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7% overall. The modified clipless intrafascial neurovascular bundle-sparing technique is safe and feasible and can achieve excellent recovery of erectile function after RARP. Further large-scale prospective comparative studies are warranted.Nature reserves play an extraordinarily important role in conserving animal populations and their habitats. However, landscape change and unreasonable zoning designations often render these protected areas inadequate. Therefore, regular evaluation of the efficacy of protected lands is critical for maintaining and improving management strategies. Using species distribution models and GAP analysis, we assessed the changes in suitable habitat for the Brown Eared-pheasant (Crossoptilon mantchuricum) in two Chinese nature reserves between 1995 and 2013. Our results showed that the habitat suitability of Brown Eared-pheasant has changed dramatically during this period, and fragmentation analyses showed an increase in concentration area and decrease in patch area. In particular, our findings show that the national nature reserves need to adjust their ranges to ensure the conservation of this flagship species. Our study further provides a new viewpoint for evaluating the efficacy of protected lands, particularly in highly urbanized regions where conservation goals must be balanced with changing landscapes.Individuals with autism spectrum disorders (ASDs) imitate observed behavior less than age-matched and typically developing peers, resulting in deterred learning ability and social interaction. However, this deficit lacks preclinical assessment tools. A previous study has shown that mice exhibit contagious itch behavior while viewing a scratching demonstrator mouse, as opposed to an ambulating demonstrator mouse, but whether autism mouse models imitate observed scratching behavior remains unknown. Here, we investigated contagious itch behavior in the mouse model of fragile X syndrome (FXS), a common form of inherited intellectual disabilities with a high risk for ASDs. We found that the mouse model of FXS shows deficits in contagious itch behavior. Our findings can be used as a new preclinical assessment tool for measuring imitative deficits in the study of neurodevelopmental disorders including FXS.Pharmacological ascorbate (P-AscH-, high-dose, intravenous vitamin C) is cytotoxic to tumor cells in doses achievable in humans. Phase I studies in pancreatic cancer (PDAC) utilizing P-AscH- have demonstrated increases in progression free survival, suggesting a reduction in metastatic disease burden. The purpose of this study was to determine the effects of P-AscH- on metastatic PDAC. Several in vitro and in vivo mechanisms involved in PDAC metastases were investigated following treatment with P-AscH-. Serum from PDAC patients in clinical trials with P-AscH- were tested for the presence and quantity of circulating tumor cell-derived nucleases. P-AscH- inhibited invasion, basement membrane degradation, decreased matrix metalloproteinase expression, as well as clonogenic survival and viability during exposure to fluid shear stress. In vivo, P-AscH- significantly decreased formation of ascites, tumor burden over time, circulating tumor cells, and hepatic metastases. Both in vitro and in vivo findings were reversed with the addition of catalase suggesting that the effect of P-AscH- on metastatic disease is mediated by hydrogen peroxide. Finally, P-AscH- decreased CTC-derived nucleases in subjects with stage IV PDAC in a phase I clinical trial. We conclude that P-AscH- attenuates the metastatic potential of PDAC and may prove to be effective for treating advanced disease.African swine fever virus (ASFV) is the causative agent of a devastating hemorrhagic disease (ASF) that affects both domestic pigs and wild boars. Conversely, ASFV circulates in a subclinical manner in African wild pigs, including warthogs, the natural reservoir for ASFV. Together with genetic differences, other factors might be involved in the differential susceptibility to ASF observed among Eurasian suids (Sus scrofa) and African warthogs (Phacochoerus africanus). Preliminary evidence obtained in our laboratory and others, seems to confirm the effect that environmental factors might have on ASF infection. Thus, domestic pigs raised in specific pathogen-free (SPF) facilities were extremely susceptible to highly attenuated ASFV strains that were innocuous to genetically identical domestic pigs grown on conventional farms. Since gut microbiota plays important roles in maintaining intestinal homeostasis, regulating immune system maturation and the functionality of the innate/adaptive immune responses, we decided to examine whether warthog fecal microbiota transplantation (FMT) to domestic pigs affects host susceptibility to ASFV. The present work demonstrates that warthog FMT is not harmful for domestic weaned piglets, while it modifies their gut microbiota; and that FMT from warthogs to pigs confers partial protection against attenuated ASFV strains. Future work is needed to elucidate the protective mechanisms exerted by warthog FMT.Accurate and continuous monitoring of critically ill patients is frequently achieved using invasive catheters, which is technically complex. Our purpose was to evaluate the validity and accuracy of a photoplethysmography (PPG)-based remote monitoring device compared to invasive methods of arterial line (AL) and Swan-Ganz (SG) catheters in a swine model of controlled hemorrhagic shock. Following a baseline phase, hemorrhagic shock was induced in 11 pigs by bleeding 35% of their blood volume, followed by a post-bleeding follow-up phase. Animals were monitored concomitantly by the PPG device, an AL and a SG catheter, for a median period of 447 min. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP, respectively), and cardiac output (CO) were recorded continuously. The complete data set consisted of 1312 paired observations. Correlations between the PPG-based technique and the invasive methods were significant (p  0.88), with concordance rates (determined by quadrant plots) of 86%, 66% and 68%, respectively. The novel PPG-based device was accurate and valid compared to existing invasive techniques and might be used for continuous monitoring in several clinical settings following further studies.Air pollution causes hypertension, cardiovascular disease, and mortality. Asian dust (AD) reportedly induces asthma or acute myocardial infarction along with air pollution, but its impact on blood pressure (BP) is unknown. We investigated the association between short-term AD exposure and BP fluctuations in 300,952 individuals whose BP was measured during April 2005-March 2015 and divided them into AD and non-AD groups based on visitation for AD-related events. AD's occurrence, air pollutants' concentration (suspended particulate matter, SO2, NO2, photochemical oxidants), and meteorological variables (mean ambient temperature, relative humidity) were obtained from a monitoring station; AD events correlated with decreased visibility ( less then 10 km). We observed 61 AD days, with 3897 participants undergoing medical check-ups. Short-term AD exposure at lag day-0 was significantly associated with higher systolic BP (SBP), diastolic BP (DBP), and pulse rate (PR) risk (β = 1.85, 95% confidence interval (CI) 1.35-2.35 for SBP, β = 2.24, 95% CI 1.88-2.61 for DBP, β = 0.52, 95% CI 0.14-0.91 for PR) using multi-pollutant model. Population-attributable fractions exposed to AD were 11.5% for those with elevated SBP (SBP ≥ 120 mmHg) and 23.7% for those with hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). This study showed a strong association between short-term AD exposure and increased SBP and DBP.Chinese hamster (Cricetulus griseus) ovary-derived Chinese hamster ovary (CHO) cells are the most commonly used mammalian hosts for the industrial production of recombinant therapeutics because of their ability to fold, assemble, and perform post-translational modifications, such as glycosylation, on proteins. They are also valuable for their ability to grow in serum-free suspension cultures. In this study, we established a cell line derived from lung tissue of Chinese hamsters, named Chinese hamster lung (CHL)-YN cells. The biosafety of CHL-YN cells was confirmed by in vitro sterility testing, mycoplasma detection, and reverse transcriptase assays. One of the key characteristics of CHL-YN cells was their doubling time of 8.1 h in chemically defined culture medium; thus, they proliferate much faster than conventional CHO cells and general mammalian cells. Transgenes could be introduced into CHL-YN cells with high efficiency. Finally, between 50% to > 100% of the amount of glycosylated immunoglobulin G (IgG)1 produced by CHO-K1 cells was produced by CHL-YN cells over a shorter period of time. In summary, fast-growing CHL-YN cells are a unique cell line for producing recombinant proteins.18F-FDG PET/CT occupies a growing role in the diagnosis of large vessel vasculitis (LVV), illustrating enhanced uptake in the lining of large vessels. A retrospective single center study was conducted of patients who underwent 18F-FDG PET/CT scans between 2009 and 2019 at Sheba Medical Center, Israel. The imaging results were analyzed for evidence of LVV. We reviewed the PET/CT scans of 126 patients and identified 57 studies that either showed evidence of active LVV or that had been performed in patients previously treated for systemic vasculitis. In 6 patients with fevers of unknown origin and elevated inflammatory markers, PET/CT revealed LVV. Six of 13 patients previously treated for systemic vasculitis demonstrated persistent large vessel uptake. LVV was identified in 8 patients with other autoimmune diseases, and in 4 diagnosed with infectious aortitis. In 26 patients who underwent malignancy surveillance, PET/CT revealed more localized large vessel wall inflammation. Our results illustrate that PET/CT may identify large vessel wall inflammation in patients with a suspicion of LVV, and incidentally in patients who undergo malignancy surveillance. PET/CT may also help delineate the presence and extent of vessel inflammation in patients with LVV and in those with other autoimmune diseases.Anti-PD-1 antibodies revolutionized the treatment of advanced melanoma patients. However, one out of three do not respond to this therapy, with an overall poor prognosis. Identification of predictive biomarkers in patients receiving immune-based therapies is necessary for minimizing risk of toxicity and optimizing patient benefit and is still an important unmet clinical need. Recently, many studies have evaluated peripheral blood markers as potential biomarkers, but none so far have been validated. We collected at baseline peripheral blood samples from 18 consecutive advanced melanoma patients treated with anti-PD-1 therapy. Main pro- and anti-inflammatory cytokines were studied in PBMCs from baseline blood samples both evaluating mRNA expression by qRT-PCR and identifying PBMCs subpopulations by FACS analysis. We found that IFN-γ mRNA expression levels were significantly higher in responder patients compared to non-responder ones. Moreover, to better validate its role, we evaluated the IFN-γ/IL-10 ratio. This value was higher in responder patients. FACS analysis confirmed that CD4 + IFN-γ + PBMCs percentage was higher in responders. Our data suggest an interesting correlation between IFN-γ/IL-10 ratio and response to anti-PD-1 therapy in advanced melanoma patients, suggesting a new biomarker that could be easily incorporated in clinical practice.Altered resting-state functional connectivity (FC) of the amygdala (AMY) has been demonstrated to be implicated in schizophrenia (SZ) and attenuated psychosis syndrome (APS). Specifically, no prior work has investigated FC in individuals with APS using subregions of the AMY as seed regions of interest. The present study examined AMY subregion-based FC in individuals with APS and first-episode schizophrenia (FES) and healthy controls (HCs). The resting state FC maps of the three AMY subregions were computed and compared across the three groups. Correlation analysis was also performed to examine the relationship between the Z-values of regions showing significant group differences and symptom rating scores. Individuals with APS showed hyperconnectivity between the right centromedial AMY (CMA) and left frontal pole cortex (FPC) and between the laterobasal AMY and brain stem and right inferior lateral occipital cortex compared to HCs. Patients with FES showed hyperconnectivity between the right superficial AMY and left occipital pole cortex and between the left CMA and left thalamus compared to the APS and HCs respectively. A negative relationship was observed between the connectivity strength of the CMA with the FPC and negative-others score of the Brief Core Schema Scales in the APS group. We observed different altered FC with subregions of the AMY in individuals with APS and FES compared to HCs. These results shed light on the pathogenetic mechanisms underpinning the development of APS and SZ.A split-cube-resonator-based metamaterial structure that can act as a polarization- and direction-selective perfect absorber for the infrared region is theoretically and experimentally demonstrated. The structure, fabricated by direct laser writing and electroless silver plating, is comprised of four layers of conductively-coupled split-cube magnetic resonators, appropriately rotated to each other to bestow the desired electromagnetic properties. We show narrowband polarization-selective perfect absorption when the structure is illuminated from one side; the situation is reversed when illuminating from the other side, with the orthogonal linear polarization being absorbed. The absorption peak can be tuned in a wide frequency range by a sparser or denser arrangement of the split cube resonators, allowing to cover the entire atmospheric transparency window. The proposed metamaterial structure can find applications in polarization-selective thermal emission at the IR atmospheric transparency window for radiative cooling, in cost-effective infrared sensing devices, and in narrowband filters and linear polarizers in reflection mode.The purpose was to review the incidence of in situ carcinoma in Iceland after initiating population-based mammography screening in 1987 and to compare management of ductal carcinoma in situ (DCIS) between Iceland and the Uppsala-Örebro region (UÖR) in Central Sweden. The Icelandic Cancer Registry provided data on in situ breast carcinomas for women between 1957 and 2017. Clinical data for women with DCIS between 2008 and 2014 was extracted from hospital records and compared to women diagnosed in UÖR. In Iceland, in situ carcinoma incidence increased from 7 to 30 per 100 000 women per year, following the introduction of organised mammography screening. The proportion of in situ carcinoma of all breast carcinomas increased from 4 to 12%. More than one third (35%) of women diagnosed with DCIS in Iceland were older than 70 years versus 18% in UÖR. In Iceland, 49% of all DCIS women underwent mastectomy compared to 40% in UÖR. The incidence of in situ carcinoma in Iceland increased four-fold after the uptake of population-based mammography screening causing considerable risk of overtreatment. Differences in treatment of DCIS were seen between Iceland and UÖR, revealing the importance of quality registration for monitoring patterns of management.Rainbow trout has a male heterogametic (XY) sex determination system controlled by a major sex-determining gene, sdY. Unexpectedly, a few phenotypically masculinised fish are regularly observed in all-female farmed trout stocks. To better understand the genetic determinism underlying spontaneous maleness in XX-rainbow trout, we recorded the phenotypic sex of 20,210 XX-rainbow trout from a French farm population at 10 and 15 months post-hatching. The overall masculinisation rate was 1.45%. We performed two genome-wide association studies (GWAS) on a subsample of 1139 individuals classified as females, intersex or males using either medium-throughput genotyping (31,811 SNPs) or whole-genome sequencing (WGS, 8.7 million SNPs). The genomic heritability of maleness ranged between 0.48 and 0.62 depending on the method and the number of SNPs used for the estimation. At the 31K SNPs level, we detected four QTL on three chromosomes (Omy1, Omy12 and Omy20). Using WGS information, we narrowed down the positions of the two QTL detected on Omy1 to 96 kb and 347 kb respectively, with the second QTL explaining up to 14% of the total genetic variance of maleness. Within this QTL, we detected three putative candidate genes, fgfa8, cyp17a1 and an uncharacterised protein (LOC110527930), which might be involved in spontaneous maleness of XX-female rainbow trout.Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML). NPM1 mutations are always heterozygous. In addition, NPM1 has a number of different splice variants with the major variant encoded by exons 1-9 and 11-12 (NPM1.1). Further variants include NPM1.2 which lacks exons 8 and 10 and NPM1.3 which comprises exons 1-10 (and so lacks the region of sequence mutated in AML). In this study we quantified the expression of these three variants in 108 AML patient samples with and without NPM1 mutations and also assessed the level of expression from the wild-type and mutant alleles in variants NPM1.1 and NPM1.2. The results show that NPM1.1 is the most commonly expressed variant, however transcripts from wild-type and mutated alleles do not occur at equal levels, with a significant bias toward the mutated allele. Considering the involvement of mutant nucleophosmin in the progression and maintenance of AML, a bias towards mutated transcripts could have a significant impact on disease maintenance.Amecephala pusilla gen. et sp. nov. is described and illustrated on the basis of a well-preserved female psyllid (Liadopsyllidae) in a piece of Cretaceous Myanmar amber. The new genus differs from other members of Liadopsyllidae in details of the antennae and forewings. For the first time, the presence of a circumanal ring is documented for Mesozoic psyllids. Based on differences in the length of female terminalia, it is suggested that Liadopsyllidae may have displayed a diversified oviposition biology. As far as known, Liadopsyllidae lack a pulvillus, a putative autapomorphy supporting the monophyly of Liadopsyllidae. An identification key to genera and an annotated checklist of known Liadopsyllidae species are provided. New synonyms and combinations are proposed and the status of the subfamily Miralinae is discussed.It is necessary to identify suitable alternative crops to ensure the nutritional demands of a growing global population. The genome of Moringa oleifera, a fast-growing drought-tolerant orphan crop with highly valuable agronomical, nutritional and pharmaceutical properties, has recently been reported. We model here gene family evolution in Moringa as compared with ten other flowering plant species. Despite the reduced number of genes in the compact Moringa genome, 101 gene families, grouping 957 genes, were found as significantly expanded. Expanded families were highly enriched for chloroplastidic and photosynthetic functions. Indeed, almost half of the genes belonging to Moringa expanded families grouped with their Arabidopsis thaliana plastid encoded orthologs. Microsynteny analysis together with modeling the distribution of synonymous substitutions rates, supported most plastid duplicated genes originated recently through a burst of simultaneous insertions of large regions of plastid DNA into the nuclear genome. These, together with abundant short insertions of plastid DNA, contributed to the occurrence of massive amounts of plastid DNA in the Moringa nuclear genome, representing 4.71%, the largest reported so far. Our study provides key genetic resources for future breeding programs and highlights the potential of plastid DNA to impact the structure and function of nuclear genes and genomes.The roles played by several inflammatory factors in screening for prostate cancer (PCa) among gray area patients, namely those with serum prostate-specific antigen (PSA) levels between 4 and 10 ng/ml, have not been completely identified, and few effective diagnostic nomograms have been developed exclusively for these patients. We aimed to investigate new independent predictors of positive biopsy (PB) results and develop a novel diagnostic nomogram for this group of patients. The independent predictors of PB results were identified, and a nomogram was constructed using multivariate logistic regression analysis based on a cohort comprising 401 Gy area patients diagnosed at Xijing Hospital (Xi'an, China) between January 2016 and December 2019. The predictive accuracy of the nomogram was assessed using the receiver operating characteristic curve, and the nomogram was calibrated by comparing the prediction with the observation. The performance of the nomogram was further validated using an independent cohort. Finally, lymphocyte-to-monocyte ratio (LMR) > 4.11 and red blood cell distribution width (RDW)-standard deviation (SD) > 42.9 fl were identified as independent protective predictors of PB results, whereas PSA density (PSAD) > 0.141 was identified as an independent risk predictor. The nomogram established using PSAD, LMR, and RDW-SD was perfectly calibrated, and its predictive accuracy was superior to that of PSAD in both internal and external validations (0.827 vs 0.769 and 0.765 vs 0.713, respectively). This study is the first to report the importance of LMR and RDW-SD in screening for PCa among gray area patients and to construct an exclusive nomogram to predict the individual risk of positive 13-core biopsy results in this group of patients. With superior performance over PSAD, our nomogram will help increase the accuracy of PCa screening, thereby avoiding unnecessary biopsy.This work combines state-of-the-art methods (DNA metabarcoding) with classic approaches (visual stomach content characterization and stable isotope analyses of nitrogen (δ15N) and carbon (δ13C)) to investigate the trophic ecology of anchovy (Engraulis encrasicolus) and sardine (Sardina pilchardus) at high taxonomic and spatial resolution in the Western Mediterranean Sea. Gut contents observed are in accordance with the dietary plasticity generally described for anchovy and sardine, suggesting a diet related to the opportunistic ingestion of available prey in a certain area and/or time. Genetic tools also showed modest inter-specific differences regarding ingested species. However, inter-specific and intra-specific differences in ingested prey frequencies and prey biomass reflected a latitudinal signal that could indicate a more effective predation on large prey like krill by anchovy versus sardine, as well as a generalized higher large prey ingestion by both species southwards. In fact, both species presented lower δ15N in the northernmost area. This latitudinal gradient indicates changes in the trophic ecology of anchovy and sardine that coincide with previously described better biological conditions for fish in the southern part of the study area as well as higher landings of both species in recent years.In the aftermath of the financial crisis of 2007-2009, the growing body of literature on financial networks has widely documented the predictive power of topological characteristics (e.g., degree centrality measures) to explain the systemic impact or systemic exposure of financial institutions. This study shows that considering alternative topological measures based on local sub-network environment improves our ability to identify systemic institutions. To provide empirical evidence, we apply a two-step procedure. First, we recover network communities (i.e., close-peer environment) on a spillover network of financial institutions. Second, we regress alternative measures of vulnerability (i.e. firm's losses)on three levels of topological measures the global level (i.e., firm topological characteristics computed over the whole system), local level (i.e., firm topological characteristics computed over the community to which it belongs), and aggregated level by averaging individual characteristics over the community. The sample includes 46 financial institutions (banks, broker-dealers, and insurance and real-estate companies) listed in the Standard & Poor's 500 index. Our results confirm the informational content of topological metrics based on a close-peer environment. Such information is different from that embedded in traditional system-wide topological metrics and can help predict distress of financial institutions in times of crisis.A majority of experimental disciplines face the challenge of exploring large and high-dimensional parameter spaces in search of new scientific discoveries. Materials science is no exception; the wide variety of synthesis, processing, and environmental conditions that influence material properties gives rise to particularly vast parameter spaces. Recent advances have led to an increase in the efficiency of materials discovery by increasingly automating the exploration processes. Methods for autonomous experimentation have become more sophisticated recently, allowing for multi-dimensional parameter spaces to be explored efficiently and with minimal human intervention, thereby liberating the scientists to focus on interpretations and big-picture decisions. Gaussian process regression (GPR) techniques have emerged as the method of choice for steering many classes of experiments. We have recently demonstrated the positive impact of GPR-driven decision-making algorithms on autonomously-steered experiments at a synchrotron beamline. However, due to the complexity of the experiments, GPR often cannot be used in its most basic form, but rather has to be tuned to account for the special requirements of the experiments. Two requirements seem to be of particular importance, namely inhomogeneous measurement noise (input-dependent or non-i.i.d.) and anisotropic kernel functions, which are the two concepts that we tackle in this paper. Our synthetic and experimental tests demonstrate the importance of both concepts for experiments in materials science and the benefits that result from including them in the autonomous decision-making process.Uterine rupture is a serious public health concern that causes high maternal and perinatal morbidity and mortality in the developing world. Few of the studies conducted in Ethiopia show a high discrepancy in the prevalence of uterine rupture, which ranges between 1.6 and 16.7%. There also lacks a national study on this issue in Ethiopia. This systematic and meta-analysis, therefore, was conducted to assess the prevalence and determinants of uterine rupture in Ethiopia. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic review and meta-analysis of studies. All observational published studies were retrieved using relevant search terms in Google scholar, African Journals Online, CINHAL, HINARI, Science Direct, Cochrane Library, EMBASE and PubMed (Medline) databases. Newcastle-Ottawa assessment checklist for observational studies was used for critical appraisal of the included articles. The meta-analysis was done with STATA version 14 software. Thure. Therefore, intervention programs should address the identified factors to reduce the prevalence of uterine rupture.Delta opioid receptor (DOR) agonists have been identified as a promising novel therapy for headache disorders. DORs are broadly expressed in several peripheral and central regions important for pain processing and mood regulation; and it is unclear which receptors regulate headache associated symptoms. In a model of chronic migraine-associated pain using the human migraine trigger, nitroglycerin, we observed increased expression of DOR in cortex, hippocampus, and striatum; suggesting a role for these forebrain regions in the regulation of migraine. To test this hypothesis, we used conditional knockout mice with DORs deleted from forebrain GABAergic neurons (Dlx-DOR), and investigated the outcome of this knockout on the effectiveness of the DOR agonist SNC80 in multiple headache models. In DOR loxP controls SNC80 blocked the development of acute and chronic cephalic allodynia in the chronic nitroglycerin model, an effect that was lost in Dlx-DOR mice. In addition, the anti-allodynic effects of SNC80 were lost in a model of opioid induced hyperalgesia/medication overuse headache in Dlx-DOR conditional knockouts. In a model reflecting negative affect associated with migraine, SNC80 was only effective in loxP controls and not Dlx-DOR mice. Similarly, SNC80 was ineffective in the cortical spreading depression model of migraine aura in conditional knockout mice. Taken together, these data indicate that forebrain DORs are necessary for the action of DOR agonists in relieving headache-related symptoms and suggest that forebrain regions may play an important role in migraine modulation.Although cells of mushroom-producing fungi typically contain paired haploid nuclei (n + n), most Armillaria gallica vegetative cells are uninucleate. As vegetative nuclei are produced by fusions of paired haploid nuclei, they are thought to be diploid (2n). Here we report finding haploid vegetative nuclei in A. gallica at multiple sites in southeastern Massachusetts, USA. Sequencing multiple clones of a single-copy gene isolated from single hyphal filaments revealed nuclear heterogeneity both among and within hyphae. Cytoplasmic bridges connected hyphae in field-collected and cultured samples, and we propose nuclear migration through bridges maintains this nuclear heterogeneity. Growth studies demonstrate among- and within-hypha phenotypic variation for growth in response to gallic acid, a plant-produced antifungal compound. The existence of both genetic and phenotypic variation within vegetative hyphae suggests that fungal individuals have the potential to evolve within a single generation in response to environmental variation over time and space.Capsule endoscopy (CE) is a widely used, minimally invasive alternative to traditional endoscopy that allows visualisation of the entire small intestine. Patient preparation can help to obtain a cleaner intestine and thus better visibility in the resulting videos. However, studies on the most effective preparation method are conflicting due to the absence of objective, automatic cleanliness evaluation methods. In this work, we aim to provide such a method capable of presenting results on an intuitive scale, with a relatively light-weight novel convolutional neural network architecture at its core. We trained our model using 5-fold cross-validation on an extensive data set of over 50,000 image patches, collected from 35 different CE procedures, and compared it with state-of-the-art classification methods. From the patch classification results, we developed a method to automatically estimate pixel-level probabilities and deduce cleanliness evaluation scores through automatically learnt thresholds. We then validated our method in a clinical setting on 30 newly collected CE videos, comparing the resulting scores to those independently assigned by human specialists. We obtained the highest classification accuracy for the proposed method (95.23%), with significantly lower average prediction times than for the second-best method. In the validation of our method, we found acceptable agreement with two human specialists compared to interhuman agreement, showing its validity as an objective evaluation method.Unicompartmental knee arthroplasty and total knee arthroplasty are well established treatment options for end-stage osteoarthritis, UKA still remains infrequently used if you take all knee arthroplasties into account. An important factor following knee arthroplasty is pain control in the perioperative experience, as high postoperative pain level is associated with persistent postsurgical pain. There is little literature which describes pain values and the need for pain medication following UKA and/or TKA. So far, no significant difference in pain has been found between UKA and TKA. The aim of the study was to evaluate differences in the postoperative course in unicompartmental knee arthroplasty vs. total knee arthroplasty regarding the need for pain medication and patient-reported outcomes including pain scores and side effects. We hypothesized that unicompartmental knee arthroplasty is superior to total knee arthroplasty in terms of postoperative pain values and the need of pain medication. In this project, unicompartmental knee arthroplasty, patients showed lower pain scores, a reduced need for pain medication and better patient subjective parameters in the early postoperative course in this study.In this paper, we have investigated thermally stratified MHD flow of an Oldroyd-B fluid over an inclined stretching surface in the presence of heat generation/absorption. Similarity solutions for the transformed governing equations are obtained. The reduced equations are solved numerically using the Runge-Kutta Fehlberg method with shooting technique. The influences of various involved parameters on velocity profiles, temperature profiles, local skin friction, and local Nusselt number are discussed. Numerical values of local skin friction and local Nusselt number are computed. The significant outcomes of the study are that the velocity decreases when the radiation parameter [Formula see text] is increased while the temperature profile is increased for higher values of radiation parameter [Formula see text] in case of opposing flow, moreover, growth in Deborah number [Formula see text] enhance the velocity and momentum boundary layer. The heat transfer rate is decrease due to magnetic strength but increase with the increased values of Prandtl and Deborah numbers. The results of this model are closely matched with the outputs available in the literature.Trajectory optimization with musculoskeletal models can be used to reconstruct measured movements and to predict changes in movements in response to environmental changes. It enables an exhaustive analysis of joint angles, joint moments, ground reaction forces, and muscle forces, among others. However, its application is still limited to simplified problems in two dimensional space or straight motions. The simulation of movements with directional changes, e.g. curved running, requires detailed three dimensional models which lead to a high-dimensional solution space. We extended a full-body three dimensional musculoskeletal model to be specialized for running with directional changes. Model dynamics were implemented implicitly and trajectory optimization problems were solved with direct collocation to enable efficient computation. Standing, straight running, and curved running were simulated starting from a random initial guess to confirm the capabilities of our model and approach efficacy, tracking and predictive power. Altogether the simulations required 1 h 17 min and corresponded well to the reference data. The prediction of curved running using straight running as tracking data revealed the necessity of avoiding interpenetration of body segments. In summary, the proposed formulation is able to efficiently predict a new motion task while preserving dynamic consistency. Hence, labor-intensive and thus costly experimental studies could be replaced by simulations for movement analysis and virtual product design.Neuroblastoma resection represents a major challenge in pediatric surgery, because of the high risk of complications. Fluorescence-guided surgery (FGS) could lower this risk by facilitating discrimination of tumor from normal tissue and is gaining momentum in adult oncology. Here, we provide the first molecular-targeted fluorescent agent for FGS in pediatric oncology, by developing and preclinically evaluating a GD2-specific tracer consisting of the immunotherapeutic antibody dinutuximab-beta, recently approved for neuroblastoma treatment, conjugated to near-infrared (NIR) fluorescent dye IRDye800CW. We demonstrated specific binding of anti-GD2-IRDye800CW to human neuroblastoma cells in vitro and in vivo using xenograft mouse models. Furthermore, we defined an optimal dose of 1 nmol, an imaging time window of 4 days after administration and show that neoadjuvant treatment with anti-GD2 immunotherapy does not interfere with fluorescence imaging. Importantly, as we observed universal, yet heterogeneous expression of GD2 on neuroblastoma tissue of a wide range of patients, we implemented a xenograft model of patient-derived neuroblastoma organoids with differential GD2 expression and show that even low GD2 expressing tumors still provide an adequate real-time fluorescence signal. Hence, the imaging advancement presented in this study offers an opportunity for improving surgery and potentially survival of a broad group of children with neuroblastoma.16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.Azaleas (Ericaceae) comprise one of the most diverse ornamental plants, renowned for their cultural and economic importance. We present a chromosome-scale genome assembly for Rhododendron simsii, the primary ancestor of azalea cultivars. Genome analyses unveil the remnants of an ancient whole-genome duplication preceding the radiation of most Ericaceae, likely contributing to the genomic architecture of flowering time. Small-scale gene duplications contribute to the expansion of gene families involved in azalea pigment biosynthesis. We reconstruct entire metabolic pathways for anthocyanins and carotenoids and their potential regulatory networks by detailed analysis of time-ordered gene co-expression networks. MYB, bHLH, and WD40 transcription factors may collectively regulate anthocyanin accumulation in R. simsii, particularly at the initial stages of flower coloration, and with WRKY transcription factors controlling progressive flower coloring at later stages. This work provides a cornerstone for understanding the underlying genetics governing flower timing and coloration and could accelerate selective breeding in azalea.The World Health Organization (WHO) called, in 2012, for a validated strategy towards Taenia solium taeniasis/cysticercosis control and elimination. Estimating pig force-of-infection (FoI, the average rate at which susceptible pigs become infected) across geographical settings will help understand local epidemiology and inform effective intervention design. Porcine cysticercosis (PCC) age-prevalence data (from 15 studies in Latin America, Africa and Asia) were identified through systematic review. Catalytic models were fitted to the data using Bayesian methods, incorporating uncertainty in diagnostic performance, to estimate rates of antibody seroconversion, viable metacestode acquisition, and seroreversion/infection loss. There was evidence of antibody seroreversion across 5 studies, and of infection loss in 6 studies measured by antigen or necropsy, indicating transient serological responses and natural resolution of infection. Concerted efforts should be made to collect robust data using improved diagnostics to better understand geographical heterogeneities in T. solium transmission to support post-2020 WHO targets.Climate change is already affecting agro-ecosystems and threatening food security by reducing crop productivity and increasing harvest uncertainty. Mobilizing crop diversity could be an efficient way to mitigate its impact. We test this hypothesis in pearl millet, a nutritious staple cereal cultivated in arid and low-fertility soils in sub-Saharan Africa. We analyze the genomic diversity of 173 landraces collected in West Africa together with an extensive climate dataset composed of metrics of agronomic importance. Mapping the pearl millet genomic vulnerability at the 2050 horizon based on the current genomic-climate relationships, we identify the northern edge of the current areas of cultivation of both early and late flowering varieties as being the most vulnerable to climate change. We predict that the most vulnerable areas will benefit from using landraces that already grow in equivalent climate conditions today. However, such seed-exchange scenarios will require long distance and trans-frontier assisted migrations. Leveraging genetic diversity as a climate mitigation strategy in West Africa will thus require regional collaboration.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Optical resolution of far-field optical microscopy is limited by the diffraction of light, while diverse light-matter interactions are used to push the limit. The image resolution limit depends on the type of optical microscopy; however, the current theoretical frameworks provide oversimplified pictures of image formation and resolution that only address individual types of microscopy and light-matter interactions. To compare the fundamental optical resolutions of all types of microscopy and to codify a unified image-formation theory, a new method that describes the influence of light-matter interactions on the resolution limit is required. Here, we develop an intuitive technique using double-sided Feynman diagrams that depict light-matter interactions to provide a bird's-eye view of microscopy classification. This diagrammatic methodology also allows for the optical resolution calculation of all types of microscopy. We show a guidepost for understanding the potential resolution and limitation of all optical microscopy. This principle opens the door to study unexplored theoretical questions and lead to new applications.Objective was to analyse bacterial composition and abundance of Clostridioides difficile in gut microbiome of patients with C. difficile infection (CDI) in association with clinical characteristics. Whole metagenome sequencing of gut microbiome of 26 CDI patients was performed, and the relative abundance of C. difficile and its toxin genes was measured. Clinical characteristics of the patients were obtained through medical records. A strong correlation between the abundance of C. difficile and tcdB genes in CDI patients was found. The relative abundance of C. difficile in the gut microbiome ranged from undetectable to 2.8% (median 0.089). Patients with fever exhibited low abundance of C. difficile in their gut, and patients with fewer C. difficile organisms required long-term anti-CDI treatment. Abundance of Bifidobacterium and Bacteroides negatively correlated with that of C. difficile at the genus level. CDI patients were clustered using the bacterial composition of the gut one with high population of Enterococcus (cluster 1, n = 12) and another of Bacteroides or Lactobacillus (cluster 2, n = 14). Cluster1 showed significantly lower bacterial diversity and clinical cure at the end of treatment. Additionally, patients with CDI exhibited increased ARGs; notably, blaTEM, blaSHV and blaCTX-M were enriched. C. difficile existed in variable proportion of the gut microbiome in CDI patients. CDI patients with Enterococcus-rich microbiome in the gut had lower bacterial diversity and poorer clinical cure.Leishmaniasis encompasses a spectrum of diseases caused by a protozoan belonging to the genus Leishmania. The parasite is transmitted by the bite of sand flies, which inoculate the promastigote forms into the host's skin while acquiring a blood meal. Nyssomyia neivai is one of the main vectors of tegumentary leishmaniasis (TL) in Brazil. Southeastern Brazil is an endemic region for TL but also overlaps with an endemic focus for pemphigus foliaceus (PF), also known as Fogo Selvagem. Salivary proteins of sand flies, specifically maxadilan and LJM11, have been related to pemphigus etiopathogenesis in the New World, being proposed as an environmental trigger for autoimmunity. We present a comprehensive description of the salivary transcriptome of the N. neivai, using deep sequencing achieved by the Illumina protocol. In addition, we highlight the abundances of several N. neivai salivary proteins and use phylogenetic analysis to compare with Old- and New-World sand fly salivary proteins. The collection of protein sequences associated with the salivary glands of N. neivai can be useful for monitoring vector control strategies as biomarkers of N. neivai, as well as driving vector-vaccine design for leishmaniasis. Additionally, this catalog will serve as reference to screen for possible antigenic peptide candidates triggering anti-Desmoglein-1 autoantibodies.Drought is an important environmental stress that has negative effects on plant growth leading to a reduction in yield. In this study, the positive role of nanoparticles of SiO2, Se, and Se/SiO2 (SiO2-NPs, Se-NPs and Se/SiO2-NPs) has been investigated in modulating negative effects of drought on the growth and yield of strawberry plants. Spraying of solutions containing nanoparticles of SiO2, Se, and Se/SiO2 (50 and 100 mg L-1) improved the growth and yield parameters of strawberry plants grown under normal and drought stress conditions (30, 60, and 100%FC). Plants treated with Se/SiO2 (100 mg L-1) preserved more of their photosynthetic pigments compared with other treated plants and presented higher levels of key osmolytes such as carbohydrate and proline. This treatment also increased relative water content (RWC), membrane stability index (MSI) and water use efficiency (WUE). In addition, exogenous spraying of Se/SiO2 increased drought tolerance through increasing the activity of antioxidant enzymes including catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX) and superoxide dismutase (SOD) as well as decreasing lipid peroxidation and hydrogen peroxide (H2O2) content. Increase in biochemical parameters of fruits such as anthocyanin, total phenolic compounds (TPC), vitamin C and antioxidant activity (DPPH) in strawberry plants treated with Se/SiO2 under drought stress revealed the positive effects of these nanoparticles in improving fruit quality and nutritional value. In general, our results supported the positive effect of the application of selenium and silicon nanoparticles, especially the absolute role of Se/SiO2 (100 mg L-1), on the management of harmful effects of soil drought stress not only in strawberry plants, but also in other agricultural crops.Three hundred and sixty 1-day-old male broiler chicks were randomly allocated to 4 treatments of 6 replicates to evaluate the effects of cLFchimera, a recombinant antimicrobial peptide (AMP), on gut health attributes of broiler chickens under necrotic enteritis (NE) challenge. Treatments were as follows (T1) unchallenged group fed with corn-soybean meal (CSM) without NE challenge and additives (NC); (T2) group fed with CSM and challenged with NE without any additives (PC); (T3) PC group supplemented with 20 mg cLFchimera/kg diet (AMP); (T4) PC group supplemented with 45 mg antibiotic (bacitracin methylene disalicylate)/kg diet (antibiotic). Birds were sampled for villi morphology, ileal microbiota, and jejunal gene expression of cytokines, tight junctions proteins, and mucin. Results showed that AMP ameliorated NE-related intestinal lesions, reduced mortality, and rehabilitated jejunal villi morphology in NE challenged birds. While the antibiotic non-selectively reduced the count of bacteria, AMP restored microflora balance in the ileum of challenged birds. cLFchimera regulated the expression of cytokines, junctional proteins, and mucin transcripts in the jejunum of NE challenged birds. In conclusion, cLFchimera can be a reliable candidate to substitute growth promoter antibiotics, while more research is required to unveil the exact mode of action of this synthetic peptide.The precision and accuracy of quantifying semi-volatile organic compounds (SVOCs) in solution by GC/MS, particularly when volume errors are unpredictable or difficult to control, are improved by utilizing internal standards (IS). Not obvious though is the extent to which timing IS addition affects measurement. To illustrate this fact, the mean concentrations of 60 SVOCs (40 or 80 μg/mL) in two identical solutions into which IS were added at different times are compared in this study. In one solution, IS were added promptly on preparation (reference); in the other, IS were added after 36 days of incubation (treatment). To investigate the role that temperature might play here as well, equal fractions of each solution were incubated at - 20 °C, 4 °C or 22 °C. Results, as determined by one-way ANOVA, show that there were no differences between the reference solutions at the beginning and after 36 days (F3,236 = 0.244, p = 0.865), but that significant differences exist between the reference solutions collectively and the treatment irrespective of temperature (F6,413 = 6.76, p = 1.99e-06). These results, confirmed by a post hoc analysis, suggest that uncertainty is introduced into SVOC quantitation when internal standards are not added promptly into SVOCs solutions on preparation.Currently, type 2 diabetes mellitus (T2DM) and obesity are major global public health issues, and their prevalence in the United Arab Emirates (UAE) are among the highest in the world. In 2019, The UAE diabetes national prevalence was 15.4%. In recent years there has been a considerable investigation of predictive biomarkers associated with these conditions. This study analysed fasting (8 h) blood samples from an obese, normoglycemic cohort and an obese, T2DM cohort of UAE nationals, employing clinical chemistry analysis, 1D 1H NMR and mass spectroscopy (FIA-MS/MS and LC-MS/MS) techniques. The novel findings reported for the first time in a UAE population revealed significant differences in a number of metabolites in the T2DM cohort. Metabolic fingerprints identified by NMR included BCAAs, trimethylamine N-oxide, β-hydroxybutyrate, trimethyl uric acid, and alanine. A targeted MS approach showed significant differences in lysophosphatidylcholines, phosphatidylcholines, acylcarnitine, amino acids and sphingomyelins; Lyso.
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