Objective. To establish a PCR- SSP method for discriminating as many HLA- A* 02 alleles, which could easily be introduced into a routine laboratory. Methods. In this study we typed HLA- A* 02 polymorphisms by a sequen...Objective. To establish a PCR- SSP method for discriminating as many HLA- A* 02 alleles, which could easily be introduced into a routine laboratory. Methods. In this study we typed HLA- A* 02 polymorphisms by a sequence- specific primer (SSP) method, which involved round 1 and round 2 PCR reactions to detect 17 HLA- A* 02 alleles (they are HLA- A* 0201- 0217 alleles) covering exon 2 and exon 3. Results. We have found that DNA sample concentration and purity were the most important variables in determining the quality of the results. For identifying correct band size, the size marker used was important. We noticed that different PCR machines performed differently. By this method, we detected 20 HLA- A* 02 positive genomic DNA samples and found 4 kinds of HLA- A* 02 alleles. They were HLA- A* 0201, 0203, 0206 and 0210. Conclusion. The HLA- A* 02 PCR- SSP method was proven to be a reliable and easily applicable typing method. Our results suggest that the SSP described here provides an optimal HLA- A* 02 typing technique that may be useful in selecting donor- recipient pairs in bone marrow transplantation between unrelated individuals.展开更多
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central ne...Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.展开更多
Nitrogen(N)enrichment has resulted in widespread alteration of grassland ecosystem processes and functions mainly through disturbance in soil enzyme activities.However,we lack a comprehensive understanding of how N de...Nitrogen(N)enrichment has resulted in widespread alteration of grassland ecosystem processes and functions mainly through disturbance in soil enzyme activities.However,we lack a comprehensive understanding of how N deposition affects specific key soil enzymes that mediate plant-soil feedback of grassland.Here,with a meta-analysis on 1446 cases from field observations in China,we show that N deposition differently affects soil enzymes associated with soil biochemical processes.Specifically,N-promoted C,N,and P-acquiring hydrolase activities significantly increased by 8.73%,7.67%,and 8.69%,respectively,related to an increase in microbial-specific enzyme secretion.The increased relative N availability and soil acidification were two potential mechanisms accounting for the changes in soil enzyme activities with N enrichment.The mixed N addition in combination of NH_(4)NO_(3) and urea showed greater stimulation effect on soil enzyme activities.However,the high rate and long-term N addition tended to weaken the positive responses of soil C-,Nand P-acquiring hydrolase activities to N enrichment.Spatially increased mean annual precipitation and temperature primarily promoted the positive effects of N enrichment on N-and P-acquiring hydrolase activities,and the stimulation of C-and N-acquiring hydrolase activities by N enrichment was intensified with the increase in soil depth.Finally,multimodal inference showed that grassland type was the most important regulator of responses of microbial C,N,and P-acquiring hydrolase activities to N enrichment.This meta-analysis provides a comprehensive insight into understanding the key role of N enrichment in shaping soil enzyme activities of grassland ecosystems.展开更多
BACKGROUND The incidence of type 2 diabetes mellitus(T2DM)in children and adolescents is increasing,yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated...BACKGROUND The incidence of type 2 diabetes mellitus(T2DM)in children and adolescents is increasing,yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated comorbidities.AIM To assess the effectiveness of current pharmacological treatments in managing T2DM in children and adolescents.The protocol of the study was registered in PROSPERO(CRD42022382165).METHODS Searches were performed in PubMed,EMBASE,Scopus,and ClinicalTrials.gov for publications between 1990 to September 2024 without language restrictions.Randomized control trials(RCTs)of pharmacotherapy in children and adolescents with T2DM(aged<19 years)were included.The primary outcome was a change in glycated hemoglobin(HbA1c)from baseline to follow-up.Secondary outcomes were changes in body weight,body mass index(BMI),total cholesterol,triglycerides,high density lipoprotein,and low-density lipoprotein from baseline,and incidence of adverse events during study periods.Screening,full-text review,data extraction,and assessments of risk of bias were done by two reviewers.Conflicts on each step were resolved by a third reviewer.Data analysis was performed using Review Manager Version 6.5(RevMan 6.5)and‘R’software via RStudio,‘meta’and‘netmeta’.RESULTS A total of 12 studies having low to moderate risk of bias with 1658 participants,and follow-up duration 12-52 weeks were included.In our network meta-analysis,compared to control(s),the reduction of HbA1c was sig-nificantly larger for dulaglutide[mean difference(MD),95%confidence interval:-1.20,-2.12 to-0.28],followed by dapagliflozin(-0.94,-1.44 to-0.44),liraglutide(-0.91,-1.37 to-0.45),empagliflozin(-0.87,-1.40 to-0.34),exenatide(-0.59,-1.07 to-0.11)and linagliptin(-0.45,-0.87 to-0.02)while other drugs had little or no effect.While liraglutide was associated with a change in body weight[MD-2.41(-4.68,-0.14)kg],no other drug treatment was associated with significant changes in body weight,BMI,and lipids.Apart from level 1 hypoglycemia with liraglutide[risk difference(RD):0.20,0.04-0.37]and minor adverse events with dulaglutide(RD:0.24,0.08-0.40),no other treatment was associated with excess risk of hypoglycemia or minor or major adverse events.CONCLUSION Pharmacotherapy of T2DM with dulaglutide,dapagliflozin,liraglutide,empagliflozin,exenatide,and linagliptin in children is associated with modest reduction of HbA1c.Larger RCTs with longer follow-up durations are needed to guide better therapeutic decision making.展开更多
Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization o...Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.展开更多
Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodi...Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodies.The latest European Society for Paediatric Gastroenterology,Hepatology,and Nutrition(ESPGHAN)2020 guidelines have excluded human leukocyte antigen(HLA)genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value,limited availability,and high cost in some countries.However,HLA genetic testing remains valuable in certain clinical contexts.This study provided practical indications for when to request and how to interpret HLA genotyping,emphasizing its continued relevance for CD diagnosis in specific cases.We also proposed a strategy for monitoring the risk of developing type 1 diabetes(T1D)in patients with CD,based on the risk stratification carried by different HLA genotypes.A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in2012,when HLA genotyping became mandatory for the diagnosis of CD.We identified key clinical scenarios where HLA testing remains useful.Several high risk HLA-DQ genotypes strongly associated with CD were highlighted,including HLA-DQ2.5/HLA-DQ2.2and HLA-DQ2.5/HLA-DQ2.5.Notably,while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD,it appears to confer protection against T1D.To support clinical practice,we presented a table clarifying commonly used HLA terminology,and another summarized the main clinical situations in which HLAgenotyping should still be considered.These findings underscore the dual role of HLA testing:Not only can it help rule out CD in selected cases,but it also identifies patients with CD at risk for T1D,guiding personalized monitoring strategies.展开更多
The information from sparsely logged wellbores is currently under-utilized in reservoir simulation models and their proxies using deep and machine learning (DL/ML).This is particularly problematic for large heterogene...The information from sparsely logged wellbores is currently under-utilized in reservoir simulation models and their proxies using deep and machine learning (DL/ML).This is particularly problematic for large heterogeneous gas/oil reservoirs being considered for repurposing as gas storage reservoirs for CH_(4),CO_(2) or H_(2) and/or enhanced oil recovery technologies.Lack of well-log data leads to inadequate spatial definition of complex models due to the large uncertainties associated with the extrapolation of petrophysical rock types (PRT) calibrated with limited core data across heterogeneous and/or anisotropic reservoirs.Extracting well-log attributes from the few well logs available in many wells and tying PRT predictions based on them to seismic data has the potential to substantially improve the confidence in PRT 3D-mapping across such reservoirs.That process becomes more efficient when coupled with DL/ML models incorporating feature importance and optimized,dual-objective feature selection techniques.展开更多
BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of co...BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile.展开更多
BACKGROUND Pyroptosis and ubiquitination have been identified as key processes influencing the pathogenesis of diabetes mellitus(DM).AIM To investigate the genes associated with the ubiquitin-proteasome system(UPS)and...BACKGROUND Pyroptosis and ubiquitination have been identified as key processes influencing the pathogenesis of diabetes mellitus(DM).AIM To investigate the genes associated with the ubiquitin-proteasome system(UPS)and pyroptosis in type 2 DM(T2DM),and elucidate their mechanisms of action in T2DM.METHODS The datasets GSE76894,GSE41762,and GSE86469 were utilized in this study.UPS-related genes(UPSGs)and pyroptosis-related genes(PRGs)were obtained from existing literature.Differential expression analysis was performed to identify differentially expressed genes(DEGs).DEGs were intersected with UPSGs and PRGs to identify differentially expressed UPSGs and PRGs.Ubiquitin-pyroptosisrelated biomarkers were determined using Spearman’s correlation,t-tests,and receiver operating characteristic curve analysis.Pathway enrichment of biomarkers was assessed using Gene Set Enrichment Analysis(GSEA).Single sample GSEA(ssGSEA)and Spearman’s correlation were used to analyze the relationship between biomarkers and immune cells.A competitive endogenous RNA network was constructed.Subsequently,drugs related to the biomarkers were identified and a gene-drug network was established.In dataset GSE86469,single-cell sequencing was utilized to determine cell types.Finally,the expression levels of biomarkers were validated through quantitative PCR(qPCR)and western blot analysis.RESULTS A total of 581 DEGs were identified in GSE76894.Four genes[ATP binding cassette subfamily C member 8(ABCC8),retinol binding protein 4(RBP4),Ras protein-specific guanine nucleotide-releasing factor 1(RASGRF1),and solute carrier family 34 member 2(SLC34A2)]were identified as ubiquitin-pyroptosis-related biomarkers in T2DM,based on consistent expression trends and significant differences in GSE76894 and GSE41762.These biomarkers were enriched in oxidative phosphorylation and mitogen-activated protein kinase signaling pathways,which are relevant to DM.ssGSEA revealed significant differences in the enrichment scores of nine immune cell types between groups.A total of 17 microRNAs(miRNAs)and 36 long non-coding RNAs(lncRNAs)were identified,forming numerous miRNA-lncRNA interactions.Additionally,22 drugs related to the biomarkers,such as gliclazide and tretinoin,were identified.In GSE86469,eight cell types,including alpha and beta cells,were characterized.qPCR and western blot analysis confirmed that the expression trends of RASGRF1 and SLC34A2 were consistent with the findings in GSE76894.CONCLUSION This study identified four ubiquitin-pyroptosis-related biomarkers(ABCC8,RBP4,RASGRF1,and SLC34A2)in T2DM through bioinformatics analysis,providing novel insights into the diagnosis and treatment of T2DM.展开更多
BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asi...BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asia has a high T2D burden,and many studies have reported varying prevalence rates of DD in this area.AIM To estimate the pooled prevalence of DD among patients with T2D in South Asia,as it is crucial for developing effective therapeutic strategies.METHODS This systematic review and meta-analysis included cross-sectional studies conducted in South Asian countries involving adults with T2D and reported the prevalence of DD.The studies were identified by searching multiple electronic databases and registries from the inception of each database to January 30,2025,using prespecified search terms.Four authors screened and extracted data independently.Meta-analyses were conducted using RStudio software with a random-effects model.The primary outcome was the pooled prevalence of DD.RESULTS Thirty-seven cross-sectional studies(28 from India,five from Bangladesh,and two each from Pakistan and Sri Lanka)with mostly high methodological quality involving 11500 subjects were included.The pooled prevalence of DD was 44%(95%confidence interval:35-53,I2=97.4%).The prevalence of DD was highest in Pakistan(85%),followed by India and Bangladesh(42%each),and Sri Lanka(25%).Emotional burden was the most prevalent form of DD(60%),followed by treatment regimen-related distress(51%),interpersonal distress(31%),and physician-related distress(17%).Meta-regression analysis revealed no significant associations between the prevalence of DD and publication year,sample size,proportion of females,age,duration of diabetes,insulin usage,glycated hemoglobin levels,or diabetic complications.CONCLUSION South Asians with T2D seem to experience a relatively high burden of DD,and the emotional burden is the most common form of DD in this area.Larger studies utilizing unique tools and involving a broader participant base from the region would provide better epidemiological data for effectively planning high-quality diabetes care in South Asian countries.展开更多
About 44%of the world’s cocoa is produced in one single country,Côte d’Ivoire.Providing this important raw material,most Ivorian cocoa farmers live in severe poverty,which,despite a multitude of sector interven...About 44%of the world’s cocoa is produced in one single country,Côte d’Ivoire.Providing this important raw material,most Ivorian cocoa farmers live in severe poverty,which,despite a multitude of sector interventions,is still widespread,affecting social and environmental sustainability in cocoa production.In this context,cocoa farmers are still often treated as a homogeneous group of small-scale producers(mainly males),resulting in interventions being conceptualized as one-size-fits-all approaches and failing to deliver support schemes that take farmers’specific conditions appropriately into account.Applying a broader typology approach that combines farm characteristics with farmers’characteristics,this study aims to delineate Ivorian cocoa farmers and their farms into specific types in order to improve advice for targeted sustainability interventions and living income(LI)potentials.Principal component analysis and hierarchical clustering analysis of a household dataset collected in 2022 in five cocoa-growing regions of Côte d’Ivoire were chosen to identify types of male-headed farms.To assure gender sensitive analysis,a female-headed farm type was created artificially.The specific characteristics of the identified types were captured using descriptive analysis.Descriptive statistics and non-parametric tests were then applied to examine the relationships between these farm types and various outcomes.Additionally,a binary logistic model was used to estimate the probability of these links in relation to variables relevant for achieving a LI.Finally,Spearman non-parametric correlation was used to identify eventual differences in the strength of relationships between key variables per farm type.Three different types of male-headed farms are identified:type 1(the most productive and diversified farms with larger size),type 2(middle-sized farms with strong focus on cash crops),and type 3(small-sized farms with a good level of diversification for self-consumption).The artificially created type 4 represents female-headed farms with the smallest size.On average,none of these farm types achieves a LI.However,type 1 shows the smallest LI gap,while type 4 is by far the worst.Our analyses reveal underlying socio-economic factors systematically disadvantaging female-headed cocoa farms,most notably limited access to land and other material assets.The key contribution of this study lies in the empirical identification of the different characteristics of farms in a given farming system,thereby identifying the need for targeted support interventions.Type-specific recommendations are made,showing pathways to provide tailored programs to farmers of different types in order to reduce their LI gaps.展开更多
INTRODUCTION Cardiovascular system involvement is an important determinant of long-term prognosis in patients with systemic lupus erythematosus(SLE).Aneurysmal dilatation of the aortic root combined with Stanford type...INTRODUCTION Cardiovascular system involvement is an important determinant of long-term prognosis in patients with systemic lupus erythematosus(SLE).Aneurysmal dilatation of the aortic root combined with Stanford type A aortic dissection(TAAD)is a highly catastrophic complication in these patients.展开更多
BACKGROUND Type 2 diabetes(T2D)is a major health concern globally and its prevalence is expected to continue to escalate.Lifestyle intervention is an integral part of T2D management.Meal replacements are often used as...BACKGROUND Type 2 diabetes(T2D)is a major health concern globally and its prevalence is expected to continue to escalate.Lifestyle intervention is an integral part of T2D management.Meal replacements are often used as part of lifestyle intervention programs in T2D and weight management programs.There are various trials being carried out to date;however,a thorough review regarding the usage of meal replacement on its types,dosage and associated outcomes and adverse events is still lacking.AIM To provide a comprehensive overview on existing studies regarding meal replacement usage among patients with T2D,and map out glycemic and weightrelated outcomes along with adverse effects incidences.METHODS This scoping review is conducted based on Arksey and O’Malley’s seminal framework for scoping reviews.A systematic search has been done for studies published between January 2020 and January 2024 across six online databases(Cochrane Library,PubMed,Science Direct,Scopus,Web of Science and Ebscohost Discovery)using specific keywords.Two researchers independently assessed the eligibility of the studies and extracted the data.The selected articles and extracted data were reviewed by all researchers.RESULTS The initial search resulted in an initial count of 53922 articles from which 133 articles were included in this review after eligibility screening.Included studies were categorized based on meal replacement type into low calorie/energy,low glycemic index,protein-rich,low-fat,diabetes-specific formulas,and combined lifestyle intervention programs.Fifty-nine studies reported improvements on hemoglobin A1c,and 70 studies reported positive changes in weight or BMI after the meal replacement intervention.The combination of meal replacements with education,counseling or structured lifestyle interventions has proved to be effective.Only 13 studies reported occurrence of adverse events related to the intervention.Most of the reported incidents were of mild occurrences with constipation being the most reported adverse event.CONCLUSION The results suggest that meal replacements,especially when combined with lifestyle intervention programs and counseling,are an effective and safe strategy in glycemic and weight management among patients with T2D.展开更多
Xiyu conglomerate is a significant and extensively distributed geological formation in western China.A clear understanding of its properties and the establishment of a classification system are essential for selecting...Xiyu conglomerate is a significant and extensively distributed geological formation in western China.A clear understanding of its properties and the establishment of a classification system are essential for selecting appropriate research methods to investigate its engineering mechanical behavior.Based on geological data from eight typical Xiyu conglomerate geological belts and seven hydropower projects,this study summarizes the main engineering geological characteristics,and analyzes the fabric characteristics of various components of the conglomerate through laboratory tests and statistical analysis.A comprehensive classification system is proposed for Xiyu conglomerate based on two key criteria:(1)grain size distribution,quantified by the d_(50)(median grain diameter),and(2)cementation type,identified via mineralogical and geochemical analysis.This system divides Xiyu conglomerate into nine distinct categories,each defined by specific engineering geological and petrofabric properties.The results reveal that,even within the same region,the grain size composition and distribution of Xiyu conglomerate are highly heterogeneous.While the chemical composition of the cementing materials is generally consistent,notable differences in cement properties arise primarily from variations in mineral content,particularly the proportion of calcareous material(dolomite,calcite,and quartz).Conglomerates with gray or grayish-blue matrices typically exhibit higher calcareous content,whereas those with earth-yellow or khaki matrices contain less calcareous material and are predominantly argillaceous-cemented.Additionally,Xiyu conglomerate shows higher porosity compared to conventional rocks.The proposed classification method based on engineering geological and fabric characteristics offers a geological basis for further determining the engineering mechanical properties of various Xiyu conglomerate types.This approach holds potential for addressing the challenges related to unclear classification and difficulty in accurately defining mechanical parameters for Xiyu conglomerate across different regions.展开更多
Objective:To assess the burden of Group B Streptococcus(GBS)and analyze the distribution of scrotypes in relation to their source.The review highlights data gaps in transmission dynamics and regional food consumption ...Objective:To assess the burden of Group B Streptococcus(GBS)and analyze the distribution of scrotypes in relation to their source.The review highlights data gaps in transmission dynamics and regional food consumption practices,which are esscntial for designing cffective public health strategies and advancing vaccine development.Methods:Scarches were conducted in Web of Science,MEDLINE,Science Direct,PubMcd,and Scopus databases to find studies related to GBS during 1990-2025.Eligible studies were those that described prevalence,scrotype distribution or scquence type(ST)of GBS in Southeast Asian countries.Random-cffects meta-analysis was used to pool data.Results:A total of 26 studies met the inclusion criteria from cight countries.The pooled estimate of maternal GBS colonization was 15.1%,with scrotypesII,v,ⅡI,V,and I a accounting for the majority of cases(91.24%)in the Southcast Asia studies.Data on ST was limited;however,ST1 was found to be predominant in Malaysia and Thailand,while ST283 was notably linked to the consumption of raw fish.Conclusions:The pooled estimate of the maternal colonization with GBS was 15.1%which is cquivalent to many other primary and review reports worldwide.Distribution of scrotype and ST is needed to be studied in Southcast Asian countries to devise cffective preventive measures.These findings underscore thc importance of surveillance and tailored prevention strategies to combat GBS infections in Southcast Asia.展开更多
High reliability applications in dense access scenarios have become one of the main goals of 6G environments.To solve the access collision of dense Machine Type Communication(MTC)devices in cell-free communication sys...High reliability applications in dense access scenarios have become one of the main goals of 6G environments.To solve the access collision of dense Machine Type Communication(MTC)devices in cell-free communication systems,an intelligent cooperative secure access scheme based on multi-agent reinforcement learning and federated learning is proposed,that is,the Preamble Slice Orderly Queue Access(PSOQA)scheme.In this scheme,the preamble arrangement is combined with the access control.The preamble arrangement is realized by preamble slices which is from the virtual preamble pool.The access devices learn to queue orderly by deep reinforcement learning.The orderly queue weakens the random and avoids collision.A preamble slice is assigned to an orderly access queue at each access time.The orderly queue is determined by interaction information among multiple agents.With the federated reinforcement learning framework,the PSOQA scheme is implemented to guarantee the privacy and security of agents.Finally,the access performance of PSOQA is compared with other random contention schemes in different load scenarios.Simulation results show that PSOQA can not only improve the access success rate but also guarantee low-latency tolerant performances.展开更多
BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the ther...BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the therapeutic effects of beinaglutide in patients with overweight/obesity with/without type 2 diabetes.METHODS RCTs involving patients receiving beinaglutide in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The change from baseline in body weight was the primary outcome;secondary outcomes included changes in body mass index(BMI),waist circumference(WC),blood pressure,glycemic parameters,lipids,and adverse events(AEs).RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MDs),odds ratios(ORs),or risk ratios(RRs)with 95%confidence intervals(95%CIs).RESULTS Six RCTs(n=800)with mostly some concerns about the risk of bias were included.Over 12-24 weeks,beinaglutide 0.1-0.2 mg thrice daily was superior to the control group in reducing total(MD=-3.25 kg,95%CI:-4.52 to-1.98,I^(2)=84%,P<0.00001)and percent(MD=-4.13%,95%CI:-4.87 to-3.39,I^(2)=54%,P<0.00001)body weight reduction.Beinaglutide also outperformed the control group in achieving weight loss by 5%(OR 4.61)and 10%(OR=5.34).The superiority of beinaglutide vs the control group was also found in reducing BMI(MD=-1.22 kg/m^(2),95%CI:-1.67 to-0.77)and WC(MD=-2.47 cm,95%CI:-3.74 to-1.19]).Beinaglutide and the control group had comparable impacts on blood pressure,glycemic parameters,insulin resistance,hepatic transaminases,and lipid profile.Beinaglutide posed higher risks of treatment discontinuation due to AEs(RR=3.15),nausea(RR=4.51),vomiting(RR=8.19),palpitation(RR=3.95),headache(RR=2.87),and dizziness(RR=6.07)than the control.However,the two groups had identical risks of total and serious AEs,diarrhea,fatigue,and hypoglycemia.CONCLUSION Short-term data from RCTs suggested that beinaglutide causes modest benefits in reducing body weight,BMI,and WC,with no significant difference in glycemic and other metabolic endpoints compared to the control arm.Safety data were consistent with those of the other drugs in the glucagon-like polypeptide-1 receptor agonist class.Larger RCTs are warranted to prove the longer-term metabolic benefits of beinaglutide.展开更多
This paper explores the possibility of using machine learning algorithms to predict type 2 diabetes.We selected two commonly used classification models:random forest and logistic regression,modeled patients’clinical ...This paper explores the possibility of using machine learning algorithms to predict type 2 diabetes.We selected two commonly used classification models:random forest and logistic regression,modeled patients’clinical and lifestyle data,and compared their prediction performance.We found that the random forest model achieved the highest accuracy,demonstrated excellent classification results on the test set,and better distinguished between diabetic and non-diabetic patients by the confusion matrix and other evaluation metrics.The support vector machine and logistic regression perform slightly less well but achieve a high level of accuracy.The experimental results validate the effectiveness of the three machine learning algorithms,especially random forest,in the diabetes prediction task and provide useful practical experience for the intelligent prevention and control of chronic diseases.This study promotes the innovation of the diabetes prediction and management model,which is expected to alleviate the pressure on medical resources,reduce the burden of social health care,and improve the prognosis and quality of life of patients.In the future,we can consider expanding the data scale,exploring other machine learning algorithms,and integrating multimodal data to further realize the potential of artificial intelligence(AI)in the field of diabetes.展开更多
BACKGROUND Current evidence suggests that commonly used antidiabetic drugs have varying effects on cancer risk.Some antidiabetics offer protective effects against cancer,whereas others may increase risk in specific po...BACKGROUND Current evidence suggests that commonly used antidiabetic drugs have varying effects on cancer risk.Some antidiabetics offer protective effects against cancer,whereas others may increase risk in specific populations.AIM To comprehensively compare the effects of different antidiabetic drugs on the risk of various cancers in patients with type 2 diabetes mellitus(T2DM)through a systematic review and network meta-analysis.METHODS Four databases(PubMed,EMBASE,Cochrane Library,and Web of Science)were searched from their inception until April 11,2025.Published randomized controlled trials that enrolled at least 100 participants and had an intervention duration of at least 1 year were included.The inclusion criteria were studies involving adult patients with T2DM and interventions that compared different classes of antidiabetic drugs with a placebo or another antidiabetic drug.Network meta-analysis was conducted using Stata 17.0 software.Confidence in network meta-analysis was used to assess the quality of evidence regarding the risk of cancer associated with different antidiabetic drugs.RESULTS A total of 13535 articles were identified.After applying the inclusion and exclusion criteria,87 high-quality studies involving 216106 patients and 26 different drugs across seven classes were included in this study.Indirect evidence from network meta-analysis revealed some heterogeneity;however,this did not affect the reliability of the results.The results indicated that antidiabetic drugs did not increase the overall risk of cancer compared with placebo.In contrast,some antidiabetic medications demonstrated a more pronounced advantage in reducing cancer risk,such as dipeptidyl peptidase-4 inhibitors for thyroid and rectal cancers;sodium-glucose co-transporter type 2 inhibitors for lung and bronchial cancers;sulfonylureas for gastric and colon cancers;biguanides for pancreatic cancer;insulin for bladder cancer;glucagon-like peptide-1 receptor agonists for prostate,uterine,hepatocellular,renal,and hematologic cancers;and thiazolidinediones for breast cancer.CONCLUSION Antidiabetic drugs reduce cancer risk in patients with T2DM.However,given the limitations in the number and quality of the included studies,our conclusions should be interpreted with caution.More large-scale,high-quality clinical trials are required to validate our findings towards the optimization of comprehensive cancer management strategies for patients with T2DM.展开更多
文摘Objective. To establish a PCR- SSP method for discriminating as many HLA- A* 02 alleles, which could easily be introduced into a routine laboratory. Methods. In this study we typed HLA- A* 02 polymorphisms by a sequence- specific primer (SSP) method, which involved round 1 and round 2 PCR reactions to detect 17 HLA- A* 02 alleles (they are HLA- A* 0201- 0217 alleles) covering exon 2 and exon 3. Results. We have found that DNA sample concentration and purity were the most important variables in determining the quality of the results. For identifying correct band size, the size marker used was important. We noticed that different PCR machines performed differently. By this method, we detected 20 HLA- A* 02 positive genomic DNA samples and found 4 kinds of HLA- A* 02 alleles. They were HLA- A* 0201, 0203, 0206 and 0210. Conclusion. The HLA- A* 02 PCR- SSP method was proven to be a reliable and easily applicable typing method. Our results suggest that the SSP described here provides an optimal HLA- A* 02 typing technique that may be useful in selecting donor- recipient pairs in bone marrow transplantation between unrelated individuals.
基金supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil(CNPq)(312286/2023-6,307201/2023-6,and Instituto Nacional Saude Cerebral INSC,No.406020/2022-1)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro-FAPERJ(E-26/010.002260/2019,E-26/010.001652/2019,E-26/010.101036/2018,E-26/202.774/2018,E-26/210.240/2020,E-26/211.138/2021,26/210.823/2021,E-26/211.325/2021,E-26/210.779/2021,E-26/201.086/2022,E-26/210.312/2022,E-26/203.262/2023,E-26/200.195/2023)(to LEBS)。
文摘Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA28110300)National Natural Science Foundation of China(No.U23A2004)+3 种基金Natural Science Foundation of Jilin Province,China(No.YDZJ202201ZYTS522)Science and Technology Cooperation Program between Jilin Province and Chinese Academy of Sciences(No.2023SYHZ0053)Innovation Team Program of Northeast Institute of Geography and Agroecology,Chinese Academy of Sciences(No.2023CXTD02)the European Commission under Marie Sk?odowska-Curie(No.101034371)。
文摘Nitrogen(N)enrichment has resulted in widespread alteration of grassland ecosystem processes and functions mainly through disturbance in soil enzyme activities.However,we lack a comprehensive understanding of how N deposition affects specific key soil enzymes that mediate plant-soil feedback of grassland.Here,with a meta-analysis on 1446 cases from field observations in China,we show that N deposition differently affects soil enzymes associated with soil biochemical processes.Specifically,N-promoted C,N,and P-acquiring hydrolase activities significantly increased by 8.73%,7.67%,and 8.69%,respectively,related to an increase in microbial-specific enzyme secretion.The increased relative N availability and soil acidification were two potential mechanisms accounting for the changes in soil enzyme activities with N enrichment.The mixed N addition in combination of NH_(4)NO_(3) and urea showed greater stimulation effect on soil enzyme activities.However,the high rate and long-term N addition tended to weaken the positive responses of soil C-,Nand P-acquiring hydrolase activities to N enrichment.Spatially increased mean annual precipitation and temperature primarily promoted the positive effects of N enrichment on N-and P-acquiring hydrolase activities,and the stimulation of C-and N-acquiring hydrolase activities by N enrichment was intensified with the increase in soil depth.Finally,multimodal inference showed that grassland type was the most important regulator of responses of microbial C,N,and P-acquiring hydrolase activities to N enrichment.This meta-analysis provides a comprehensive insight into understanding the key role of N enrichment in shaping soil enzyme activities of grassland ecosystems.
文摘BACKGROUND The incidence of type 2 diabetes mellitus(T2DM)in children and adolescents is increasing,yet there is limited information on the available pharmacological interventions to combat T2DM and prevent associated comorbidities.AIM To assess the effectiveness of current pharmacological treatments in managing T2DM in children and adolescents.The protocol of the study was registered in PROSPERO(CRD42022382165).METHODS Searches were performed in PubMed,EMBASE,Scopus,and ClinicalTrials.gov for publications between 1990 to September 2024 without language restrictions.Randomized control trials(RCTs)of pharmacotherapy in children and adolescents with T2DM(aged<19 years)were included.The primary outcome was a change in glycated hemoglobin(HbA1c)from baseline to follow-up.Secondary outcomes were changes in body weight,body mass index(BMI),total cholesterol,triglycerides,high density lipoprotein,and low-density lipoprotein from baseline,and incidence of adverse events during study periods.Screening,full-text review,data extraction,and assessments of risk of bias were done by two reviewers.Conflicts on each step were resolved by a third reviewer.Data analysis was performed using Review Manager Version 6.5(RevMan 6.5)and‘R’software via RStudio,‘meta’and‘netmeta’.RESULTS A total of 12 studies having low to moderate risk of bias with 1658 participants,and follow-up duration 12-52 weeks were included.In our network meta-analysis,compared to control(s),the reduction of HbA1c was sig-nificantly larger for dulaglutide[mean difference(MD),95%confidence interval:-1.20,-2.12 to-0.28],followed by dapagliflozin(-0.94,-1.44 to-0.44),liraglutide(-0.91,-1.37 to-0.45),empagliflozin(-0.87,-1.40 to-0.34),exenatide(-0.59,-1.07 to-0.11)and linagliptin(-0.45,-0.87 to-0.02)while other drugs had little or no effect.While liraglutide was associated with a change in body weight[MD-2.41(-4.68,-0.14)kg],no other drug treatment was associated with significant changes in body weight,BMI,and lipids.Apart from level 1 hypoglycemia with liraglutide[risk difference(RD):0.20,0.04-0.37]and minor adverse events with dulaglutide(RD:0.24,0.08-0.40),no other treatment was associated with excess risk of hypoglycemia or minor or major adverse events.CONCLUSION Pharmacotherapy of T2DM with dulaglutide,dapagliflozin,liraglutide,empagliflozin,exenatide,and linagliptin in children is associated with modest reduction of HbA1c.Larger RCTs with longer follow-up durations are needed to guide better therapeutic decision making.
基金supported by the National Key Research and Development Program of China(2022YFD1800904)the National Natural Science Foundation of China(31972650 and 32102673)+1 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX22_0780)the China Postdoctoral Science Foundation(2020M682297)。
文摘Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.
基金Supported by Fondazione di Sardegna,No.2020.2284.
文摘Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodies.The latest European Society for Paediatric Gastroenterology,Hepatology,and Nutrition(ESPGHAN)2020 guidelines have excluded human leukocyte antigen(HLA)genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value,limited availability,and high cost in some countries.However,HLA genetic testing remains valuable in certain clinical contexts.This study provided practical indications for when to request and how to interpret HLA genotyping,emphasizing its continued relevance for CD diagnosis in specific cases.We also proposed a strategy for monitoring the risk of developing type 1 diabetes(T1D)in patients with CD,based on the risk stratification carried by different HLA genotypes.A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in2012,when HLA genotyping became mandatory for the diagnosis of CD.We identified key clinical scenarios where HLA testing remains useful.Several high risk HLA-DQ genotypes strongly associated with CD were highlighted,including HLA-DQ2.5/HLA-DQ2.2and HLA-DQ2.5/HLA-DQ2.5.Notably,while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD,it appears to confer protection against T1D.To support clinical practice,we presented a table clarifying commonly used HLA terminology,and another summarized the main clinical situations in which HLAgenotyping should still be considered.These findings underscore the dual role of HLA testing:Not only can it help rule out CD in selected cases,but it also identifies patients with CD at risk for T1D,guiding personalized monitoring strategies.
文摘The information from sparsely logged wellbores is currently under-utilized in reservoir simulation models and their proxies using deep and machine learning (DL/ML).This is particularly problematic for large heterogeneous gas/oil reservoirs being considered for repurposing as gas storage reservoirs for CH_(4),CO_(2) or H_(2) and/or enhanced oil recovery technologies.Lack of well-log data leads to inadequate spatial definition of complex models due to the large uncertainties associated with the extrapolation of petrophysical rock types (PRT) calibrated with limited core data across heterogeneous and/or anisotropic reservoirs.Extracting well-log attributes from the few well logs available in many wells and tying PRT predictions based on them to seismic data has the potential to substantially improve the confidence in PRT 3D-mapping across such reservoirs.That process becomes more efficient when coupled with DL/ML models incorporating feature importance and optimized,dual-objective feature selection techniques.
文摘BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile.
基金Supported by National Natural Science Foundation of China,No.82270863 and No.82470849Major Project of Anhui Provincial University Research Program,No.2023AH040400+1 种基金Joint Fund for Medical Artificial Intelligence,No.MAI2023Q026the Project of Health Commission Scientific Research in Anhui Province,No.AHWJ2024Aa20477.
文摘BACKGROUND Pyroptosis and ubiquitination have been identified as key processes influencing the pathogenesis of diabetes mellitus(DM).AIM To investigate the genes associated with the ubiquitin-proteasome system(UPS)and pyroptosis in type 2 DM(T2DM),and elucidate their mechanisms of action in T2DM.METHODS The datasets GSE76894,GSE41762,and GSE86469 were utilized in this study.UPS-related genes(UPSGs)and pyroptosis-related genes(PRGs)were obtained from existing literature.Differential expression analysis was performed to identify differentially expressed genes(DEGs).DEGs were intersected with UPSGs and PRGs to identify differentially expressed UPSGs and PRGs.Ubiquitin-pyroptosisrelated biomarkers were determined using Spearman’s correlation,t-tests,and receiver operating characteristic curve analysis.Pathway enrichment of biomarkers was assessed using Gene Set Enrichment Analysis(GSEA).Single sample GSEA(ssGSEA)and Spearman’s correlation were used to analyze the relationship between biomarkers and immune cells.A competitive endogenous RNA network was constructed.Subsequently,drugs related to the biomarkers were identified and a gene-drug network was established.In dataset GSE86469,single-cell sequencing was utilized to determine cell types.Finally,the expression levels of biomarkers were validated through quantitative PCR(qPCR)and western blot analysis.RESULTS A total of 581 DEGs were identified in GSE76894.Four genes[ATP binding cassette subfamily C member 8(ABCC8),retinol binding protein 4(RBP4),Ras protein-specific guanine nucleotide-releasing factor 1(RASGRF1),and solute carrier family 34 member 2(SLC34A2)]were identified as ubiquitin-pyroptosis-related biomarkers in T2DM,based on consistent expression trends and significant differences in GSE76894 and GSE41762.These biomarkers were enriched in oxidative phosphorylation and mitogen-activated protein kinase signaling pathways,which are relevant to DM.ssGSEA revealed significant differences in the enrichment scores of nine immune cell types between groups.A total of 17 microRNAs(miRNAs)and 36 long non-coding RNAs(lncRNAs)were identified,forming numerous miRNA-lncRNA interactions.Additionally,22 drugs related to the biomarkers,such as gliclazide and tretinoin,were identified.In GSE86469,eight cell types,including alpha and beta cells,were characterized.qPCR and western blot analysis confirmed that the expression trends of RASGRF1 and SLC34A2 were consistent with the findings in GSE76894.CONCLUSION This study identified four ubiquitin-pyroptosis-related biomarkers(ABCC8,RBP4,RASGRF1,and SLC34A2)in T2DM through bioinformatics analysis,providing novel insights into the diagnosis and treatment of T2DM.
文摘BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asia has a high T2D burden,and many studies have reported varying prevalence rates of DD in this area.AIM To estimate the pooled prevalence of DD among patients with T2D in South Asia,as it is crucial for developing effective therapeutic strategies.METHODS This systematic review and meta-analysis included cross-sectional studies conducted in South Asian countries involving adults with T2D and reported the prevalence of DD.The studies were identified by searching multiple electronic databases and registries from the inception of each database to January 30,2025,using prespecified search terms.Four authors screened and extracted data independently.Meta-analyses were conducted using RStudio software with a random-effects model.The primary outcome was the pooled prevalence of DD.RESULTS Thirty-seven cross-sectional studies(28 from India,five from Bangladesh,and two each from Pakistan and Sri Lanka)with mostly high methodological quality involving 11500 subjects were included.The pooled prevalence of DD was 44%(95%confidence interval:35-53,I2=97.4%).The prevalence of DD was highest in Pakistan(85%),followed by India and Bangladesh(42%each),and Sri Lanka(25%).Emotional burden was the most prevalent form of DD(60%),followed by treatment regimen-related distress(51%),interpersonal distress(31%),and physician-related distress(17%).Meta-regression analysis revealed no significant associations between the prevalence of DD and publication year,sample size,proportion of females,age,duration of diabetes,insulin usage,glycated hemoglobin levels,or diabetic complications.CONCLUSION South Asians with T2D seem to experience a relatively high burden of DD,and the emotional burden is the most common form of DD in this area.Larger studies utilizing unique tools and involving a broader participant base from the region would provide better epidemiological data for effectively planning high-quality diabetes care in South Asian countries.
基金This work was conducted in the frame of the accompanying research on strategies for improving farmer families’incomes and sustainable cocoa production funded by the German Federal Ministry for Economic Cooperation and Development(BMZ).
文摘About 44%of the world’s cocoa is produced in one single country,Côte d’Ivoire.Providing this important raw material,most Ivorian cocoa farmers live in severe poverty,which,despite a multitude of sector interventions,is still widespread,affecting social and environmental sustainability in cocoa production.In this context,cocoa farmers are still often treated as a homogeneous group of small-scale producers(mainly males),resulting in interventions being conceptualized as one-size-fits-all approaches and failing to deliver support schemes that take farmers’specific conditions appropriately into account.Applying a broader typology approach that combines farm characteristics with farmers’characteristics,this study aims to delineate Ivorian cocoa farmers and their farms into specific types in order to improve advice for targeted sustainability interventions and living income(LI)potentials.Principal component analysis and hierarchical clustering analysis of a household dataset collected in 2022 in five cocoa-growing regions of Côte d’Ivoire were chosen to identify types of male-headed farms.To assure gender sensitive analysis,a female-headed farm type was created artificially.The specific characteristics of the identified types were captured using descriptive analysis.Descriptive statistics and non-parametric tests were then applied to examine the relationships between these farm types and various outcomes.Additionally,a binary logistic model was used to estimate the probability of these links in relation to variables relevant for achieving a LI.Finally,Spearman non-parametric correlation was used to identify eventual differences in the strength of relationships between key variables per farm type.Three different types of male-headed farms are identified:type 1(the most productive and diversified farms with larger size),type 2(middle-sized farms with strong focus on cash crops),and type 3(small-sized farms with a good level of diversification for self-consumption).The artificially created type 4 represents female-headed farms with the smallest size.On average,none of these farm types achieves a LI.However,type 1 shows the smallest LI gap,while type 4 is by far the worst.Our analyses reveal underlying socio-economic factors systematically disadvantaging female-headed cocoa farms,most notably limited access to land and other material assets.The key contribution of this study lies in the empirical identification of the different characteristics of farms in a given farming system,thereby identifying the need for targeted support interventions.Type-specific recommendations are made,showing pathways to provide tailored programs to farmers of different types in order to reduce their LI gaps.
文摘INTRODUCTION Cardiovascular system involvement is an important determinant of long-term prognosis in patients with systemic lupus erythematosus(SLE).Aneurysmal dilatation of the aortic root combined with Stanford type A aortic dissection(TAAD)is a highly catastrophic complication in these patients.
文摘BACKGROUND Type 2 diabetes(T2D)is a major health concern globally and its prevalence is expected to continue to escalate.Lifestyle intervention is an integral part of T2D management.Meal replacements are often used as part of lifestyle intervention programs in T2D and weight management programs.There are various trials being carried out to date;however,a thorough review regarding the usage of meal replacement on its types,dosage and associated outcomes and adverse events is still lacking.AIM To provide a comprehensive overview on existing studies regarding meal replacement usage among patients with T2D,and map out glycemic and weightrelated outcomes along with adverse effects incidences.METHODS This scoping review is conducted based on Arksey and O’Malley’s seminal framework for scoping reviews.A systematic search has been done for studies published between January 2020 and January 2024 across six online databases(Cochrane Library,PubMed,Science Direct,Scopus,Web of Science and Ebscohost Discovery)using specific keywords.Two researchers independently assessed the eligibility of the studies and extracted the data.The selected articles and extracted data were reviewed by all researchers.RESULTS The initial search resulted in an initial count of 53922 articles from which 133 articles were included in this review after eligibility screening.Included studies were categorized based on meal replacement type into low calorie/energy,low glycemic index,protein-rich,low-fat,diabetes-specific formulas,and combined lifestyle intervention programs.Fifty-nine studies reported improvements on hemoglobin A1c,and 70 studies reported positive changes in weight or BMI after the meal replacement intervention.The combination of meal replacements with education,counseling or structured lifestyle interventions has proved to be effective.Only 13 studies reported occurrence of adverse events related to the intervention.Most of the reported incidents were of mild occurrences with constipation being the most reported adverse event.CONCLUSION The results suggest that meal replacements,especially when combined with lifestyle intervention programs and counseling,are an effective and safe strategy in glycemic and weight management among patients with T2D.
基金Xinjiang Water Science and Technology Special Project,Grant/Award Numbers:XSKJ-2022-05,XSKJ-2023-30State Grid Co.,LTD.Technology Project,Grant/Award Number:5108-202218280A-2-301-XG。
文摘Xiyu conglomerate is a significant and extensively distributed geological formation in western China.A clear understanding of its properties and the establishment of a classification system are essential for selecting appropriate research methods to investigate its engineering mechanical behavior.Based on geological data from eight typical Xiyu conglomerate geological belts and seven hydropower projects,this study summarizes the main engineering geological characteristics,and analyzes the fabric characteristics of various components of the conglomerate through laboratory tests and statistical analysis.A comprehensive classification system is proposed for Xiyu conglomerate based on two key criteria:(1)grain size distribution,quantified by the d_(50)(median grain diameter),and(2)cementation type,identified via mineralogical and geochemical analysis.This system divides Xiyu conglomerate into nine distinct categories,each defined by specific engineering geological and petrofabric properties.The results reveal that,even within the same region,the grain size composition and distribution of Xiyu conglomerate are highly heterogeneous.While the chemical composition of the cementing materials is generally consistent,notable differences in cement properties arise primarily from variations in mineral content,particularly the proportion of calcareous material(dolomite,calcite,and quartz).Conglomerates with gray or grayish-blue matrices typically exhibit higher calcareous content,whereas those with earth-yellow or khaki matrices contain less calcareous material and are predominantly argillaceous-cemented.Additionally,Xiyu conglomerate shows higher porosity compared to conventional rocks.The proposed classification method based on engineering geological and fabric characteristics offers a geological basis for further determining the engineering mechanical properties of various Xiyu conglomerate types.This approach holds potential for addressing the challenges related to unclear classification and difficulty in accurately defining mechanical parameters for Xiyu conglomerate across different regions.
文摘Objective:To assess the burden of Group B Streptococcus(GBS)and analyze the distribution of scrotypes in relation to their source.The review highlights data gaps in transmission dynamics and regional food consumption practices,which are esscntial for designing cffective public health strategies and advancing vaccine development.Methods:Scarches were conducted in Web of Science,MEDLINE,Science Direct,PubMcd,and Scopus databases to find studies related to GBS during 1990-2025.Eligible studies were those that described prevalence,scrotype distribution or scquence type(ST)of GBS in Southeast Asian countries.Random-cffects meta-analysis was used to pool data.Results:A total of 26 studies met the inclusion criteria from cight countries.The pooled estimate of maternal GBS colonization was 15.1%,with scrotypesII,v,ⅡI,V,and I a accounting for the majority of cases(91.24%)in the Southcast Asia studies.Data on ST was limited;however,ST1 was found to be predominant in Malaysia and Thailand,while ST283 was notably linked to the consumption of raw fish.Conclusions:The pooled estimate of the maternal colonization with GBS was 15.1%which is cquivalent to many other primary and review reports worldwide.Distribution of scrotype and ST is needed to be studied in Southcast Asian countries to devise cffective preventive measures.These findings underscore thc importance of surveillance and tailored prevention strategies to combat GBS infections in Southcast Asia.
基金supported in part by the National Natural Science Foundation of China under grants 61771255in part by the Provincial and Ministerial Key Laboratory Open Project under grant 20190904in part by the Key Technologies R&D Program of Jiangsu (Prospective and Key Technologies for Industry)under Grants BE2022067,BE2022067-1 and BE2022067-2。
文摘High reliability applications in dense access scenarios have become one of the main goals of 6G environments.To solve the access collision of dense Machine Type Communication(MTC)devices in cell-free communication systems,an intelligent cooperative secure access scheme based on multi-agent reinforcement learning and federated learning is proposed,that is,the Preamble Slice Orderly Queue Access(PSOQA)scheme.In this scheme,the preamble arrangement is combined with the access control.The preamble arrangement is realized by preamble slices which is from the virtual preamble pool.The access devices learn to queue orderly by deep reinforcement learning.The orderly queue weakens the random and avoids collision.A preamble slice is assigned to an orderly access queue at each access time.The orderly queue is determined by interaction information among multiple agents.With the federated reinforcement learning framework,the PSOQA scheme is implemented to guarantee the privacy and security of agents.Finally,the access performance of PSOQA is compared with other random contention schemes in different load scenarios.Simulation results show that PSOQA can not only improve the access success rate but also guarantee low-latency tolerant performances.
文摘BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the therapeutic effects of beinaglutide in patients with overweight/obesity with/without type 2 diabetes.METHODS RCTs involving patients receiving beinaglutide in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The change from baseline in body weight was the primary outcome;secondary outcomes included changes in body mass index(BMI),waist circumference(WC),blood pressure,glycemic parameters,lipids,and adverse events(AEs).RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MDs),odds ratios(ORs),or risk ratios(RRs)with 95%confidence intervals(95%CIs).RESULTS Six RCTs(n=800)with mostly some concerns about the risk of bias were included.Over 12-24 weeks,beinaglutide 0.1-0.2 mg thrice daily was superior to the control group in reducing total(MD=-3.25 kg,95%CI:-4.52 to-1.98,I^(2)=84%,P<0.00001)and percent(MD=-4.13%,95%CI:-4.87 to-3.39,I^(2)=54%,P<0.00001)body weight reduction.Beinaglutide also outperformed the control group in achieving weight loss by 5%(OR 4.61)and 10%(OR=5.34).The superiority of beinaglutide vs the control group was also found in reducing BMI(MD=-1.22 kg/m^(2),95%CI:-1.67 to-0.77)and WC(MD=-2.47 cm,95%CI:-3.74 to-1.19]).Beinaglutide and the control group had comparable impacts on blood pressure,glycemic parameters,insulin resistance,hepatic transaminases,and lipid profile.Beinaglutide posed higher risks of treatment discontinuation due to AEs(RR=3.15),nausea(RR=4.51),vomiting(RR=8.19),palpitation(RR=3.95),headache(RR=2.87),and dizziness(RR=6.07)than the control.However,the two groups had identical risks of total and serious AEs,diarrhea,fatigue,and hypoglycemia.CONCLUSION Short-term data from RCTs suggested that beinaglutide causes modest benefits in reducing body weight,BMI,and WC,with no significant difference in glycemic and other metabolic endpoints compared to the control arm.Safety data were consistent with those of the other drugs in the glucagon-like polypeptide-1 receptor agonist class.Larger RCTs are warranted to prove the longer-term metabolic benefits of beinaglutide.
文摘This paper explores the possibility of using machine learning algorithms to predict type 2 diabetes.We selected two commonly used classification models:random forest and logistic regression,modeled patients’clinical and lifestyle data,and compared their prediction performance.We found that the random forest model achieved the highest accuracy,demonstrated excellent classification results on the test set,and better distinguished between diabetic and non-diabetic patients by the confusion matrix and other evaluation metrics.The support vector machine and logistic regression perform slightly less well but achieve a high level of accuracy.The experimental results validate the effectiveness of the three machine learning algorithms,especially random forest,in the diabetes prediction task and provide useful practical experience for the intelligent prevention and control of chronic diseases.This study promotes the innovation of the diabetes prediction and management model,which is expected to alleviate the pressure on medical resources,reduce the burden of social health care,and improve the prognosis and quality of life of patients.In the future,we can consider expanding the data scale,exploring other machine learning algorithms,and integrating multimodal data to further realize the potential of artificial intelligence(AI)in the field of diabetes.
基金Supported by National Natural Science Foundation of China,No.82305205Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine,No.2023-QNRC2-A05+1 种基金Safeguard Project of Guang’anmen Hospital,China Academy of Chinese Medical Sciences,No.GAMHH9324001Special Program for the Training of Outstanding Young Scientific and Technological Talents Under the Basic Scientific Research Operating Expenses of the China Academy of Chinese Medical Sciences,No.ZZ18-YQ-011.
文摘BACKGROUND Current evidence suggests that commonly used antidiabetic drugs have varying effects on cancer risk.Some antidiabetics offer protective effects against cancer,whereas others may increase risk in specific populations.AIM To comprehensively compare the effects of different antidiabetic drugs on the risk of various cancers in patients with type 2 diabetes mellitus(T2DM)through a systematic review and network meta-analysis.METHODS Four databases(PubMed,EMBASE,Cochrane Library,and Web of Science)were searched from their inception until April 11,2025.Published randomized controlled trials that enrolled at least 100 participants and had an intervention duration of at least 1 year were included.The inclusion criteria were studies involving adult patients with T2DM and interventions that compared different classes of antidiabetic drugs with a placebo or another antidiabetic drug.Network meta-analysis was conducted using Stata 17.0 software.Confidence in network meta-analysis was used to assess the quality of evidence regarding the risk of cancer associated with different antidiabetic drugs.RESULTS A total of 13535 articles were identified.After applying the inclusion and exclusion criteria,87 high-quality studies involving 216106 patients and 26 different drugs across seven classes were included in this study.Indirect evidence from network meta-analysis revealed some heterogeneity;however,this did not affect the reliability of the results.The results indicated that antidiabetic drugs did not increase the overall risk of cancer compared with placebo.In contrast,some antidiabetic medications demonstrated a more pronounced advantage in reducing cancer risk,such as dipeptidyl peptidase-4 inhibitors for thyroid and rectal cancers;sodium-glucose co-transporter type 2 inhibitors for lung and bronchial cancers;sulfonylureas for gastric and colon cancers;biguanides for pancreatic cancer;insulin for bladder cancer;glucagon-like peptide-1 receptor agonists for prostate,uterine,hepatocellular,renal,and hematologic cancers;and thiazolidinediones for breast cancer.CONCLUSION Antidiabetic drugs reduce cancer risk in patients with T2DM.However,given the limitations in the number and quality of the included studies,our conclusions should be interpreted with caution.More large-scale,high-quality clinical trials are required to validate our findings towards the optimization of comprehensive cancer management strategies for patients with T2DM.
