Background: Rapid advancement of stem cell (SC) therapies provides both opportunities and risks for patients and physicians alike. Physicians have a role in counseling patients about unproven SC therapies, requiring a basic level of knowledge and access to information about SCs. Objective: This study sought to assess SC-related knowledge of and attitudes among physicians in Jordan to elucidate areas of deficiency that can be addressed. Methods: A cross-sectional survey, comprising questions on demographics and SC knowledge and attitudes, was designed as a scoring system to evaluate physicians’ knowledge and attitudes. Participants were recruited from 10 major hospitals in Jordan over 3 months between February and April 2019. The internal consistency of the scoring scales was calculated using Cronbach’s alpha reliability coefficient. Gender differences were evaluated with an independent t-test. Results: 382 physicians in Jordan completed the survey (59.9% response rate). They demonstrated a low/moderate level of overall SC knowledge (51.3%), but most lacked confidence in their ability to answer patients’ questions about SC therapies (64.7%). However, the total attitude score was moderate/high positive (66.8%) and most were interested in learning more about SCs (80.8%). Male physicians reported significantly more knowledge than females (p<0.0001). Conclusions: This study reveals Jordanian physicians’ hesitancy to counsel patients about SC therapies, largely due to gaps in knowledge. However, overall attitudes toward SC research and therapies are positive. The results of this study demonstrate a need to cover SC-related information in medical curricula in Jordan, as well as to support initiatives to regulate SC tourism in Jordan.

The polysaccharidic mucilage is a widespread plant trait with diverse features, often present around plant structures in contact with the environment, providing numerous functions including protection and adhesion. In myxodiasporous species, a mucilage is released upon the imbibition of the seed (myxospermy) or the fruit (myxocarpy), and therefore can play roles in the early seedling stages. It is unclear whether myxodiaspory has one or multiple evolutionary origins and why it disappeared in several species. Here, we summarize the recent advances on (i) the mucilage and mucilage secretory cell diversity, (ii) the evolution of the molecular actors involved in myxospermy underlying the observed inter- and intra-species natural diversity and (iii) the recently identified ecological functions. At the intra-species level, a high polymorphism was detected for a few genes in relation to the observed morphological diversity. Well characterized transcriptions factors interact in master regulatory complexes to balance carbon partitioning in Arabidopsis thaliana seeds. These transcription factors were sequentially recruited during seed plant evolution to control diverse traits including myxospermy, and their functions in seeds seem to be conserved across Rosids. Historically, the ecological functions of seed mucilage were mostly related to germination and seed dissemination but recently some exosystemic functions were uncovered such as soil micro-organism control and plant establishment support.

Here we show that substituting the ten protons in the dianion of a bispentalene derivative (C18H102-) by six Si2+ dications produces a minimum energy structure with two planar tetracoordinate carbons (ptC). In Si6C18, the ptCs are embedded in the terminal C5 pentagonal rings and participate in a three-center, two-electron (3c-2e) Si-ptC-Si σ-bond. Our exploration of the potential energy surface identifies a triphenylene derivative as the putative global minimum. But robustness to Born-Oppenheimer molecular dynamics (BOMD) simulations at 900 and 1500 K supports bispentalene derivative kinetic stability. Chemical bonding analysis reveals ten delocalized π-bonds, which, according to Hückel’s 4n+2 π-electron rule, would classify it as an aromatic system. Magnetically induced current density analysis reveals the presence of intense local paratropic currents and a weakly global diatropic current, the latter agreeing with the possible global aromatic character of this specie.

Giant congenital melanocytic nevi are brown-black lesions larger than 20 cm caused by benign proliferation of melanocytes. They either regress or progress in time in matters of thickness and size and may transform to malignancies. Here we report a twelve year old patient with giant melanocytic nevus of the scalp.

Theoretical and empirical studies have shown that species radiations are facilitated when a trait under divergent natural selection is also involved in sexual selection. It is yet unclear how quick and effective radiations are where sexual selection is unrelated to the ecological environment. We address this question using grasshopper species of the genus Chorthippus, which have evolved strong assortative mating while lacking noticeable eco-morphological divergence. Mitochondrial genomes suggest that the radiation is relatively recent, dating to the mid-Pleistocene, which leads to extensive incomplete lineage sorting throughout the mitochondrial and the nuclear genomes. Nuclear data show extremely low genomic differentiation among species, yet hybrids are absent in sympatric localities. Demographic analyses shed some light into these seemingly contradictory patterns. The estimated demographic model shows a long period of geographic isolation, followed by secondary contact and extensive introgression. This suggests that an initial period of geographic isolation might favor the coupling of male signaling and female preference, which currently maintains species boundaries in the face of long-term gene flow. More generally, these results suggest that sexual selection can lead to radiations without a primary role of divergent natural selection, resulting in cryptic species that are genetically, morphologically and ecologically similar, but otherwise behave mostly as good biological species.

Endemics co-occur because they evolved in situ and persist regionally or because they evolved ex situ and later dispersed to shared habitats, generating evolutionary or ecological endemicity centres, respectively. We investigate whether different endemicity centres can intertwine in the region ranging from Alps to Sicily, by studying their butterfly fauna. We gathered an extensive occurrence dataset for butterflies of the study area (27,123 records, 269 species, in cells of 0.5x0.5 degrees of latitude-longitude). We applied molecular-based delimitation methods (GMYC model) to 26,557 COI sequences of Western Palearctic butterflies. We identified entities based on molecular delimitations and the most recent checklist of European butterflies and objectively attributed occurrences to their most probable entity. We obtained a zoogeographic regionalisation based on the 69 endemics of the area. Using phylogenetic ANOVA we tested if endemics from different centres differ from each other and from non-endemics for key ecological traits and divergence time. Endemicity showed high incidence in the Alps and Southern Italy. The regionalisation separated the Alps from the Italian Peninsula and Sicily. The endemics of different centres showed a high turnover and differed in phenology and distribution traits. Endemics are on average younger than non-endemics and the Peninsula-Sicily endemics also have lower variance in divergence than those from the Alps. The observed variation identifies Alpine endemics as paleoendemics, now occupying an ecological centre, and the Peninsula-Sicily ones as neoendemics, that diverged in the region since the Pleistocene. The results challenge the common view of the Alpine-Apennine area as a single “Italian refugium”.

Biological invasions are recognized as one of the factors causing biodiversity loss. Incomplete reproductive isolation with a closely related species can result in hybridization when a non-native species is introduced into a new habitat. Management of hybrids is essential for biodiversity conservation; however, the distinction between the two species becomes a challenge in cases of hybrids with similar characteristics to native species. Although image recognition technology can be a powerful tool for identifying hybrids, studies have yet to utilize deep learning approaches. Hence, this study aimed to identify hybrids between native Japanese giant salamanders (Andrias japonicus) and non-native Chinese giant salamanders (Andrias davidianus) using EfficientNet and smartphone images. We used smartphone images of 11 native individuals (with 5 training and 6 test images) and 20 hybrid individuals (with 5 training and 15 test images). In our experimental environment, an AI model constructed with efficientNet-V2 showed 100% accuracy in identifying hybrids. In addition, highlighting the regions that influenced the AI model’s predictions using Grad-CAM revealed that salamander head spots are responsible for correctly classifying native and hybrid species. The results of this study revealed that our approach is one of the methods that enable the identification of hybrids, which was previously considered difficult without identification by the experts. Furthermore, since this study achieved high-performance identification using smartphone images, it is expected to be applied to a wide range of low-cost identification using citizen science.

Chenopodium quinoa (quinoa) is considered a superfood, as it has favourable nutrient composition and is gluten free. Quinoa has high tolerance to several abiotic stresses, i.e. salinity, water deficit (drought) and cold. The tolerance mechanisms are yet to be elucidated. Quinoa has Epidermal Bladder Cells (EBCs) that densely cover the shoot surface, particularly the younger parts of the plant. Here, we report on the EBC’s primary and secondary metabolomes, as well as the lipidome in response to abiotic stresses. EBCs were isolated from plants after cold, heat, high-light, water deficit and salt treatments. We used untargeted Gas Chromatography-Mass Spectrometry (GC-MS) to analyse metabolites and untargeted and targeted Liquid Chromatography-MS (LC-MS) for lipids and secondary metabolite analyses. We identified 64 primary metabolites, including sugars, organic acids and amino acids, 19 secondary metabolites, including phenolic compounds, betanin and saponins and 240 lipids categorized in five groups including glycerolipids and phospholipids. Although we found only few changes in the metabolic composition of bladders in response to abiotic stresses, metabolites related with heat, cold and high-light treatments, but not salt stress, were changed significantly. Na+ concentrations were low in EBCs with all treatments, and approximately two orders of magnitude lower than K+ concentrations.

Many transgenic animals have been produced using CRISPR–Cas9 technology to edit specific genes. However, there are few guidelines for the application of this technique in cattle. The goal of this study was to produce trait-improved cattle using the genome editing technology CRISPR–Cas9. Myostatin (MSTN) was selected as a target locus and synthetic mRNA of sgRNA and Cas9 was microinjected into bovine in vitro fertilized embryos. As a result, 17 healthy calves were born and 3 of these showed MSTN mutation rates of 10.5%, 45.4%, and 99.9%, respectively. Importantly, the offspring with the 99.9% MSTN mutation rate had biallelic mutation (-12bp) and a doubling muscle growth phenotype. In conclusion, we showed that the genome editing technology CRISPR–Cas9 can produce genetically modified calves with improved traits.

Background: Concern exists regarding adequacy of visualization of stress echocardiograms performed without intravenous contrast in persons with Class III obesity (body mass index ≥ 40 kg/m2). Methods: Dobutamine stress echocardiography (DSE) was performed on 128 candidates for bariatric surgery with class III obesity without chest pain or pre-existent coronary artery disease (CAD). DSE without intravenous contrast was initially performed on 62 patients with class III obesity, then was subsequently was performed with intravenous contrast on 66 patients with class III obesity. Left ventricular (LV) regional wall motion was assessed at baseline and peak stress using the 16-segment model. Results: In the intravenous contrast group 1046 of 1056 LV segments studied (99.1%) were well-visualized and interpretable at baseline and 1044 of 1056 LV segments studied (98.9%) were well-visualized and interpretable at peak stress. In the non-contrast group 905 of 992 segments studied (91.2%) were well-visualized and interpretable at baseline and 886 of 992 segments studied (89.3%) were well-visualized and interpretable at peak stress. A significantly greater number of LV segments were well-visualized and interpretable in the intravenous contrast group than in the group compared to the non-contrast group, at baseline and at peak stress (p < 0.00001 for both). DSE was positive for ischemia in 1 patient. All patients underwent bariatric surgery without cardiovascular complications. Six months after surgery, all patients were alive; none developed cardiovascular events. Conclusion: The use of intravenous contrast during DSE significantly improves visualization and interpretability of LV segments in patients with class III obesity.

Patterns of biodiversity provide insights into the processes that shape biological communities around the world. Variation in species diversity along biogeographical or ecological gradients, such as latitude or precipitation, can be attributed to variation in different components of biodiversity: changes in the total abundance (i.e. more-individual effects) and changes in the regional species abundance distribution (SAD). Rarefaction curves can provide a tool to partition these sources of variation on diversity, but first must be converted to a common unit of measurement. Here, we partition species diversity gradients into components of the SAD and abundance using the effective number of species (ENS) transformation of the individual-based rarefaction curve. Because the ENS curve is unconstrained by sample size, it can act as a standardized unit of measurement when comparing effect sizes among different components of biodiversity change. We illustrate the utility of the approach using two datasets spanning latitudinal diversity gradients in trees and marine reef fish, and find contrasting results. Whereas the diversity gradient of fish was mostly associated with variation in abundance (86%), the tree diversity gradient was mostly associated with variation in the SAD (59%). These results suggest that local fish diversity may be limited by energy through the more-individuals effect, while species pool effects are the larger determinant of tree diversity. We suggest that the framework of the ENS-curve has the potential to quantify the underlying factors influencing most aspects of diversity change.

To enable the people involved in a software development process to communicate and reason close to their area of knowledge, we are investigating a method to formalize and integrate knowledge of multiple domains into domain models and into specifications in terms of those domain models. For this purpose, we have previously defined a set of method objectives, and an initial version of the method –called MuDForM. This paper reports on the methodical support for using a domain model as terminology to define other specifications, and feature specifications in particular. We performed a case study to validate how well the method helps in the specification of processes and to realize the case-specific objectives of the customer. The case study pertains to the formalization of the ISO26262 standard for functional safety in the automotive domain. We found that our method is suitable to systematically formalize a process that is described in natural language, such that there is a clear separation of domain-specific concepts, unambiguous process specifications, and concepts from outside the domain and process of interest. We have extended our method with concepts, steps, and guidelines for grammatical analysis, for the formalization of constraints, and for the specification of processes. The case-specific results are the unambiguous specification of a part of the ISO26262 processes.

Background: Local impedance (LI) can indirectly measure catheter contact and tissue temperature during radiofrequency catheter ablation (RFCA). However, data on the effects of catheter contact angle on LI parameters are scarce. This study aimed to evaluate the influence of catheter contact angle on LI changes and lesion size with 2 different LI-sensing catheters in a porcine experimental study. Methods: Lesions were created by the INTELLANAV MiFi™ OI (MiFi) and the INTELLANAV STABLEPOINT™ (STABLEPOINT). RFCA was performed with 30 watts and a duration of 30 seconds. The CF (0, 5, 10, 20, and 30 g) and catheter contact angle (30°, 45°, and 90°) were changed in each set (n=8 each). The LI rise, LI drop, and lesion size were evaluated. Results: The LI rise increased as CF increased. There was no angular dependence with the LI rise under all CFs in the MiFi. On the other hand, the LI rise at 90° was lower than at 30° under 5 and 10 g of CF in STABLEPOINT. The LI drop increased as CF increased. Regarding the difference in catheter contact angles, the LI drop at 90° was lower than that at 30° for both catheters. The maximum lesion widths and surface widths were smaller at 90° than at 30°, whereas there were no differences in lesion depths. Conclusion: The LI drop and lesion widths at 90° were significantly smaller than those at 30°, although the lesion depths were not different among the 3 angles for the MiFi and STABLEPOINT.

The scale-up of bioprocesses is still one of the major obstacles in biotechnological industry. Scale-down bioreactors were identified as valuable tools to investigate the heterogeneities observed in large-scale tanks in laboratory-scale. Additionally, computational fluid dynamics (CFD) simulations can be used to gain information about fluid flow in tanks used for production. Here we present the rational design and comprehensive characterization of a scale-down setup, in which a flexible and modular plug-flow reactor is connected to a stirred tank bioreactor. With the help of CFD the mixing time difference between differently scaled bioreactors were evaluated and used as scale-down criterium. Additionally, it was used to characterize the setup at conditions were experiments could technically not be performed. This was the first time a scale-down setup was tested on high cell density Escherichia coli cultivations to produce industrial relevant antigen-binding fragments (Fab). Reduced biomass and product yields were observed during the scale-down cultivations. Additionally, the intracellular Fab fraction was increased by using the setup. The results show that including CFD in the design and characterization of a scale-down reactor can help to keep a connection to production scale and also gain intensive knowledge about the setup, which enhances usability.

For the treatment of Covid-19 patients with remdesivir, poor renal- and liver function were both exclusion criteria in randomized clinical trials (RCTs) and contra-indication for treatment. Also, nephrotoxicity and hepatotoxicity are reported as adverse events. We retrospectively reviewed renal- and liver functions of covid-19 patients who received remdesivir in the 15 days after treatment initiation. Approximately 20% of the patient population met RCT exclusion criteria. In total, 11% of the patients had a decrease in estimated glomerular filtration rate larger than 10 ml/min/1.73m2. Also, 25% and 35% had increased alanine transaminase and aspartate transaminase levels, respectively. However, serious adverse events were limited. Therefore, contra-indications based on kidney- and liver function should not be absolute for remdesivir treatment in patients with Covid-19 if these functions are monitored regularly.

Echocardiography is commonly utilized in patients with acute respiratory distress syndrome (ARDS) for assessment of cardiac function, volume status, and the potential development of acute cor pulmonale. In severe ARDS, prone positioning is frequently used, which imposes technical challenges during transthoracic echocardiography (TTE) image acquisition. Moreover, prone positioning can affect cardiopulmonary function in ways that are reflected on the echocardiographic findings in this position. Historically, a transesophageal approach was recommended when a patient is prone, with few studies reporting utility of TTE in this setting. However, recent publications have begun to address this knowledge gap. This review explores recent literature addressing the use of TTE in prone patients with ARDS, with a special focus on the cardiopulmonary effects of proning and potential solutions to the technical difficulties that arise in this position.

Objective: To review the effect of the COVID-19 pandemic on the presentation of Cervical cancer. Design/ Setting: Retrospective study involving the Regional Cancer Centres in the M62 Group. Methods: Data was collected for two equal time periods. All cervical cancers were included and FIGO 2018 staging was used for the data collection. P values were calculated using binomial hypothesis test for the difference in staging. Time from symptoms to diagnosis was assessed using a normal distribution test. All other calculations were performed using chi-squared test. Statistical significance was considered if p values were <0.05. Main outcome measures: Histology, stage at diagnosis, date of onset of symptoms, investigation and type of treatment. Results: A total of 406 cases of cervical cancer were reviewed; 233 from May – October 2019 (pre-COVID) and 173 between May – October 2020 (post COVID); representing a significant reduction in new cervical cancer diagnoses of 25% post COVID (p<0.001) There was a 42% increase in the delay from start of symptoms to diagnosis Post COVID. Pre COVID, 27% of patients presented with Stage 3 or 4 disease, whilst during COVID this was 38%; statistically significant (p <0.001). When we evaluated the treatments received between the two time periods, this was also statistically significant (chi-squared, p=0.0005). Conclusions: This study has demonstrated a statistically significant increase in the stage of cervical cancer at diagnosis and a change in treatment for cervical cancer following the onset of COVID-19. The implications of this are discussed.

Severe fever with thrombocytopaenia syndrome virus (SFTSV) and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in SFTS and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19 patients and also investigated the role of IL-10 in vitro studies: LPS-induced THP-1-derived macrophages, SFTSV infection of THP-1 cells, and SARS-CoV-2 infection of THP-1 cells. In this study, we found that levels of both IL-10 and IL-6 were significantly elevated, the level of TGF-β was significantly decreased and IL-10 was elevated earlier than IL-6 in severe and critical COVID-19 and fatal SFTS patients, and inhibition of IL-10 signalling decreased the production of IL-6 and elevated that of TGF-β. Therefore, the hyperproduction of IL-10 and IL-6 and the low production of TGF-β have been linked to cytokine storm-induced mortality in fatal SFTS and severe and critically ill COVID-19 patients and that IL-10 can play an important role in the host immune response to severe and critical SARS-CoV-2 and fatal SFTSV infection.