Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications. Full article

Navigation lies at the core of social robotics, enabling robots to navigate and interact seamlessly in human environments. The primary focus of human-aware robot navigation is minimizing discomfort among surrounding humans. Our review explores user studies, examining factors that cause human discomfort, to perform the grounding of social robot navigation requirements and to form a taxonomy of elementary necessities that should be implemented by comprehensive algorithms. This survey also discusses human-aware navigation from an algorithmic perspective, reviewing the perception and motion planning methods integral to social navigation. Additionally, the review investigates different types of studies and tools facilitating the evaluation of social robot navigation approaches, namely datasets, simulators, and benchmarks. Our survey also identifies the main challenges of human-aware navigation, highlighting the essential future work perspectives. This work stands out from other review papers, as it not only investigates the variety of methods for implementing human awareness in robot control systems but also classifies the approaches according to the grounded requirements regarded in their objectives. Full article

In this paper,we study the following non-local problem in fractional Orlicz–Sobolev spaces: ${(-{\Delta }_{\Phi })}^{s}u+V\left(x\right)a\left(\right|u\left|\right)u=f(x,u),x\in {\mathbb{R}}^N$, where ${(-{\Delta }_{\Phi })}^s(s\in (0,1))$ denotes the non-local and maybe non-homogeneous operator, the so-called fractional $\Phi$-Laplacian. Without assuming the Ambrosetti–Rabinowitz type and the Nehari type conditions on the non-linearity f, we obtain the existence of ground state solutions for the above problem with periodic potential function $V\left(x\right)$. The proof is based on a variant version of the mountain pass theorem and a Lions’ type result in fractional Orlicz–Sobolev spaces. Full article

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6–10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-β) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients. Full article

The paracrine signaling pathways for the crosstalk between pericytes and endothelial cells are essential for the coordination of cell responses to challenges such as hypoxia in both healthy individuals and pathological conditions. Ischemia–reperfusion injury (IRI), one of the causes of cellular dysfunction and death, is associated with increased expression of genes involved in cellular adaptation to a hypoxic environment. Hypoxic inducible factors (HIFs) have a central role in the response to processes initiated by IRI not only linked to erythropoietin production but also because of their participation in inflammation, angiogenesis, metabolic adaptation, and fibrosis. While pericytes have an essential physiological function in erythropoietin production, a lesser-known role of HIF stabilization during IRI is that pericytes’ HIF expression could influence vascular remodeling, cell loss and organ fibrosis. Better knowledge of mechanisms that control functions and consequences of HIF stabilization in pericytes beyond erythropoietin production is advisable for the development of therapeutic strategies to influence disease progression and improve treatments. Thus, in this review, we discuss the dual roles—for good or bad—of HIF stabilization during IRI, focusing on pericytes, and consequences in particular for the kidneys. Full article

A safety plateau in the construction industry has been reported in the US and Canada, which has prompted researchers to seek new factors affecting construction safety performance. Tapping into advancements in the theory of human and organizational behaviors can yield valuable new perspectives. Therefore, by leveraging the advancement of the Job Demand Control Support model in the field of occupational safety and health, this paper firstly tested the impact of one newly added hindrance stressor (i.e., interpersonal conflicts on construction sites) by researchers on organizational behaviors on the safety performance of construction workers, based on two cross-sectional studies in the US and Canada. Differentiations were made between conflicts with supervisors and conflicts with coworkers. One personal resource factor, i.e., individual resilience, was also considered in this paper. A “causal” chain that shows the mitigation impact of individual resilience on conflicts with supervisors or coworkers, and the adverse impact of conflicts with supervisors or coworkers, on unsafe events were found to hold true for both US and Canadian construction sites, based on the results from measurement invariance tests and structural equation modelling. Recommendations regarding how to improve construction workers’ individual resilience and reduce interpersonal conflicts on site, thereby reducing safety incidents on site, are provided. Full article

This study aimed to evaluate the influence of films based on chitosan and rosemary extract on the physicochemical, microbiological, and oxidative characteristics of beef. Refrigerated steaks of Longissimus dorsi were distributed in a factorial arrangement (4 × 4) into four treatments consisting of four edible films (control; chitosan; chitosan + 4% rosemary extract; and chitosan + 8% rosemary extract) and four days of aging (0, 2, 4, and 8 days). Incorporating 4% or 8% rosemary extract into the chitosan film improved the characteristics of the films in terms of moisture absorption and elasticity. The edible coatings with chitosan and rosemary extract and the different days of aging increased the tenderness and decreased the lipid oxidation of beef. In addition, the chitosan films containing rosemary extract increased the water-holding capacity and decreased the cooking losses of beef. The films containing 4% and 8% rosemary extract decreased the development of mesophilic and psychrotrophic bacteria and Staphylococcus ssp. in beef. We recommend incorporating 4% rosemary extract into chitosan-based coatings to preserve the quality of refrigerated beef. Full article

The ability to detect underwater objects accurately is important in marine environmental engineering. Although many kinds of underwater object detection algorithms with relatively high accuracy have been proposed, they involve a large number of parameters and floating point operations (FLOPs), and often fail to yield satisfactory results in complex underwater environments. In light of the demand for an algorithm with the capability to extract high-quality features in complex underwater environments, we proposed a one-stage object detection algorithm called the enhanced feature-based underwater object detection algorithm (EF-UODA), which was based on the architecture of Next-ViT, the loss function of YOLOv8, and Ultralytics. First, we developed a highly efficient module for convolutions, called efficient multi-scale pointwise convolution (EMPC). Second, we proposed a feature pyramid architecture called the multipath fast fusion-feature pyramid network (M2F-FPN) based on different modes of feature fusion. Finally, we integrated the Next-ViT and the minimum point distance intersection over union loss functions in our proposed algorithm. Specifically, on the URPC2020 dataset, EF-UODA surpasses the state-of-the-art (SOTA) convolution-based object detection algorithm YOLOv8X by 2.9% mean average precision (mAP), and surpasses the SOTA ViT-based object detection algorithm real-time detection transformer (RT-DETR) by 2.1%. Meanwhile, it achieves the lowest FLOPs and parameters. The results of extensive experiments showed that EF-UODA had excellent feature extraction capability, and was adequately balanced in terms of the number of FLOPs and parameters. Full article

Tourism seasonality as a tourist demand concentration in specific seasons is still a big challenge for Mediterranean islands’ tourism policies. Overtourism occurs during high tourist seasons, and undertourism occurs during low tourist seasons, creating undesirable economic, social, and environmental effects on sustainability. However, the imbalance of tourism demand, specifically in fragile territories such as islands, needs specific policies based on scientific evidence. This article examines tourism seasonality dynamics in the Mediterranean islands, thoroughly analysing tourist overnights on island destinations. The adopted methodology uses a set of statistical indicators, such as peak factor intensity, calculated in a time series analysis from 2008 to 2018. The results of this article allow us to understand the importance for the Mediterranean islands to plan a resilient, sustainable, and harmonious tourism policy, using strategies to contain seasonal peaks and creating new tourist demand in the low season months. Full article

The role of metabolic traits in ischemic stroke (IS) has been explored through observational studies and a few Mendelian randomization (MR) studies employing limited methods in European populations. This study aimed to investigate the causal effects of metabolic traits on IS in both East Asian and European populations utilizing multiple MR methods based on genetic insights. Two-sample and multivariable MR were performed, and MR estimates were calculated as inverse-variance weighted (IVW), weighted median, and penalized weighted median. Pleiotropy was assessed by MR–Egger and Mendelian randomization pleiotropy residual sum and outlier tests. Systolic blood pressure (SBP) was associated with an increased risk of IS by IVW in both European (OR_IVW: 1.032, 95% CI: 1.026–1.038, p < 0.001) and Japanese populations (OR_IVW: 1.870, 95% CI: 1.122–3.116, p = 0.016), which was further confirmed by other methods. Unlike the European population, the evidence for the association of diastolic blood pressure (DBP) with IS in the Japanese population was not stable. No evidence supported an association between the other traits and IS (all Ps > 0.05) in both races. A positive association was found between SBP and IS in two races, while the results of DBP were only robust in Europeans. Full article

Artificial intelligence (AI) has been recently introduced into clinical dentistry, and it has assisted professionals in analyzing medical data with unprecedented speed and an accuracy level comparable to humans. With the help of AI, meaningful information can be extracted from dental databases, especially dental radiographs, to devise machine learning (a subset of AI) models. This study focuses on models that can diagnose and assist with clinical conditions such as oral cancers, early childhood caries, deciduous teeth numbering, periodontal bone loss, cysts, peri-implantitis, osteoporosis, locating minor apical foramen, orthodontic landmark identification, temporomandibular joint disorders, and more. The aim of the authors was to outline by means of a review the state-of-the-art applications of AI technologies in several dental subfields and to discuss the efficacy of machine learning algorithms, especially convolutional neural networks (CNNs), among different types of patients, such as pediatric cases, that were neglected by previous reviews. They performed an electronic search in PubMed, Google Scholar, Scopus, and Medline to locate relevant articles. They concluded that even though clinicians encounter challenges in implementing AI technologies, such as data management, limited processing capabilities, and biased outcomes, they have observed positive results, such as decreased diagnosis costs and time, as well as early cancer detection. Thus, further research and development should be considered to address the existing complications. Full article

A novel high depth-to-width ratio of 15:1 narrow-gap gas metal arc welding technique was developed for the welding of S500Q steel in a horizontal butt joint. The bead arrangement of the I groove was optimized to produce a high-quality connection with the upper sidewall of the joint. The microstructure and mechanical properties were observed and evaluated by optical microscopy, scanning electron microscopy, tensile testing, and micro-hardness and impact toughness testing at 1/5, 2/5, 3/5, and 4/5 thickness of the joint. The 3/5 T position exhibited the highest strength, which was attributed to the presence of finer carbide precipitates. The highest micro-hardness appeared at 4/5 T. The highest impact toughness appeared at 3/5 T. The formation of coarse granular bainite was the major reason for the decrease in impact toughness in other regions. A microscopic fracture at 1/5 T and 3/5 T was further analyzed. It was observed that the width of the fibrous zone at 3/5 T was significantly larger than that at 1/5 T. The radial zones at 1/5 T were observed to exhibit cleavage, with secondary cracks on the fracture surface. Full article

Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in the regulation of apoptosis. More recent studies showed that survivin is a component of the chromosome passenger complex and acts as an essential mediator of mitotic progression. Other potential functions of survivin, such as mitochondrial function and autophagy, have also been proposed. Survivin has emerged as an attractive target for cancer therapy because its overexpression has been found in most human cancers and is frequently associated with chemotherapy resistance, recurrence, and poor survival rates in cancer patients. In this review, we discuss our current understanding of how survivin mediates various aspects of malignant transformation and drug resistance, as well as the efforts that have been made to develop therapeutics targeting survivin for the treatment of cancer. Full article

Fetal organs and organoids are important tools for studying organ development. Recently, porcine organs have garnered attention as potential organs for xenotransplantation because of their high degree of similarity to human organs. However, to meet the prompt demand for porcine fetal organs by patients and researchers, effective methods for producing, retrieving, and cryopreserving pig fetuses are indispensable. Therefore, in this study, to collect fetuses for kidney extraction, we employed cesarean sections to preserve the survival and fertility of the mother pig and a method for storing fetal kidneys by long-term cryopreservation. Subsequently, we evaluated the utility of these two methods. We confirmed that the kidneys of pig fetuses retrieved by cesarean section that were cryopreserved for an extended period could resume renal growth when grafted into mice and were capable of forming renal organoids. These results demonstrate the usefulness of long-term cryopreserved fetal pig organs and strongly suggest the effectiveness of our comprehensive system of pig fetus retrieval and fetal organ preservation, thereby highlighting its potential as an accelerator of xenotransplantation research and clinical innovation. Full article

Unhealthy lifestyles among adolescents are reaching alarming levels and have become a major public health problem. This study aimed to assess the relationship between sleep time, physical activity (PA) time, screen time (ST), and nutritional literacy (NL). Methods: This cross-sectional online study involving adolescents aged 10–18 years was conducted in September 2020 in 239 schools in Chongqing, China. NL was measured using the “Nutrition Literacy Scale for middle school students in Chongqing (CM-NLS)”. According to the recommended by the Chinese dietary guidelines (2022), we divided the sleep time of junior high school students into <9 h and ≥9 h, high school students into <8 h and ≥8 h, divided the workdays into weekend PA time < 1 h and ≥1 h, and divided the workdays into weekend ST < 2 h and ≥2 h. The multinomial logistic regression model was used to examine the association. Results: A total of 18,660 adolescents (50.2% males) were included. The proportion of participants that were junior high school students and attended boarding schools was 57.2% and 65.3%, respectively. Compared with senior high school students, junior high school students had a higher level of NL. Whether on workdays or weekends, participants with sleep time ≥ 8/9 h, PA time ≥ 1 h, and ST < 2 h per day had higher levels of NL. On weekdays, participants who met the sleep time ≥ 8 h/9 h (OR = 1.48, 95% CI: 1.36, 1.62) and PA time ≥ 1 h (OR = 1.69, 95% CI: 1.59, 1.81) had higher reporting of NL levels. Conclusions: Sleep time, PA time, and ST were positively correlated with NL among adolescents, especially junior high school students. Full article

The intensity of the odor in food-grade paraffin waxes is a pivotal quality characteristic, with odor panel ratings currently serving as the primary criterion for its assessment. This study presents an innovative method for assessing odor intensity in food-grade paraffin waxes, employing headspace gas chromatography with mass spectrometry (HS/GC-MS) and integrating total ion spectra with advanced machine learning (ML) algorithms for enhanced detection and quantification. Optimization was conducted using Box–Behnken design and response surface methodology, ensuring precision with coefficients of variance below 9%. Analytical techniques, including hierarchical cluster analysis (HCA) and principal component analysis (PCA), efficiently categorized samples by odor intensity. The Gaussian support vector machine (SVM), random forest, partial least squares regression, and support vector regression (SVR) algorithms were evaluated for their efficacy in odor grade classification and quantification. Gaussian SVM emerged as superior in classification tasks, achieving 100% accuracy, while Gaussian SVR excelled in quantifying odor levels, with a coefficient of determination (R²) of 0.9667 and a root mean square error (RMSE) of 6.789. This approach offers a fast, reliable, robust, objective, and reproducible alternative to the current ASTM sensory panel assessments, leveraging the analytical capabilities of HS-GC/MS and the predictive power of ML for quality control in the petrochemical sector’s food-grade paraffin waxes. Full article

FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin. Full article

While FXR has shown promise in regulating bile acid synthesis and maintaining glucose and lipid homeostasis, undesired side effects have been observed in clinical trials. To address this issue, the development of intestinally restricted FXR modulators has gained attention as a new avenue for drug design with the potential for safer systematic effects. Our review examines all currently known intestinally restricted FXR ligands and provides insights into the steps taken to enhance intestinal selectivity. Full article

Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis. Given that LIN28B acts by negatively regulating the biogenesis of the tumor suppressor let-7 miRNAs, we reasoned that selective interference with the LIN28B/let-7 miRNA interaction would increase let-7 miRNA levels, ultimately leading to reduced NB aggressiveness. Here, we selected (−)-epigallocatechin 3-gallate (EGCG) out of 4959 molecules screened as the molecule with the best inhibitory activity on LIN28B/let-7 miRNA interaction and showed that treatment with PLC/PLGA-PEG nanoparticles containing EGCG (EGCG-NPs) led to an increase in mature let-7 miRNAs and a consequent inhibition of NB cell growth. In addition, EGCG-NP pretreatment reduced the tumorigenic potential of NB cells in vivo. These experiments suggest that the LIN28B/let-7 miRNA axis is a good therapeutic target in NB and that EGCG, which can interfere with this interaction, deserves further preclinical evaluation. Full article

The orphan nuclear receptor ERRα is the most extensively researched member of the estrogen-related receptor family and holds a pivotal role in various functions associated with energy metabolism, especially in tissues characterized by high energy requirements, such as the heart, skeletal muscle, adipose tissue, kidney, and brain. Abscisic acid (ABA), traditionally acknowledged as a plant stress hormone, is detected and actively functions in organisms beyond the land plant kingdom, encompassing cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. Its ancient, cross-kingdom role enables ABA and its signaling pathway to regulate cell responses to environmental stimuli in various organisms, such as marine sponges, higher plants, and humans. Recent advancements in understanding the physiological function of ABA and its mammalian receptors in governing energy metabolism and mitochondrial function in myocytes, adipocytes, and neuronal cells suggest potential therapeutic applications for ABA in pre-diabetes, diabetes, and cardio-/neuroprotection. The ABA/LANCL1-2 hormone/receptor system emerges as a novel regulator of ERRα expression levels and transcriptional activity, mediated through the AMPK/SIRT1/PGC-1α axis. There exists a reciprocal feed-forward transcriptional relationship between the LANCL proteins and transcriptional coactivators ERRα/PGC-1α, which may be leveraged using natural or synthetic LANCL agonists to enhance mitochondrial function across various clinical contexts. Full article

TDs appear more often in patients with higher TB grades in stage III CRC. A higher TB grade and a growing number of TDs were statistically significantly associated with shorter overall survival. These results could give additional emphasis to the importance of TB as an adverse prognostic factor since a strong relationship with TDs has been demonstrated. Full article

Introduction: Although gifted children can express high cognitive skills, they can also show socioemotional difficulties. Drawing from Olson’s circumplex model, the present paper assessed the role of family functioning in internalizing and externalizing problems in gifted children. Materials and Methods: 362 mothers and their 362 gifted children were included. The unbalanced subscales of the FACES IV—disengagement, enmeshment, rigidity, and chaos—and the CBCL were administered to mothers. The children completed the WISC-IV. Results: The model predicting internalizing problems was significant and explained 5.6% of the variance. Only rigidity had an independent and positive effect on internalizing problems in gifted children over and above sociodemographic variables and QI, whereas disengagement, enmeshment, and chaos were not associated with internalizing problems. The model predicting externalizing problems was significant and explained 10% of the variance. Again, rigidity was the only variable that had an independent and positive effect on externalizing problems in gifted children over and above sociodemographic variables and QI, whereas disengagement, enmeshment, and chaos were not associated with externalizing problems in this population. Discussion: Rigid families with a low ability to change in conditions that require readjustment appear to increase the risk of both internalizing and externalizing problems in gifted children. Although further studies are needed to support these preliminary findings, parental support interventions aimed at increasing flexibility appear to be useful. Full article