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Virtual reality (VR) training has become valuable in sports to improve motor behavior and train specific situations under standardized conditions. However, studies comparing conventional training with VR training are rare, especially for advanced athletes. Furthermore, it remains unclear whether the performance improvement achieved through VR training can be transferred to the real world (RW). Therefore, we present a study analyzing sports-specific response training using a head-mounted display (HMD) combined with conventional training and its transfer to RW. In ten training sessions over 6 weeks, a VR training group (VRG, n = 15) performed virtual karate training (10 min) combined with a conventional training (80 min), while a conventional training group (CG, n = 12) conducted only conventional training (90 min) at the same time. The VR training consisted of the athlete responding to various karate attacks performed by a virtual opponent in a karate-specific manner. The study design included a pretest, an intermediate test (after 5 training sessions), and a posttest. We analyzed sports-specific response behavior concerning the competition-relevant karate attacks Gyaku-Zuki jodan (GZj) and Kizami-Zuki (KZ) using the parameters ‘response time’, and the “response quality” when the athletes had to react to attacks of a virtual opponent in VR and a real opponent in RW. For the parameter “response time,” improvements were detected only for the VRG in VR concerning GZj and KZ. For the parameter “response quality” for both groups, no improvements could be found. Furthermore, athletes provided positive feedback regarding the integration of VR training into conventional training.

Abstract In Arabidopsis thaliana, the Sigma factor B regulator RsbQ‐like family of α/β hydrolases contains the strigolactone (SL) receptor DWARF14 (AtD14), the karrikin receptor KARRIKIN INSENSITIVE2 (AtKAI2), and DWARF14‐LIKE2 (AtDLK2), a protein of unknown function. Despite very similar protein folds, AtD14 and AtKAI2 differ in size and architecture of their ligand binding pockets, influencing their substrate specificity. We present the 1.5 Å crystal structure of AtDLK2, revealing the smallest ligand binding pocket in the protein family, bordered by two unique glycine residues. We identified a gatekeeper residue in the protein's lid domain and present a pyrrolo‐quinoline‐dione compound that inhibits AtDLK2's enzymatic activity.

Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. This suggests that LVs bind via displayed CAR molecules to CAR antigen-expressing cells. The relevance for CAR-T cell manufacturing was evaluated when PBMCs and B-ALL malignant B cells were mixed and transduced with anti-CD19 or anti-CD20 CAR-displaying LVs in clinically relevant doses to mimic transduction conditions of unpurified patient leukapheresis samples. Malignant B cells were transduced at higher levels with LVs displaying anti-CD19 CARs compared to LVs displaying non-binding control constructs. Stability of gene transfer was confirmed by applying a potent LV inhibitor and long-term cultures for 10 days. Our findings provide a potential explanation for the emergence of CAR-B cells pointing to safer manufacturing procedures with reduced risk of this rare type of relapse in the future.

Previous studies have shown that the CD40L-CD40 signaling axis plays a role in atherosclerosis. Here the authors investigate the cell-specific functions of the most relevant CD40L-expressing cell types in atherosclerosis. Deficiency of T cell-derived CD40L reduces and stabilizes plaques through impaired Th1 polarization while platelet-derived CD40L ameliorates atherothrombosis.

Abstract Background With a reported rate of 0.7–20%, postoperative spinal implant infection (PSII) is one of the most common complications after spine surgery. While in arthroplasty both haematoma formation and perioperative blood loss have been identified as risk factors for developing periprosthetic joint infections and preoperative anaemia has been associated with increased complication rates, literature on the aetiology of PSII remains limited. Methods We performed a matched-pair analysis of perioperative haemoglobin (Hb) and haematocrit (Hct) levels in aseptic and septic spine revision surgeries. 317 patients were included, 94 of which were classified as septic according to previously defined criteria. Patients were matched according to age, body mass index, diabetes, American Society of Anesthesiologists score and smoking habits. Descriptive summaries for septic and aseptic groups were analysed using Pearson chi-squared for categorical or Student t test for continuous variables. Results Fifty patients were matched and did not differ significantly in their reason for revision, mean length of hospital stay, blood transfusion, operating time, or number of levels operated on. While there was no significant difference in preoperative Hb or Hct levels, the mean difference between pre- and postoperative Hb was higher in the septic group (3.45 ± 1.25 vs. 2.82 ± 1.48 g/dL, p = 0.034). Conclusions We therefore show that the intraoperative Hb-trend is a predictor for the development of PSII independent of the amount of blood transfusions, operation time, number of spinal levels operated on and hospital length of stay, which is why strategies to reduce intraoperative blood loss in spine surgery need to be further studied.

Climatic change alters the frequency and intensity of natural hazards. In order to assess potential future changes in flood seasonality in the Rhine River basin, we analyse changes in streamflow, snowmelt, precipitation and evapotranspiration at 1.5, 2.0 and 3.0 ∘C global warming levels. The mesoscale hydrological model (mHM) forced with an ensemble of climate projection scenarios (five general circulation models under three representative concentration pathways) is used to simulate the present and future climate conditions of both pluvial and nival hydrological regimes. Our results indicate that future changes in flood characteristics in the Rhine River basin are controlled by increases in antecedent precipitation and diminishing snowpacks. In the pluvial-type sub-basin of the Moselle River, an increasing flood potential due to increased antecedent precipitation encounters declining snowpacks during winter. The decrease in snowmelt seems to counterbalance increasing precipitation, resulting in only small and transient changes in streamflow maxima. For the Rhine Basin at Basel, rising temperatures cause changes from solid to liquid precipitation, which enhance the overall increase in precipitation sums, particularly in the cold season. At the gauge at Basel, the strongest increases in streamflow maxima show up during winter, when strong increases in liquid precipitation encounter almost unchanged snowmelt-driven runoff. The analysis of snowmelt events for the gauge at Basel suggests that at no point in time during the snowmelt season does a warming climate result in an increase in the risk of snowmelt-driven flooding. Snowpacks are increasingly depleted with the course of the snowmelt season. We do not find indications of a transient merging of pluvial and nival floods due to climate warming. To refine attained results, next steps need to be the representation of glaciers and lakes in the model set-up, the coupling of simulations to a streamflow component model and an independent validation of the snow routine using satellite-based snow cover maps.

In various domains, virtual reality (VR) has emerged as a valuable tool for simulating specific scenarios and facilitating training within controlled and secure conditions. As peripheral vision plays a crucial role in numerous contexts, it must be duly considered in VR simulations. However, while peripheral vision was examined in VR, comparisons between VR and the real world (RW) are rarely made. Therefore, this study is aimed at comparing RW and VR reaction times (RTs) to peripheral visual stimuli and the field of view (FOV). This comparison is achieved using the peripheral perception‐R (PP‐R) of the Vienna Test System and a programmed virtual replica. The virtual replica underwent additional testing, revealing good reliability for RTs but only moderate to poor for measurements of the participant's FOV. The comparison between the two environments indicates slower RTs to peripheral visual stimuli in VR than in RW. This observed discrepancy is consistent with the results of previous studies investigating RTs to foveal stimuli and can be partially explained by the latencies in the hardware and software configurations used. Nevertheless, the observed correlations between the RTs in both conditions suggest comparable visual processing within the peripheral visual field and affirm the decent replication of the real PP‐R in VR. Overall, the study's results support the usage of VR as a tool for practicing and examining specific scenarios, including peripheral vision. The discrepancies revealed in the RTs between VR and RW emphasize the need to continue examining hardware and software components in VR research. [ABSTRACT FROM AUTHOR]

Aims. We investigate the ability of a simultaneous fitting of comet 67P/Churyumov-Gerasimenko's non-gravitational forces, torques, and total water-outgassing rate, as observed by Rosetta, to constrain complex thermophysical models of cometary material. Methods. We extend the previous work of fitting geographically defined surface outgassing models to the Rosetta observations by testing the effects of a more detailed geomorphological mapping, the resolution of the shape-model used, self-heating by neighbouring facets on the shape-model, thermal inertia in the outgassing solution, and the variation in the momentum coupling between the gas and the nucleus. We also directly compare the non-gravitational acceleration curves available in the literature. Results. We correct an error in the calculation of pole-orientation in the previous paper. We find that, under the assumptions of the model, non-gravitational forces and torques are driven by water sublimation from the nucleus, thermal inertia and self-heating have only minor effects, spatially uniform activity cannot explain 67P's non-gravitational dynamics, spatially uniform momentum transfer cannot explain 67P's non-gravitational dynamics, and different terrain types have different instantaneous responses to insolation. Conclusions. Consolidated terrain facing south on 67P/Churyumov-Gerasimenko has a high outgassing flux, a steep response to insolation, and a large gas momentum transfer coefficient. Instead, that facing north behaves differently, producing little to no water outgassing, and with a lower momentum transfer efficiency. Dusty terrain also has a lower outgassing rate and momentum transfer efficiency, and either depletes its volatile component or is buried in fall-back as the comet approaches the Sun. Momentum transfer appears correlated with insolation, likely due to an increased enhancement in the gas temperature as the dust it flows through is heated. [ABSTRACT FROM AUTHOR]

Introduction: Sensory-processing sensitivity (SPS) refers to interindividual differences in sensitivity to positive and negative environmental stimuli and reflects the concept of differential susceptibility. The Highly Sensitive Person Scale (HSPS) has been utilized to capture the multifaceted experiences of highly sensitive individuals. The scale's total score (i.e., the sum of the subfactors) is an indicator of high sensitivity. However, it cannot differentiate between the contributions of the specific subfactors. Consequently, interpreting the total score cannot help resolve the current theoretical debate about how individuals integrate the positive and negative aspects of sensitivity, whereas a multidimensional profile should be able to offer a more comprehensive understanding. Intriguingly, in variable-centered research, the subfactors' differential associations with external constructs in negative or positive trait spaces have suggested heterogeneity (i.e., interindividual differences) among highly sensitive individuals. Thus, person-centered approaches should be better suited to address this heterogeneity. Methods: To explore heterogeneity within the highly sensitive population, we conducted a three-step Latent Profile Analysis in two independent Germanspeaking samples (N = 1,102; N = 526). Subsequently, we employed the Five-Factor Model of personality to provide a detailed description of the latent sensitivity groups. Results: Beyond the frequently identified quantitative three-class differentiation of sensitivity groups, we obtained a four-class model that included two qualitatively different high-sensitivity groups, each displaying distinct HSPS subfactor and personality patterns that corresponded to prototypical personality profiles. Within these high sensitivity groups, (i) the Confident Sensitivity Group exhibited average Neuroticism, significantly above-average Openness, and slightly above-average Extraversion. By contrast, (ii) the Vulnerable Sensitivity Group displayed the typical personality pattern of significantly above-average Neuroticism, below-average Extraversion, and slightly above-average Openness. Personality analyses revealed that features such as passiveness, internalizing tendencies, giftedness, and aesthetics, often commonly ascribed to all highly sensitive individuals, are features that differ across distinct sensitivity groups. Discussion: To avoid over- or underestimating sensitivity effects, future research should consider these interindividual differences in highly sensitive individuals. For instance, studies could focus on the different associations of sensitivity groups with abilities, health aspects, emotion regulation and intervention outcomes, taking into account the different environmental factors that shape the type of sensitivity. [ABSTRACT FROM AUTHOR]

We study the response of a quantitative trait to exponential directional selection in a finite haploid population, both at the genetic and the phenotypic level. We assume an infinite sites model, in which the number of new mutations per generation in the population follows a Poisson distribution (with mean Θ) and each mutation occurs at a new, previously monomorphic site. Mutation effects are beneficial and drawn from a distribution. Sites are unlinked and contribute additively to the trait. Assuming that selection is stronger than random genetic drift, we model the initial phase of the dynamics by a supercritical Galton–Watson process. This enables us to obtain time-dependent results. We show that the copy-number distribution of the mutant in generation n , conditioned on non-extinction until n , is described accurately by the deterministic increase from an initial distribution with mean 1. This distribution is related to the absolutely continuous part W + of the random variable, typically denoted W , that characterizes the stochasticity accumulating during the mutant's sweep. A suitable transformation yields the approximate dynamics of the mutant frequency distribution in a Wright–Fisher population of size N. Our expression provides a very accurate approximation except when mutant frequencies are close to 1. On this basis, we derive explicitly the (approximate) time dependence of the expected mean and variance of the trait and of the expected number of segregating sites. Unexpectedly, we obtain highly accurate approximations for all times, even for the quasi-stationary phase when the expected per-generation response and the trait variance have equilibrated. The latter refine classical results. In addition, we find that Θ is the main determinant of the pattern of adaptation at the genetic level, i.e., whether the initial allele-frequency dynamics are best described by sweep-like patterns at few loci or small allele-frequency shifts at many. The number of segregating sites is an appropriate indicator for these patterns. The selection strength determines primarily the rate of adaptation. The accuracy of our results is tested by comprehensive simulations in a Wright–Fisher framework. We argue that our results apply to more complex forms of directional selection. • Accurate and tractable time-dependent results at genetic and phenotypic level. • Explicit approximations for the initial phase of polygenic adaptation. • Refined classical, quantitative genetics results for the stationary phase. • Population-wide mutation rate characterizes genetic pattern of adaptation. • Number of segregating sites is an indicator of the pattern of adaptation. [ABSTRACT FROM AUTHOR]

Inflammation is a driving force of tendinopathy. The oxidation of phospholipids by free radicals is a consequence of inflammatory reactions and is an important indicator of tissue damage. Here, we have studied the impact of oxidized phospholipids (OxPAPC) on the function of human tenocytes. We observed that treatment with OxPAPC did not alter the morphology, growth and capacity to produce collagen in healthy or diseased tenocytes. However, since OxPAPC is a known modulator of the function of immune cells, we analyzed whether OxPAPC-treated immune cells might influence the fate of tenocytes. Co-culture of tenocytes with immature, monocyte-derived dendritic cells treated with OxPAPC (Ox-DCs) was found to enhance the proliferation of tenocytes, particularly those from diseased tendons. Using transcriptional profiling of Ox-DCs, we identified amphiregulin (AREG), a ligand for EGFR, as a possible mediator of this proliferation enhancing effect, which we could confirm using recombinant AREG. Of note, diseased tenocytes were found to express higher levels of EGFR compared to tenocytes isolated from healthy donors and show a stronger proliferative response upon co-culture with Ox-DCs, as well as AREG treatment. In summary, we identify an AREG-EGFR axis as a mediator of a DC-tenocyte crosstalk, leading to increased tenocyte proliferation and possibly tendon regeneration. [ABSTRACT FROM AUTHOR]

The Saxon Library Society (SäBiG) has been involved in the protests against PEGIDA in Dresden and has co-organized demonstrations. SäBiG has been both praised and criticized for this, as it has been accused of acting without authorization and not being neutral. Libraries are perceived as neutral and trustworthy institutions that work non-partisan and politically independent. However, they can participate in demonstrations to make a statement for democracy and human rights. The Saxon State Library and the Saxon Library Society have examined the role of libraries as places of democracy in a study. Saxon library websites, acquisition and personnel figures, as well as third-party funding, were analyzed. Two libraries were subsequently invited for funding. The Hoyerswerda City Library received full funding for its project "Open Workshop of Democracy" and the Ebersbach-Neugersdorf City Library received partial funding for its collaboration with the cultural and educational center Lebens(t)räume e. V. The Saxon State Library also plans to create an association and initiative navigator to promote cooperation with non-profit organizations. In the face of increasing pressure from the right, the interviewees emphasize the importance of libraries as memory institutions and the need to defend democracy. Libraries should expand their digital presence and provide attractive offers for information and opinion formation. They should also cooperate more closely with other educational institutions and civil society organizations. Libraries can thus be a bulwark of democracy and make an important contribution to strengthening democracy. [Extracted from the article]

Attalea phalerata Martius ex Spreng is a palm tree that is widely distributed in the Central-West region of Brazil. In this study, we investigated whether the oil-loaded nanocapsules of A. phalerata (APON) have acute and long-lasting antihypertensive effects in male spontaneously hypertensive rats (SHR), as well as explored the underlying molecular mechanisms. APON was prepared using the interfacial polymer deposition method. The particle size, polydispersity index, and zeta potential were investigated using dynamic and electrophoretic light scattering. The antihypertensive effects of APON (administered at doses of 1, 3, and 10 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. To investigate the molecular pathways involved, we used pharmacological antagonists and inhibitors that target prostaglandin/cyclic adenosine monophosphate, nitric oxide/cyclic guanosine monophosphate, and potassium channels. Both acute and prolonged administration of APON (at doses of 3 and 10 mg/kg) resulted in a significant reduction in systolic, diastolic, and mean arterial pressure. Prior treatment with a non-selective nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester), guanylyl cyclase inhibitor (methylene blue), or non-selective calcium-sensitive K+ channel blocker (tetraethylammonium) abolished the antihypertensive effects of APON. Our study showed that A. phalerata oil-loaded nanocapsules have a significant antihypertensive effect in SHR after both short-term and long-term (7-day) use. This effect seems to rely on the vascular endothelium function and involves the NO-cGMP-K+ channel pathway. This research suggests a new direction for future studies to definitively prove the therapeutic benefits of APON in treating cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract Multiple sulfatase deficiency (MSD) is a lysosomal storage disease caused by a deficiency of formylglycine‐generating enzyme due to SUMF1 defects. MSD may be misdiagnosed as metachromatic leukodystrophy (MLD), as neurological and neuroimaging findings are similar, and arylsulfatase A (ARSA) deficiency and enhanced urinary sulfatide excretion may also occur. While ARSA deficiency seems a cause for neurological symptoms and later neurodegenerative disease course, deficiency of other sulfatases results in clinical features such as dysmorphism, dysostosis, or ichthyosis. We report on a girl and a boy of the same origin presenting with severe ARSA deficiency and neurological and neuroimaging features compatible with MLD. However, exome sequencing revealed not yet described homozygosity of the missense variant c.529G > C, p.Ala177Pro in SUMF1. We asked whether dynamics of disease course differs between MSD and MLD. Comparison to a cohort of 59 MLD patients revealed different disease course concerning onset and disease progression in both MSD patients. The MSD patients showed first gross motor symptoms earlier than most patients with juvenile MLD (

Abstract Background Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition. Methods Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients. Results Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p

Abstract Octenidine dihydrochloride (OCT) is a widely used antiseptic molecule, promoting skin wound healing accompanied with improved scar quality after surgical procedures. However, the mechanisms by which OCT is contributing to tissue regeneration are not yet completely clear. In this study, we have used a superficial wound model by tape stripping of ex vivo human skin. Protein profiles of wounded skin biopsies treated with OCT-containing hydrogel and the released secretome were analyzed using liquid chromatography-mass spectrometry (LC–MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Proteomics analysis of OCT-treated skin wounds revealed significant lower levels of key players in tissue remodeling as well as reepithelization after wounding such as pro-inflammatory cytokines (IL-8, IL-6) and matrix-metalloproteinases (MMP1, MMP2, MMP3, MMP9) when compared to controls. In addition, enzymatic activity of several released MMPs into culture supernatants was significantly lower in OCT-treated samples. Our data give insights on the mode of action based on which OCT positively influences wound healing and identified anti-inflammatory and protease-inhibitory activities of OCT.