Emerging role of exosomes in ulcerative colitis: Targeting NOD-like receptor family pyrin domain containing 3 inflammasome

Ulcerative colitis(UC)is a chronic recurrent inflammatory bowel disease.Despite ongoing advances in our understanding of UC,its pathogenesis is yet unelu-cidated,underscoring the urgent need for novel treatment strategies for patients with UC.Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules,such as proteins,RNAs,DNA,and metabolites.The NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β(IL-1β)and IL-18,triggering the inflammatory response to a pathogenic agent or injury.Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome,with vital roles in the pathological process of UC.Here,recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC.First,the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized.Finally,an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are high-lighted.

System Reliability Analysis Method Based on T-S FTA and HE-BN

For high-reliability systems in military,aerospace,and railway fields,the challenges of reliability analysis lie in dealing with unclear failure mechanisms,complex fault relationships,lack of fault data,and uncertainty of fault states.To overcome these problems,this paper proposes a reliability analysismethod based on T-S fault tree analysis(T-S FTA)and Hyper-ellipsoidal Bayesian network(HE-BN).The method describes the connection between the various systemfault events by T-S fuzzy gates and translates them into a Bayesian network(BN)model.Combining the advantages of T-S fault tree modeling with the advantages of Bayesian network computation,a reliability modeling method is proposed that can fully reflect the fault characteristics of complex systems.Experts describe the degree of failure of the event in the form of interval numbers.The knowledge and experience of experts are fused with the D-S evidence theory to obtain the initial failure probability interval of the BN root node.Then,the Hyper-ellipsoidal model(HM)constrains the initial failure probability interval and constructs a HE-BN for the system.A reliability analysismethod is proposed to solve the problem of insufficient failure data and uncertainty in the degree of failure.The failure probability of the system is further calculated and the key components that affect the system’s reliability are identified.The proposedmethod accounts for the uncertainty and incompleteness of the failure data in complex multi-state systems and establishes an easily computable reliability model that fully reflects the characteristics of complex faults and accurately identifies system weaknesses.The feasibility and accuracy of the method are further verified by conducting case studies.

An Improved CREAM Model Based on DS Evidence Theory and DEMATEL

Cognitive Reliability and Error Analysis Method(CREAM)is widely used in human reliability analysis(HRA).It defines nine common performance conditions(CPCs),which represent the factors thatmay affect human reliability and are used to modify the cognitive failure probability(CFP).However,the levels of CPCs are usually determined by domain experts,whichmay be subjective and uncertain.What’smore,the classicCREAMassumes that the CPCs are independent,which is unrealistic.Ignoring the dependence among CPCs will result in repeated calculations of the influence of the CPCs on CFP and lead to unreasonable reliability evaluation.To address the issue of uncertain information modeling and processing,this paper introduces evidence theory to evaluate the CPC levels in specific scenarios.To address the issue of dependence modeling,the Decision-Making Trial and Evaluation Laboratory(DEMATEL)method is used to process the dependence among CPCs and calculate the relative weights of each CPC,thus modifying the multiplier of the CPCs.The detailed process of the proposed method is illustrated in this paper and the CFP estimated by the proposed method is more reasonable.

Sparse Reconstructive Evidential Clustering for Multi-View Data

Although many multi-view clustering(MVC) algorithms with acceptable performances have been presented, to the best of our knowledge, nearly all of them need to be fed with the correct number of clusters. In addition, these existing algorithms create only the hard and fuzzy partitions for multi-view objects,which are often located in highly-overlapping areas of multi-view feature space. The adoption of hard and fuzzy partition ignores the ambiguity and uncertainty in the assignment of objects, likely leading to performance degradation. To address these issues, we propose a novel sparse reconstructive multi-view evidential clustering algorithm(SRMVEC). Based on a sparse reconstructive procedure, SRMVEC learns a shared affinity matrix across views, and maps multi-view objects to a 2-dimensional humanreadable chart by calculating 2 newly defined mathematical metrics for each object. From this chart, users can detect the number of clusters and select several objects existing in the dataset as cluster centers. Then, SRMVEC derives a credal partition under the framework of evidence theory, improving the fault tolerance of clustering. Ablation studies show the benefits of adopting the sparse reconstructive procedure and evidence theory. Besides,SRMVEC delivers effectiveness on benchmark datasets by outperforming some state-of-the-art methods.

Genetic Evidence for Causal Association Between Hypertension and Chronic Pain:A Bidirectional Two-Sample Mendelian Randomization Study

Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In the present study,Mendelian randomization(MR)was employed to examine the potential causal relationship between hypertension and risk of chronic pain.Methods The study data were derived from the pooled dataset of the genome-wide association study(GWAS),enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest,abdominal,joint,back,limb,and multisite chronic pain.We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting(IVW),MR-Egger,weighted median,and weighted mode,quantified by odds ratio(OR).Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache(OR=1.007,95%CI:1.003-1.011,P=0.002)and limb pain(OR=1.219,95%CI:1.033-1.439,P=0.019).No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR(P>0.05).In addition,there was no potential causal association between secondary hypertension and chronic pain(P>0.05).Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain,and no causal relationship was found between secondary hypertension and chronic pain.These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.

Glacial debris flow susceptibility mapping based on combined models in the Parlung Tsangpo Basin,China

Machine learning(ML)-based prediction models for mapping hazard(e.g.,landslide and debris flow)susceptibility have been widely developed in recent research.However,in some specific areas,ML models have limited application because of the uncertainties in identifying negative samples.The Parlung Tsangpo Basin exemplifies a region prone to recurrent glacial debris flows(GDFs)and is characterized by a prominent landform featuring deep gullies.Considering the limitations of the ML model,we developed and compared two combined statistical models(FA-WE and FA-IC)based on factor analysis(FA),weight of evidence(WE),and the information content(IC)method.The final GDF susceptibility maps were generated by selecting 8 most important static factors and considering the influence of precipitation.The results show that the FA-IC model has the best performance.The areas with a very high susceptibility to GDFs are primarily located in the narrow valley section upstream,on both sides of the valley in the middle and downstream of the Parlung Tsangpo River,and in the narrow valley section of each tributary.These areas encompass 86 gullies and are characterized as"narrow and steep".

An Evidence-Based CoCoSo Framework with Double Hierarchy Linguistic Data for Viable Selection of Hydrogen Storage Methods

Hydrogen is the new age alternative energy source to combat energy demand and climate change.Storage of hydrogen is vital for a nation’s growth.Works of literature provide different methods for storing the produced hydrogen,and the rational selection of a viable method is crucial for promoting sustainability and green practices.Typically,hydrogen storage is associated with diverse sustainable and circular economy(SCE)criteria.As a result,the authors consider the situation a multi-criteria decision-making(MCDM)problem.Studies infer that previous models for hydrogen storage method(HSM)selection(i)do not consider preferences in the natural language form;(ii)weights of experts are not methodically determined;(iii)hesitation of experts during criteria weight assessment is not effectively explored;and(iv)three-stage solution of a suitable selection of HSM is unexplored.Driven by these gaps,in this paper,authors put forward a new integrated framework,which considers double hierarchy linguistic information for rating,criteria importance through inter-criteria correlation(CRITIC)for expert weight calculation,evidence-based Bayesian method for criteria weight estimation,and combined compromise solution(CoCoSo)for ranking HSMs.The applicability of the developed framework is testified by using a case example of HSM selection in India.Sensitivity and comparative analysis reveal the merits and limitations of the developed framework.

Using clinical cases to guide healthcare

Evidence-based practice(EBP)has been the gold standard in healthcare for nearly three centuries and aims to assist physicians in providing the safest and most effective healthcare for their patients.The well-established hierarchy of evidence lists systematic reviews and meta-analyses at the top however these methodologies are not always appropriate or possible and in these instances case-control studies,case series and case reports are utilised to support EBP.Case-control studies allow simultaneous study of multiple risk factors and can be performed rapidly and relatively cheaply.A recent example was during the Coronavirus pandemic where case-control studies were used to assess the efficacy of personal protective equipment for healthcare workers.Case series and case reports also play a role in EBP and are particularly useful to study rare diseases such as inflammatory bowel disease in transgender and gender non-conforming individuals.They are also vital in generating and disseminating early signals and encouraging further research.Whilst these methodologies have weaknesses,particularly with regards to bias and loss of patient confidentiality for rare pathologies,they have an important part to play in EBP and when appropriately utilised can significantly impact upon clinical practice.

Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines

Background:The European Society for Medical Oncology(ESMO)guidelines are among the most comprehensive and widely used clinical practice guidelines(CPGs)globally.However,the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated.This study assessed ESMO CPG levels of evidence(LOE)and grades of recommendations(GOR),as well as their trends over time across various cancer settings.Methods:We manually extracted every recommendation with the Infectious Diseases Society of America(IDSA)classification from each CPG.We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types.Results:Among the 1,823 recommendations in the current CPG,30%were classified as LOEⅠ,and 43%were classified as GOR A.Overall,there was a slight decrease in LOEⅠ(−2%)and an increase in the proportion of GOR A(+1%)in the current CPG compared to previous versions.The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials(LOEⅠ–Ⅱ)shows a decrease(71%vs.63%,p=0.009)while recommendations based on lower levels of evidence(LOEⅢ–Ⅴ)show an increase(29%vs.37%,p=0.01)between previous and current version.In the current versions,the highest proportion of LOEⅠ(42%)was found in recommendations related to pharmacotherapy,while the highest proportion of GOR A recommendations was found in the areas of pathology(50%)and diagnostic(50%)recommendations.Significant variability in LOEⅠand GOR A recommendations and their changes over time was observed across different cancer types.Conclusion:One-third of the current ESMO CPG recommendations are supported by the highest level of evidence.More well-designed randomized clinical trials are needed to increase the proportion of LOEⅠand GOR A recommendations,ultimately leading to improved outcomes for cancer patients.

Are case reports valuable?Exploring their role in evidence based medicine and patient care

Case reports,often overlooked in evidence-based medicine(EBM),play a pivotal role in healthcare research.They provide unique insights into rare conditions,novel treatments,and adverse effects,serving as valuable educational tools and generating new hypothesis.Despite their limitations in generalizability,case reports contribute significantly to evidence-based practice by offering detailed clinical information and fostering critical thinking among healthcare professionals.By acknowledging their limitations and adhering to reporting guidelines,case reports can contribute significantly to medical knowledge and patient care within the evolving landscape of EBM.This editorial explores the intrinsic value of case reports in EBM and patient care.

Sedimentary environment and organic matter accumulation of Wufeng-Longmaxi shales,southwest Yangtze Plate,China:Insights from geochemical and petrological evidence

Upper Ordovician-Lower Silurian Wufeng-Longmaxi Formation is the most developed strata of shale gas in southern China.Due to the complex sedimentary environment adjacent to the Kangdian Uplift,the favorable area for organic-rich shale development is still undetermined.The authors,therefore,focus on the mechanism of accumulation of organic matter and the characterization of the sedimentary environment of the Wufeng-Longmaxi Shales to have a more complete understanding and new discovering of organic matter enrichment and favorable area in the marginal region around Sichuan Basin.Multiple methods were applied in this study,including thin section identification,scanning electron microscopy(SEM)observations and X-ray diffraction(XRD),and elemental analysis on outcrop samples.Five lithofacies have been defined according to the mineralogical and petrological analyses,including mudstone,bioclastic limestone,silty shale,dolomitic shale,and carbonaceous siliceous shale.The paleo-environments have been reconstructed and the organic enrichment mechanism has been identified as a reduced environment and high productivity.The Wufeng period is generally a suboxic environment and the early Longmaxi period is a reducing environment based on geochemical characterization.High dolomite content in the study area is accompanied by high TOC,which may potentially indicate the restricted anoxic environment formed by biological flourishing in shallower water.And for the area close to the Kangdian Uplift,the shale gas generation capability is comparatively favorable.The geochemical parameters implied that new favorable areas for shale gas exploration could be targeted,and more shale gas resources in the mountain-basin transitional zone might be identified in the future.

Research on Early Warning of Banking Crises from the Perspective of Credit Structures

The relationship between credit expansion and banking crises is complex and cannot be fully explained by total credit alone.A systematic analysis of the relationship between the amount and structure of total credit and banking crises is important for an objective prediction of the influence of potential financial risks.This paper,drawing on data from 15 selected countries,delves into the power of credit indicators in the early warning of banking crises from the perspectives of industrial structure,sector structure,and term structure of credit.Various machine learning methods were used,including Logistic Regression,Random Forest,Decision Tree,Support Vector Machine(SVM),Bagging,and Boosting models.The empirical findings indicate that credit expansion plays a crucial role in triggering banking crises.However,total credit is better suited for the early warning of short-term banking crises,whereas credit structure is more useful for the early warning of long-term banking crises.Moreover,in an early warning system,identifying key early warning indicators is more meaningful than merely increasing the number of indicators.Machine learning can somewhat enhance the early warning power,but it may not always be robust.Therefore,more attention should be paid to potential systemic banking crises resulting from an imbalance in credit structure while regulating the total credit threshold.

A New Definition of P-Value Involving the Maximum Likelihood Estimator

We present here an alternative definition of the P-value for statistical hypothesis test of a real-valued parameter for a continuous random variable X. Our approach uses neither the notion of Type I error nor the assumption that null hypothesis is true. Instead, the new P-value involves the maximum likelihood estimator, which is usually available for a parameter such as the mean μ or standard deviation σ of a random variable X with a common distribution.

Real-World Evidence in Localized Pancreatic: Coping with Uncertainty in Unselected Populations

Background: Localized pancreatic cancer, including resectable (R), borderline resectable (BR) and locally advanced unresectable disease (LAU), is considered in clinical guidelines for diverse treatment options based on clinical trials in selected populations. Hence, exploring with real world evidence (RWE) clinicians’ preferences for treatment options and their results seems pertinent. Methods: In a set of consecutive patients with localized pancreatic cancer assisted in a third level hospital from January 2013 to December 2022, medical records, symptoms, diagnostic process, distribution between subtypes, and treatment plans, with safety and efficacy results, were assessed. Results: A total of 152 patients with localized disease were included (43.4% R, 21.0% BR, 33.6% LAU). The population characteristics exemplified differences between daily practice and clinical trials. Tumor location and symptoms were as expected. Treatment plan was conditioned by PS or comorbidities in 23.0% of patients. In patients with R disease, surgery followed by different adjuvant chemotherapy (CT) regimes was the antineoplastic treatment of choice (64.8%) with efficacy results (OS 37.5 months;95% CI 18.4 - 56.7), in the range of contemporary standards. The common use of neoadjuvant CT for BR disease (94.4%), with surgery in 50% of them, and its results (OS 30.8 months;95% CI 10.5 - 51.2) reflected current controversies of treatment recommendations and evolution in this scenario. Paliative CT with or without radiotherapy was the standard specific treatment in LAU disease (95.1%) with survival results (PFS: 10.8 months;95% CI 8.8 - 12.7. OS: 20.3 months;95% CI 13.5 - 27.2) that justify the distinct character and the specific study of this entity. Conclusion: RWE for localized pancreatic cancer aroused from the analysis of this population confirms the distinct nature of patients assisted in daily practice, as well as mirrors the complexity of decision making in clinical assumptions in which achieving stronger evidence should be paramount.

Non-alcoholic fatty liver disease in type 2 diabetes:Emerging evidence of benefit of peroxisome proliferator-activated receptors agonists and incretin-based therapies

Nonalcoholic fatty liver disease(NAFLD)is a global epidemic,affecting more than half of the people living with type 2 diabetes(T2D).The relationship between NAFLD and T2D is bidirectional and the presence of one perpetuates the other,which significantly increases the hepatic as well as extrahepatic complications.Until recently,there was no approved pharmacological treatment for NAFLD/nonalcoholic steatohepatitits(NASH).However,there is evidence that drugs used for diabetes may have beneficial effects on NAFLD.Insulin sensitizers acting through peroxisome proliferator-activated receptor(PPAR)modulation act on multiple levels of NAFLD pathogenesis.Pioglitazone(PPARγ agonist)and saroglitazar(PPARα/γagonist)are particularly beneficial and recommended by several authoritative bodies for treating NAFLD in T2D,although data on biopsyproven NASH are lacking with the latter.Initial data on elafibanor(PPARα/δ agonist)and Lanifibranor(pan PPAR agonist)are promising.On the other hand,incretin therapies based on glucagon-like peptide-1(GLP-1)receptor agonists(GLP-1RA)and dual-and triple-hormone receptor co-agonists reported impressive weight loss and may have anti-inflammatory and antifibrotic properties.GLP-1 RAs have shown beneficial effects on NAFLD/NASH and more studies on potential direct effects on liver function by dual-and triple-agonists are required.Furthermore,the long-term safety of these therapies in NAFLD needs to be established.Collaborative efforts among healthcare providers such as primary care doctors,hepatologists,and endocrinologists are warranted for selecting patients for the best possible management of NAFLD in T2D.

Preceptors'experiences in guiding nursing students to use research findings and to implement evidence-based practice

Objective:Evidence-based practices(EBPs)have been taught to students by identifying the best evidence/evidence from research results.However,the experiences of Indonesian nurse preceptors in helping students implement research findings have not been explored thoroughly.This study aimed to explore Indonesian nurse preceptors in guiding nursing students to use research findings.Methods:This study used interpretive phenomenology analysis that involves 9 nurse preceptors from hospitals in West Kalimantan,Indonesia.Semi-structured in-depth interviews were recorded and then transcribed verbatim.Results:Three themes were generated during the analysis:“types of student supervision,”“issues during supervision,”and“the need for research literacy and supervision.”Conclusions:Nurse preceptors need support to supervise the nursing students to use research findings.In addition to upgrading nursing skills,nurse preceptors must receive training in research and its utilization.Developing an appropriate strategy to assist students in using research findings will enhance the promotion of evidence-based nursing practices on a daily basis.

Security Risk Assessment in Container Terminals:Empirical Evidence from Greece

The most prominent risk assessment techniques are founded on the values of measuring and controlling the frequency and the consequences of risks in order to assure an“acceptable level”of“safeness”mainly in the lines of environmental,health and hygiene and port product issues.This paper examines security risk assessment approaches within the emerging role of ports.This paper contributes to the current literature by considering the ports of Greece as a case in point and by measuring the degree of its security risk orientation based on certain valid risk factors drawn from the current literature.Moreover,it presents a security risk assessment methodology into the domain of port container terminals.Their potential for ports were quantitatively and qualitatively assessed by discussing issues of security approaches within the maritime industry,in order to facilitate improvement strategies.A two-dimension empirical study was conducted,in a time range of ten years(2010-2020)in order to provide evidence regarding security risk assessment in the port container terminal of Thessaloniki,in Greece.The findings of this study have significant strategic policy implications and shed more light on the role of security risks in the overall risk orientation of container terminals in practice.Finally,further research directions in security risk in ports are proposed.

Summary of the Best Evidence for Tube Feeding Intolerance in Critically Ill Children

Objective:To summarize the evidence of tube feeding intolerance in critically ill children,aiming to provide evidence-based information for clinical nursing staff.Methods:Evidence search was done in Chinese and English databases to guide network and professional associations at home and abroad.The search time limit was from January 2014 to January 2024,nearly 10 years of relevant literature,mainly including guidelines,consensus,expert advice,best practice,evidence summary,system evaluation,and meta-analysis.Literature quality evaluation and evidence extraction were independently performed by two researchers.Results:This paper included 13 articles,including three guidelines,three systematic evaluations,three expert opinions,and four expert consensus.Twenty-six pieces of evidence were summarized from 10 aspects of feeding intolerance definition,team building,nutritional assessment,nutritional preparation,feeding protocol,feeding route,feeding management,pipeline management,gastric residual volume,and drug application.Conclusion:This paper summarized the evidence of tube feeding intolerance in critically ill children,which can provide evidence-based information for clinical practice.The abdominal signs should be closely observed when evaluating feeding intolerance,focusing on the prevention and reduction of feeding interruption.

Extension of Paraconsistent Many-Valued Similarity Method to Group Decision

The Paraconsistent Many-Valued Similarity (PMVS) method for multi-attribute decision making will be incomplete as a decision model if it is not extended to the realm of group decision-making. Therefore, in this article, our primary objective is to show how the paraconsistent many-valued similarity method can be used to solve group decision-making problems involving choice making or ranking of a finite set of decision alternatives. Moreover, since weights are very important parameters in multi-attribute decision-making, we have introduced the Borda rule to calculate the weights of experts and that of every criterion under consideration. To demonstrate how the proposed method works, a numerical example on energy sources of an economy from the points of view of a group of experts is investigated. Further, we compare the results of this new approach with that of fuzzy TOPSIS group decision-making method to illustrate the robustness and effectiveness of the former.

The Practice and Exploration of Applying EBM to Bilingual Teaching of Medical Genetics at OSBCM

In the process of teaching medical genetics of undergraduate clinical medicine, the practice and exploration of applying EBM to the bilingual teaching of OSBCM medical genetics are carried out. Using CBL and PBL as the carrier can make up for the shortcomings of a single teaching mode, synthesize the advantages of multiple teaching modes. It starts from integrating the basic theoretical knowledge of medicine and clinical practice knowledge, improving students’ bilingual level of medical genetics, cultivating students’ literature retrieval ability, and promoting early clinical, multi-clinical and repeated clinical consciousness for medical students. Therefore, it is more conducive to cultivate students’ ability to learn independently, accurately analyze and solve problems, improve medical students’ clinical thinking ability and scientific research awareness, improve medical students’ ability of international communication, and lay a solid foundation for improving medical students’ future post competence, innovative spirit and lifelong learning ability.