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Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms. Significant correlations were identified between specific AABs and symptoms such as fever, muscle aches, anosmia, and dysgeusia. Notably, anti-AGTR1 antibodies, which contribute to endothelial glycocalyx (eGC) degradation, a process reversed by losartan, have emerged as strong predictors of core symptoms. AAB levels increased with symptom accumulation, peaking in patients exhibiting all four key symptoms. These findings highlight the role of AABs, particularly anti-AGTR1 antibodies, in determining symptom severity and suggest their involvement in the pathophysiology of COVID-19, including vascular complications. [ABSTRACT FROM AUTHOR]

For the first time under laboratory conditions, the virulence of a unique cypovirus strain, DsCPV-1, which has broad host specificity, was tested on nontarget aquatic organisms (natural species: Gammarus lacustris, Anopheles messeae, Coenagrion lunulatum, Cloeon robusta, Chironomus sp., Ilyocoris cimicoides, and Plea minutissima; laboratory species: Aedes aegypti and Daphnia magna), a terrestrial pollinator species (Apis mellifera), and an entomophage (Podisus maculiventris). The probability of this virus's accumulation in the bodies of invertebrates and of its transmission along a trophic chain was evaluated by two approaches: bioassays and a molecular diagnostic analysis. In the bioassays, there was no significant increase in mortality among all the tested aquatic and terrestrial nontarget species exposed to DsCPV-1 as compared with control groups (no virus). When we fed Podisus maculiventris with caterpillars having active DsCPV-1 infection (i.e., with the virus replicating in the host) no viral replication was observed in bug. No replication was also observed in mosquitos as well as in bee after viral treatment. Thus, the results show that the DsCPV-1 virus has excellent environmental safety toward many invertebrate species and can be recommended for the control of lepidopteran pests in forestry and agriculture as insecticide with light effect on environment. [ABSTRACT FROM AUTHOR]

Many existing solutions for the automatic assessment of open-ended questions predominantly rely on machine learning models, primarily focusing on aspects such as writing style and assigning a final score. However, these solutions often overlook the crucial factor of feedback content relevance, specifically, how well the response aligns with the content of the original question. This research introduces a novel approach aimed at enhancing the rapid feedback essential for this type of assessment. The approach involves identifying individual cognitive deficiencies among students and providing guidance for their remediation. The primary objective is to seamlessly integrate pedagogical guidelines founded on competencies and skills by leveraging an educational recommendation system. This system incorporates the concepts of ontology learning, ontology alignment algorithms, action recommendation algorithms tailored to each student's unique needs. As the main outcomes, a case study is presented, illustrating each step of the system. [ABSTRACT FROM AUTHOR]

Peltophorum dubium, a common tree in areas close to agricultural activity in the Brazilian Cerrado, is vulnerable to damage from the drift of picloram, an herbicide widely used in pastures and agriculture in Brazil. The aim was to evaluate the application of 0.0; 19.2; 38.4; 76.8; 153.6; 307.2 g e. a. ha−1 of picloram, in simulated drift, on P. dubium, as well as its use as a bioindicator plant for herbicide contamination. The doses of picloram applied to the plants caused symptoms typical of the action of picloram on sensitive plants and led to the death of P. dubium at the highest doses tested. At its highest dose, picloram caused a 52.86% reduction in photosynthetic rate, 42.51% in transpiration rate, and 64.28% in stomatal conductance compared to the non-treated control. Picloram at a dose of 19.2 g e. a. ha−1 caused a reduction in N content and utilization and reduced plant protein. Picloram drift causes severe damage to P. dubium, reinforcing the concern about the risks of contamination with the herbicide. The species acted as a bioindicator of picloram in the environment and could be used in biomonitoring herbicide contamination. [ABSTRACT FROM AUTHOR]

Background: Hereditary amyloid transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare, inherited, multisystemic, progressive adult-onset disease, affecting sensorimotor nerves, and various organs. It is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate, forming amyloid fibrils. Patisiran is a small, double-stranded interfering RNA encapsulated in a lipid nanoparticle, designed to enter hepatocytes and selectively target TTR mRNA to reduce both variant TTR and wild-type TTR (wt). This study presents a multicenter, real-life experience of patisiran’s effectiveness and safety in ATTRv-PN. Methods: We enrolled genetically confirmed ATTRv-PN patients from 29 specialized Italian centers. All subjects underwent neurological assessments, including familial amyloid polyneuropathy (FAP) staging, the Neuropathy Impairment Score (NIS), quality-of-life assessment using the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire, and the Compound Autonomic Dysfunction Test (CADT). Additional assessments included baseline and follow-up measures of serum NT-proBNP and interventricular septal thickness. Results: A total of 181 ATTRv patients (69% male) were enrolled. Neurological onset was reported in 60.2% of cases. At baseline, 83.4% of patients exhibited multisystemic involvement, while only 16.6% presented isolated polyneuropathy. For approximately 70% of patients, patisiran was the first treatment; the remainder transitioned from tafamidis or inotersen. Following treatment, most patients demonstrated stabilization of neuropathy progression, regardless of baseline disease severity or genotype. The treatment was well-tolerated, with 90% of patients reporting no adverse events. Conclusion: Patisiran can be considered a valid therapeutic option for the management of patients with ATTRv amyloidosis. Considering its mechanism of action, similar outcomes could also be expected with the wider utilization of newly approved gene silencers for ATTRv therapy, such as vutrisiran. [ABSTRACT FROM AUTHOR]

In this paper, we prove the existence of a periodic smooth finite-dimensional center manifold near a nonhyperbolic cycle in classical delay differential equations by using the Lyapunov–Perron method. The results are based on the rigorous functional analytic perturbation framework for dual semigroups (sun–star calculus). The generality of the dual perturbation framework ensures that the results extend to a much broader class of evolution equations. [ABSTRACT FROM AUTHOR]

We previously examined the antitumor effects of short interfering RNA nanoparticles targeting mammalian target of rapamycin (mTOR) in an orthotopic pancreatic cancer mouse model. We herein report the inhibitory effects of the mTOR inhibitor rapamycin on tumor growth in a novel established mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Gemcitabine, 5-fluorouracil, and gemcitabine plus nab-paclitaxel are clinically used to treat advanced pancreatic cancer. In vitro assays showed that rapamycin strongly inhibited cell invasion, while gemcitabine, 5-fluorouracil, and gemcitabine plus paclitaxel primarily inhibited cell proliferation with minimal effects on invasion. In vivo mouse experiments demonstrated that rapamycin exhibited superior antitumor activity to S-1 (a metabolically activated prodrug of 5-fluorouracil) and another mTOR inhibitor, everolimus, while its efficacy was similar to that of gemcitabine plus paclitaxel (which was used instead of nab-paclitaxel due to concerns about allergic reactions in mice to human albumin) in a mouse model of pancreatic cancer using human pancreatic cancer cell line-derived organoids. Furthermore, the combination of rapamycin with gemcitabine plus paclitaxel exerted synergistic inhibitory effects on the growth of pancreatic cancer tumors. Although the inhibition of tumor growth was significantly stronger in everolimus-treated mice than in control mice, there were no additive anti-growth effects when combined with gemcitabine plus paclitaxel. The present results suggest that the combination of rapamycin with gemcitabine plus paclitaxel achieved the greatest reduction in tumor volumes in the mouse xenograft model and, thus, has significant clinical promise. [ABSTRACT FROM AUTHOR]

It is believed that a lower temperature setting of hypothermic circulatory arrest (HCA) in thoracic aortic surgery causes coagulopathy, resulting in excessive bleeding. However, experimental studies that eliminate clinical factors are lacking. The objective of this study is to investigate the influence of the temperature setting of HCA on coagulation in a pig model. Ten pigs were divided into the following two groups: moderate temperature at 28 °C (group M, n = 5) or lower temperature at 20 °C (group L, n = 5). Two hours of HCA during a total of 4 h of cardiopulmonary bypass (CPB) were performed. Blood samples were obtained at the beginning (T1) and the end (T2) of the surgery, and coagulation capability was analyzed through standard laboratory tests (SLTs) and rotational thromboelastometry (ROTEM). In SLTs, hemoglobin, fibrinogen, platelet count, prothrombin time, and activated partial thromboplastin time were analyzed. In ROTEM analyses, clotting time and clot formation time of EXTEM, maximum clot firmness (MCF), and maximum clot elasticity (MCE) of EXTEM and FIBTEM were analyzed. Fibrinogen decreased significantly in both groups (group M, p = 0.008; group L, p = 0.0175) at T2, and FIBTEM MCF and MCE also decreased at T2. There were no differences regarding changes in parameters of SLTs and ROTEM between groups. CPB decreases coagulation capacity, contributed by fibrinogen. However, a lower temperature setting of HCA at 20 °C for 2 h did not significantly affect coagulopathy compared to that of HCA at 28 °C after re-warming to 37 °C. [ABSTRACT FROM AUTHOR]

Key message: Karrikin plays a more critical role in affecting the homeostasis of ABA and cytokinins, while strigolactones play a more critical role in influencing the homeostasis of jasmonic acid and gibberellins. Strigolactones (SLs) and karrikins (KARs) regulate plant growth and development through their crosstalk, and through the crosstalk between them and other phytohormones, such as abscisic acid (ABA) and auxin. However, how SL and KAR signaling pathways influence the levels of other phytohormones is still unknown. Here, we performed a comparative transcriptome analysis of the Arabidopsis thaliana double mutant dwarf14 karrikin-insensitive 2 (d14 kai2), deficient in SL and KAR perception, and the wild-type (WT) using their rosette leaves. Ten gene ontology terms related to phytohormones were enriched with differentially expressed genes derived from the ‘d14 kai2 vs WT’ comparison. Our data revealed that the levels of auxin, ABA and salicylic acid (SA) were higher in d14 and kai2 single and d14 kai2 mutant plants than in WT, which was consistent with the results of previous investigations. In contrast, the levels of cytokinins (CKs) were found to be lower in all single and double mutants than in WT. The levels of active gibberellins were lower in d14 and d14 kai2 mutants than in WT, while they were comparable in kai2 and WT plants. Similarly, the levels of jasmonic acid (JA) were lower in d14 and d14 kai2 plants, but higher in kai2 plants than in WT. Both transcriptome and qRT-PCR analyses indicated that SL and KAR signaling pathways affect the levels of auxin, SA, CKs, gibberellin 4 (GA4) and ABA by influencing the expression of their biosynthetic (in case of auxin, SA, GA4 and CKs) and catabolic (in case of ABA) genes. Collectively, our data demonstrated that KAI2 plays a more critical role in the homeostasis of ABA and CKs, while D14 plays a more critical role in the homeostasis of JA and gibberellins. Findings of this study indicate a complex and broad crosstalk among various phytohormones in plants, which can be considered for future exogenous applications and hormone engineering. [ABSTRACT FROM AUTHOR]

This study provides an updated assessment of the taxonomic and molecular-genetic diversity of fish species in the western Chukchi Sea, employing both traditional and modern research methodologies. The research was conducted aboard the Research Vessel Akademik Oparin in 2016, utilizing various collection methods including trawling and remotely operated vehicles (ROVs). A total of 486 specimens representing 26 species across 8 families were collected and identified. Among them, 97 specimens were partially genotyped using mitochondrial markers COI and 12S rRNA, with some specimens genotyped for one marker only and others for both. Our results confirm that the Arctic Staghorn Goby, Gymnocanthus tricuspis, remains a dominant species with a high frequency of occurrence. High occurrence was also noted for the Hamecon, Artediellus scaber, and the Shorthorn Sculpin, Myoxocephalus scorpius. The study further investigates the genetic distances within and among species, highlighting the efficacy of DNA barcoding in species identification. Phylogenetic analysis revealed distinct clusters that correspond to taxonomic relationships. Both 12S rRNA and COI markers were effective in identifying species within closely related groups, but 12S demonstrated superior performance in cases of degraded DNA samples. The efficacy of this marker highlights its utility in augmenting the global DNA barcode library and enhancing large-scale biodiversity assessments, potentially facilitating the transition to next-generation sequencing technologies. Additionally, the use of ROVs marked a non-intrusive advancement in observing fish distribution, complementing traditional capture methods. This comprehensive approach not only enhances our understanding of Arctic biodiversity, but also contributes to monitoring ecological impacts due to climatic changes. [ABSTRACT FROM AUTHOR]

A classic problem of the motion of a projectile thrown at an angle to the horizon is studied. Air resistance force and Magnus force are taken into account with the use of the quadratic laws. We consider the asymptotic motion of the projectile, i.e. the motion on a sufficiently large time interval. The equations of motion are written both in Cartesian coordinates and in natural axes. The aim of the study is the analytical determination of the characteristics of asymptotic motion—the limiting angle of inclination of the trajectory to the horizontal and the terminal velocity, and obtaining an analytical representation for the velocity hodograph. No restrictions are imposed on the initial throwing conditions and other parameters. The equations of motion in Cartesian coordinates are used to find the angle of inclination of the trajectory and the terminal velocity. The equations of motion in natural axes are used to determine velocity hodograph. The velocity hodograph is defined in the form an approximate implicit analytical formula linking the trajectory angle of the projectile to its velocity. The motion of a golf ball is presented as an example. Numerical calculations show a complete coincidence of analytically found values of required quantities with numerically found values. The proposed analytical formulas can be useful for all researchers of this classical problem. [ABSTRACT FROM AUTHOR]

This study was carried out with a multidisciplinary approach to define a method for improving territorial revitalization through enhancing the paleontological heritage, highlighting potentialities in promoting territorial valorization, particularly for inner areas. The methodology is applied to the Pietraroja site in the Campania region, which was selected because of its large scientific significance for palaeontology and geology. The Pietraroja site (Benevento) is universally known as the place in which the fossil of a small dinosaur, Scypionix samniticus, was found. This study mainly aims to broaden the fruition of the Pietraroja site by designing and creating immersive digital environments allowing for remote access from all over the world via the Internet. In this regard, innovative technologies such as virtual reality, mixed reality, and augmented reality have been utilized to set up digital spaces for visitors who can explore the features of the cultural site and appreciate its high cultural value. The adoption of these new technologies represents the way to propose to the public the cultural contents of the Pietraroja site and to tell the story of the formation of the place. [ABSTRACT FROM AUTHOR]

Unlike other geological elements with relevance to geoheritage, coal deposits have not been properly studied in Mexico. In the Sabinas Basin, NE Mexico, there are many coal pits and waste dumps where the resource is exploited, mainly from the Olmos Formation. However, the mineral is already exhausted in some areas and so the pits and dumps now have no specific use. Due to the fact that geological materials have been moved by machinery, the geological sequences and fossils of paleontological and scientific importance can, generally, be accessed, as demonstrated by about thirty-four scientific materials carried out in the Olmos Formation. Fossil dinosaurs, footprints, leaves, trunks, and fruits with high endemism have been documented and preserved in museums or collections. These fossils, mainly plants, are so abundant that they can still be observed, as happened during the fieldwork for this research. Additionally, such sites have a high educational value, acting as excellent classrooms for teaching earth sciences with practical applications in stratigraphy, sedimentology, paleontology, hydrogeology, and geological field surveys. Unfortunately, these sites could be in danger if they are used for garbage dumping, which is already happening, as this not only contaminates the shallow aquifers but erases the fossil record that is unique in NE Mexico. In this sense, a call is made to local governments and institutions to preserve this invaluable legacy, not only for Coahuila but for Mexico in general. [ABSTRACT FROM AUTHOR]

Federated and Continual Learning have emerged as promising paradigms for the privacy-aware use of Deep Learning in dynamic environments by addressing spatial and temporal constraints on data availability. However, Client Drift and Catastrophic Forgetting are fundamental obstacles to ensuring robust performance. Existing work only addresses these problems separately, neglecting the fact that the root cause behind them, namely an unexpected shift in the data distribution, is connected. We propose a unified analysis framework for building a controlled test environment where we can jointly model spatial and temporal shifts, more closely emulating real dynamic settings. By generating a 3D landscape of the combined performance impact, we show that a moderate combination of both shifts can even improve the performance of the resulting model ("Generalization Bump"). We apply a simple and commonly used method from continual learning in the federated setting and observe this reoccurring phenomenon. [ABSTRACT FROM AUTHOR]

Although a robust association between metabolic dysfunction-associated fatty liver disease (MASLD) and cardiovascular disease (CVD) has been established, the impact of MASLD on CVD risk in young adults has not been fully evaluated. This population-based study included adults aged 20–39 years who underwent health screening examinations from 2009 to 2012 based on Korean National Health Insurance Service database. MASLD was defined as a fatty liver index ≥ 30 without any other cause of steatosis, and presence of one or more cardiometabolic risk factors. The primary outcome was newly developed CVD, including myocardial infarction, ischemic stroke, and congestive heart failure. During the median 10.6 years of follow-up, MASLD was observed in 1,435,659 (25.3%) of the 5,666,728 participants. Cumulative incidence of major adverse cardiovascular events was significantly higher in individuals with MASLD compared those without steatosis (P < 0.001). The adjusted hazard ratio (HR) for myocardial infarction was 1.23 [95% CI (confidence interval): 1.18–1.27] in individuals with MASLD compared to those without steatosis. The HR for ischemic stroke and congestive heart failure were higher in individuals with MASLD compared to those without steatosis (HR, 1.12; 95% CI, 1.07–1.17 and HR, 1.18; 95% CI, 1.15–1.21, respectively]. In the subgroup analysis, the elevated HR for CVD in the MASLD group was prominent among individuals who were female and obese. MASLD was associated with an increased risk of CVD in young adults. These findings highlight the need for early intervention in patients with MASLD before they reach middle to reduce the risk of CVD, particularly among young adults in South Korea. [ABSTRACT FROM AUTHOR]

Resection has traditionally been the gold standard for treating jugular foramen schwannomas (JFSs). However, given the high risk of neurological deficits associated with surgical intervention, stereotactic radiosurgery (SRS) has emerged as a promising alternative. Despite its growing popularity for other brain tumors, there remains a paucity of data on the outcomes of SRS for JFSs. This study aims to assess the safety and efficacy of SRS as a treatment option for patients with JFSs. We searched Medline, Embase, and Web of Science databases following PRISMA guidelines. Eligible studies included randomized controlled trials and observational studies reporting ≥ 4 JFS patients treated with gamma knife radiosurgery. Comparative analysis with 95% confidence intervals (CI) under a random-effects model was utilized to pool the data. A single-arm meta-analysis evaluated tumor control, neurological deficits, and complications. The analysis included 16 studies with 348 patients and a median follow-up of 33 months. Results demonstrated a 98% (CI: 95 − 100%) rate of tumor control, a 39% (CI: 23–54%) rate of tumor shrinking, and a 19% (CI: 13–26%) rate of neurological deficits. New cranial nerve deficits occurred in 34% of patients (CI: 27–41%). SRS demonstrated a high tumor control rate for jugular foramen schwannomas. However, complications remain significant, with neurological deficits and new cranial nerve deficits post Gamma Knife radiosurgery (GKRS). These findings underscore the need for further studies, including comparative analyses between SRS and surgical resection, to better delineate the risk-benefit profile of these treatment modalities. [ABSTRACT FROM AUTHOR]

An intense surge in the equatorial electron temperature (Te) at sunrise, known as the morning Te overshoot, has been one of the defining ionospheric features since its discovery early in the Space Age. Despite decades of study, the behavior of the morning overshoot during geomagnetic storms remains poorly understood. We report a two-stage response of the morning Te overshoot to geomagnetic activity, uncovered by a neural network model. Electron temperatures show an initial enhancement during the storm's main phase, followed by a drastic depletion exceeding 1000 K and disappearance of the overshoot in the recovery phase. This two-phase change aligns with the early influence of westward prompt penetration electric field, overtaken by the development of the eastward disturbance dynamo later in the storm. These electric field changes affect vertical plasma drifts that redistribute electron densities, modifying ionospheric cooling rates. Our findings provide new insights into the dynamics of one of the most widely studied ionospheric features and showcase the potential of new-generation digital twin models of near-Earth space environment to reveal previously unrecognized physical patterns. [ABSTRACT FROM AUTHOR]

Microsomal cytochromes P450 (micCYPs) are monooxygenases located in the endoplasmic reticulum and other endomembranes of human cells. micCYPs receive electrons from specific redox partners and perform enzymatic transformations of drugs and different endogenous substrates. The large biodiversity of micCYPs leads to the idea that protein-protein interactions (PPIs) involving micCYPs are not limited to classical redox partners. This review aims to perform a systems biology analysis of the complete set of PPIs for all 33 micCYPs studied, as well as to examine the subinteractome of each micCYP. We have retrieved 287 PPIs from interactomic databases, involving 246 unique protein interactors that share a similar profile of subcellular localization with micCYPs. The number of protein interactors per micCYP unevenly varies from one to 47. Interactors of micCYPs are involved in cellular metabolism, signal transduction, cell-cell junctions, cytoskeleton organization, and intracellular or transmembrane transport. Notably, up to one-third of all interactors belong to the latter group, half of which consists of membrane transporters of compounds, metabolites, and ions (e.g., CACNA2D1, ORAI1, SCN3B, SLC7A2, SLC19A3, and SLC11A2). The CYP2C8 subinteractome is enriched with proteins involved in autophagy; CYP2S1– ERBB2 and EPH-Ephrin signaling; CYP3A4– glucuronidation. Proteins UBC, PGRMC1, and FANCG are the most frequent common interactors across various micCYPs. Nine and 12 interactors of micCYPs are involved in phosphorylation and ubiquitination, respectively; 20 interactors are 'moonlighting' proteins that are represented in the CYP3A4 subinteractome. Furthermore, micCYPs such as CYP2C9, 3A5, 2E1, 2A6, 4F2, and 4A11 may be involved in potentially binary interactions with other micCYPs. The functional implication of these CYP–CYP pairs is likely associated with modulation of their activity. Analysis of transcriptomic data revealed that some micCYP/interactor pairs exhibit tissue-, time-, and disease-specific gene expression patterns. Drugs that are metabolized by micCYPs in some cases can influence the expression of corresponding interactors at the gene or protein levels. These findings suggest that micCYPs may play roles in functions beyond their monooxygenase activity, as indicated by the spectrum of PPIs analyzed. [ABSTRACT FROM AUTHOR]

Purpose: To develop a surgical endoscopy technique for closing the defect of direct inguinal hernia and evaluate the efficacy and safety of a novel suture in the early postoperative period. Methods: A prospective randomized controlled single-center study was conducted at Yudin State Clinical Hospital (Moscow) from February to August 2024. We enrolled 142 male patients over 18 with newly diagnosed direct inguinal hernias and a hernia orifice being 1.5–3 cm, who were treated with extended Totally Extraperitoneal Plasty (eTEP) repair. The patients were randomly assigned to two equal groups: a comparison group that underwent hernia defect closure and a control group that did not receive intracorporeal sutures. Results: On postoperative day 1, ultrasound revealed seromas in 6 patients (11.7%) in the comparison group and in 22 patients (43.1%) in the control group (95% confidence interval [CI] 0.14–0.5, p = 0.05). Mean operation times were 47.25 ± 8.68 for the comparison and 43.63 ± 8.31 min for the control group. Pain intensity on day 2, assessed with a visual analog scale (VAS), was 2.57 ± 1.09 in the comparison group and 2.9 ± 1.29 in the control group, indicating mild to moderate pain. No adverse events occurred in either group 30 days postoperatively. Conclusion: This study presents a novel surgical endoscopy technique for closing direct medial inguinal hernia defects and provides anatomical feasibility. The advantages of the technique include preventing seromas and severe postoperative pain. Further randomized studies are warranted to assess long-term results of this technique and establish clinical indications for its use in surgical practice. [ABSTRACT FROM AUTHOR]

The F-type ATP synthase inhibitor bedaquiline (BDQ) is a potent inhibitor of mycobacterial growth and this inhibition cannot be rescued by fermentable carbon sources that would supply ATP by an alternative pathway (substrate level phosphorylation). To gain mechanistic insight into this phenomenon, we employed a metabolic engineering approach. We introduced into Mycobacterium smegmatis an alternative ATP production pathway by substrate-level phosphorylation, specifically through overexpression of trypanosomal acetate:succinate co-enzyme A (CoA) transferase (ASCT). Intriguingly, the overexpression of ASCT partially restored intracellular ATP levels and resulted in acquired tolerance to BDQ growth inhibition at low, but not high concentrations of BDQ. These results implicate intracellular ATP levels in modulating the growth inhibitory activity of BDQ at low concentrations. These findings shed light on the intricate interplay between BDQ and mycobacterial energy metabolism, while also providing a novel tool for the development of next-generation ATP synthase-specific inhibitors targeting mycobacteria. The ATP synthase inhibitor bedaquiline (BDQ) inhibits mycobacterial growth by depleting ATP, with gained tolerance to low BDQ concentrations through metabolic transplantation of trypanosomal SLPHOS pathway. [ABSTRACT FROM AUTHOR]

Studies suggest that mid-level features could underlie object animacy perception. In the current research, we tested whether ensemble animacy perception is based on high- or mid-level features. We used five types of images of animals and inanimate objects: color, grayscale, silhouettes, texforms – unrecognizable images that preserve mid-level texture and shape information – and scrambled images. In the series of Experiments 1, we asked participants to evaluate the animacy of single images and sets of eight images using a 10-point scale. In the series of Experiments 2, participants were shown two sets of eight images and had to choose a more animate one in the two-alternative forced-choice (2AFC) task. We found that in both paradigms, observers could report the mean animacy of the set of texform images without direct access to information about high-level features. Thus, ensemble animacy could be extracted only based on mid-level features such as shape and texture without access to more high-level information. [ABSTRACT FROM AUTHOR]

Little research has examined the role of social class in the long-term impact of the COVID-19 pandemic on mental well-being. This 4-year longitudinal study in South Korea (N = 86,872; 875,967 responses) assessed well-being before (January 2019 to January 2020) and during (January 2020 to January 2023) the COVID-19 pandemic to determine whether change in well-being during this period differed by social class. We expanded the investigation to consider transitions in social class, social distancing measures, and the mechanisms underlying well-being changes according to social class during the pandemic. In particular, we assessed the moderating effects of social class on within-person changes in well-being using conducting multilevel modeling-based analyses in four approaches. First, we found that, while higher-class individuals maintained an average well-being that was higher than that of lower-class individuals, they also experienced a steeper decline in well-being over the course of the pandemic. Relative to their pre-COVID-19 levels, they experienced a significant decrease in well-being in the first, second, and third years of COVID-19, showing no sign of recovery until the pandemic neared its end. Second, this pattern persisted without regard for critical social class transitions following the pandemic: individuals remaining in the higher class during both the pre-COVID-19 and COVID-19 periods experienced significant declines in well-being relative to baseline. Third, higher-class individuals faced larger difficulties in maintaining their well-being, particularly with respect to social distancing measures, while the well-being of lower-class individuals was less affected. Fourth, perceived changes in daily life mediated observed class difference in well-being declines, showing that higher-class individuals experienced greater changes in their daily lives due to COVID-19 than lower-class individuals did, resulting in greater declines in well-being. Taken together, these findings indicate that COVID-19 transformed components of life that are essential for the psychological health of the well-off, providing novel insights into the significant power of social class in the experiences of changes in well-being, going beyond the absolute gap that has been well-established by cross-sectional studies. This indicates the need for class-targeted interventions and policies to support well-being across all socioeconomic strata in future crises. [ABSTRACT FROM AUTHOR]

Background: Endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs) offers excellent efficacy and safety. Referral biopsies are commonly obtained prior to EMR despite their potential adverse effects. We aimed to assess the diagnostic accuracy of referral biopsy as compared with optical evaluations and the polyp's final pathology. Methods: We analyzed a cohort from two centers that included adult patients referred for EMR of LNPCPs between 2017 and 2022. The NICE classification system was used for optical classification. We compared procedural outcomes of lesions with or without a referral biopsy and diagnostic accuracy of referral biopsy and optical evaluation to the final histopathology of the resected polyp. Results: Of 605 EMR procedures, 398 (65.8%) had referral biopsies. Polyp size was larger in the biopsy group. No significant differences were observed in en-bloc resection rate, adequate lifting, procedural bleeding, or surveillance recurrence rates. Optical biopsies had higher diagnostic concordance with final histology (Cohen's Kappa 0.62 vs. 0.55) and enhanced sensitivity for sessile serrated polyps/hyperplastic polyps (SSP/HP) and cancer as compared to referral biopsies (0.75 vs. 0.72, p < 0.01, and 0.19 vs. 0.0, p < 0.01, respectively). Optical evaluation was more accurate in non-biopsied lesions. Conclusion: Referral biopsies do not offer additional diagnostic accuracy and may reduce the accuracy of optical evaluation for LNPCPs. [ABSTRACT FROM AUTHOR]

Background: Fontan-associated liver disease (FALD) is a type of progressive liver fibrosis that occurs following Fontan surgery and can be complicated by hepatocellular carcinoma (HCC). Established treatments for FALD are lacking. Therefore, we investigated the efficacy of ursodeoxycholic acid (UDCA) in patients with FALD. Methods: This single-center retrospective study was conducted from 2003 to 2024 and involved 220 patients (103 men, 46.8%) who had been diagnosed with FALD. UDCA was administered to 113 patients presenting with liver or biliary enzyme abnormalities. We evaluated the patients' liver enzyme levels 3, 6, and 12 months after treatment. HCC developed in 10.5% and the mortality rate was 4.5%. Survival and cumulative incidence of HCC were compared between patients with and without UDCA treatment using Kaplan–Meier curves and propensity-matched analysis (n = 68 per group). Results: UDCA treatment significantly reduced the aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transferase (GGT) levels at 3 months. The mean pretreatment AST/ALT/GGT levels were 26/22/323 U/L, respectively, and decreased to 19/15/102 U/L at 3 months, 18/12/88 U/L at 6 months, and 16/19/64 U/L at 12 months. However, the total bilirubin level and platelet count did not show significant differences. The survival rate was higher and the HCC rate was lower in patients with than without UDCA treatment. The 5-year incidence rate of HCC was 5.6% in the UDCA group and 24.2% in the untreated group. Conclusions: UDCA treatment significantly reduced liver enzyme levels, including GGT, and mitigated the progression of HCC. UDCA may be beneficial for patients with FALD. [ABSTRACT FROM AUTHOR]

Background: Febrile neutropenia (FN) is a recognised adverse event associated with chemotherapy. This study investigates the impact of atezolizumab, an immune checkpoint inhibitor, on the incidence of FN in patients with non-small cell lung cancer receiving concurrent chemotherapy in Japan. Methods: This post-marketing database study was conducted using data from patients with non-small cell lung cancer provided by Medical Data Vision Co., Ltd. covering April 2008 to present. The primary outcome measured was FN incidence, and its causal association with atezolizumab use was examined by comparing the atezolizumab plus bevacizumab plus carboplatin plus paclitaxel [ABCP])-containing regimen to the BCP control group. The data period was from 1 September, 2015, to 31 December, 2021, including approval date of this drug, 21 December, 2018. Results: The database identified 301 subjects for the ABCP regimen (exposure) group, 44 for the BCP regimen (cohort design control) group during the same period, and 207 for BCP regimen (historical cohort design control) group before the approval of atezolizumab. For historical cohort design, the incidence and adjusted incidence ratios of febrile neutropenia in the exposure group to the control group were 6.13 (95% CI 2.78–13.49) and 8.19 (95% CI 3.79–25.33), respectively. Sensitivity analysis showed FN occurred in 17% (52/301) of the exposure group, 4.5% (2/44) of the cohort design control group, and 3% (7/207) of the historical cohort design control group. Conclusions: The incidence of FN was higher in the exposure group. Considering the study results, special caution is needed for FN occurrence in patients receiving atezolizumab. [ABSTRACT FROM AUTHOR]

Preoperative anemia in children is a significant clinical concern requiring precise diagnosis. Although traditional blood sample collection is effective, it poses challenges because of children's aversion and technical difficulties. Therefore, this study explores the suitability of noninvasive hemoglobin measurements in children during preoperative anesthesia consultation. Noninvasive hemoglobin measurement (SpHb®; Masimo) in children aged ≤ 17 years was performed during preoperative anesthesia consultation and compared with laboratory hemoglobin (labHb) levels. SpHb was measured in 62 children (median age: 6 years, standard deviation [SD] ± 5.3) without adverse effects but was unsuccessful in one child. The bias, limits of agreement, and root mean square error between SpHb and labHb were 0.3, −2.26– +2.8, and 1.3 g/dl, respectively. LabHb demonstrated a significant regression relationship with R2 of 0.359. LabHb was associated with a negative effect on bias [− 0.443 (CI 95: − 0.591– − 0.153, P < 0.001)], i.e., SpHb tends to underestimate labHb for high labHb values. The retest reliability between two consecutive SpHb measurements was 0.727 (P < 0.001). Double measurement of SpHb, age, weight, sex, heart rate, and perfusion index had no significant effects on accuracy. Using SpHb, a specificity of 96.3% (95% confidence interval [CI 95]: 87.3%–99.5%) and a sensitivity of 57.1% (CI 95: 18.4%–90.1%) were observed. Based on adapted cut-off values for SpHb (age-dependent cut-off values plus 0.8 g/dl), a sensitivity of 100% (CI 95: 64.6%–100%) was achieved for the investigated study collective. SpHb measurement in children is a quick procedure. The accuracy of hemoglobin measurement is insufficient for the diagnosis of anemia. Thus, whether the calculated cut-off SpHb values of this study collective can be considered for anemia screening in pediatric patients undergoing preoperative anesthesia consultation should be confirmed. Trial registration number and date of registration: This prospective study was registered at ClinicalTrials.gov (NCT03586141). [ABSTRACT FROM AUTHOR]

This paper focuses on two-point boundary value problems for autonomous second order nonlinear differential equations of the form y'' = f(y,y') which can represent many problems in physics and engineering. Analytical integration of such equations leads to an indefinite integral, which in most cases cannot be expressed by elementary functions. In addition, obtaining an analytical expression for the unknown constants of integration C1 and C2 depending on the boundary conditions is also difficult or impossible, especially when an indefinite non-elementary integral is involved. Due to these limitations the implementation of such an analytical solution is very limited. The present paper proposes an alternative analytical approach aiming at extending the usage of analytical solutions to such problems. The developed approach is based on the linearization of the right-hand side f(y) of the original nonlinear equation in the neighborhood of some value y* of the unknown solution y(x) where y* serves as a parameter in the solution yL (x, y*) of the linearized equation. A special (non-differential) equation is obtained that allows to calculate y* for each x. The proposed approach allows to obtain a solution at any selected point x, without calculating the solution at other points (in contrast to explicit numerical methods), and without solving a system of high-order nonlinear equations (in contrast to implicit numerical methods). Examples of different physical problems are presented to validate the proposed approach and demonstrate its high precision. The excellent agreement with known analytical and numerical solutions, is quantitatively estimated by the absolute and relative errors calculated using the norms L1 and L2. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the Cost-Efficiency of Atraumatic Restorative Treatment (ART) with a chemical-mechanical caries removal agent (CMCRA, Papacárie Duo GelⓇ) compared to conventional ART, based on pain perceived and time for selective removal of carious tissue, from the perspective of the Brazilian Unified Health System (SUS). Materials and methods: The Cost-Efficiency analysis was conducted using TreeAgePro software, considering a 12-month horizon and a hypothetical cohort based on Monte Carlo microsimulation. ART + CMCRA was compared to ART in deciduous teeth, based on 26,700 treatments performed on children attended by SUS in Rio de Janeiro. Direct costs were calculated in Brazilian currency using the microcosting technique. Efficiency measures related to pain and caries removal time were extracted from a high-quality randomized clinical trial. Probabilistic simulation considered a 95% confidence interval and a 5% variation in parameters, generating acceptability curves to estimate the probability of treatment choice. Results: ART + CMCRA proved superior (p < 0,001) in terms of benefit. For pain perceived efficiency, ART + CMCRA resulted in a cost increase of R$ 0.23 per procedure, with an additional benefit of 47.53%. For time efficiency, there was a cost increase of R$ 0.24 per procedure, with an additional benefit of 14.19%. Conclusion: ART + CMCRA is a cost-efficient option for SUS. The implementation of this technique in Rio de Janeiro’s public health system can be recommended due to the reduced pain, despite requiring a higher willingness to pay for the additional benefits. Clinical relevance: The adoption of ART + CMCRA in SUS can significantly improve the experience of pediatric patients by reducing pain, making dental treatment more efficient and humane. [ABSTRACT FROM AUTHOR]

Background: Treatment-related skin reactions (TRSRs) induced by enfortumab vedotin (EV) targeting nectin-4 are among the most common adverse events. However, their association with survival and treatment response is poorly understood. Methods: We retrospectively identified patients who received EV from December 2021 to April 2023 at Nagoya University Hospital and its affiliated facilities and extracted clinical data from their medical records. We evaluated cancer-specific survival (CSS) and progression-free survival (PFS) as survival outcomes and overall response rate (ORR) and disease control rate (DCR) as treatment responses between patients with and without TRSRs. Results: In total, 67 eligible patients were identified. Thirty-four patients experienced TRSRs, and the remaining 33 did not experience TRSRs. The median follow-up period was 8 months. Patients in the TRSRs group demonstrated significantly longer median CSS (15 vs. 8 months; p = 0.003) and median PFS (10 vs. 5 months; p < 0.001) than the non-TRSRs. Regarding treatment response, the patients in the TRSRs group showed a favorable, albeit nonsignificant, treatment response trend compared with those in the non-TRSRs group (ORR, 73.5% vs. 51.5%; p = 0.107; DCR, 91.2 % vs. 81.8%; p = 0.444). Conclusions: Patients with TRSRs demonstrated more prolonged survival and superior treatment responses to EV treatment. The role of TRSR as a surrogate marker of EV's efficacy should be further explored in prospective and sufficiently powered studies. [ABSTRACT FROM AUTHOR]

Background: Recent large clinical trials have revealed that sodium–glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes not only in patients with heart failure with reduced ejection fraction, but also in patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF). However, the effect of SGLT2 inhibitors on left ventricular (LV) diastolic function is still controversial. Methods and Results: The TOP-HFPEF trial (Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus) is a multicenter, double-arm, open-label, confirmatory, investigator-initiated clinical study to investigate the effect of SGLT2 inhibitor on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus. The participants are randomly assigned (1:1) to the tofogliflozin group (20 mg once daily) or the control group (administration or continuation of antidiabetic drugs other than SGLT2 inhibitors). The estimated number of patients to be enrolled in this trial is 90 in total (45 in each group). The participants are followed up for 52 weeks with tofogliflozin or control drugs. The primary endpoint is the change in E/e′ assessed by echocardiography from the baseline to the end of this study (52 weeks). This trial will also evaluate the effects of tofogliflozin on cardiovascular events, biomarkers, other echocardiographic parameters, the occurrence of atrial fibrillation, and renal function. Conclusions: The TOP-HFPEF trial will clarify the efficacy of an SGLT2 inhibitor, tofogliflozin, on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

In this work, the heterodimeric phospholipase A2, HDP-2, from viper venom was investigated for its hydrolytic activity in model myelin membranes as well as for its effects on intermembrane exchange of phospholipids (studied by phosphorescence quenching) and on phospholipid polymorphism (studied by 1H-NMR spectroscopy) to understand the role of sphingomyelin (SM) in the demyelination of nerve fibers. By using well-validated in vitro approaches, we show that the presence of SM in model myelin membranes leads to a significant inhibition of the hydrolytic activity of HDP-2, decreased intermembrane phospholipid exchange, and reduced phospholipid polymorphism. Using AutoDock software, we show that the NHδ+ group of the sphingosine backbone of SM binds to Tyr22(C=Opbδ–) of HDP-2 via a hydrogen bond which keeps only the polar head of SM inside the HDP-2's active center and positions the sn-2 acyl ester bond away from the active center, thus making it unlikely to hydrolyze the alkyl chains at the sn-2 position. This observation strongly suggests that SM inhibits the catalytic activity of HDP-2 by blocking access to other phospholipids to the active center of the enzyme. Should this observation be verified in further studies, it would offer a tantalizing opportunity for developing effective pharmaceuticals to stop the demyelination of nerve fibers by aberrant PLA2s with overt activity – as observed in brain degenerative diseases – by inhibiting SM hydrolysis and/or facilitating SM synthesis in the myelin sheath membrane. Binding of sphingomyelin (SM) to catalytic subunits of HDP-2 predicted by Autodock. SM is given in sticks representation and HDP-2P is displayed in molecular surface (A) and line stick representation (B). For the stick diagrams, emerald represents carbon, blue–nitrogen, orange–phosphorus, red–oxygen, white–hydrogen. For molecular surface and lines, green represents carbon, blue–nitrogen, red–oxygen, white–hydrogen, yellow–sulfur. Yellow broken lines identify intermolecular bonds. Arrows point to sn-2 bonds. Hydrogen bond between NHδ+ group and Tyr22(C=Opbδ–) and ionic bond between PO4– group and His48 drive the positioning of the sn-2 acyl ester bond away from the active center that suggests that SM binds non-productively in the active center of HDP-2 enzyme. [ABSTRACT FROM AUTHOR]

In the vicinity of the anticrossing region of the spin sublevels, the effective magnetic moment of the electron spin is reduced, resulting in an increase in the lifetime of the spin coherence. Based on this phenomenon, the modified electron spin echo protocol is proposed to extend the coherence relaxation time. It includes the Hahn echo sequence with the additional detuning of the magnetic field applied during the intervals between two pulses and between the refocusing pulse and the echo. The simplest system with anticrossing sublevels is an ion whose electron spin is strongly coupled to its own nucleus. To realize the proposed protocol, a narrow anticrossing region is required. The promising candidate to realize the proposed protocol is the crystal [Ho(W5O18)2]9−, whose spin transitions have been studied in the recent paper (Kundu et al. Commun Phys 6:38 (2023)). Near the clock transition, the spin evolution of the electron–nuclear spin system is described by a fictitious spin 1/2, but with the magnetic properties dictated by the properties of the ion. The numerical study shows that the spin coherence is not destroyed by the magnetic field detuning, but it reduces the phase relaxation. In addition, the use of the unequal detuning pulses results in a phase shift of the spin echo, which can be used to discriminate between the target signal and the unwanted echo contributions. [ABSTRACT FROM AUTHOR]

Purpose: Our previous study showed that the preventive effects of fosnetupitant (F-NTP) against chemotherapy-induced nausea and vomiting (CINV) were superior to those of fosaprepitant (F-APR) or aprepitant (APR). To evaluate the cost-effectiveness of F-NTP compared with F-APR or APR in Japan, a cost-utility analysis was performed. Methods: A decision tree model was developed based on real-world data to compare the CINV prevention ability of each neurokinin-1 receptor antagonist (NK1 RA) in Japanese patients receiving cisplatin-based regimens. We evaluated the patients 7 days after the first course of treatment. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated to examine the cost-effectiveness of the antiemetic therapy. The probabilities of health states and medical costs were derived from the results of our previous study. These cost-utility analyses were performed from the perspective of the payers. Results: The incremental QALYs of F-NTP relative to F-APR and APR were 0.00180 and 0.00153, respectively. The ICER of F-NTP relative to F-APR was 22,802.21 US dollars (USD) per QALY gained, which was lower than the willingness-to-pay (WTP) threshold (38,043.06 USD: 5 million Japanese Yen/QALY). Contrastingly, the ICER of F-NTP relative to APR was 40,119.64 USD/QALY, which was slightly above the WTP threshold, indicating that F-NTP may be slightly less cost-effective. Conclusion: F-NTP is more cost-effective than F-APR, but slightly less cost-effective than APR. [ABSTRACT FROM AUTHOR]

We prove that on the product of two Riemannian manifolds one of which is compact, any Killing tensor is reducible, that is, is the sum of products of Killing tensors on the factors. The same is true for the lifts to the universal cover of Killing tensors on a compact manifold with reducible holonomy. We give a local description of Killing tensors on product manifolds and present an example of a complete product manifold whose factors are locally irreducible which admits an irreducible Killing tensor field. [ABSTRACT FROM AUTHOR]

The coexistence of strong electron–electron correlation and strong spin–orbit coupling makes CaIrO3 a promising candidate for the exploration of emergent phenomena in thin film form. We have realized epitaxial CaIrO3 films on (La0.18Sr0.82)(Al0.59Ta0.41)O3 single crystal substrates with excellent crystallinity and thicknesses ranging from 3 to 32 nm. Electronic properties range from semiconducting to insulating behavior as a function of decreasing thickness and correlate with increased tetragonal distortion due to substrate-imposed strain. Hall effect measurements indicate that conduction is dominated by electron-type carriers at room temperature but crosses over to transport dominated by hole-like carriers at lower temperatures. Longitudinal magnetoresistance measurements reveal both a quadratic Lorentz dependence and an additional positive component in the field dependence that cannot be explained purely by semi-classical orbital magnetoresistance effects. [ABSTRACT FROM AUTHOR]

Purpose: Understanding pulmonary artery (PA) branches and their variations is crucial for successful lung resection. We aimed to evaluate the segmental PA branching pattern of the left upper lobe (LUL) using thin-section computed tomography (TSCT) images and 3D-CT angiography (3D-CTA). Materials and methods: This study included 108 patients who underwent CTA and left upper lobectomy. The segmental PA branching pattern of the LUL was meticulously identified by two thoracic radiologists using 3D-CTA and TSCT images. The lingular artery branches from the left PA (LPA) were classified into mediastinal type (pars mediastinalis: PM), interlobar type (pars interlobaris: PI), and PI originating from the lower portion (PI'), specifically from A8. The intraoperative findings of the PA branches of the LUL were compared with the preoperatively obtained 3D-CTA and TSCT images in each patient's case. Results: The median (range) number of LPA branches of the LUL was 4.36 (3–8). The most common number of A1 + 2 branches was two, seen in 34 cases (31.5%). One or more branches of A1 + 2c directly originating from the LPA were found in 63 cases (58.3%). The number of branches of A3 was single in 85 cases and the most frequent (78.7%). Instances where one or more branches of A3a directly originated from the LPA were found in seven cases (6.5%). A1 + 2 and A3 origins were separate and independent in 40 cases (37.0%). As the branching pattern of the lingular artery, PI/PI' was most frequent (61.1%). PI´ was observed in 26 cases (24.1%). Inter-observer agreement for A1 + 2, A1 + 2c, A3, A3a, and lingular artery branching patterns was moderate to substantial (κ = 0.53–0.72). Preoperative 3D-CTA and TSCT images identified 99.8% of LPA branches compared to intraoperative findings, except one. Conclusion: The segmental PA branching pattern of the LUL can be evaluated using TSCT and 3D-CTA images, providing precise preoperative information. [ABSTRACT FROM AUTHOR]

GdVO4:Eu3+ nanoparticles (OVNPs) have previously been shown to exhibit anti-aging effects in old rats.The accelerated aging model (overnutrition in early postnatal ontogenesis (POF)) was used to confirm the effect of OVNPs as a potential geroprotector. A comparative study of the effect of OVNPs, calorierestriction (CR) and CR-mimetic—metformin was carried out using a number of criteria: survival, prooxidant-antioxidant balance in the liver and blood, physiological parameters of male Wistar rats with accelerated aging. It was found that the survival of rats with POF was lower than that of control animals.It was found that the rate of superoxide radical formation and the content of lipid hydroperoxides in the mitochondria and microsomes of the liver and blood serum of rats with POF were higher, and the activities of glutathione peroxidases and the GSH content were significantly lower than in the control animals.It was also found that POF leads to perturbation of physiological parameters (body weight, liver weight, liver mass coefficient, body temperature and blood thyroxine concentration) characterizing the quality of life. Long-term use of OVNPs, CR or metformin in rats with accelerated aging normalized the imbalance of the prooxidant-antioxidant system, improved the physiological parameters, and increased the survival of these experimental animals. Moreover, the increase in survival was most pronounced with the use of CR and OVNPs. Considering our results andthe inadmissibility of long-term use of CR, it should be concluded that GdVO4:Eu3+ nanoparticles are promising for the development of agents that slow down the accelerated aging of an organism. [ABSTRACT FROM AUTHOR]

Hair follicle growth depends on the intricate interaction of cells within the follicle and its vascular supply. Current FDA-approved treatments like minoxidil have limitations, including side effects and the need for continuous use. Moracin M, a compound from Moraceae family, was investigated for its effects on hair growth and vascular regeneration. In our study, Moracin M significantly increased cell proliferation in human dermal papilla cells (hDPCs) during both the anagen and catagen phases and promoted cell migration in human umbilical vein endothelial cells (HUVECs) without cytotoxicity at concentrations up to 50 µM. Mechanistic analysis revealed that moracin M enhanced Wnt3a, GSK-3β phosphorylation and increased non-phospho β-catenin levels, activating Wnt signaling and upregulating transcription factors LEF, TCF, and AXIN2. This resulted in elevated levels of growth factors VEGF, FGF2, KGF, HGF and MYC in hDPCs, effects comparable to those of minoxidil. Additionally, moracin M significantly increased protein and mRNA levels of VEGF, FGF2, and KGF in hDPCs under IFN-γ-induced inflammatory conditions. Moracin M treatments also resulted in notable wound width reductions in a dose-dependent manner. Further investigation showed that moracin M stimulated MMP-2 and MMP-9 expression. These findings indicate that moracin M significantly enhances hair growth through the promotion of cell proliferation and angiogenesis, particularly via the activation of the Wnt signaling pathway in dermal papilla cells, presenting it as a promising therapeutic alternative to current treatments. [ABSTRACT FROM AUTHOR]

Urbanization is expected to reach 70% of the world's population by 2050; in Brazil, 80% of the population already lives in urban areas. This surge in urban living has led to increased energy and water consumption, increased greenhouse gas emissions, and increased resource conflicts. The resulting scarcity of water, energy, and food resources has also triggered multiple crises. One promising strategy for addressing these challenges is to integrate the dimensions associated with the water-energy-food (WEF) Nexus. We used WEAP to simulate two Brazilian watersheds for the 2020 to 2050 period, analyzing reference, alternative energy, increase Brazilian water resource management tools and climate change scenarios. The proposed watershed plans and governance actions significantly improved the sustainability index, with the committees' governance actions further contributing to the overall sustainability of complex water systems. [ABSTRACT FROM AUTHOR]

Back-action refers to a response that retro-acts on a system to tailor its properties with respect to an external stimulus. This effect is at the heart of many electronic devices such as amplifiers, oscillators, and sensors. Here, we demonstrate that back-action can be exploited to achieve non-reciprocal transport in superconducting circuits. In our devices, dissipationless current flows in one direction whereas dissipative transport occurs in the opposite direction. Supercurrent diodes presented so far rely on magnetic elements or vortices to mediate charge transport or external magnetic fields to break time-reversal symmetry. Back-action solely turns a conventional reciprocal superconducting weak link with no asymmetry between the current bias directions into a rectifier, where the critical current amplitude depends on the bias sign. The self-interaction of the supercurrent stems from the gate tunability of the critical current in metallic and semiconducting systems, which promotes nearly ideal magnetic field-free rectification with selectable polarity. The superconducting diode effect has the potential to advance the design of non-dissipative circuit components yet there are many practical aspects to overcome before reaching the application stage. Here, the authors investigate the non-reciprocal current-voltage relationship in gate-controlled metallic nanowires, demonstrating the realisation of the superconducting diode effect without the need to break time-reversal symmetry using an applied magnetic field. [ABSTRACT FROM AUTHOR]

Beta regression models are employed to model continuous response variables in the unit interval, like rates, percentages, or proportions. Their applications rise in several areas, such as medicine, environment research, finance, and natural sciences. The maximum likelihood estimation is widely used to make inferences for the parameters. Nonetheless, it is well-known that the maximum likelihood-based inference suffers from the lack of robustness in the presence of outliers. Such a case can bring severe bias and misleading conclusions. Recently, robust estimators for beta regression models were presented in the literature. However, these estimators require non-trivial restrictions in the parameter space, which limit their application. This paper develops new robust estimators that overcome this drawback. Their asymptotic and robustness properties are studied, and robust Wald-type tests are introduced. Simulation results evidence the merits of the new robust estimators. Inference and diagnostics using the new estimators are illustrated in an application to health insurance coverage data. The new R package robustbetareg is introduced. [ABSTRACT FROM AUTHOR]

Special AT-rich sequence-binding protein 2 (SATB2) is a master regulator of gene expression. Mutations of the SATB2 gene results in the SATB2-associated syndrome (SAS), a genetic disorder characterized by neurodevelopmental disabilities and autism-related phenotype. The importance of plasma as an indicator of SAS phenotypes is unknown. We aim to investigate if pathogenic variants in SATB2 are associated with alteration to relevant pathways in the plasma of SAS patients and identify key differentially regulated proteins which may serve as biomarkers to improve diagnostic and future pharmacological approaches. We used well-validated proteomic technologies to determine the proteomic profile of plasma from SAS patients compared to healthy control subjects. Bioinformatical analysis was performed to identify significant proteins and functionally enriched pathways. We identified differentially expressed proteins in the plasma of SAS patients that are significantly involved in metabolism-related pathways. Energy metabolism, glucose metabolism and vitamin metabolism pathways are significantly enriched in SAS patients as compared to healthy controls. Our study linked SATB2 mutations to the impairment of plasma proteins involved in different metabolic pathways in SAS patients. [ABSTRACT FROM AUTHOR]

Adequate assessment of the contribution of the different phases of atrial mechanical activity to the value of ejection volume and pressure developed by the ventricle is a complex and important experimental and clinical problem. A new method and an effective algorithm for controlling the interaction of isolated rat right atrial and right ventricular strips during the cardiac cycle were developed and tested in a physiological experiment. The presented functional model is flexible and has the ability to change many parameters (temperature, pacing rate, excitation delay, pre- and afterload levels, transfer length, and force scaling coefficients) to simulate different types of cardiac pathologies. For the first time, the contribution of the duration of the excitation delay of the right ventricular strips to the amount of work performed by the muscles during the cardiac cycle was evaluated. Changes in the onset of atrial systole and the delay in activation of ventricular contraction may lead to a reduction in cardiac stroke volume, which should be considered in the diagnosis and treatment of cardiovascular disease and in resynchronization therapy. [ABSTRACT FROM AUTHOR]

Purpose: In the current investigation, the effects of the mTOR inhibitors, Rapa and Torin1 on the TGF-β2-induced conjunctival fibrogenesis were studied. Study design: Experimental research. Methods: 2D and 3D cultures of HconF were subjected to the following analyses; (1) planar proliferation evaluated by TEER (2D), (2) Seahorse metabolic analyses (2D), (3) subepithelial proliferation evaluated by the 3D spheroids' size and hardness, and (4) the mRNA expression of ECM proteins and their regulators (2D and 3D). Result: Rapa or Torin1 both significantly increased planar proliferation in the non-TGF-β2-treated 2D HconF cells, but in the TGF-β2-treated cells, this proliferation was inhibited by Rapa and enhanced by Torin1. Although Rapa or Torin1 did not affect cellular metabolism in the non-TGF-β2-treated HconF cells, mTOR inhibitors significantly decreased and increased the mitochondrial respiration and the glycolytic capacity, respectively, under conditions of TGF-β2-induced fibrogenesis. Subepithelial proliferation, as evidenced by the hardness of the 3D spheroids, was markedly down-regulated by both Rapa and Torin1 independent of TGF-β2. The mRNA expressions of several ECM molecules and their regulators fluctuated in the cases of 2D vs 3D and TGF-β2 untreated vs treated cultures. Conclusion: The present findings indicate that mTOR inhibitors have the ability to increase and to reduce planar and subepithelial proliferation in HconF cells, depending on the inhibitor being used. [ABSTRACT FROM AUTHOR]

Global positioning systems have proven effective in outdoor environments, but encounter challenges in indoor applications due to the absence of direct line-of-sight with satellites. To address this limitation, novel methods are emerging to navigate obstacles in indoor settings, with a focus on achieving precise tracking at reduced costs. Indoor Positioning Systems (IPSs) based on Received Signal Strength Indicator (RSSI) are widely adopted because of their cost-effective implementation. This work introduces a new IPS that utilizes Bluetooth Low Energy (BLE) technology and RSSI in a log-distance signal propagation model optimized by a genetic algorithm to improve the positioning estimation of mobile devices. Real-time Genetic Algorithms (GA) are employed to dynamically adjust the parameters of the Signal Propagation (SP) model, taking into account the variable wave propagation characteristics in different indoor regions. This results in superior performance when compared to the traditional approach of using fixed values in the propagation model for the entire scenario. To assess the effectiveness of our Genetic Algorithm-based SP-IPS (GASP-IPS), we conducted experiments in a real indoor environment comprising multiple rooms. The results indicate that our solution can achieve 2.52 m average error, without the need for significant pre-deployment efforts. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) presents some clinical overlap with Kawasaki disease (KD). Although KD is common in Japan, the clinical characteristics of MIS-C in Japan remain unknown. Therefore, we aimed to determine the epidemiological and clinical features of MIS-C in Japan. Methods: Using a case reporting form, a nationwide registry was created between November 2020 and March 2023, involving 2,080 facilities throughout Japan. We prospectively and retrospectively enrolled patients with MIS-C. The primary outcomes were the number and incidence rates of children with MIS-C. The secondary outcomes included clinical features, such as KD phenotype, organ involvement, shock, intensive care unit admission, and coronary artery lesions. Results: Among 398 patients registered, central review identified 129 MIS-C cases (mean age: 8·8 ± 3·7 years). The overall incidence rate was estimated to be 1·5 per 100,000 COVID-19 cases, exhibiting a decline as the COVID-19 pandemic progressed, from 12·3 cases (Pre-Delta) to 1·3 cases (Omicron); 80% of MIS-C cases occurred during the Omicron variant predominant period, and 72% of children with MIS-C met the KD criteria. Cardiovascular (88%) and gastrointestinal (90%) involvement were frequent. In Japan, MIS-C cases showed comparatively less severe clinical features, with shock in 29% and admission to the intensive care unit in 12% of cases. Coronary artery lesions were identified in 15 cases (11·6%), irrespective of the presence of shock. No fatalities were reported. Conclusion: The incidence of MIS-C was low in Japan. The clinical features distinctively exhibited a more KD-like phenotype, with less severe clinical features. [ABSTRACT FROM AUTHOR]

A comprehensive statistical analysis of the distributions of the adhesion strength (σ) developed during a long-term contact (up to 2 months) of two identical specimens of an amorphous entangled polymer at a very low temperature (T) of 24 °C with respect to the bulk glass transition temperature (Tg), below Tg by 80 °C, was carried out. For this purpose, two representative glassy polymers, polystyrene [PS; three PSs differing markedly in the number-average molecular weight (Mn) from 75 to 966 kg/mol] and poly(methyl methacrylate) (PMMA; Mn = 43.5 kg/mol), were selected. Keeping in contact the two specimens of PS or PMMA at T = 24 °C resulted in self-bonding at PS–PS and PMMA–PMMA interfaces. The as-self-bonded interfaces were shear fractured in tension to measure their σ values. The four σ distribution sets obtained for such a low T for the first time were examined using a number of common formal tests for normality and graphical statistical methods, including Weibull's model. In general, the σ distributions for the PS with the highest Mn = 966 kg/mol were described more correctly than those for the other three polymers, regardless of the statistical methods applied. These results were compared with those obtained after self-bonding at a significantly higher T = Tg − 33 °C for the same polymers. The statistical parameters estimated at markedly different temperatures (T = Tg − 80 °C and Tg − 33 °C) were compared and discussed. [ABSTRACT FROM AUTHOR]

We study linearizability and stable linearizability of actions of finite groups on the Segre cubic and Burkhardt quartic, using techniques from group cohomology, birational rigidity, and the Burnside formalism. [ABSTRACT FROM AUTHOR]