关键词： Alternative splicing   Arabidopsis   Cold stress   DNA-methylation   epiRILs   Nucleosome occupancy  

摘要： How stable and temperature-dependent variations in DNA methylation and nucleosome occupancy influence alternative splicing (AS) remains poorly understood in plants. To answer this, we generated transcriptome, whole-genome bisulfite, and MNase sequencing data for an epigenetic Recombinant Inbred Line (epiRIL) of A. thaliana at normal and cold temperature. For comparative analysis, the same data sets for the parental ecotype Columbia (Col-0) were also generated, whereas for DNA methylation, previously published high confidence methylation profiles of Col-0 were used. Significant epigenetic differences in an identical genetic background were observed between Col-0 and epiRIL lines under normal and cold temperatures. Our transcriptome data revealed that differential DNA methylation and nucleosome occupancy modulate expression levels of many genes and AS in response to cold. Collectively, DNA methylation and nucleosome levels exhibit characteristic patterns around intron-exon boundaries at normal and cold conditions, and any perturbation in them, in an identical genetic background is sufficient to modulate AS in Arabidopsis.

摘要： Objective The aim of this systematic review was to analyse current literature and reported cases of multisystem inflammatory syndrome in children (MISC), concerning its clinical spectrum, complications associated, therapeutic strategies and distinguishing features of other clinical syndromes. Methods Extensive literature research was performed in MEDLINE (through PubMed), Scopus and Web of Science from December 2019 to December 2020. First analysis included all article titles and abstracts screening to identify relevant studies, and second analysis included a full-text screening of previously selected studies. Eligibility was assessed independently by two authors, and disagreements were resolved by discussion and consensus. Data were extracted on MISC definition, demographic data, clinical features, diagnostic tests, laboratory analysis and imaging, therapeutical approach and outcomes. Results Common symptoms included gastrointestinal (70%), rash (57%) and cardiovascular (52% with shock). Notable differences with Kawasaki disease were identified including age, clinical presentation and cardiac involvement. Thirty per cent presented positive severe acute respiratory syndrome coronavirus-2 reverse transcription polymerase chain reaction and 51% positive serologies. Sixty-two per cent received intravenous immunoglobulin and 42% glucocorticoids. Sixty-two per cent required intensive care and 21 children died (<2%). Severe presentations were associated with neurological symptoms, hepatitis and acute kidney injury. Conclusions MISC raises concern on its severe cardiac involvement at presentation, with frequent intensive care and immunomodulatory therapy need. Short-term outcomes seem to be favourable, with cardiac dysfunction recovery and low mortality rates.

关键词： SARS-CoV-2   Viral infection   Biomedicine   general   Immunology   Infectious Diseases  

摘要： There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisystem inflammatory syndrome in children versus hospitalized control patients revealed differential cytokine responses, IgM/IgG/IgA epitope diversity, antibody binding and avidity. Apart from spike and nucleocapsid, IgG/IgA recognized epitopes in nonstructural protein (NSP) 2, NSP3, NSP12-NSP14 and open reading frame (ORF) 3a-ORF9. Peptides representing epitopes in NSP12, ORF3a and ORF8 demonstrated SARS-CoV-2 serodiagnosis. Antibody-binding kinetics with 24 SARS-CoV-2 proteins revealed antibody parameters that distinguish children with mild/moderate versus severe COVID-19 or multisystem inflammatory syndrome in children. Antibody avidity to prefusion spike correlated with decreased illness severity and served as a clinical disease indicator. The fusion peptide and heptad repeat 2 region induced SARS-CoV-2-neutralizing antibodies in rabbits. Thus, we identified SARS-CoV-2 antibody signatures in children associated with disease severity and delineate promising serodiagnostic and virus neutralization targets. These findings might guide the design of serodiagnostic assays, prognostic algorithms, therapeutics and vaccines in this important but understudied population. Pediatric COVID-19 can be associated with subsequent multisystem inflammatory syndrome in children (MIS-C), but how these pathologies are related or differ is unclear. Here the authors compare and contrast pediatric COVID-19 and MIS-C immunophenotypes using SARS-CoV-2 antibody fingerprinting proteomics.

关键词： apalutamide   applesauce   food vehicles   swallowing   tea   water  

摘要： Patients may have difficulty swallowing a whole daily dose of 240 mg (4 x 60-mg tablets) of apalutamide. One of the unique properties of apalutamide tablets is easy disintegration and dispersion when mixed into aqueous vehicles, avoiding the need to crush/split the tablets. To evaluate whether this method of apalutamide tablet administration would be conducive in a patient setting, different variations in preparation were evaluated, and one preparation was tested in humans. In vitro compatibility studies evaluated purity, dose, or stability of different variations of apalutamide in applesauce/yogurt/orange juice/green tea. An open-label, randomized, crossover phase 1 study in healthy men determined the bioavailability of an apalutamide-applesauce mixture versus whole tablets based on maximum plasma analyte concentration (C-max), area under the plasma analyte concentration-time curve: AUC(0-72h) and AUC(0-168h). Different amounts of applesauce/yogurt/orange juice/green tea as well as durations (up to 6 hours) did not affect the total apalutamide content available. The phase 1 study (n = 12) showed increased total exposure of 5% and peak exposure of 27.6% when comparing the apalutamide-applesauce mixture with whole-tablet administration. Variations in preparation times and total content for applesauce/yogurt/orange juice/green tea did not affect the purity, dose, or stability of apalutamide. An apalutamide-applesauce mixture is a suitable alternative administration method to whole tablets.

关键词： medium-rise buildings   residential buildings   retrofit   space cooling   space heating  

摘要： The European Union recently set the target of doubling building retrofit rates through the European Green Deal. Currently, more than half of the households' energy consumption is accounted for space conditioning, with southern European countries experiencing increasing demand for cooling systems over the past decade. Herein, the performance of market-available heating and cooling systems that can replace the existing low-efficiency systems in multiresidential buildings in Greece is compared. The study's objectives are to minimize the operating greenhouse gas emissions and the life-cycle cost. Results demonstrate that air-to-air heat pumps have the lowest life-cycle cost. In areas where natural gas is not available, the replacement of the diesel-oil boiler with a biomass boiler leads to a 48% to 73% decrease of the operating greenhouse gas emissions. In areas where natural gas is available, the gas absorption heat pump has the lowest operating greenhouse gas emissions, demonstrating a reduction between 40% and 54% when compared to a conventional gas boiler;however, it dramatically increases the life-cycle cost, making it less attractive than heat pumps and condensing gas boilers. The findings are in line with the current residential space conditioning market, while indicating the potential of biomass boilers and gas absorption heat pumps.

关键词： bread wheat   TaGS3   alternative splicing   grain weight   grain size  

摘要： The heterotrimeric G-protein mediates growth and development by perceiving and transmitting signals in multiple organisms. Alternative splicing (AS), a vital process for regulating gene expression at the post-transcriptional level, plays a significant role in plant adaptation and evolution. Here, we identified five splicing variants of G(gamma) subunit gene TaGS3 (TaGS3.1 to TaGS3.5), which showed expression divergence during wheat polyploidization, and differential function in grain weight and size determination. TaGS3.1 overexpression significantly reduced grain weight by 5.89% and grain length by 5.04%, while TaGS3.2-3.4 overexpression did not significantly alter grain size compared to wild type. Overexpressing TaGS3.5 significantly increased the grain weight by 5.70% and grain length by 4.30%. Biochemical assays revealed that TaGS3 isoforms (TaGS3.1-3.4) with an intact OSR domain interact with WGB1 to form active G(beta gamma) heterodimers that further interact with WGA1 to form inactive G(alpha beta gamma) heterotrimers. Truncated isoforms TaGS3.2-3.4 , which lack the C-terminal Cys-rich region but have enhanced binding affinity to WGB1, antagonistically compete with TaGS3.1 to bind WGB1, while TaGS3.5 with an incomplete OSR domain does not interact with WGB1. Taking these observations together, we proposed that TaGS3 differentially regulates grain size via AS, providing a strategy by which the grain size is fine-tuned and regulated at the post-transcriptional level.

关键词： Vertical femoral neck fractures   Medial buttress sliding plate   Femoral neck system   Biomechanics  

摘要： Background: No consensus has been reached for the treatment of vertical femoral neck fractures (vFNFs). Recently, two alternative methods were invented to treat vFNFs, one of which is a new plate with a sliding groove, which was designed as a substitution of the medial buttress locking plate to combine with cannulated compression screws (CCS) for reducing the breakage possibility of the proximal locking screw during the bone healing. Another one is the femoral neck system (FNS), which was believed with biomechanical superiority. This study aims to compare the biomechanics of these two new implants with three previous methods via finite element analysis (FEA) to validate whether they are suitable for the treatment of vFNFs. Methods: Five 70-degree Pauwels type III transcervical FNFs (vFNFs, AO/OTA 31B2.3(r)) models were built and fixed by CCS augmented with the newly designed sliding groove buttress plate (CCS+BS) and FNS. For comparison, models fixed by three parallel cannulated compression screws (CCS), biplane double-supported screw fixation (BDSF), CCS augmented with a medial buttress locking plate (CCS+BL) were also built. A 2100N load was applied along with the mechanical axis. Parameters of the maximal stress as well as the maximal displacement of the implants and bone, the maximal relative displacement of interfragments, and the stiffness, were analyzed to compare the biomechanical characteristics of the five models. Results: CCS+BS and CCS+BL showed stronger fixation strength with improved stiffness (1012.05N/mm, 1092.04N/mm), reduced maximal displacement of the implants (1.976mm, 1.838mm) and bone (2.075mm, 1.923mm), when compared with CCS (925.11N/mm, 2.158mm and 2.270mm) and BDSF (842.36N/mm, 2.299mm and 2.493mm). While FNS showed the weakest stiffness (593.22N/mm) and largest maximal displacement of the implants (3.234mm) and bone (3.540mm) among the five models. Conclusions: CCS+BS has a better biomechanical performance than CCS and BDSF, which offers a

关键词： Complementary and alternative medicine   Documentation concordance   Electronic medical record   Integrative medicine   Medical education   Patient-provider communication  

摘要： Background and purpose: Over half of patients utilize complementary and alternative medicine (CAM), yet fewer than 10 % of physicians inquire about use. This prospective cohort study sought to increase patient-provider communication about CAM through electronic medical record (EMR) prompts and education, as well as study concordance rates of physician and nursing CAM-related documentation. Materials and methods: Recordings in history and physical (H&P) documents authored by first-year pediatric residents were used as a proxy for communication. Rates of documentation were assessed at baseline, after the introduction of an EMR prompt, and after an educational intervention. Nursing documentation was compared with resident documents to assess rates of concordance regarding CAM-related documentation. Results: Baseline CAM-related documentation rate was 24 % and increased to 50 % after introducing an EMR CAM prompt (p < 0.001). No significant change occurred after education: 38 % had CAM-related documentation (p = 0.09). Physician and nursing documentation concordance rates were 58 % at baseline, 48 % after introduction of prompts, and 35 % after introducing education. Conclusion: Visual cues alone may be effective in increasing patient-provider communication about CAM, though low concordance between physician and nursing documentation may suggest variability in how CAM is defined and inquired about.

关键词： Input–   output tables   Regional modelling   CHARM   Inter-regional trade flows  

摘要： The main scope of the paper is to review the construction method of (multi-)regional input-output tables (RIOTs) in the Czech Republic at the NUTS 3 regional level. We compare the estimation of regional IO tables based on a modified cross-hauling adjusted regionalisation method (CHARM) applied by the authors with application of the hybrid approach of (Sixta and Vltavska in Stat Stat Econ J 97:4-14, 2017) from the Department of Statistics at the University of Economics in Prague. The aim of the presented paper is to contribute to the discussion about the suitability of alternative methodological approaches from the perspective of quality and time. We assume that despite the lack of official, published RIOTs by state statistical offices, the existing methodology of the relatively simpler non-survey CHARM method represents an adequate option for the generation of regional input-output tables suitable for further analytical research.

关键词： erythropoietin   myelodysplastic syndromes   transfusion