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Prescribed-performance control (PPC) for high-power dynamics with time-varying unknown control coefficients requires to address two open problems: (a) given a Nussbaum function, which properties hold for the power of the Nussbaum function? (b) to avoid high gains, how to design a switching gain that increases only when the tracking error is close to violate the performance bounds? To address the first problem, we show with a counterexample and a positive example that only some Nussbaum functions are suited to handle time-varying unknown control coefficients for high-power dynamics. To address the second problem, we propose a new switching conditional inequality. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular events represent a major cause of non-graft-related death after liver transplant. Evidence suggest that chronic inflammation associated with a remarkable oxidative stress in the presence of endothelial dysfunction and procoagulant environment plays a major role in the promotion of thrombosis. However, the underlying molecular mechanisms are not completely understood., Objectives: In order to elucidate the mechanisms of posttransplant thrombosis, the aim of the present study was to investigate the role of oxidation-induced structural and functional fibrinogen modifications in liver transplant recipients., Methods: A case-control study was conducted on 40 clinically stable liver transplant recipients and 40 age-matched, sex-matched, and risk factor-matched controls. Leukocyte reactive oxygen species (ROS) production, lipid peroxidation, glutathione content, plasma antioxidant capacity, fibrinogen oxidation, and fibrinogen structural and functional features were compared between patients and controls., Results: Patients displayed enhanced leukocyte ROS production and an increased plasma lipid peroxidation with a reduced total antioxidant capacity compared with controls. This systemic oxidative stress was associated with fibrinogen oxidation with fibrinogen structural alterations. Thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in patients compared with controls. Moreover, steatotic graft and smoking habit were associated with high fibrin degradation rate., Conclusion: ROS-induced fibrinogen structural changes might increase the risk of thrombosis in liver transplant recipients., (© 2024 The Author(s).)

Purpose: Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut-lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM)., Methods: 16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances., Results: In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC., Conclusion: Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut-lung communication., (© 2024. The Author(s).)

Considerable evidence has accumulated regarding the molecular relationship between gut microbiota (GM) composition and the onset (clinical presentation and prognosis of ulcerative colitis (UC)). In addition, it is well documented that short-chain fatty acid (SCFA)-producing bacteria may play a fundamental role in maintaining an anti-inflammatory intestinal homeostasis, but sulfate- and sulfite reducing bacteria may be responsible for the production of toxic metabolites, such as hydrogen sulfide and acetate. Hence, the present study aimed to assess the GM composition - focusing on sulfate-reducing bacteria (SRB) - in patients with severe, severe-active and moderate UC. Each one of the six enrolled patients provided two stool samples in the following way: one sample was cultivated in a modified SRB-medium before 16S rRNA sequencing and the other was not cultivated. Comparative phylogenetic analysis was conducted on each sample. Percentage of detected gut microbial genera showed considerable variation based on the patients' disease severity and cultivation in the SRB medium. In detail, samples without cultivation from patients with moderate UC showed a high abundance of the genera Bacteroides , Bifidobacterium and Ruminococcus, but after SRB cultivation, the dominant genera were Bacteroides , Klebsiella and Bilophila . On the other hand, before SRB cultivation, the main represented genera in patients with severe UC were Escherichia-Shigella , Proteus , Methanothermobacter and Methanobacterium . However, after incubation in the SRB medium Bacteroides, Proteus, Alistipes and Lachnoclostridium were predominant. Information regarding GM compositional changes in UC patients may aid the development of novel therapeutic strategies (e.g., probiotic preparations containing specific bacterial strains) to counteract the mechanisms of virulence of harmful bacteria and the subsequent inflammatory response that is closely related to the pathogenesis of inflammatory bowel diseases., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interests., (Copyright: © 2024 Kushkevych et al.)

Free fatty acids (FFA) have gained research interest owing to their functions in both local and systemic immune regulation. Changes in the serum levels of anti-inflammatory short chain fatty acids (SCFA), primarily derived from the gut microbiota, and pro-inflammatory medium (MCFA) and long (LCFA) chain fatty acids, derived from either the gut microbiota or the diet, have been associated with autoimmunity. Circulating FFA were retrospectively analysed by a gas chromatography-mass spectrometry method in the serum of 18 patients with pemphigus vulgaris (PV) at the baseline and 6 months (n = 10) after immunosuppressive treatments, and 18 healthy controls (HC). Circulating FFA were correlated with the Pemphigus Disease Area Index (PDAI) and serum concentrations of interferon-gamma (IFN-γ), Interleukin (IL)-17A, IL-5, IL-10 and IL-21. Principal Component analysis computed on FFA abundances revealed significant differences in the profile of SCFA (p = 0,012), MCFA (p = 0.00015) and LCFA (p = 0,035) between PV patients and HC, which were not significantly changed by immunosuppressive treatments. PV patients showed a significantly lower serum concentration of propionic (p < 0.0005) and butyric (p < 0.0005) acids, SCFA with anti-inflammatory functions, while hexanoic (p < 0.0005) and hexadecanoic (p = 0.0006) acids, pro-inflammatory MCFA and LCFA respectively, were over-represented. Treatments induced a significant decrease of hexanoic (p = 0.035) and a further increase of hexadecanoic (p = 0.046) acids. Positive correlations emerged between IFN-γ and acetic acid (Rho = 0.60), IFN-γ and hexanoic acid (Rho = 0.46), IL-5 and both hexadecanoic acid (Rho = 0.50) and octadecanoic acid (Rho = 0.53), butyric acid and PDAI (Rho = 0.53). PV was associated with a remarked imbalance of circulating FFA compared to HC. The serum alterations of SCFA, MCFA, and LCFA may contribute to promoting inflammation in PV. Deeper insights into the immunomodulatory functions of these molecules may pave the way for personalized dietary interventions in PV patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Actor-critic (AC) cooperative multiagent reinforcement learning (MARL) over directed graphs is studied in this article. The goal of the agents in MARL is to maximize the globally averaged return in a distributed way, i.e., each agent can only exchange information with its neighboring agents. AC methods proposed in the literature require the communication graphs to be undirected and the weight matrices to be doubly stochastic (more precisely, the weight matrices are row stochastic and their expectation are column stochastic). Differently from these methods, we propose a distributed AC algorithm for MARL over directed graph with fixed topology that only requires the weight matrix to be row stochastic. Then, we also study the MARL over directed graphs (possibly not connected) with changing topologies, proposing a different distributed AC algorithm based on the push-sum protocol that only requires the weight matrices to be column stochastic. Convergence of the proposed algorithms is proven for linear function approximation of the action value function. Simulations are presented to demonstrate the effectiveness of the proposed algorithms.

Background: Emerging evidence suggests that breast microbiota dysbiosis contributes to cancer initiation, progression, prognosis and treatment efficacy. Anyway, available data are referred only to female patients, and studies on males are completely missing. Male breast cancer (MBC) is 70-100 times less frequent, but the mortality rate adjusted to incidence is higher in men than in females. Currently, MBC diagnostic approaches and treatments have generally been extrapolated from the clinical experience gained in women, while few studies focus on characterizing male cancer biology. Taking into account the rising importance of the oncobiome field and the need of MBC targeted studies, we explored the breast cancer oncobiome of male and female patients., Methods: 16S rRNA gene sequencing was performed in 20 tumor and 20 non-pathological adjacent FFPE breast tissues from male and female patients., Results: We documented, for the first time, the presence of a sexually dimorphic breast-associated microbiota, here defined as "breast microgenderome". Moreover, the paired analysis of tumor and non-pathological adjacent tissues suggests the presence of a cancer-associated dysbiosis in male patients, with surrounding tissue conserving a healthier microbiome, whereas in female patients, the entire breast tissue is predisposed to cancer development. Finally, the phylum Tenericutes, especially the genera Mesoplasma and Mycobacterium, could to be involved in breast carcinogenesis, in both sexes, deserving further investigation, not only for its role in cancer development but even as potential prognostic biomarker., Conclusions: Breast microbiota characterization can enhance the understanding of male breast cancer pathogenesis, being useful for detection of new prognostic biomarkers and development of innovative personalized therapies, remarking the relevant gender differences., (© 2023. The Author(s).)

The effects of cocaine on microbiota have been scarcely explored. Here, we investigated the gut (GM) and oral (OM) microbiota composition of cocaine use disorder (CUD) patients and the effects of repetitive transcranial magnetic stimulation (rTMS). 16S rRNA sequencing was used to characterize GM and OM, whereas PICRUST2 assessed functional changes in microbial communities, and gas-chromatography was used to evaluate fecal short and medium chain fatty acids. CUD patients reported a significant decrease in alpha diversity and modification of the abundances of several taxa in both GM and OM. Furthermore, many predicted metabolic pathways were differentially expressed in CUD patients' stool and saliva samples, as well as reduced levels of butyric acid that appear restored to normal amounts after rTMS treatment. In conclusion, CUD patients showed a profound dysbiotic fecal and oral microbiota composition and function and rTMS-induced cocaine abstinence determined the restoration of eubiotic microbiota., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background and Aim: In recent decades, obesity prevalence has reached epidemic proportions and considering the pivotal role of gut microbiota (GM) in the regulation of energy balance, alternative non-pharmacological approaches involving probiotics' administration have been proposed. The aim of the present study was to evaluate the effect of Lactiplantibacillus plantarum IMC 510® supplementation on anthropometric and biochemical parameters, GM composition and functionality, and gastrointestinal and general symptoms of overweight/obese subjects., Methods: Forty overweight/obese subjects were randomly assigned to daily consume the probiotic Lactiplantibacillus plantarum IMC 510® or placebo for 3 months. Before and after the administration period, anthropometric and biochemical parameters, self-administered questionnaires, and plasma and stool samples were obtained from each participant. The GM characterization was performed with 16S rRNA sequencing, while fecal short (SCFAs) and medium (MCFAs) chain fatty acids were analyzed with a gas chromatography-mass spectrometry protocol., Results: Compared to placebo, probiotic supplementation determined a significant decrease in body weight, BMI, waist circumference, waist-to-height ratio, and blood glucose. Moreover, probiotic administration produced a significant decrease of the genera Hafnia-Obesumbacterium and Romboutsia and an increase of Succiniclasticum spp.; conversely, placebo administration resulted in the decrease of Actinomycetaceae and an increase of both Alloprevotella spp. and of the levels of pro-inflammatory hexanoic and heptanoic acids., Conclusion: Thanks to its effect in increasing some beneficial gut bacteria and lowering effects on waist circumference, fasting glucose levels and gastrointestinal symptoms of obese subjects, Lactiplantibacillus plantarum IMC 510® supplementation could represent a future and encouraging strategy for the prevention or treatment of obesity., Competing Interests: MMC and MCV were employed by Synbiotec S.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pagliai, Coman, Baldi, Dinu, Nannini, Russo, Curini, Colombini, Lotti, Pallecchi, Di Gloria, Bartolucci, Ramazzotti, Verdenelli, Sofi and Amedei.)

Currently, colorectal cancer (CRC) represents the third most common malignancy and the second most deadly cancer worldwide, with a higher incidence in developed countries. Like other solid tumors, CRC is a heterogeneous genomic disease in which various alterations, such as point mutations, genomic rearrangements, gene fusions or chromosomal copy number alterations, can contribute to the disease development. However, because of its orderly natural history, easily accessible onset location and high lifetime incidence, CRC is ideally suited for preventive intervention, but the many screening efforts of the last decades have been compromised by performance limitations and low penetrance of the standard screening tools. The advent of next-generation sequencing (NGS) has both facilitated the identification of previously unrecognized CRC features such as its relationship with gut microbial pathogens and revolutionized the speed and throughput of cataloguing CRC-related genomic alterations. Hence, in this review, we summarized the several diagnostic tools used for CRC screening in the past and the present, focusing on recent NGS approaches and their revolutionary role in the identification of novel genomic CRC characteristics, the advancement of understanding the CRC carcinogenesis and the screening of clinically actionable targets for personalized medicine., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

A major depressive disorder is a serious mental illness characterized by a pervasive low mood that negatively concerns personal life, work life, or education, affecting millions of people worldwide. To date, due to the complexity of the disease, the most common and effective treatments consist of a multi-therapy approach, including psychological, social, and pharmacological support with antidepressant drugs. In general, antidepressants are effective in correcting chemical imbalances of neurotransmitters in the brain, but recent evidence has underlined the pivotal role of gut microbiota (GM) also in the regulation of their pharmacokinetics/pharmacodynamics, through indirect or direct mechanisms. The study of these complex interactions between GM and drugs is currently under the spotlight, and it has been recently named "pharmacomicrobiomics". Hence, the purpose of this review is to summarize the contribution of GM and its metabolites in depression, as well as their role in the metabolism and activity of antidepressant drugs, in order to pave the way for the personalized administration of antidepressant therapies.

Introduction: Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process: namely, valve fibrosis with its area narrowing, impaired blood flow, and final calcification phase. Nowadays, the only treatment is the surgical valve replacement. As for other cardiovascular diseases, growing evidence suggest an active role of the immune system in the calcification process that could be modulated by the microbiota. To address this point, we aimed to investigate and characterize, for the first time, the presence of a valve microbiota and associated immune response in human CAVD., Method: Calcified aortic valve (CAV) samples from twenty patients (11 from Germany and 9 from Italy) with diagnosis of severe symptomatic CAVD were used to assess the presence of infiltrating T cells, by cloning approach, and to characterize the valve microbiota, by 16S rRNA gene sequencing (NGS)., Results: We documented the presence of infiltrating T lymphocytes, especially the T helper subset, in CAV samples. Moreover, we found a tissue-associated microbiota in freshly collected CAV samples, which was significantly different in Italian and German patients, suggesting potential correlation with other cardiovascular risk factors., Conclusion: The presence of microbiota in inflamed CAV samples represents the right trigger point to explain the valve calcification process, encouraging further studies to explore the potential link between bacteria and adaptive immune response and to define the critical role of local microbiota-immunity axis on CAVD development., Competing Interests: Conflict of Interest: The authors have declared no conflict of interest., (Copyright: © 2023 Curini et al.)

Lignans are non-flavonoid polyphenols present in a wide range of foods frequently consumed in the Western world, such as seeds, vegetables and fruits, and beverages such as coffee, tea and wine. In particular, the human gut microbiota (GM) can convert dietary lignans into biologically active compounds, especially enterolignans (i.e., enterolactone and enterodiol), which play anti-inflammatory and anti-oxidant roles, act as estrogen receptor activators and modulate gene expression and/or enzyme activity. Interestingly, recent evidence documenting those dietary interventions involving foods enriched in lignans have shown beneficial and protective effects on various human pathologies, including colorectal and breast cancer and cardiovascular diseases. However, considering that more factors (e.g., diet, food transit time and intestinal redox state) can modulate the lignans bioactivation by GM, there are usually remarkable inter-individual differences in urine, fecal and blood concentrations of enterolignans; hence, precise and validated analytical methods, especially gas/liquid chromatography coupled to mass spectrometry, are needed for their accurate quantification. Therefore, this review aims to summarize the beneficial roles of enterolignans, their interaction with GM and the new methodological approaches developed for their evaluation in different biological samples, since they could be considered future promising nutraceuticals for the prevention of human chronic disorders.

This article investigates the distributed time-varying optimization problem for second-order multiagent systems (MASs) under limited interaction ranges. The goal is to seek the minimum of the sum of local time-varying cost functions (CFs), where each CF is only available to the corresponding agent. Limited communication range refers to the scenario where the agents have limited sensing and communication capabilities, that is, a pair of agents can communicate with each other only if their distance is within a certain range. To handle such a problem, a new continuous connectivity-preserving mechanism is presented to preserve the connectivity of the considered network. Then, two distributed optimization algorithms are presented to solve the optimization problem with time-varying CFs and time-invariant CFs, respectively. Theoretical analysis and two numerical examples are provided to verify the effectiveness of the methods.