Background Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. Methods An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. Results An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Conclusions Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.

“Prosocial Behavior‘‘ means cooperating and acting in a way to benefit others. Since more and more diverse road users (such as electronic bicycles, scooters, etc.) but also vehicles at different levels of automation are sharing the safety-critical road environment, acting prosocial will become increasingly important in the future for both human and automated traffic participants. A few papers so far have already begun to address this issue, but currently, there exist no systematic methodological approaches to research this area. In the proposed workshop, we plan to define more specifically what characterizes prosocial behavior in future traffic scenarios where automated and manual vehicles meet and interact with all kinds of vulnerable road users. We further want to identify important scenarios and discuss potential evaluation methods for researching prosocial behavior. Ultimately, these findings will be integrated into a research agenda actively pursued by cooperation initiated during this event.

The Hedgehog (Hh) signaling pathway is essential for normal embryonic development, while its hyperactivation in the adult organism is associated with the development of various cancers. The role of the Hh signaling pathway in ovarian cancer has not been sufficiently investigated. Therefore, the present study investigated the role of protein patched homolog 1 (PTCH1), a component of the Hh signaling pathway, and changes in the promoter methylation status of the corresponding gene in a cohort of low-(LGSC) and high-grade serous ovarian carcinomas (HGSC) and HGSC cell lines (OVCAR8 and OVSAHO). PTCH1 protein expression level was analyzed using immunohistochemistry in tissue samples and immunofluorescence and western blotting in cell lines. DNA methylation patterns of the PTCH1 gene were analyzed using methylation-specific PCR. PTCH1 protein expression was significantly higher in HGSCs and LGSCs compared with controls (healthy ovaries and fallopian tubes). Similarly, ovarian cancer cell lines exhibited significantly higher PTCH1 protein expression compared with a normal fallopian tube non-ciliated epithelial cell line (FNE1). PTCH1 protein fragments of different molecular weights were detected in all cell lines, indicating possible proteolytic cleavage of this protein, resulting in the generation of soluble N-terminal fragments that are translocated to the nucleus. DNA methylation of the PTCH1 gene promoter was exclusively detected in a proportion of HGSC (13.5%) but did not correlate with protein expression. PTCH1 protein was highly expressed in serous ovarian carcinoma tissues and cell lines, while PTCH1 promoter methylation was only detected in HGSC. Further investigation is required to elucidate the possible mechanisms of PTCH1 activation in serous ovarian carcinomas.

Efforts to reduce air pollution in developing countries may require increased use of biomass fuels. Even biomass fuels are a sustainable alternative to fossil fuels there is limited quantitative information concerning heavy metal content in their ashes. Therefore, this study focuses on the determination of the heavy metal concentrations in wood pellet ash obtained from the combustion of 10 pellet brans from Bosnia and Herzegovina and Italy, the effects of adding the ashes to soils, and the assessment of health risk assessment. Ash content was determined by gravimetric method. The amount and composition of ash remaining after combustion of wood pellets varies considerably according to the type of biomass and wood from which the pellet is made. Samples were prepared by wet digestion using HNO3, and heavy metals are determined by atomic absorption spectroscopy-flame and graphite furnace. The results showed that the lowest concentration in ashes was obtained for Co 0.01 mg kg−1 and the highest for Fe 571.63 mg kg−1. The Hazard Index (HI), calculated for non-cancerous substances for children was 2.23E−01, and the total Risk index was 4.54E−05. As for adults, HI was 1.51E−02, while the Risk index value was 3.21E−06. Human health risk calculated through HI and Risk index for children and adults associated with analyzed pellets is not of significant concern. The calculated enrichment factor and metal pollution index for wood pellet ashes indicate the risk of soil contamination with heavy metals. From this point of view, analyzed samples of ashes could be a serious contaminant of soil, so further monitoring is required.

Summary This protocol describes a synthetic genomics pipeline to clone and engineer the entire 190-kbp genome of the African swine fever virus (ASFV) genotype II in yeast using transformation-associated recombination cloning. The viral genome was cloned using DNA directly extracted from a clinical sample. In addition, the precise deletion of a non-essential gene and its replacement by a synthetic reporter gene cassette are presented. This protocol is applicable to other ASFV genotypes and other large DNA viruses.

We present a complete analysis of Lepton Flavor Universality (LFU) violations in leptonic τ decays in motivated models addressing the B-physics anomalies, based on the SU(4)×SU(3)×SU(2)×U(1) gauge group. We show that the inclusion of vector-like fermions, required by B-physics data, leads to sizable modifications of the leading-log results derived within an Effective Field Theory approach. In the motivated parameter-space region relevant to the B-physics anomalies, the models predict a few per-mil decrease of the effective W -boson coupling to τ , within the reach of future experiments.

Background The pandemic of Coronavirus infectious disease 2019 (COVID-19) poses a major public health challenge, and an effective vaccine is the potential mechanism to resolve this specific situation. The present study aimed to evaluate acceptance of COVID-19 vaccination among patients attending the Oncology Clinic of University Clinical Hospital Mostar. Material/Methods This cross-sectional observational study enrolled 364 patients with cancer from the Oncology Clinic of University Clinical Hospital Mostar during February 2021. Data were collected using a questionnaire that captured general information about the participants and their attitudes toward COVID-19 vaccination. Results Of the participants, 41.8% answered “Yes” when asked if they would take the vaccine once it becomes available, 37.6% answered “Not sure”, and 20.6% answered “No”. For patients in favor of vaccination, the main reasons reported were fear of getting sick (77.6%), the desire to contribute to herd immunity (57.8%), and trusting the recommendations of health professionals (57.2%). The main reasons for the patients’ vaccination refusal/indecision were doubts about the results from clinical trials of COVID-19 vaccines (49.1%), concerns about adverse effects (24.5%), and confusion about the various vaccine options (19.8%). The majority of participants (82.4%) stated that recommendation by their oncologist could influence their decision about vaccination. Of the participants who indicated unwillingness (refusal or indecision) to be vaccinated against COVID-19, 65.3% stated that recommendation by their oncologist could influence their decision about vaccination. Conclusions The findings from the present study showed most patients had refused or were indecisive regarding immunization with COVID-19 vaccine. Increasing physician awareness of this situation may result in higher rates of vaccination.

Azoheteroarenes are relatively new photoswitchable compounds, where one of the phenyl rings of an azobenzene molecule is replaced by a heteroaromatic five-membered ring. Recent findings on methylated azoheteroarenes show that these photoswitches have potential in various optically addressable applications. The thermal stability of molecular switches is one of the primary factors considered in the design process. For molecular memory or energy storage devices, long thermal relaxation times are required. However, inducing a short thermal isomerization lifetime is required to release stored energy or as an alternative to photoswitching to avoid overlapping absorption spectra that reduce switching fidelity. In this study, we investigate how oriented external electric fields can be used to tune the thermal isomerization properties of three unsubstituted heteroaryl azo compounds-azoimidazole, azopyrazole, and azopyrrole. We show that favorable electric field orientations can increase the thermal half-life of studied molecules by as much as 60 times or reduce it from tens of days to seconds, compared to their half-life values in the field-free environment. A deeper understanding of the relationship between structure and kinetic properties provides insight as to how molecular switches can be designed for their electric field response in switching applications.

Heavy metals are naturally occurring elements, but they are regarded as significant environmental pollutants due to their high density and high toxicity even at low concentrations. The aim of this paper is the evaluation of the pollution level of heavy metals in the river and riverbank sediments, as well as the estimation of their origin and spatial differences along the course of the Vrbas River through Banja Luka. The concentrations of metals have been assessed using the Inductively coupled plasma ? optical emission spectrometry and Advanced mercury analyzer for mercury determination. The anthropogenic impact on heavy metal concentration in sediments was estimated by the calculating of pollution indices: geoaccumulation index (Igeo), contamination factor (Cf), pollution load index (PLI) and potential ecological risk index (Er). Obtained results indicate that there is no statistically significant spatial difference in metal concentration, indicating that heavy metals in sediments have a constant source. The anthropogenic impact expressed by the values of pollution indices showed that sites are generally uncontaminated by Co, Cr and V and moderately contaminated by Zn, Cu and Ni. On the contrary, lead, mercury and cadmium pose the highest ecological risk. The anthropogenic source of Pb, Hg and Cd is industry, municipal waste and the combustion of fossil fuels. The obtained results demonstrate the high ecological risk and the need for environ-mental monitoring, with the aim to support an efficient strategy to reduce local pollution and contamination of the investigated system.