effective associative toehold length in response to the input target. Design guidelines were established to achieve robust elongation without incurring additional leakages. Three hairpin initiators with different combinations of elongated associative toehold (4 → 6 nt, 5 → 8 nt and 6 → 9 nt) were shortlisted from the design framework for further discussion. The circuit performance improved in terms of reaction kinetics, equilibrium signal generated and limit of detection. Overall, the elongated associative toehold served as a built-in function to stabilize and favour the forward, desired reaction when triggered.
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