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We provide a concurrent measurement of the hydrogen and oxygen nuclear kinetic energies in the water molecule across melting at 270 K in the solid phase and 276 K in the liquid phase. Experimental values are obtained by analyzing the neutron Compton profiles of each atomic species in a deep inelastic neutron scattering experiment. The concurrent measurement of the atom kinetic energy of both hydrogen and oxygen allows the estimate of the total kinetic energy per molecule due to the motion of nuclei, specifically 35.3 ± 0.8 and 34.8 ± 0.8 kJ/mol for the solid and liquid phases, respectively. Such a small difference supports results from ab initio simulations and phenomenological models from the literature on the mechanism of competing quantum effects across the phase change. Despite the experimental uncertainties, the results are consistent with the trend from state-of-the-art computer simulations, whereby the atom and molecule kinetic energies in the liquid phase would be slightly lower than in the solid phase. Moreover, the small change of nuclear kinetic energy across melting can be used to simplify the calculation of neutron-related environmental dose in complex locations, such as high altitude or polar neutron radiation research stations where liquid water and ice are both present: for neutron energies between hundreds of meV and tens of keV, the total scattering cross section per molecule in the two phases can be considered the same, with the macroscopic cross section only depending upon the density changes of water near the melting point. [ABSTRACT FROM AUTHOR]

In this study, first-order necessary optimality conditions, in the form of a weak maximum principle, are derived for discrete optimal control problems with mixed equality and inequality constraints. Such conditions are achieved by using the Dubovitskii–Milyutin formalism approach. Nondegenerate conditions are obtained under the constant rank of the subspace component (CRSC) constraint qualification, which is an important generalization of both the Mangasarian–Fromovitz and constant rank constraint qualifications. Beyond its theoretical significance, CRSC has practical importance because it is closely related to the formulation of optimization algorithms. In addition, an instance of a discrete optimal control problem is presented in which CRSC holds while other stronger regularity conditions do not. [ABSTRACT FROM AUTHOR]

Introduction: Immunoglobulins (Ig) reactive with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are present in humans and were previously associated with eating disorders. In this longitudinal study involving patients with anorexia nervosa (AN), we determined whether α-MSH in serum is bound to IgG and analyzed long-term dynamics of both α-MSH peptide and α-MSH-reactive Ig in relation to changes in BMI and gut microbiota composition. Methods: The study included 64 adolescents with a restrictive form of AN, whose serum samples were collected at hospital admission, discharge, and during a 1-year follow-up visit and 41 healthy controls, all females. Results: We found that in both study groups, approximately 40% of serum α-MSH was reversibly bound to IgG and that levels of α-MSH-reactive IgG but not of α-MSH peptide in patients with AN were low at hospital admission but recovered 1 year later. Total IgG levels were also low at admission. Moreover, BMI-standard deviation score correlated positively with α-MSH IgG in both groups studied but negatively with α-MSH peptide only in controls. Significant correlations between the abundance of specific bacterial taxa in the gut microbiota and α-MSH peptide and IgG levels were found in both study groups, but they were more frequent in controls. Conclusion: We conclude that IgG in the blood plays a role as an α-MSH-binding protein, whose characteristics are associated with BMI in both patients with AN and controls. Furthermore, the study suggests that low production of α-MSH-reactive IgG during the starvation phase in patients with AN may be related to altered gut microbiota composition. [ABSTRACT FROM AUTHOR]

This research focused on the synthesis of biphasic titania nanowires from commercially available anatase titania via hydrothermal method to improve its antimicrobial activity. The electron microscope scanning (SEM) showed that the titania nanowires structures were successfully synthesized with width varying from 17 to 96 nm and length from 0.7 to 8 μm. The titania nanowires have biphasic structure of brookite and anatase, as observed from the X-ray diffraction pattern. The band gap was calculated from the ultraviolet–visible diffuse reflectance spectroscopy (UV–Vis DRS) spectra at 3.3eV, which is between the range of pure anatase and pure brookite band gap. The crystallite size of the titania nanowires was calculated using the Scherer equation and showed a much smaller crystallite size compared to commercial titania. The antimicrobial activity of the titania nanowires was then investigated against gram-negative and gram-positive bacteria. They exhibited improved antimicrobial activity against the Gram-negative Pseudomonas aeruginosa and Escherichia coli along with Gram-positive Bacillus subtilis. Interestingly, their inhibition zone was comparable to the antibiotic tetracycline. Meanwhile, the commercial titania did not show any antimicrobial activity on any tested bacterial strains. The improved antimicrobial activity of the titania nanowires was attributed to its biphasic phase, small particle size, and its one-dimensional morphology. [ABSTRACT FROM AUTHOR]

Several efforts have been extensively accomplished for the amelioration of the cancer treatments using different types of new drugs and less invasives therapies in comparison with the traditional therapeutic modalities, which are widely associated with numerous drawbacks, such as drug resistance, non-selectivity and high costs, restraining their clinical response. The application of natural compounds for the prevention and treatment of different cancer cells has attracted significant attention from the pharmaceuticals and scientific communities over the past decades. Although the use of nanotechnology in cancer therapy is still in the preliminary stages, the application of nanotherapeutics has demonstrated to decrease the various limitations related to the use of natural compounds, such as physical/chemical instability, poor aqueous solubility, and low bioavailability. Despite the nanotechnology has emerged as a promise to improve the bioavailability of the natural compounds, there are still limited clinical trials performed for their application with various challenges required for the pre-clinical and clinical trials, such as production at an industrial level, assurance of nanotherapeutics long-term stability, physiological barriers and safety and regulatory issues. This review highlights the most recent advances in the nanocarriers for natural compounds secreted from plants, bacteria, fungi, and marine organisms, as well as their role on cell signaling pathways for anticancer treatments. Additionally, the clinical status and the main challenges regarding the natural compounds loaded in nanocarriers for clinical applications were also discussed. [ABSTRACT FROM AUTHOR]

Objective: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression. Methods: In a preclinical study, we explored whether AN‐derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase‐cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety‐like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests. Results: Neither antibiotic‐induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose‐stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients. Discussion: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic‐induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies. Public Significance: While our study did not reveal direct impacts of AN‐associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic‐induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa. [ABSTRACT FROM AUTHOR]

Introduction: Catheter-related infections (CBRSIs) are a widespread problem that increase morbidity and mortality in intensive care unit (ICU) patients and management costs. Objective: The main aim of this study was to assess the prevalence of CBRSIs in an intensive care unit following international literature guidelines for managing vascular lines in critically ill patients. These guidelines include changing vascular lines every 7 days, using needle-free devices and port protectors, standardising closed infusion lines, employing chlorhexidine-impregnated dressings, and utilising sutureless devices for catheter securement. Materials and Methods: This single-centre retrospective observational study was conducted in a general Italian ICU. This study included all eligible patients aged > 1 year who were admitted between January 2018 and December 2022. Results: During the study period, 1240 patients were enrolled, of whom 9 were diagnosed with a CRBSI. The infection rate per 1000 catheters/day was as follows: femorally inserted central catheter, 1.04; centrally inserted central catheter, 0.77; pulmonary arterial catheter 0.71, arterial catheter, 0.1; and peripherally inserted central catheter and continuous veno-venous haemodialysis dialysis catheters equal to 0. No difference in CRBSI was observed between the years included in the study (p = 0.874). The multivariate analysis showed an association between the diagnosis of CBRSI and Nursing Activities Score (per single point increase β = 0.04–95%CI: −0.01–0.09, p = 0.048), reason for ICU admission—trauma (β = 0.77–95%CI: −0.03–1.49, p = 0.039), and use of therapeutic hypothermia (β = 2.06, 95%CI: 0.51–3.20, p < 0.001). Implementing the study protocol revealed a cost of EUR 130.00/patient, equivalent to a daily cost of EUR 15.20 per patient. Conclusions: This study highlights the importance of implementing a catheter care bundle to minimise the risk of CRBSI and the associated costs in the ICU setting. A policy change for infusion set replacement every 7 days has helped to maintain the CRBSI rate below the recommended rate, resulting in significant cost reduction and reduced production of ICU waste [ABSTRACT FROM AUTHOR]

In the present work, the use of enzymatic hydrolysis to obtain cellulose nanofibers composed of purified cellulose from sugarcane bagasse (SCB) and oil palm empty fruit bunches (OPEFBs) was addressed. First, the cellulose was purified by applying hydrothermal treatments conducted at various temperatures (180 and 200 °C) and times (10, 20 and 30 min) and then 2% (m/v) sodium chlorite treatment. Then, enzymatic hydrolysis was conducted for 24, 48 or 72 h using cellulase from Trichoderma reesei at 50 °C and pH = 5.0 to isolate the cellulose nanofibers. The composition, morphology, crystallinity, thermal stability and zeta potential characteristics were evaluated for each cellulosic material. The crystallinity index increased significantly after hydrothermal pretreatment and bleaching from 42.6% to 87.3% and from 42.5% to 86.1% for SCB and OPEFB, respectively. In addition, the obtained pulps showed better thermal stability than residues when used as feedstock. Enzymatic hydrolysis was effective at extracting cellulose nanofibers, as long as the reaction time was controlled to less than 48 h, to avoid compromising the crystallinity and thermal stability of the isolated nanostructures. The enzymatic pathway is a promising alternative to the use of acid catalysts. [ABSTRACT FROM AUTHOR]

Lung cancer is a leading cause of cancer-related death worldwide that needs updated therapies to contrast both the serious side effects and the occurrence of drug resistance. A panel of non-small cell lung cancer (NSCLC) cells were herein employed as cancer models. Eight structurally related gold(I) and gold(III) complexes with NHC and halides or triphenylphosphane ligands were investigated as lung cancer cell growth inhibitors. As expected, gold compounds with PPh3 were found to be more cytotoxic than homoleptic [(NHC)2-Au(I)]X or heteroleptic NHC-Au(I)X or NHC-Au(III)X3 complexes. Mixed ligand gold(I) compounds exhibiting the linear NHC-AuPPh3 (compound 7) or the trigonal NHC-Au(Cl)PPh3 (compound 8) arrangements at the central metal were found to be the best lung cancer cytotoxic compounds. Analysis of the TrxR residual activity of the treated cells revealed that these compounds efficiently inhibit the most accredited molecular target for gold compounds, the TrxR, with compound 8 reaching more than 80% activity reduction in lung cells. Some of the current cancer lung therapy protocols consist of specific lung cancer cell cytotoxic agents combined with antifolate drugs; interestingly, the herein gold compounds are both TrxR and antifolate inhibitors. The human DHFR was inhibited with IC50 ranging between 10–21 µM, depending on substrate concentrations, proceeding by a likely allosteric mechanism only for compound 8. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells play an important role in the surveillance of viral infections and cancer. NK cell antibody-dependent cellular cytotoxicity (ADCC) and direct cytotoxicity are mediated by the recognition of antibody-coated target cells through the Fc gamma receptor IIIA (FcγRIIIa/CD16) and by ligands of activating/inhibitory NK receptors, respectively. Allelic variants of the FCGR3A gene include the high-affinity single-nucleotide polymorphism (SNP) rs396991 (V176F), which is associated with the efficacy of monoclonal antibody (mAb) therapies, and the SNP rs10127939 (L66H/R). The contribution of FCGR3A SNPs to NK cell effector functions remains controversial; therefore, we generated a panel of eight NK-92 cell lines expressing specific combinations of these SNPs and tested their cytotoxicities. NK-92 cells were stably transfected with plasmids containing different combinations of FCGR3A SNPs. Messenger RNA and FcγRIIIa/CD16 cell surface expressions were detected using new generation sequencing (NGS) and flow cytometry, respectively. All FcγRIIIa/CD16-transfected NK-92 cell lines exhibited robust ADCC against three different target cell lines with minor differences. In addition, enhanced direct NK cytotoxicity against K562 target cells was observed, suggesting a mechanistic role of FcγRIIIa/CD16 in direct NK cytotoxicity. In conclusion, we generated eight FcγRIIIa/CD16-transfected NK-92 cell lines carrying different combinations of two of the most studied FCGR3A SNPs, representing the major genotypes described in the European population. The functional characterization of these cell lines revealed differences in ADCC and direct NK cytotoxicity that may have implications for the design of adoptive cancer immunotherapies using NK cells and tumor antigen-directed mAbs. [ABSTRACT FROM AUTHOR]

Myxoid liposarcomas are malignant soft-tissue sarcomas whose treatment represents a challenge, even for the most experienced surgeon. In this study, we report on our experience with the treatment of myxoid liposarcomas of the thigh. Our retrospective analysis included myxoid liposarcomas of the thigh treated with surgical resection between 2016 and 2022. Resection margins, complications, local recurrences, and metastases were recorded. The oncological outcome of each case was evaluated at their latest follow-up. Adjuvant therapies were administered according to the ESMO guidelines. Functionality was assessed with the MSTS score before surgery and at the patients' latest follow-up. Thirty cases (ten high-grade and 20 low-grade) were included. The mean diameter was 11.8 cm. Twenty-four cases had wide margins (80%) and six (20%) were marginal. Five cases (60% marginal) had local recurrences (17%). Marginal resection was associated with a higher risk of local recurrence (p = 0.041). Three cases with high-grade tumors (10%) developed metastases. At the patients' latest follow-up, their mean MSTS score had risen from 22.9 to 27.3. While tumor grade influences the risk of metastases, the quality of resection margins can determine the local recurrence rate. An adequate surgery can lead to good post-operative functional outcomes. [ABSTRACT FROM AUTHOR]

Despite the great diversity of Brazilian anuran species, there are still many knowledge gaps about the acoustic communication of these animals. Among the species, those classified as 'Data Deficient' have the greatest gaps in knowledge on their behavior. This is the case of Boana ericae, a species belonging to the Boana pulchella group, endemic to the Chapada dos Veadeiros National Park region, in the northeast of the state of Goiás, Central Brazil. Three distinct call types (A, B, and C) are currently known for B. ericae, with the type A call associated with attracting reproductive partners and the type C call presenting a territorial function. We recorded the vocalizations of 10 individuals of this species and found the presence of vocalizations composing three new note types (D, E, and F). Our results indicate that air temperature and body condition influenced the acoustic parameters of the advertisement and aggressive calls of this species. We also observed that some acoustic parameters of the advertisement calls can be used for individual recognition for showing greater variation among individuals than intra-individually. Our results add new information regarding the vocal repertoire in this species, expanding their known intra-individual classification of the acoustic parameters. [ABSTRACT FROM AUTHOR]

Brewer's spent grain (BSG) was used as a sustainable and healthy ingredient in two cereal bar formulations, with honey (H) and chocolate (C) used as the binding systems' characterizing ingredients. The two bars, formulated using three levels of BSG (H1: 8.5%; H2: 12.7%; H3: 21.2%; C1: 3.9%; C2: 7.7%; C3: 15.5%) and stored for 20 days, were studied from a physicochemical perspective and compared to non-enriched control bars. The analysis showed that BSG enriched the bars with minerals, B vitamins, proteins, and fibers, meeting the required contents for the "high fiber" nutritional claim. Moisture content and water activity decreased with increasing BSG quantity and storage time. Higher BSG content increased flexibility in H bars after 7 days, while decreasing water content and increasing hardness in C bars at 1 storage day. Higher BSG levels darkened the samples' color with little change during storage. In addition, a consumer sensory test was conducted. The results showed that providing information on BSG had little impact on liking, purchase intent, and sensory perception. In addition, under blind conditions, H bars were considered more natural and healthier than the C bars; however, these differences were not significant in the informed conditions. This study shows the potential use of upcycled ingredients in cereal bars and highlights the central role of the sensory experience on consumer appreciation, considering also information provision. [ABSTRACT FROM AUTHOR]

Simple Summary: Honeybees are vital pollinators, essential for maintaining ecosystems and biodiversity, but there is rising concern about the health of managed honey bee colonies, especially in heavily human-influenced ecosystems. Multiple factors contribute to this decline, including environmental conditions, forage quality, and pesticide use. These elements have a complex effect on the health and nutritional status of honeybee colonies and influence their response to disease and various stressors. In this study, the authors propose a new approach to assess colony health by correlating common measures of colony strength such as honey and pollen reserves, the number of bees, and brood with hemolymph proteins, common bee pathogens (Varroa destructor and Nosema spp.), and essential trace elements (iron, zinc, and copper). Significant correlations were found between hemolymph proteins and colony performance measures, and between V. destructor and hemolymph proteins and iron content. In conclusion, this study confirms the need for a more holistic approach to honeybee health considering all the relevant aspects and critical points that may affect colony survival. Environment, forage quality, management practices, pathogens, and pesticides influence honeybee responses to stressors. This study proposes an innovative approach to assess colony health and performance using molecular diagnostic tools by correlating hemolymph proteins with common measures of colony strength, prevalent honeybee pathogens (Varroa destructor and Nosema spp.), and essential trace elements (iron, zinc and copper). Colonies were selected from four apiaries located in different environmental and foraging conditions in the province of Bologna (Italy). Hemolymph samples were taken from June to October 2019. The Varroa infestation of the colonies was estimated by assessing the natural mortality of the mites, while the bees were tested for Nosema spp. spores using a microscopic method. Hemolymph proteins were quantified and separated using SDS-PAGE, and colony performance was assessed by determining adult bees, total brood, honey, and pollen reserves. The biomarkers measured proved to be useful for monitoring changes in performance and trophic conditions during summer and early autumn. Significant correlations were found between hemolymph proteins and colony performance measures. A positive correlation between pollen reserves, vitellogenin, and hexamerin 70a highlights the importance of these proteins for successful overwintering. In October, Varroa infestation was negatively correlated with total proteins, vitellogenin, apolipophorin II, transferrin, and hexamerin 70a, with negative implications for overwintering; furthermore, Varroa infestation was also negatively correlated with iron content, potentially affecting iron homeostasis. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP), although a rare disease, is the most frequent subepidermal autoimmune disorder. Treatment with gliptins, used for type 2 diabetes, was reported as associated with BP onset. To identify HLA alleles that may reflect a higher susceptibility to BP in the Italian population, we analysed 30 patients affected by idiopathic bullous pemphigoid (IBP) and 86 gliptin‐associated BP (GABP) patients. A significant association between HLA‐DQB1*03:01 allele and IBP and GABP patients was found. Of note, both IBP and GABP were significantly associated with one of the following haplotypes: DRB1*11:01, DRB3*02:02, DQA1*05:05, DQB1*03:01 or DRB1*11:04, DRB3*02:02, DQA1*05:05 and DQB1*03:01. These data identify, for the first time, potential markers of susceptibility to BP in the Italian population, especially when associated with gliptin intake. [ABSTRACT FROM AUTHOR]

Dense arrangements of binding sites within nucleotide sequences can collectively influence downstream transcription rates or initiate biomolecular interactions. For example, natural promoter regions can harbor many overlapping transcription factor binding sites that influence the rate of transcription initiation. Despite the prevalence of overlapping binding sites in nature, rapid design of nucleotide sequences with many overlapping sites remains a challenge. Here, we show that this is an NP-hard problem, coined here as the nucleotide String Packing Problem (SPP). We then introduce a computational technique that efficiently assembles sets of DNA-protein binding sites into dense, contiguous stretches of double-stranded DNA. For the efficient design of nucleotide sequences spanning hundreds of base pairs, we reduce the SPP to an Orienteering Problem with integer distances, and then leverage modern integer linear programming solvers. Our method optimally packs sets of 20–100 binding sites into dense nucleotide arrays of 50–300 base pairs in 0.05–10 seconds. Unlike approximation algorithms or meta-heuristics, our approach finds provably optimal solutions. We demonstrate how our method can generate large sets of diverse sequences suitable for library generation, where the frequency of binding site usage across the returned sequences can be controlled by modulating the objective function. As an example, we then show how adding additional constraints, like the inclusion of sequence elements with fixed positions, allows for the design of bacterial promoters. The nucleotide string packing approach we present can accelerate the design of sequences with complex DNA-protein interactions. When used in combination with synthesis and high-throughput screening, this design strategy could help interrogate how complex binding site arrangements impact either gene expression or biomolecular mechanisms in varied cellular contexts. Author summary: The way protein binding sites are arranged on DNA can influence the regulation and transcription of downstream genes. Areas with a high concentration of binding sites can enable complex interplay between transcription factors, a feature that is exploited by natural promoters. However, designing synthetic promoters that contain dense arrangements of binding sites is a challenge. The task involves overlapping many binding sites, each typically about 10 nucleotides long, within a constrained sequence area, which becomes increasingly difficult as sequence length decreases and binding site variety increases. We introduce an approach to design nucleotide sequences with optimally packed protein binding sites, which we call the nucleotide String Packing Problem (SPP). We show that the SPP can be solved efficiently using integer linear programming to identify the densest arrangements of binding sites for a specified sequence length. We show how adding additional constraints, like the inclusion of sequence elements with fixed positions, allows for the design of bacterial promoters. The presented approach enables the rapid design and study of nucleotide sequences with complex, dense binding site architectures. [ABSTRACT FROM AUTHOR]

The consumption of whole grains has several health benefits, however, most US consumers - including young adults - do not meet the recommended consumption intake. To understand the underlying factors affecting the intention and consumption of whole grain pasta, a survey based on the Theory of Planned Behavior (TPB) was developed and administered to US college students. For four weeks, participants (n = 325) either did not receive any information (control) or received weekly messages on the health benefits of whole grain pasta (e.g., high fiber and niacin contents) in the forms of gain- (treatment 1) or loss-framed (treatment 2) information. Variables of the TPB model and consumers' perceptions were investigated both at Time 1, when the first message was received (week 0), and at Time 2, one month after the intervention (week 4). Results from the two moments were compared. We found that the TPB measures and perceived usefulness were not influenced by the treatment group; however, the gain-framed message engendered greater message engagement than the loss-framed one. Finally, results from the structural equation model showed that attitude, subjective norms, and perceived behavioral control were positively associated with the intention to consume whole grain pasta, and the intention was a strong determinant of participants' behavior. Based on our results, implications and suggestions for future studies are discussed. [ABSTRACT FROM AUTHOR]

The self-splicing group II introns are bacterial and organellar ancestors of the nuclear spliceosome and retro-transposable elements of pharmacological and biotechnological importance. Integrating enzymatic, crystallographic, and simulation studies, we demonstrate how these introns recognize small molecules through their conserved active site. These RNA-binding small molecules selectively inhibit the two steps of splicing by adopting distinctive poses at different stages of catalysis, and by preventing crucial active site conformational changes that are essential for splicing progression. Our data exemplify the enormous power of RNA binders to mechanistically probe vital cellular pathways. Most importantly, by proving that the evolutionarily-conserved RNA core of splicing machines can recognize small molecules specifically, our work provides a solid basis for the rational design of splicing modulators not only against bacterial and organellar introns, but also against the human spliceosome, which is a validated drug target for the treatment of congenital diseases and cancers. Splicing is a vital biological reaction and a druggable pathway to treat infection, genetic diseases and cancer. Here, the authors describe how splicing is modulated by small molecules that target the conserved splicing active site in the group II introns. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum cytokine levels are altered in individuals with AN. Previous research has largely focused on adult patients, assuming a low-grade pro-inflammatory state. The serum levels of the cytokine tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and IL-15, which are pro-inflammatory, were examined in 63 female adolescents with AN and 41 age-matched healthy controls (HC). We included three time points (admission, discharge, and 1-year follow-up) and investigated the clinical data to assess whether the gut microbiota was associated with cytokine alterations. Relative to the HC group, serum levels of IL-1β and IL-6 were significantly lower during the acute phase (admission) of AN. IL-1β expression was normalised to control levels after weight recovery. TNF-α levels were not significantly different between the AN and HC groups. IL-15 levels were significantly elevated in patients with AN at all time points. We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome. In contrast to most findings for adults, we observed lower levels of the pro-inflammatory cytokines IL-1β and IL-6 in adolescent patients, whereas the level of IL-15 was consistently increased. Thus, the presence of inflammatory dysregulation suggests a varied rather than uniform pro-inflammatory state. [ABSTRACT FROM AUTHOR]

Objectives: The management of idiopathic subglottic stenosis (iSGS) poses a clinical challenge due to high recurrence rates following both endoscopic and open approaches, often leading to tracheostomy. The activation of abnormal T-cells and cytokine pathways has been linked to iSGS pathogenesis. Autologous adipose tissue centrifugation yields lipoaspirate, offering optimal anti-inflammatory effects and biocompatibility widely utilized in various medical settings. This report presents the first 3 cases employing endoscopic dilation (ED) in combination with local lipoaspirate injection to address recurrent iSGS. Methods: A prospective observational study was conducted, involving multidisciplinary evaluation by the Tracheal Team at the University of Modena. Patients meeting specific criteria were directed to undergo ED + lipoaspirate injection. Results: Three patients fulfilled the inclusion criteria. The mean number of prior endoscopic procedures performed was 8. Endoscopic examination revealed 90% stenosis in patient A, 60% stenosis in patient B, and 60% stenosis in patient C. All patients presented inflammatory tissue or incipient granulations at the stenotic site, with an average time of 6 months between previous procedures. After 15 months, none of the patients required further procedures, and endoscopic examination revealed a significant reduction or disappearance of inflammatory tissue with a stable airway lumen. Conclusions: The observed results are encouraging in terms of reducing local inflammation and halting stenosis progression, especially in cases of short-term relapsing iSGS. [ABSTRACT FROM AUTHOR]

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We present an experimental investigation of methylammonium lead tribromide single crystals in the orthorhombic, tetragonal, and cubic phases based on inelastic and deep inelastic neutron scattering experiments. We show how the average hydrogen nuclear kinetic energy, mainly affected by zero-point vibrational energies, shows differences larger compared to the changes simply related to temperature effects when moving from one phase to another. In particular, the Gaussian contribution to the average nuclear kinetic energy is larger in the tetragonal phase compared to the cubic and orthorhombic ones. Moreover, we find that the vibrational densities of states of MAPbBr3 single crystals in the orthorhombic phase are compatible with previously reported results on powder samples, and that the only vibrational modes that show slightly different frequencies compared to MAPbI3 are those in the energy range between 100 and 300 cm−1, related to librational/rotational modes. As these shifts are of about 10 cm−1 and do not affect any higher-energy vibrational mode, we conclude that the zero-point energies and average nuclear kinetic energies in the two-hybrid organic/inorganic perovskites are expected to be approximately the same within a harmonic framework. [ABSTRACT FROM AUTHOR]

Background: Promoting healthy and sustainable diets is increasingly important and the Mediterranean Diet (MD) has been recognized as an appropriate example that can be adapted to different countries. Considering that the college years are the time when US young adults are most likely to adopt unhealthy eating habits, the present study assessed adherence to the MD and the sustainability of dietary behaviors in a nationally representative sample of US university students, aiming to identify crucial levers for improving their eating behaviors. Methods: MD adherence and the adoption of healthy and sustainable dietary patterns were assessed through the KIDMED and the Sustainable-HEalthy-Diet (SHED Index questionnaires, respectively, administered through an online survey that also included sociodemographic and behavioral questions. Non-parametric and logistic regression analyses were performed. Results: A sample of 1485 participants (median (IQR) age 21.0 (19.0–22.0); 59% women) correctly completed the survey. A medium adherence to the MD was the most prevalent (47%). According to multivariate logistic regression analysis, the likelihood of being more compliant with the MD increased when meeting physical activity recommendations, having a high SHED Index score, having the willingness to purchase and eat healthy and sustainable dishes, eating ultra-processed plant-based meat alternatives foods daily, and regularly attending the university canteen. Conclusions: Encouraging dietary patterns rich in plant-based foods and with a moderate intake of animal products is crucial to increasing the adoption of healthy and sustainable diets, and university dining services represent a suitable setting to build a supportive environment that educates students on human and planetary health. [ABSTRACT FROM AUTHOR]

In an attempt to generalise knot matrix models for non-torus knots, which currently remains an open problem, we derived expressions for the Harer–Zagier transform—a discrete Laplace transform—of the HOMFLY–PT polynomial for some infinite families of twisted hyperbolic knots. Among them, we found a family of pretzel knots for which, like for torus knots, the transform has a fully factorised form, while for the remaining families considered it consists of sums of factorised terms. Their zero loci show a remarkable structure, which mostly lies on the unit circle and deviates from it only in pairs. [ABSTRACT FROM AUTHOR]

This work reports on the design and synthesis of an angiotensin-converting enzyme 2 (ACE-2) functionalized magnetic fluorescent silica nanoparticles (Fe-FSNP) as a biosensing platform to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen. Iron oxide (Fe3O4) nanoparticles were synthesized via ultrasonic-assisted coprecipitation and then coated with fluorescent silica nanoparticles (FSNP) through the sol–gel method forming the Fe-FSNP samples. Silica obtained from local geothermal powerplant was used in this work and Rhodamine B was chosen as the incorporated fluorescent dye, hence this reports for the first time ACE-2 was immobilized on the natural silica surface. The Fe-FSNP nanoparticle consists of a 18–25 nm magnetic core and a silica shell with a thickness of 30 nm as confirmed from the transmission electron microscopy image. Successful surface functionalization of the Fe-FSNP with ACE-2 as bioreceptor was conducted through hydrosylilation reaction and confirmed through the Fourier transform infrared spectroscopy. The detection of SARS-Cov-2 antigen by Fe-FSNP/ACE2 was measured through the change in its maximum fluorescence intensity at 588 nm where fluorescence- quenching had occurred. The biosensing platform showed a rapid response at 30 min with a linear range of 10–6 to 10−2 μ g ml–1. The magnetic-fluorescent properties of the nanoparticle enables an ultra-sensitive detection of SARS-Cov-2 antigen with the limit of detection as low as 2 fg ml–1. [ABSTRACT FROM AUTHOR]

The search for hereditary bleeding disorders (HBD) prior to invasive procedures in children is primarily based on personal and family bleeding history. Although several scores are available, they have only been evaluated in specific situations or in adults. Our monocentric retrospective study aimed to analyze the association between clinical history and four scores (HEMSTOP, PBQ, ISTH-BAT, TOSETTO) and the diagnosis of MHC in children referred to the University Hospital of Montpellier for hemostasis investigations. A total of 117 children were retrospectively included in the study. Of these, 57 (49%) were diagnosed with HBD, with 30 having primary bleeding disorders and 27 having coagulation disorders. The diagnosis of HBD was significantly associated with gingival bleeding, which was present in 30% of HBD patients. In our population, only the HEMSTOP score showed an association with the diagnosis of HBD, but it was positive in only 48% of patients. By including gingival bleeding as a factor, we modified the HEMSTOP score, which increased its sensitivity from 0.45 to 0.53. When examining primary bleeding disorders, the modified HEMSTOP score, with the inclusion of gingival bleeding, enables us to diagnose 63% of patients (see Fig. 1). Conclusion: Therefore, gingival bleeding should be considered a useful factor in bleeding history for HBD diagnosis. Adding this symptom to a screening score such as HEMSTOP improves its sensitivity. To confirm our findings, a prospective study is required. Trial registration: Study registration number: NCT05214300. What is Known: • Screening for hereditary bleeding disorder diseases is a necessity and a challenge in children. • Minor disorders of primary hemostasis are the most common, but often escape standard coagulation tests. What is New: • Gingival bleeding is a frequent symptom that is easy to investigate and may point to a primary hemostasis disorder. • Adding the gingival bleeding item to a routine screening score such as HEMSTOP improves sensitivity. [ABSTRACT FROM AUTHOR]

The adverse influence of maternal obesity on offspring metabolic health throughout the life-course is a significant public health challenge with few effective interventions. We examined if black bean powder (BBP) supplementation to a high-calorie maternal pregnancy diet or a postnatal offspring diet could offer protection against the metabolic programming of metabolic disease risk in adult offspring. Female Sprague Dawley rats were randomly assigned to one of three diets (n = 10/group) for a 3-week pre-pregnancy period and throughout gestation and lactation: (i) a low-caloric control diet (CON); (ii) a high-caloric obesity-inducing diet (HC); or (iii) the HC diet with 20% black bean powder (HC-BBP). At weaning [postnatal day (PND) 21], one male pup from each dam was weaned onto the CON diet throughout the postnatal period until adulthood (PND120). In addition, a second male from the HC group only was weaned onto the CON diet supplemented with BBP (CON-BBP). Thus, based on the maternal diet exposure and offspring postnatal diet, four experimental adult offspring groups were compared: CON/CON, HC/CON, HC-BPP/CON, and HC/CON-BBP. On PND120, blood was collected for biochemical analysis (e.g., lipids, glycemic control endpoints, etc.), and livers were excised for lipid analysis (triglycerides [TG] and cholesterol) and the mRNA/protein expression of lipid-regulatory targets. Compared with the CON/CON group, adult offspring from the HC/CON group exhibited a higher (p < 0.05) body weight (BW) (682.88 ± 10.67 vs. 628.02 ± 16.61 g) and hepatic TG (29.55 ± 1.31 vs. 22.86 ± 1.85 mmol/g). Although maternal BBP supplementation (HC-BBP/CON) had little influence on metabolic outcomes, the consumption of BBP in the postnatal period (HC/CON-BBP) lowered hepatic TG and cholesterol compared with the other treatment groups. Reduced hepatic TG in the HC/CON-BBP was likely associated with lower postnatal BW gain (vs. HC/CON), lower mRNA and protein expression of hepatic Fasn (vs. HC/CON), and lower serum leptin concentration (vs. CON/CON and HC groups). Our results suggest that the postnatal consumption of a black-bean-powder-supplemented diet may protect male rat offspring against the programming of obesity and dyslipidemia associated with maternal obesity. Future work should investigate the bioactive fraction of BBP responsible for the observed effect. [ABSTRACT FROM AUTHOR]

In the past several years, augmented Lagrangian methods have been successfully applied to several classes of nonconvex optimization problems, inspiring new developments in both theory and practice. In this paper we bring most of these recent developments from nonlinear programming to the context of optimization on Riemannian manifolds, including equality and inequality constraints. Many research have been conducted on optimization problems on manifolds, however only recently the treatment of the constrained case has been considered. In this paper we propose to bridge this gap with respect to the most recent developments in nonlinear programming. In particular, we formulate several well-known constraint qualifications from the Euclidean context which are sufficient for guaranteeing global convergence of augmented Lagrangian methods, without requiring boundedness of the set of Lagrange multipliers. Convergence of the dual sequence can also be assured under a weak constraint qualification. The theory presented is based on so-called sequential optimality conditions, which is a powerful tool used in this context. The paper can also be read with the Euclidean context in mind, serving as a review of the most relevant constraint qualifications and global convergence theory of state-of-the-art augmented Lagrangian methods for nonlinear programming. [ABSTRACT FROM AUTHOR]

The Fritz John (FJ) and Karush--Kuhn--Tucker (KKT) conditions are fundamental tools for characterizing minimizers and form the basis of almost all methods for constrained optimization. Since the seminal works of Fritz John, Karush, Kuhn, and Tucker, FJ/KKT conditions have been enhanced by adding extra necessary conditions. Such an extension was initially proposed by Hestenes in the 1970s and later extensively studied by Bertsekas and collaborators. In this work, we revisit enhanced KKT stationarity for standard (smooth) nonlinear programming. We argue that every KKT point satisfies the usual enhanced versions found in the literature. Therefore, enhanced KKT stationarity only concerns the Lagrange multipliers. We then analyze some properties of the corresponding multipliers under the quasi-normality constraint qualification (QNCQ), showing in particular that the set of so-called quasinormal multipliers is compact under QNCQ. Also, we report some consequences of introducing an extra abstract constraint to the problem. Given that enhanced FJ/KKT concepts are obtained by aggregating sequential conditions to FJ/KKT, we discuss the relevance of our findings with respect to the well-known sequential optimality conditions, which have been crucial in generalizing the global convergence of a well-established safeguarded augmented Lagrangian method. Finally, we apply our theory to mathematical programs with complementarity constraints and multiobjective problems, improving and elucidating previous results in the literature. [ABSTRACT FROM AUTHOR]

In the past, identification of HLA alleles was limited to sequencing the region of the gene coding for the peptide binding groove, resulting in a lack of sequence information in the HLA database, challenging HLA allele assignment software programs. We investigated full-length sequences of 19 HLA class I and 7 HLA class II alleles, and we extended another 47 HLA class I alleles with sequences of 5′ and 3′ UTR regions that were all not yet available in the IPD-IMGT/HLA database. We resolved 8638 unknown nucleotides in the coding sequence of HLA class I and 2139 of HLA class II. Furthermore, with full-length sequencing of the 26 alleles, more than 90 kb of sequence information was added to the non-coding sequences, whereas extension of the 47 alleles resulted in the addition of 5.5 kb unknown nucleotides to the 5′ UTR and > 31.7 kb to the 3′ UTR region. With this information, some interesting features were observed, like possible recombination events and lineage evolutionary origins. The continuing increase in the availability of full-length sequences in the HLA database will enable the identification of the evolutionary origin and will help the community to improve the alignment and assignment accuracy of HLA alleles. [ABSTRACT FROM AUTHOR]

The criteria of "Distinctness, Uniformity and Stability" as well as a high "overall quality index" are used to register the Italian modern varieties to the national register. Differently, local conservation varieties can be certified under different EU Directives that facilitate, as an overall objective, the preservation of biodiversity and the containment of genetic erosion. In recent years, products derived from ancient grains are perceived to be healthier and more sustainable by consumers, especially in Italy, with consequent higher market prices. The ancient tetraploid wheat varieties registered in the national register of conservation varieties amount to 28, 24 of which are Sicilian. They are supposed to have wide genetic variability compared to modern ones, making them vulnerable to fraud because they are difficult to trace. It is therefore important to have tools able to discriminate between autochthonous Sicilian varieties. This can be completed by gluten proteins composition, which also provides information on the technological properties of derived products. Fifty-one accessions belonging to twenty-two ancient varieties of Sicilian tetraploid (mostly durum) wheat were analyzed. Although wide intra-accession and intra-varietal variability measurements were assessed, the gliadin pattern of bulks of seeds belonging to each variety was discriminatory. Moreover, differences in technological attitudes were found between landraces. This paves the way to use gluten protein patterns for traceability, allowing local farmers and producers to valorize their products and assure consumers regarding the transparency of the entire supply chain. [ABSTRACT FROM AUTHOR]

This article begins by examining contemporary theories of imperialism, then highlights the relevance of older interpretations. As a matter of fact, Lenin's theory—especially when he speaks of a "merger of banking capital and industrial capital," anticipates the direct and indirect role played by financial capital in the export of capital by the center to the periphery. Such export reinforces the drainage of surplus value towards the center through the double process of unequal exchange and overexploitation. The article then returns to Marx who maintains that imperialism could be explained by the downward trend in the profit rate in developed countries, when the latter do not find enough means to counteract it at home and look for new ones through colonization and international trade. Marx suggests another counter-trend which is confirmed today: the transfer of productive work to the periphery, because only productive labor creates value. The article finally focuses on the case of China, by asking: How was it able, unlike other countries and despite unequal exchange, to benefit from foreign investments, thus to emancipate itself from imperialism? And what does it do in turn to help other underdeveloped countries develop without subjugating them? [ABSTRACT FROM AUTHOR]

In current clinical practice, transplant clinicians create collaborative working relationships with histocompatibility laboratory scientists to identify the risk of long‐term graft failure, which may assist in establishing strategies for treatment and surveillance. Transplant immunology research also focuses on optimizing human leukocyte antibody tissue typing and defines the most effective test for detecting the presence of donor‐specific antibodies. Although several studies have been conducted, data on pediatric heart transplant recipients are limited. Epitope load information may be utilized to identify donors with permissible human leukocyte antibody mismatches to increase transplant success. Although current guidelines do not consider human leukocyte antibody epitope‐based matching tools, these guidelines could be useful for identifying recipients at a high risk of donor‐specific antibody production, which would be appropriate for routine donor‐specific antibody screening to initiate early interventions to prevent antibody‐mediated rejection. Human leukocyte antibody matching at the epitope level offers an effective approach for identifying acceptable mismatches in sensitized patients and provides information about epitope loads. In the future, eplet matching may be used to define the best immunosuppressive therapy protocol for cardiothoracic organ transplantation. This report provides an overview of the role of human leukocyte antibodies in heart and lung transplantation. [ABSTRACT FROM AUTHOR]

Understanding the factors that influence acoustic activity of anuran species is essential for proper species management and herein, we investigated the influence of landscape metrics (% native vegetation cover and number of patches), latitude and climatic variables (temperature and relative humidity) on the acoustic activity of Physalaemus cuvieri. We used Passive Acoustic Monitoring (PAM) to record the acoustic activity in males of the target species in 29 water bodies distributed throughout the Cerrado, the Brazilian savanna. We investigated whether the rate of call emission by P. cuvieri males is influenced by predictor variables based on generalized linear mixed models. The call rate of P. cuvieri males was influenced only by air temperature variation throughout night. We found a peak of acoustic activity in the warmer hours in the beginning of the night followed by a decrease as the air temperature declines throughout the dawn. Contrary to our expectations, we did not find any significant influence of latitude, relative humidity or landscape metrics (number of fragments or percentage of native vegetation cover) on the acoustic activity of P. cuvieri. The impacts of landscape metrics on the acoustic activity of P. cuvieri are not significant, because it is a species with more generalist ecological requirements, which to allow the individuals to move across the landscape to be successful in colonizing water bodies situated in altered environments. Previous studies have suggested that changes in temperature may affect species phenology, since individuals alter their vocal activity, or their time spent in chorus in response to climate change. In this sense, our results are important because they allow us to predict the impact of future climate change on the acoustic activity of the target species, as well as demographic implications. We tested the influence of latitude, landscape metrics and climatic variables on the acoustic activity of Physalaemus cuvieri. The acoustic activity of Physalaemus cuvieri is strongly influenced by weather conditions, specifically air temperature. Latitude and landscape metrics did not influence the call emission rates of P. cuvieri males. [ABSTRACT FROM AUTHOR]

Background: Reconstructions of the proximal femur after massive resections represent one of the main challenges in orthopedic oncology. Among the possible treatments, megaprostheses represent one of the most used and reliable reconstructive approaches. Although literature about their outcomes has flourished through the last decades, a consensus rehabilitative treatment is still far from being established. Materials and methods: We evaluated the functional results of all our oncologic cases treated between 2016 and 2022 that could follow our standardized post-operative rehabilitative approach, consisting in progressive hip mobilization and early weight-bearing. Results: Twenty-two cases were included in our study. On average, their hospitalization lasted 15.1 days. The seated position was achieved on average within 3.7 days after surgery, the standing position reached 5.4 after surgery, while assisted deambulation was started 6.4 days after surgery. After a mean post-operative follow-up of 44.0 months, our patients' mean MSTS score was 23.2 (10–30). Our data suggested a statistically significant inverse linear correlation between post-operative functionality and patients' age, resection length, and the start of deambulation. Conclusions: A correct rehabilitation, focused on early mobilization and progressive weight-bearing, is crucial to maximize patients' post-operative functional outcomes. [ABSTRACT FROM AUTHOR]