BACKGROUND Obesity is a chronic and multifactorial disease with a variety of potential treatment options available.Currently,there are several multidisciplinary therapeutic options for its management,including conserv...BACKGROUND Obesity is a chronic and multifactorial disease with a variety of potential treatment options available.Currently,there are several multidisciplinary therapeutic options for its management,including conservative,endoscopic,and surgical treatment.AIM To clarify indications,technical aspects,and outcomes of bariatric endoscopy.METHODS Narrative review of current literature based on electronic databases including MEDLINE(PubMed),Cochrane Library,and SciELO.RESULTS Bariatric endoscopy is in constant development and comprises primary and revisional treatment options as well as management of surgical complications.Various devices act upon different mechanisms of action,which may be individualized to each patient.Despite favorable results for the endoscopic treatment of obesity,prospective randomized studies with long-term follow-up are required to fully validate primary and revisional endoscopic therapies.Regarding the management of bariatric surgery complications,endoscopic therapy may be considered the procedure of choice in a variety of situations.Still,as there is no standardized algorithm,local experience should be considered in decision-making.CONCLUSION The treatment of patients with obesity is complex,and a multidisciplinary approach is essential.Bariatric endoscopy has shown impressive results both in the treatment of obesity and its surgical complications,and therefore,must be part of the armamentarium in the fight against this disease.展开更多
In the last decade, the world of academia has faced a period of strong/severe resource constraints/reduction. At the same time, there has been an increasing interest of the Ministry of Research （MIUR） in designing m...In the last decade, the world of academia has faced a period of strong/severe resource constraints/reduction. At the same time, there has been an increasing interest of the Ministry of Research （MIUR） in designing methods to evaluate University performance in order to rank efficient Universities and to reduce potential inefficiencies, so providing the administration authorities with measures that may be used for an optimal resources allocation. With this increasing interest in University performance, a wide academic debate has emerged about the models and measures adopted, based on several quantitative measures of inputs that, sometimes, have been borrowed from the Italian Health organizational model, much more consolidated in its experience. We cite, for all, the students evaluation in terms of standard cost within the resources allocation model introduced last year, and the ＂customers＂ satisfaction measurement, whose main goal is to provide an independent system of regular evaluation of student satisfaction and of the University teaching quality. The aim of this paper is to deal with the students opinion about the quality of teaching, as perceived as ＂users＂ while attending their academic courses in the health area. We agree with the statement that the high quality of healthcare services provided to the community depends also on the main factor, the human capital involved in supplying them. In Italy, the academic courses belonging to the health area provide the access to a limited number of students who passed a hard selection. This rule was introduced by the law n.264/1999 to harmonize the Italian University system to the European one in order to guarantee the high quality of students higher education in this field. And that quality of the education, according to the law, depended on the places in the classrooms, on the equipment and scientific laboratories for teaching; on the teaching staff and technical personnel; on the assistance and tutoring service, on the apprenticeships and places available in laboratories and classrooms equipped for practical, on the presence of technical-practical and laboratory activities. For the Government, that is the main donor for Italian Universities, the level of student satisfaction is of great importance to evaluate the quality of their courses. It is actually measured by different points of view as quality of teachers, teaching materials and logistical support. The law n.370/1999 states that Italian Universities have to systematically carry out a survey on the satisfaction of ＂teaching＂ of their students; this survey is named Opinione degli studenti . Recently, the National Agency of Evaluation （ANVUR） has been entrusted to oversee the related processes. Since 2013, the University of Bail, like the other Universities, has adopted the ANVUR guidelines.展开更多
Background:The topic of this review is the study of the gut microbiota(GM),and the use of probiotics,especially in humans,as a new frontier in the field of prevention and health in general.The beneficial effects and f...Background:The topic of this review is the study of the gut microbiota(GM),and the use of probiotics,especially in humans,as a new frontier in the field of prevention and health in general.The beneficial effects and functions performed by probiotics in the GM are increasingly at the centre of both scientific,medical,and pharmaceutical interest.It is now known that diet and probiotics can modify the GM,although in these situations there is a need for greater and more in-depth research regarding the methods and timing of treatment.However,the relationship between physical activity,GM,and probiotics is still largely unclear,as regards certain mechanisms between physical exercise and probiotics in humans.Discussion:In this study,we tried to demonstrate whether and how physical exercise was able to alter the composition of the microbiota and how probiotics can facilitate it.Therefore,alteration of the microbiota was considered in terms of both diversity and composition.Conclusions:The ones examined propose vastly different physical exercises,both in terms of timing and type of intervention itself,and the use of probiotics.展开更多
Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic ...Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.展开更多
The South Aral Seabed is an extreme dryland ecosystem undergoing rapid transformation yet remains misrepresented or absent in global land cover datasets.Conventional vegetation indices,specifically the Normalized Diff...The South Aral Seabed is an extreme dryland ecosystem undergoing rapid transformation yet remains misrepresented or absent in global land cover datasets.Conventional vegetation indices,specifically the Normalized Difference Vegetation Index(NDVI),perform poorly in such environments due to their limited ability to distinguish sparse vegetation from highly reflective saline and sandy soils.This study evaluated the effectiveness of the Modified Soil Adjusted Vegetation Index(MSAVI)for improving land cover classification in the South Aral Seabed and conducted a decadal analysis of land cover change between 2013 and 2023 using Landsat 8 imagery(30 m resolution).A spectral index-based classification framework was developed,combining MSAVI with the Normalized Difference Water Index(NDWI)and Salinity Index 1(SI1)to reduce spectral confusion between vegetation,saline soils,and surface water.The MSAVI-based classification achieved an overall accuracy of 77.96%(Kappa coefficient=0.71),supported by 313 field-collected validation points from 2023.While the multi-index approach enabled finer discrimination of ecologically important classes,particularly separating salt pans from solonchak soils,it resulted in a lower overall accuracy(73.80%),highlighting a trade-off between class separability and classification performance.Land cover change analysis revealed a highly dynamic landscape,with 52.96%of the study area transitioning between classes over the decade.Transformed areas(16,893 km2)exceeded stable zones(15,004 km2),driven primarily by rapid desiccation and salinization.Solonchak soils increased at an annual rate of 5.58%,while surface water bodies declined by 4.83%per year.Concurrently,sparse or distressed vegetation increased by 1.43%annually,reflecting ongoing afforestation efforts.This study provides the first MSAVI-based and medium-resolution land cover baseline for the South Aral Seabed and demonstrates that soil-adjusted vegetation indices are essential for reliable dryland classification where conventional indices fail.The proposed spectral index framework offers a replicable methodology applicable to other global drylands facing similar land degradation and restoration challenges.展开更多
Leveraging high-precision lattice QCD data on the equation of state and baryon number susceptibility at a vanishing chemical potential,we constructed a Bayesian holographic QCD model and systematically analyzed the th...Leveraging high-precision lattice QCD data on the equation of state and baryon number susceptibility at a vanishing chemical potential,we constructed a Bayesian holographic QCD model and systematically analyzed the thermodynamic properties of heavy quarkonium in QCD matter under varying temperatures and chemical potentials.We computed the quark-antiquark interquark distance,potential energy,entropy,binding energy,and internal energy.We present detailed posterior distribution results of the thermodynamic quantities of heavy quarkonium,including maximum a posteriori(MAP)value estimates and 95%confidence levels(CL).Through numerical simulations and theoretical analysis,we find that an increase in the temperature and chemical potential reduces the quark distance,thereby facilitating the dissociation of heavy quarkonium and leading to a suppressed potential energy.The increase in temperature and chemical potential also raises the entropy and entropy force,further accelerating the dissociation of heavy quarkonium.The calculated results of binding energy indicate that a higher temperature and chemical potential enhance the tendency of heavy quarkonium to dissociate into free quarks.The internal energy also increases with rising temperature and chemical potential.These findings provide significant theoretical insights into the properties of strongly interacting matter under extreme conditions and lay a solid foundation for the interpretation and validation of future experimental data.Finally,we also present the results for the free energy,entropy,and internal energy of a single quark.展开更多
The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays a...The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.展开更多
The development of sustainable sludge management systems requires looking at them with a new vision in which the concepts of SD(Sustainable Development)must integrate those of CE(Circular Economy),both concepts subjec...The development of sustainable sludge management systems requires looking at them with a new vision in which the concepts of SD(Sustainable Development)must integrate those of CE(Circular Economy),both concepts subject to the principles of TD(Thermodynamics),thus allowing the adoption of actions that are all the more effective the more complete the evaluation of the social dimension has been.This involves a new“Way of thinking”which sees the sludge system as the“Locomotive”of the entire wastewater/sludge treatment train and is developed through“Ways of acting”which includes both“Technical”actions to maximize recoveries of useful materials and/or or energy,and“Socio/Institutional”actions to overcome barriers linked to local cultures and traditions,also considering that the specific local context heavily influences the choices capable of satisfying the concepts of CE.It follows the need of issuing realistic and applicable regulations and overcoming social barriers,such as lack of infrastructure and/or qualified personnel,to achieve an effective integration of the concepts of CE with the more general ones of sustainability.展开更多
Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality worldwide,necessitating innovative treatment strategies.Surgical resection and liver transplantation continue to be the gold standards f...Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality worldwide,necessitating innovative treatment strategies.Surgical resection and liver transplantation continue to be the gold standards for early-stage HCC;however,advances in imaging and minimally invasive techniques have improved patient selection and outcomes.Additionally,the emergence of targeted therapies and immunotherapy has transformed the treatment landscape for advanced HCC.This review highlights the efficacy of agents such as tyrosine kinase inhibitors,alongside emerging options like immune checkpoint inhibitors,which have shown promise in clinical trials.Furthermore,the role of locoregional therapies,including ablation in the setting of combined treatment,transar-terial chemoembolization and transarterial radioembolization with flow catheters,cone-beam computed tomo-graphy and 4D navigation guidance,is examined in the context of bridging therapies for patients awaiting surgical intervention.The integration of multidisciplinary care approaches and personalized treatment plans is crucial for optimizing outcomes.Future directions for HCC treatment are discussed,including the potential of novel biomarkers in prognosis and treatment response.This comprehensive overview aims to equip clinicians with the latest insights and foster collaborative efforts to improve HCC patient management and survival rates.展开更多
BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury...BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.展开更多
This paper addresses the diagnosability analysis problem under external malicious attacks of a networked discrete event system modeled by labeled Petri net.In particular,we focus on a stealthy replacement attack to al...This paper addresses the diagnosability analysis problem under external malicious attacks of a networked discrete event system modeled by labeled Petri net.In particular,we focus on a stealthy replacement attack to alter or corrupt the observation of the system,in which the transition labels are replaced by others or empty string,and its attack stealthiness requires that the corrupted observations should be contained in the behavior of system.The aim of this work is,from an attacker viewpoint,to design a stealthy replacement attack for violating the diagnosability of system.To this end,we first build a new structure,called complete unfolded verifier,with the notion of a predefined elementary unsound path that leads to the violation of diagnosability,which is used to enumerate all the potential attacked paths to be transformed into elementary unsound ones.Then an optimal attack synthesis problem in terms of minimum energy cost is formulated by determining whether an elementary unsound path is generated via solving a set of integer nonlinear programming problems.Finally,we show that the nonlinear programming problems can be transformed into integer linear programming problems by introducing additional linear constraints.Examples are used to illustrate the proposed attack strategy.展开更多
The composition of the vaginalmicrobiota(VMB)influences the health of the female reproductive tract.Several studies have shown how the absence of lactobacilli causes an imbalance in the vaginal microbial community,fav...The composition of the vaginalmicrobiota(VMB)influences the health of the female reproductive tract.Several studies have shown how the absence of lactobacilli causes an imbalance in the vaginal microbial community,favoring the development of infections.The present study aims to evaluate the relationship between the VMB and human papillomavirus(HPV)infection to clarify the role of the vaginal microbiota in the persistence and clearance of HPV.Many researchers have provided the scientific community with information on the composition of the microbiota and how it may also influence HPV infection and the development of cervical cancer.Studies have shown that the main Lactobacilli species that favor HPV clearance are Lactobacillus(L.)iners and L.gasseri.In this review,we focused on the general aspects of the interaction between HPV and the VMB,evaluating the influence of the microbiota on the immune system and the effect on different physiologic stages of women’s lives,like pregnancy and menopause.The diversity of the VMB worldwide was also assessed.The association between lactobacilli composition,ethnicity,and cancer must be related to other factors(age,smoking,physiological factors)and co-infections.New formulations of probiotics and innovative surgical removal systems that preserve the integrity of the VMB are also being developed to prevent and reduce the incidence of cervical cancer.More research and understanding are needed on a very complex topic such as the VMB.展开更多
Purpose–This paper investigates how high-speed rail(HSR)influences socioeconomic inequality by providing the first systematic bibliometric review of research trends,methodological approaches and thematic structures.I...Purpose–This paper investigates how high-speed rail(HSR)influences socioeconomic inequality by providing the first systematic bibliometric review of research trends,methodological approaches and thematic structures.It examines whether HSR fosters balanced regional development or reinforces spatial disparities.Design/methodology/approach–Using the Bibliometrix R package,237 records were retrieved from the Web of Science(1985–2024).Citation indicators,keyword co-occurrence and collaboration networks were combined with natural language processing(NLP)to classify studies by territorial scale,methodology,economic variables and inequality outcomes.Findings–The paper offers the first structured overview of how the literature conceptualizes the link between HSR and inequality.It highlights persistent gaps–scarcity of city-level analyses,limited socioeconomic indicators and reliance on Chinese case studies–providing a foundation for more comparative and interdisciplinary research.Originality/value–This paper contributes by offering a structured overview of how the literature has conceptualized and measured the relationship between HSR and inequality.By identifying persistent research gaps–such as the scarcity of city-level analyses,limited use of socioeconomic indicators,and overreliance on Chinese case studies–it provides a foundation for more comparative and interdisciplinary approaches.The study informs policymakers and researchers on how to design future infrastructure projects that balance efficiency with equity.展开更多
Recurrent aphthous stomatitis(RAS)is a very frequent condition in developed countries whose basic symptom is a lesion referred to as an aphthous ulcer.High levels of interleukin(IL)-1 and IL-6 and low salivary levels ...Recurrent aphthous stomatitis(RAS)is a very frequent condition in developed countries whose basic symptom is a lesion referred to as an aphthous ulcer.High levels of interleukin(IL)-1 and IL-6 and low salivary levels of IL-10 are the basis of RAS pathogenesis.Sublingual supplements based on IL-10 can be very useful in reducing the phenomenon of aphthous recurrence in patients with RAS.An observational clinical experience with a group of 5 patients with RAS receiving a commercially available IL-10-based supplement was reported by the authors.The findings revealed a subsequent reduction in the incidence of mouth ulcers.展开更多
In this work, we address the codiagnosability analysis problem of a networked discrete event system under malicious attacks. The considered system is modeled by a labeled Petri net and is monitored by a series of site...In this work, we address the codiagnosability analysis problem of a networked discrete event system under malicious attacks. The considered system is modeled by a labeled Petri net and is monitored by a series of sites, in which each site possesses its own set of sensors, without requiring communication among sites or to any coordinators. A net is said to be codiagnosable with respect to a fault if at least one site could deduce the occurrence of this fault within finite steps. In this context, we focus on a type of malicious attack that is called stealthy intermittent replacement attack. The stealthiness demands that the corrupted observations should be consistent with the system's normal behavior, while the intermittent replacement setting entails that the replaced transition labels must be recovered within a bounded of consecutive corrupted observations(called as K-corruption intermittent attack). Particularly, there exists a coordination between attackers that are separately effected on different sites, which holds the same corrupted observation for each common transition under attacks. From an attacker viewpoint, this work aims to design Kcorruption intermittent attacks for violating the codiagnosability of systems. For this purpose, we propose an attack automaton to analyze K-corruption intermittent attack for each site, and build a new structure called complete attack graph that is used to analyze all the potential attacked paths. Finally, an algorithm is inferred to obtain the K-corruption intermittent attacks, and examples are given to show the proposed attack strategy.展开更多
Checkpoint inhibitors,particularly programmed cell death-1/programmed death-ligand 1(PD-1/PDL1)inhibitors,have significantly advanced the treatment of Hodgkin lymphoma(HL),especially in relapsed or refractory cases.Ho...Checkpoint inhibitors,particularly programmed cell death-1/programmed death-ligand 1(PD-1/PDL1)inhibitors,have significantly advanced the treatment of Hodgkin lymphoma(HL),especially in relapsed or refractory cases.However,challenges such as resistance,immune-related adverse events(irAEs),and the need for effective patient selection remain.This review aims to explore the mechanisms of resistance to checkpoint inhibitors,including alterations in the tumor microenvironment,loss of antigen presentation,and T-cell exhaustion.Overcoming resistance may involve combination therapies,such as pairing PD-1 inhibitors with other immune checkpoint inhibitors or targeted therapies like Brentuximab vedotin.Additionally,next-generation inhibitors targeting molecules like lymphocyte-activation gene 3(LAG-3)and T-cell immunoglobulin and mucin-domain containing-3(TIM-3)show promise in addressing resistance mechanisms not overcome by PD-1 inhibitors.Identifying reliable biomarkers to predict response to checkpoint inhibitors is critical for optimizing treatment,with ongoing research focusing on tumor mutational burden(TMB),inflammatory markers,and genetic profiling.Future clinical trials will aim to refine treatment regimens,optimize therapeutic combinations,and minimize adverse effects to maximize patient benefit.展开更多
While exerting their metabolic activities in the gastrointestinal milieu,probiotics impact the host well-being by boosting immunity,treating metabolic disorders,and modulating microbiota and metabolome.Due to the high...While exerting their metabolic activities in the gastrointestinal milieu,probiotics impact the host well-being by boosting immunity,treating metabolic disorders,and modulating microbiota and metabolome.Due to the high incidence of gluten-based disorders,the present work aims to deeply explore the metabolism of two selected microbial consortia(MCs)during gluten digestion under simulated gastrointestinal conditions.Featured by high protease and peptidase activity,both MCs accounted for different lactic acid bacteria and Bacillus strains that were combined with two commercial protease enzymes.Gluten substrates were used as purified extracts,white and whole wheat breads.Control samples,instead,relied onto the microbial enzyme lack.Twenty-four hours of simulated digestion were sufficient to completely hydrolyze gluten in one of the two MC-containing experimental sets,and the relative 48 h-digested extract did not alter the cytokine expression in duodenal biopsies from celiac disease(CeD)patients.When digested samples were assayed for antioxidant and phytase activities,microbial enzymes demonstrated to significantly improve both 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)and 1,1-diphenyl-2-picrylhydrazyl(DPPH)scavenging activity and to decrease the phytic acid concentration.The inspection of the free amino acid profiles allowed for distinguishing the two MCs,whereas the detection of a heterogeneous panel of volatile organic compounds supported the presence/activity of microbial enzymes without statistically significant differences between MCs.As functional contribution,digested extracts with MCs also proved to reduce the inflammatory cytokine concentrations in cell lines exposed to lipopolysaccharide trigger.Therefore,in line with studies exploring novel adjuvant therapies,the present innovative probiotic consortium featured by high gluten-hydrolyzing metabolism also showed the capability to improve various parameters usually found to be altered in patients affected by gluten-based disorders or CeD.展开更多
Although numerous studies have examined the impact of ESG practices on bank profitability,the results remain inconclusive,underscoring the importance of analyzing ESG components separately.This study examines the impa...Although numerous studies have examined the impact of ESG practices on bank profitability,the results remain inconclusive,underscoring the importance of analyzing ESG components separately.This study examines the impact of ESG performance—in each of its individual dimensions—on the profitability of 192 European listed banks over the period 2009–2019,a critical decade following the 2008 global financial crisis.Via a panel regression model,the findings suggest that environmental practices deliver more immediate benefits.While governance practices are vital for ensuring stability,they do not appear to be sufficient to drive short-term variations in profitability.Moreover,social practices are negatively related to profitability.To address this finding,this study adopts the One Health approach,fostering the need for policy-makers and bank managers to integrate this perspective into bank’s approach to sustainability in a more holistic and forward-thinking vision of social responsibility via the exploitation of specialized expertise.展开更多
Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by t...Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by the defoliation and drying of the whole tree were observed in the Jazan,El Baha,Najran,and Asir regions.The purpose of this investigation was to isolate and identify the Fusarium species recovered from symptomatic coffee trees.The developed fungi were initially characterized based on their morphological features followed by molecular phylogenetic multi-locus analysis of the combined sequences of ITS,TEF1-α,RPB2,and CaM.Twenty-five isolates were recovered from 28 samples.All fungal isolates were categorized morphologically under the genus Fusarium.Phylogenetic analysis positioned all the representative 15 isolates into one cluster grouping together with Neocosmospora falciformis(formerly F.falciforme)confirming their taxonomic position.Pathogenicity tests of the N.falciformis isolates were subsequently conducted on coffee seedlings,and the results revealed that all isolates induced wilt symptoms resembling those recorded in the field,and the incidence was 100%.The fungicide sensitivity test of seven investigated fungicides revealed that Maxim XL^(®) followed by Moncut^(®) exhibited the highest inhibitory effect against N.falciformis KSA 24-14,reaching 93.33%and 91.67%,respectively.To our knowledge,N.falciformis is a new causal pathogen of coffee wilt in Saudi Arabia.Remarkably,these results offer important insights for devising effective approaches to monitor and control such diseases.展开更多
Melanoma,the most aggressive form of skin cancer,remains a significant clinical challenge due to the high metastatic potential and drug resistance.This review explores the pivotal roles of angiogenesis and vasculogeni...Melanoma,the most aggressive form of skin cancer,remains a significant clinical challenge due to the high metastatic potential and drug resistance.This review explores the pivotal roles of angiogenesis and vasculogenic mimicry in melanoma progression and treatment resistance.Angiogenesis,driven primarily by VEGF/VEGFR signaling,is critical for tumor sustenance but is often insufficient under hypoxic conditions,prompting melanoma cells to adapt by forming vascular-like structures(i.e.,vasculogenic mimicry).These structures enable melanoma cells to mimic endothelial functions and are linked to increased metastasis and poor prognosis.Molecular drivers,including VE-cadherin,EphA2,and hypoxia-inducible factors,have been identified as key regulators of these processes.Current anti-angiogenic agents have limited efficacy in advanced/metastatic melanoma due to tumor plasticity and the interplay between angiogenesis and vasculogenic mimicry.The review highlights the need for therapeutic strategies targeting both mechanisms,emphasizing the importance of combination treatments to overcome resistance.Future research should aim to elucidate the molecular underpinnings of angiogenesis and vasculogenic mimicry to improve melanoma management and patient outcomes.展开更多
文摘BACKGROUND Obesity is a chronic and multifactorial disease with a variety of potential treatment options available.Currently,there are several multidisciplinary therapeutic options for its management,including conservative,endoscopic,and surgical treatment.AIM To clarify indications,technical aspects,and outcomes of bariatric endoscopy.METHODS Narrative review of current literature based on electronic databases including MEDLINE(PubMed),Cochrane Library,and SciELO.RESULTS Bariatric endoscopy is in constant development and comprises primary and revisional treatment options as well as management of surgical complications.Various devices act upon different mechanisms of action,which may be individualized to each patient.Despite favorable results for the endoscopic treatment of obesity,prospective randomized studies with long-term follow-up are required to fully validate primary and revisional endoscopic therapies.Regarding the management of bariatric surgery complications,endoscopic therapy may be considered the procedure of choice in a variety of situations.Still,as there is no standardized algorithm,local experience should be considered in decision-making.CONCLUSION The treatment of patients with obesity is complex,and a multidisciplinary approach is essential.Bariatric endoscopy has shown impressive results both in the treatment of obesity and its surgical complications,and therefore,must be part of the armamentarium in the fight against this disease.
文摘In the last decade, the world of academia has faced a period of strong/severe resource constraints/reduction. At the same time, there has been an increasing interest of the Ministry of Research （MIUR） in designing methods to evaluate University performance in order to rank efficient Universities and to reduce potential inefficiencies, so providing the administration authorities with measures that may be used for an optimal resources allocation. With this increasing interest in University performance, a wide academic debate has emerged about the models and measures adopted, based on several quantitative measures of inputs that, sometimes, have been borrowed from the Italian Health organizational model, much more consolidated in its experience. We cite, for all, the students evaluation in terms of standard cost within the resources allocation model introduced last year, and the ＂customers＂ satisfaction measurement, whose main goal is to provide an independent system of regular evaluation of student satisfaction and of the University teaching quality. The aim of this paper is to deal with the students opinion about the quality of teaching, as perceived as ＂users＂ while attending their academic courses in the health area. We agree with the statement that the high quality of healthcare services provided to the community depends also on the main factor, the human capital involved in supplying them. In Italy, the academic courses belonging to the health area provide the access to a limited number of students who passed a hard selection. This rule was introduced by the law n.264/1999 to harmonize the Italian University system to the European one in order to guarantee the high quality of students higher education in this field. And that quality of the education, according to the law, depended on the places in the classrooms, on the equipment and scientific laboratories for teaching; on the teaching staff and technical personnel; on the assistance and tutoring service, on the apprenticeships and places available in laboratories and classrooms equipped for practical, on the presence of technical-practical and laboratory activities. For the Government, that is the main donor for Italian Universities, the level of student satisfaction is of great importance to evaluate the quality of their courses. It is actually measured by different points of view as quality of teachers, teaching materials and logistical support. The law n.370/1999 states that Italian Universities have to systematically carry out a survey on the satisfaction of ＂teaching＂ of their students; this survey is named Opinione degli studenti . Recently, the National Agency of Evaluation （ANVUR） has been entrusted to oversee the related processes. Since 2013, the University of Bail, like the other Universities, has adopted the ANVUR guidelines.
文摘Background:The topic of this review is the study of the gut microbiota(GM),and the use of probiotics,especially in humans,as a new frontier in the field of prevention and health in general.The beneficial effects and functions performed by probiotics in the GM are increasingly at the centre of both scientific,medical,and pharmaceutical interest.It is now known that diet and probiotics can modify the GM,although in these situations there is a need for greater and more in-depth research regarding the methods and timing of treatment.However,the relationship between physical activity,GM,and probiotics is still largely unclear,as regards certain mechanisms between physical exercise and probiotics in humans.Discussion:In this study,we tried to demonstrate whether and how physical exercise was able to alter the composition of the microbiota and how probiotics can facilitate it.Therefore,alteration of the microbiota was considered in terms of both diversity and composition.Conclusions:The ones examined propose vastly different physical exercises,both in terms of timing and type of intervention itself,and the use of probiotics.
文摘Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.
基金supported by the United Kingdom(UK)Darwin Initiative(28-003).
文摘The South Aral Seabed is an extreme dryland ecosystem undergoing rapid transformation yet remains misrepresented or absent in global land cover datasets.Conventional vegetation indices,specifically the Normalized Difference Vegetation Index(NDVI),perform poorly in such environments due to their limited ability to distinguish sparse vegetation from highly reflective saline and sandy soils.This study evaluated the effectiveness of the Modified Soil Adjusted Vegetation Index(MSAVI)for improving land cover classification in the South Aral Seabed and conducted a decadal analysis of land cover change between 2013 and 2023 using Landsat 8 imagery(30 m resolution).A spectral index-based classification framework was developed,combining MSAVI with the Normalized Difference Water Index(NDWI)and Salinity Index 1(SI1)to reduce spectral confusion between vegetation,saline soils,and surface water.The MSAVI-based classification achieved an overall accuracy of 77.96%(Kappa coefficient=0.71),supported by 313 field-collected validation points from 2023.While the multi-index approach enabled finer discrimination of ecologically important classes,particularly separating salt pans from solonchak soils,it resulted in a lower overall accuracy(73.80%),highlighting a trade-off between class separability and classification performance.Land cover change analysis revealed a highly dynamic landscape,with 52.96%of the study area transitioning between classes over the decade.Transformed areas(16,893 km2)exceeded stable zones(15,004 km2),driven primarily by rapid desiccation and salinization.Solonchak soils increased at an annual rate of 5.58%,while surface water bodies declined by 4.83%per year.Concurrently,sparse or distressed vegetation increased by 1.43%annually,reflecting ongoing afforestation efforts.This study provides the first MSAVI-based and medium-resolution land cover baseline for the South Aral Seabed and demonstrates that soil-adjusted vegetation indices are essential for reliable dryland classification where conventional indices fail.The proposed spectral index framework offers a replicable methodology applicable to other global drylands facing similar land degradation and restoration challenges.
基金supported in part by the National Key Research and Development Program of China(No.2022YFA1604900)the National Natural Science Foundation of China(NSFC)(Nos.12405154,12235016,12221005,12435009,12275104,92570117)+7 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB34030000)the Fundamental Research Funds for the Central UniversitiesOpen fund for Key Laboratories of the Ministry of Education(No.QLPL2024P01)CUHK-Shenzhen University Development Fund(Nos.UDF01003041 and UDF03003041)Shenzhen Peacock Fund(No.2023TC0007)Ministry of Science and Technology of China(No.2024YFA1611004)the European Union–Next Generation EU through the research(No.P2022Z4P4B)“SOPHYA-Sustainable Optimized PHYsics Algorithms:fundamental physics to build an advanced society”under the program PRIN 2022 PNRR of the Italian Ministero dell’Universitàe Ricerca(MUR)。
文摘Leveraging high-precision lattice QCD data on the equation of state and baryon number susceptibility at a vanishing chemical potential,we constructed a Bayesian holographic QCD model and systematically analyzed the thermodynamic properties of heavy quarkonium in QCD matter under varying temperatures and chemical potentials.We computed the quark-antiquark interquark distance,potential energy,entropy,binding energy,and internal energy.We present detailed posterior distribution results of the thermodynamic quantities of heavy quarkonium,including maximum a posteriori(MAP)value estimates and 95%confidence levels(CL).Through numerical simulations and theoretical analysis,we find that an increase in the temperature and chemical potential reduces the quark distance,thereby facilitating the dissociation of heavy quarkonium and leading to a suppressed potential energy.The increase in temperature and chemical potential also raises the entropy and entropy force,further accelerating the dissociation of heavy quarkonium.The calculated results of binding energy indicate that a higher temperature and chemical potential enhance the tendency of heavy quarkonium to dissociate into free quarks.The internal energy also increases with rising temperature and chemical potential.These findings provide significant theoretical insights into the properties of strongly interacting matter under extreme conditions and lay a solid foundation for the interpretation and validation of future experimental data.Finally,we also present the results for the free energy,entropy,and internal energy of a single quark.
文摘The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.
文摘The development of sustainable sludge management systems requires looking at them with a new vision in which the concepts of SD(Sustainable Development)must integrate those of CE(Circular Economy),both concepts subject to the principles of TD(Thermodynamics),thus allowing the adoption of actions that are all the more effective the more complete the evaluation of the social dimension has been.This involves a new“Way of thinking”which sees the sludge system as the“Locomotive”of the entire wastewater/sludge treatment train and is developed through“Ways of acting”which includes both“Technical”actions to maximize recoveries of useful materials and/or or energy,and“Socio/Institutional”actions to overcome barriers linked to local cultures and traditions,also considering that the specific local context heavily influences the choices capable of satisfying the concepts of CE.It follows the need of issuing realistic and applicable regulations and overcoming social barriers,such as lack of infrastructure and/or qualified personnel,to achieve an effective integration of the concepts of CE with the more general ones of sustainability.
文摘Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality worldwide,necessitating innovative treatment strategies.Surgical resection and liver transplantation continue to be the gold standards for early-stage HCC;however,advances in imaging and minimally invasive techniques have improved patient selection and outcomes.Additionally,the emergence of targeted therapies and immunotherapy has transformed the treatment landscape for advanced HCC.This review highlights the efficacy of agents such as tyrosine kinase inhibitors,alongside emerging options like immune checkpoint inhibitors,which have shown promise in clinical trials.Furthermore,the role of locoregional therapies,including ablation in the setting of combined treatment,transar-terial chemoembolization and transarterial radioembolization with flow catheters,cone-beam computed tomo-graphy and 4D navigation guidance,is examined in the context of bridging therapies for patients awaiting surgical intervention.The integration of multidisciplinary care approaches and personalized treatment plans is crucial for optimizing outcomes.Future directions for HCC treatment are discussed,including the potential of novel biomarkers in prognosis and treatment response.This comprehensive overview aims to equip clinicians with the latest insights and foster collaborative efforts to improve HCC patient management and survival rates.
文摘BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.
基金supported in part by the IN2CCAM Project that had received funding from the European Union’s Horizon Europe research and Innovation Programme(101076791).
文摘This paper addresses the diagnosability analysis problem under external malicious attacks of a networked discrete event system modeled by labeled Petri net.In particular,we focus on a stealthy replacement attack to alter or corrupt the observation of the system,in which the transition labels are replaced by others or empty string,and its attack stealthiness requires that the corrupted observations should be contained in the behavior of system.The aim of this work is,from an attacker viewpoint,to design a stealthy replacement attack for violating the diagnosability of system.To this end,we first build a new structure,called complete unfolded verifier,with the notion of a predefined elementary unsound path that leads to the violation of diagnosability,which is used to enumerate all the potential attacked paths to be transformed into elementary unsound ones.Then an optimal attack synthesis problem in terms of minimum energy cost is formulated by determining whether an elementary unsound path is generated via solving a set of integer nonlinear programming problems.Finally,we show that the nonlinear programming problems can be transformed into integer linear programming problems by introducing additional linear constraints.Examples are used to illustrate the proposed attack strategy.
文摘The composition of the vaginalmicrobiota(VMB)influences the health of the female reproductive tract.Several studies have shown how the absence of lactobacilli causes an imbalance in the vaginal microbial community,favoring the development of infections.The present study aims to evaluate the relationship between the VMB and human papillomavirus(HPV)infection to clarify the role of the vaginal microbiota in the persistence and clearance of HPV.Many researchers have provided the scientific community with information on the composition of the microbiota and how it may also influence HPV infection and the development of cervical cancer.Studies have shown that the main Lactobacilli species that favor HPV clearance are Lactobacillus(L.)iners and L.gasseri.In this review,we focused on the general aspects of the interaction between HPV and the VMB,evaluating the influence of the microbiota on the immune system and the effect on different physiologic stages of women’s lives,like pregnancy and menopause.The diversity of the VMB worldwide was also assessed.The association between lactobacilli composition,ethnicity,and cancer must be related to other factors(age,smoking,physiological factors)and co-infections.New formulations of probiotics and innovative surgical removal systems that preserve the integrity of the VMB are also being developed to prevent and reduce the incidence of cervical cancer.More research and understanding are needed on a very complex topic such as the VMB.
文摘Purpose–This paper investigates how high-speed rail(HSR)influences socioeconomic inequality by providing the first systematic bibliometric review of research trends,methodological approaches and thematic structures.It examines whether HSR fosters balanced regional development or reinforces spatial disparities.Design/methodology/approach–Using the Bibliometrix R package,237 records were retrieved from the Web of Science(1985–2024).Citation indicators,keyword co-occurrence and collaboration networks were combined with natural language processing(NLP)to classify studies by territorial scale,methodology,economic variables and inequality outcomes.Findings–The paper offers the first structured overview of how the literature conceptualizes the link between HSR and inequality.It highlights persistent gaps–scarcity of city-level analyses,limited socioeconomic indicators and reliance on Chinese case studies–providing a foundation for more comparative and interdisciplinary research.Originality/value–This paper contributes by offering a structured overview of how the literature has conceptualized and measured the relationship between HSR and inequality.By identifying persistent research gaps–such as the scarcity of city-level analyses,limited use of socioeconomic indicators,and overreliance on Chinese case studies–it provides a foundation for more comparative and interdisciplinary approaches.The study informs policymakers and researchers on how to design future infrastructure projects that balance efficiency with equity.
文摘Recurrent aphthous stomatitis(RAS)is a very frequent condition in developed countries whose basic symptom is a lesion referred to as an aphthous ulcer.High levels of interleukin(IL)-1 and IL-6 and low salivary levels of IL-10 are the basis of RAS pathogenesis.Sublingual supplements based on IL-10 can be very useful in reducing the phenomenon of aphthous recurrence in patients with RAS.An observational clinical experience with a group of 5 patients with RAS receiving a commercially available IL-10-based supplement was reported by the authors.The findings revealed a subsequent reduction in the incidence of mouth ulcers.
基金supported in part by the IN2CCAM project that has received funding from the European Union's Horizon Europe research and innovation programme(101076791)the National Natural Science Foundation of China(62403378)the Natural Science Basic Research Program of Shaanxi Province(2024JC-YBQN-0669)
文摘In this work, we address the codiagnosability analysis problem of a networked discrete event system under malicious attacks. The considered system is modeled by a labeled Petri net and is monitored by a series of sites, in which each site possesses its own set of sensors, without requiring communication among sites or to any coordinators. A net is said to be codiagnosable with respect to a fault if at least one site could deduce the occurrence of this fault within finite steps. In this context, we focus on a type of malicious attack that is called stealthy intermittent replacement attack. The stealthiness demands that the corrupted observations should be consistent with the system's normal behavior, while the intermittent replacement setting entails that the replaced transition labels must be recovered within a bounded of consecutive corrupted observations(called as K-corruption intermittent attack). Particularly, there exists a coordination between attackers that are separately effected on different sites, which holds the same corrupted observation for each common transition under attacks. From an attacker viewpoint, this work aims to design Kcorruption intermittent attacks for violating the codiagnosability of systems. For this purpose, we propose an attack automaton to analyze K-corruption intermittent attack for each site, and build a new structure called complete attack graph that is used to analyze all the potential attacked paths. Finally, an algorithm is inferred to obtain the K-corruption intermittent attacks, and examples are given to show the proposed attack strategy.
文摘Checkpoint inhibitors,particularly programmed cell death-1/programmed death-ligand 1(PD-1/PDL1)inhibitors,have significantly advanced the treatment of Hodgkin lymphoma(HL),especially in relapsed or refractory cases.However,challenges such as resistance,immune-related adverse events(irAEs),and the need for effective patient selection remain.This review aims to explore the mechanisms of resistance to checkpoint inhibitors,including alterations in the tumor microenvironment,loss of antigen presentation,and T-cell exhaustion.Overcoming resistance may involve combination therapies,such as pairing PD-1 inhibitors with other immune checkpoint inhibitors or targeted therapies like Brentuximab vedotin.Additionally,next-generation inhibitors targeting molecules like lymphocyte-activation gene 3(LAG-3)and T-cell immunoglobulin and mucin-domain containing-3(TIM-3)show promise in addressing resistance mechanisms not overcome by PD-1 inhibitors.Identifying reliable biomarkers to predict response to checkpoint inhibitors is critical for optimizing treatment,with ongoing research focusing on tumor mutational burden(TMB),inflammatory markers,and genetic profiling.Future clinical trials will aim to refine treatment regimens,optimize therapeutic combinations,and minimize adverse effects to maximize patient benefit.
文摘While exerting their metabolic activities in the gastrointestinal milieu,probiotics impact the host well-being by boosting immunity,treating metabolic disorders,and modulating microbiota and metabolome.Due to the high incidence of gluten-based disorders,the present work aims to deeply explore the metabolism of two selected microbial consortia(MCs)during gluten digestion under simulated gastrointestinal conditions.Featured by high protease and peptidase activity,both MCs accounted for different lactic acid bacteria and Bacillus strains that were combined with two commercial protease enzymes.Gluten substrates were used as purified extracts,white and whole wheat breads.Control samples,instead,relied onto the microbial enzyme lack.Twenty-four hours of simulated digestion were sufficient to completely hydrolyze gluten in one of the two MC-containing experimental sets,and the relative 48 h-digested extract did not alter the cytokine expression in duodenal biopsies from celiac disease(CeD)patients.When digested samples were assayed for antioxidant and phytase activities,microbial enzymes demonstrated to significantly improve both 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)and 1,1-diphenyl-2-picrylhydrazyl(DPPH)scavenging activity and to decrease the phytic acid concentration.The inspection of the free amino acid profiles allowed for distinguishing the two MCs,whereas the detection of a heterogeneous panel of volatile organic compounds supported the presence/activity of microbial enzymes without statistically significant differences between MCs.As functional contribution,digested extracts with MCs also proved to reduce the inflammatory cytokine concentrations in cell lines exposed to lipopolysaccharide trigger.Therefore,in line with studies exploring novel adjuvant therapies,the present innovative probiotic consortium featured by high gluten-hydrolyzing metabolism also showed the capability to improve various parameters usually found to be altered in patients affected by gluten-based disorders or CeD.
基金ARD receives support within the GRINS project–Growing Resilient,INclusive and Sustainable from the European Union Next-Generation EU(GRINS PE00000018,CUP:H23C24000110006,Spoke 4 Sustainable Finance)PT received research support by a grant from the Italian Research Center on High Performance Computing,Big Data and Quantum Computing(ICSC)funded by EU-Next Generation EU(PNRR-HPC,CUP:C83C22000560007).
文摘Although numerous studies have examined the impact of ESG practices on bank profitability,the results remain inconclusive,underscoring the importance of analyzing ESG components separately.This study examines the impact of ESG performance—in each of its individual dimensions—on the profitability of 192 European listed banks over the period 2009–2019,a critical decade following the 2008 global financial crisis.Via a panel regression model,the findings suggest that environmental practices deliver more immediate benefits.While governance practices are vital for ensuring stability,they do not appear to be sufficient to drive short-term variations in profitability.Moreover,social practices are negatively related to profitability.To address this finding,this study adopts the One Health approach,fostering the need for policy-makers and bank managers to integrate this perspective into bank’s approach to sustainability in a more holistic and forward-thinking vision of social responsibility via the exploitation of specialized expertise.
基金funded by the Deanship of Scientific Research,Vice Presidency for Graduate Studies and Scientific Research,King Faisal University,Saudi Arabia,for supporting this work for work through grant number KFU242134.
文摘Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by the defoliation and drying of the whole tree were observed in the Jazan,El Baha,Najran,and Asir regions.The purpose of this investigation was to isolate and identify the Fusarium species recovered from symptomatic coffee trees.The developed fungi were initially characterized based on their morphological features followed by molecular phylogenetic multi-locus analysis of the combined sequences of ITS,TEF1-α,RPB2,and CaM.Twenty-five isolates were recovered from 28 samples.All fungal isolates were categorized morphologically under the genus Fusarium.Phylogenetic analysis positioned all the representative 15 isolates into one cluster grouping together with Neocosmospora falciformis(formerly F.falciforme)confirming their taxonomic position.Pathogenicity tests of the N.falciformis isolates were subsequently conducted on coffee seedlings,and the results revealed that all isolates induced wilt symptoms resembling those recorded in the field,and the incidence was 100%.The fungicide sensitivity test of seven investigated fungicides revealed that Maxim XL^(®) followed by Moncut^(®) exhibited the highest inhibitory effect against N.falciformis KSA 24-14,reaching 93.33%and 91.67%,respectively.To our knowledge,N.falciformis is a new causal pathogen of coffee wilt in Saudi Arabia.Remarkably,these results offer important insights for devising effective approaches to monitor and control such diseases.
基金supported by the European Union-Next Generation EU-PNRR M6C2-Investment 2.1 Enhancement and Strengthening of Biomedical Research in the NHS-Project:PNRR-MCNT2-2023-12377670(Grant No.CUP F93C24000250007).
文摘Melanoma,the most aggressive form of skin cancer,remains a significant clinical challenge due to the high metastatic potential and drug resistance.This review explores the pivotal roles of angiogenesis and vasculogenic mimicry in melanoma progression and treatment resistance.Angiogenesis,driven primarily by VEGF/VEGFR signaling,is critical for tumor sustenance but is often insufficient under hypoxic conditions,prompting melanoma cells to adapt by forming vascular-like structures(i.e.,vasculogenic mimicry).These structures enable melanoma cells to mimic endothelial functions and are linked to increased metastasis and poor prognosis.Molecular drivers,including VE-cadherin,EphA2,and hypoxia-inducible factors,have been identified as key regulators of these processes.Current anti-angiogenic agents have limited efficacy in advanced/metastatic melanoma due to tumor plasticity and the interplay between angiogenesis and vasculogenic mimicry.The review highlights the need for therapeutic strategies targeting both mechanisms,emphasizing the importance of combination treatments to overcome resistance.Future research should aim to elucidate the molecular underpinnings of angiogenesis and vasculogenic mimicry to improve melanoma management and patient outcomes.
