BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the import...BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the importance of early detection and intervention.Inflammatory pathways are key contributors to these conditions,and recent research has identified members of the tumor necrosis factor(TNF)receptor superfamily as potential biomarkers.However,their association with renal and retinal dysfunction in individuals with intermediate hyperglycemia(IH)remains underexplored.The Early Prevention of Diabetes Complications(ePREDICE)trial provides a valuable cohort to investigate these associations and improve risk assessment strategies.AIM To identify inflammatory biomarkers associated with early renal and retinal dysfunction in individuals with IH.Specifically,we evaluate the diagnostic and prognostic potential of TNF receptor superfamily members[TNF receptor 1(TNF-R1),TNF receptor 2(TNF-R2)],T-cell immunoglobulin and mucin domain 3(TIM-3)/HAVCR2,galectin-3,and interleukin-6(IL-6)in detecting kidney dysfunction and retinopathy in this high-risk population.By understanding their roles,we seek to enhance early screening methods and inform personalized intervention strategies.METHODS A cross-sectional analysis of 967 individuals with IH from the ePREDICE trial was conducted.Participants underwent comprehensive anthropometric and biochemical assessments.Key inflammatory biomarkers,including TNF-R1,TNF-R2,TIM-3/HAVCR2,galectin-3,and IL-6,were quantified using immunoassays.Renal function was assessed using estimated glomerular filtration rate(eGFR)and albuminuria,while retinopathy was evaluated through fundoscopic examination.Statistical analyses included adjusted mean comparisons,correlation studies,and receiver operating characteristic curve analysis to assess biomarker diagnostic accuracy.RESULTS TNF-R1,TNF-R2,and TIM-3/HAVCR2 were significantly associated with reduced filtration function(eGFR<60 mL/minute/1.73 m^(2))and albuminuria,with area under the curve(AUC)values between 0.815 and 0.845.TIM-3/HAVCR2 emerged as the strongest predictor of retinopathy(AUC=0.737).Strong correlations(r>0.75)were observed among TNF-R1,TNF-R2,and TIM-3/HAVCR2,suggesting a coordinated role in inflammatory pathways.CONCLUSION Our findings highlight the potential of TNF receptor superfamily members as biomarkers for early-stage renal and retinal complications in individuals with IH.Their integration into clinical screening protocols could facilitate earlier detection,improving patient stratification and personalized management strategies.Further longitudinal studies are necessary to validate their predictive value and potential for guiding therapeutic interventions in IH and early diabetes management.展开更多
BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease de...BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.展开更多
Vaginal carriage of Group B Streptococcus (GBS) is a maternal and child health issue. Our objective was to determine the prevalence of GBS carriage;identify the factors associated with this carriage and determine the ...Vaginal carriage of Group B Streptococcus (GBS) is a maternal and child health issue. Our objective was to determine the prevalence of GBS carriage;identify the factors associated with this carriage and determine the antibiotic sensitivity of the isolated strains. We conducted a cross-sectional and prospective study in rural Senegal (in the health district of Sokone). Socio-demographic, clinical and gynaeco-obstetrical data were collected. Vaginal swabs were taken by the midwives on specific settings in order to test for GBS and other High Risk Vaginal Bacteria (HRVB). Antibiotic susceptibility testing was done according to the recommendations of the CA SFM/EUCAST 2020. In total, 100 pregnant women were targeted and 97 pregnant women were included. Their age ranged from 18 to 40 years with 64.9% (63/97) of participants belonging to the “20 - 30” age group. The overall prevalence of Group B Streptococcus carriage was 15.5% (15/97). However, the proportion of women with at least one high risk infectious bacteria was 29.89% (29/97). No statistically significant differences were found between GBS carriage and the potential factors studied. However, the study also looked for the presence of other high-risk bacteria and coinfections were indeed found between GBS and E. coli and Staphylococcus aureus. Antibiotic susceptibility testing shows that GBS strains were fully susceptible to penicillin G, erythromycin, clindamycin, chloramphenicol, rifampicin and vancomycin. Sensitivities to norfloxacin and gentamycin were 73.3% and 86.7% respectively. In contrast, high resistance to tetracycline (86.7%) was observed. GBS carriage remains a major public health issue because of its consequences for the mother and the newborn. Correct screening and proper monitoring of strain susceptibility remain one of the most effective means of patient management and care.展开更多
Head and neck squamous cell carcinoma(HNSCC)is a devastating disease.Despite morbid treatment,5-year survival rates remain poor(28%-67%)[1].There is a significant knowledge gap regarding how the microbiota may impact ...Head and neck squamous cell carcinoma(HNSCC)is a devastating disease.Despite morbid treatment,5-year survival rates remain poor(28%-67%)[1].There is a significant knowledge gap regarding how the microbiota may impact HNSCC treatment efficacy[2].We used microbiome data from two independent cohorts to test and validate the hypothesis that oral bacteria are associated with HNSCC prognosis and in vitro models to investigate mechanistic underpinnings.Methods are detailed in Supplementary Materials.展开更多
Introduction Individual patient data(IPD)meta-analysis by Choi et al.(1)compared hepatocellular carcinoma(HCC)risk between the entecavir(ETV)and tenofovir(TDF)in treatment-naïve chronic hepatitis B(CHB)patients u...Introduction Individual patient data(IPD)meta-analysis by Choi et al.(1)compared hepatocellular carcinoma(HCC)risk between the entecavir(ETV)and tenofovir(TDF)in treatment-naïve chronic hepatitis B(CHB)patients using a multivariable Cox proportional hazards model from 11 Asian studies,totaling 42,939 patients receiving nucles(t)tide analogues(NAs)for more than one year.展开更多
This work addresses the problem of supervised classification for highly correlated highdimensional data describing non-independent observations to identify SNPs related to a phenotype.We use a general penalized linear...This work addresses the problem of supervised classification for highly correlated highdimensional data describing non-independent observations to identify SNPs related to a phenotype.We use a general penalized linear mixed model with a single random effect that performs simultaneous SNP selection and population structure adjustment in highdimensional prediction models.Specifically,the model simultaneously selects variables and estimates their effects,taking into account correlations between individuals.Single nucleotide polymorphisms(SNPs)are a type of genetic variation and each SNP represents a difference in a single DNA building block,namely a nucleotide.Previous research has shown that SNPs can be used to identify the correct source population of an individual and can act in isolation or simultaneously to impact a phenotype.In this regard,the study of the contribution of genetics in infectious disease phenotypes is of great importance.In this study,we used uncorrelated variables from the construction of blocks of correlated variables done in a previous work to describe the most related observations of the dataset.The model was trained with 90%of the observations and tested with the remaining 10%.The best model obtained with the generalized information criterion(GIC)identified the SNP named rs2493311 located on the first chromosome of the gene called PRDM16((PR/SET domain 16))as the most decisive factor in malaria attacks.展开更多
In a recent study published in Science,1 Gordon et al.investigate the host-pathogen interactome of the coronaviruses SARS-CoV-1,SARS-CoV-2,and MERS-CoV,all of which caused lethal outbreaks in the past two decades.They...In a recent study published in Science,1 Gordon et al.investigate the host-pathogen interactome of the coronaviruses SARS-CoV-1,SARS-CoV-2,and MERS-CoV,all of which caused lethal outbreaks in the past two decades.They functionally characterize a number of these interactions,leveraging the information to identify promising candidate molecules for drug-repurposing.展开更多
基金Supported by the Instituto de Salud Carlos Ⅲ(ISCⅢ)Through the Project Co-Funded by the European Union,No.PI20-00487,No.PI23-00119 and No.PI24-01630.
文摘BACKGROUND Diabetes and its associated microvascular complications,such as nephropathy and retinopathy,significantly impact global health.These complications often begin in the prediabetic stage,emphasizing the importance of early detection and intervention.Inflammatory pathways are key contributors to these conditions,and recent research has identified members of the tumor necrosis factor(TNF)receptor superfamily as potential biomarkers.However,their association with renal and retinal dysfunction in individuals with intermediate hyperglycemia(IH)remains underexplored.The Early Prevention of Diabetes Complications(ePREDICE)trial provides a valuable cohort to investigate these associations and improve risk assessment strategies.AIM To identify inflammatory biomarkers associated with early renal and retinal dysfunction in individuals with IH.Specifically,we evaluate the diagnostic and prognostic potential of TNF receptor superfamily members[TNF receptor 1(TNF-R1),TNF receptor 2(TNF-R2)],T-cell immunoglobulin and mucin domain 3(TIM-3)/HAVCR2,galectin-3,and interleukin-6(IL-6)in detecting kidney dysfunction and retinopathy in this high-risk population.By understanding their roles,we seek to enhance early screening methods and inform personalized intervention strategies.METHODS A cross-sectional analysis of 967 individuals with IH from the ePREDICE trial was conducted.Participants underwent comprehensive anthropometric and biochemical assessments.Key inflammatory biomarkers,including TNF-R1,TNF-R2,TIM-3/HAVCR2,galectin-3,and IL-6,were quantified using immunoassays.Renal function was assessed using estimated glomerular filtration rate(eGFR)and albuminuria,while retinopathy was evaluated through fundoscopic examination.Statistical analyses included adjusted mean comparisons,correlation studies,and receiver operating characteristic curve analysis to assess biomarker diagnostic accuracy.RESULTS TNF-R1,TNF-R2,and TIM-3/HAVCR2 were significantly associated with reduced filtration function(eGFR<60 mL/minute/1.73 m^(2))and albuminuria,with area under the curve(AUC)values between 0.815 and 0.845.TIM-3/HAVCR2 emerged as the strongest predictor of retinopathy(AUC=0.737).Strong correlations(r>0.75)were observed among TNF-R1,TNF-R2,and TIM-3/HAVCR2,suggesting a coordinated role in inflammatory pathways.CONCLUSION Our findings highlight the potential of TNF receptor superfamily members as biomarkers for early-stage renal and retinal complications in individuals with IH.Their integration into clinical screening protocols could facilitate earlier detection,improving patient stratification and personalized management strategies.Further longitudinal studies are necessary to validate their predictive value and potential for guiding therapeutic interventions in IH and early diabetes management.
文摘BACKGROUND Chronic liver disease(CLD)causes approximately two million deaths each year,and its clinical diagnosis and management remain challenging.Ultrasound is currently the most widely used technique for disease detection.AIM To propose a practical cut-off value for identifying patients with hepatocellular carcinoma(HCC)among those with compensated advanced CLD or healthy individuals using the GALAD score,an algorithm based on a formula that incorporates gender,age,serum alpha-fetoprotein(AFP),AFP-L3,and des-gamma-carboxy prothrombin values.METHODS This cross-sectional analysis was conducted using prospectively collected data from five cohorts(n=1431)comprising healthy individuals,cirrhosis,and HCC patients.These subjects were enrolled from an Italian retrospective cohort,including patients from the IRCCS“Saverio de Bellis”,Department of Gastroenterology,the University of Modena and Reggio Emilia Gastroenterology Department,and the Padua University Hospital and the Department of Gastroenterology,Hepatology,Infectious diseases and Endocrinology,Hannover Medical School.RESULTS Using healthy subjects as reference,a GALAD score cut-off of-1.67 identified HCC with a sensitivity of 89.77%and specificity of 97.59%.Individuals with GALAD values>-1.67 exhibited a moderate to very high probability(over 90%)of having HCC.When cirrhotic patients were used as the reference category,a cut-off of-0.77 yielded a sensitivity of 78.17%and a specificity of 89.55%.CONCLUSION We strongly recommend incorporating this GALAD cut-off into clinical guidelines for the screening of patients with a compensated advanced CLD who are at high risk of developing HCC.Given the rapid global rise in metabolic-associated steatotic liver disease(MASLD)-related CLD,future research should prioritize larger MASLD cohorts to establish the most appropriate GALAD cut-off for diagnostic use,compared to healthy controls and to patients with other forms of CLD.
文摘Vaginal carriage of Group B Streptococcus (GBS) is a maternal and child health issue. Our objective was to determine the prevalence of GBS carriage;identify the factors associated with this carriage and determine the antibiotic sensitivity of the isolated strains. We conducted a cross-sectional and prospective study in rural Senegal (in the health district of Sokone). Socio-demographic, clinical and gynaeco-obstetrical data were collected. Vaginal swabs were taken by the midwives on specific settings in order to test for GBS and other High Risk Vaginal Bacteria (HRVB). Antibiotic susceptibility testing was done according to the recommendations of the CA SFM/EUCAST 2020. In total, 100 pregnant women were targeted and 97 pregnant women were included. Their age ranged from 18 to 40 years with 64.9% (63/97) of participants belonging to the “20 - 30” age group. The overall prevalence of Group B Streptococcus carriage was 15.5% (15/97). However, the proportion of women with at least one high risk infectious bacteria was 29.89% (29/97). No statistically significant differences were found between GBS carriage and the potential factors studied. However, the study also looked for the presence of other high-risk bacteria and coinfections were indeed found between GBS and E. coli and Staphylococcus aureus. Antibiotic susceptibility testing shows that GBS strains were fully susceptible to penicillin G, erythromycin, clindamycin, chloramphenicol, rifampicin and vancomycin. Sensitivities to norfloxacin and gentamycin were 73.3% and 86.7% respectively. In contrast, high resistance to tetracycline (86.7%) was observed. GBS carriage remains a major public health issue because of its consequences for the mother and the newborn. Correct screening and proper monitoring of strain susceptibility remain one of the most effective means of patient management and care.
基金Wilson+Olegario:Philanthropy through Guys Cancer Charity(MRF)Guys Cancer Charity(MRF)Cancer Research UK through the City of London Cancer Centre(MRF)Fondazione Regionale per la Ricerca Biomedica,grant ID 2721017(JI).
文摘Head and neck squamous cell carcinoma(HNSCC)is a devastating disease.Despite morbid treatment,5-year survival rates remain poor(28%-67%)[1].There is a significant knowledge gap regarding how the microbiota may impact HNSCC treatment efficacy[2].We used microbiome data from two independent cohorts to test and validate the hypothesis that oral bacteria are associated with HNSCC prognosis and in vitro models to investigate mechanistic underpinnings.Methods are detailed in Supplementary Materials.
文摘Introduction Individual patient data(IPD)meta-analysis by Choi et al.(1)compared hepatocellular carcinoma(HCC)risk between the entecavir(ETV)and tenofovir(TDF)in treatment-naïve chronic hepatitis B(CHB)patients using a multivariable Cox proportional hazards model from 11 Asian studies,totaling 42,939 patients receiving nucles(t)tide analogues(NAs)for more than one year.
文摘This work addresses the problem of supervised classification for highly correlated highdimensional data describing non-independent observations to identify SNPs related to a phenotype.We use a general penalized linear mixed model with a single random effect that performs simultaneous SNP selection and population structure adjustment in highdimensional prediction models.Specifically,the model simultaneously selects variables and estimates their effects,taking into account correlations between individuals.Single nucleotide polymorphisms(SNPs)are a type of genetic variation and each SNP represents a difference in a single DNA building block,namely a nucleotide.Previous research has shown that SNPs can be used to identify the correct source population of an individual and can act in isolation or simultaneously to impact a phenotype.In this regard,the study of the contribution of genetics in infectious disease phenotypes is of great importance.In this study,we used uncorrelated variables from the construction of blocks of correlated variables done in a previous work to describe the most related observations of the dataset.The model was trained with 90%of the observations and tested with the remaining 10%.The best model obtained with the generalized information criterion(GIC)identified the SNP named rs2493311 located on the first chromosome of the gene called PRDM16((PR/SET domain 16))as the most decisive factor in malaria attacks.
基金Open Access funding enabled and organized by Projekt DEAL.
文摘In a recent study published in Science,1 Gordon et al.investigate the host-pathogen interactome of the coronaviruses SARS-CoV-1,SARS-CoV-2,and MERS-CoV,all of which caused lethal outbreaks in the past two decades.They functionally characterize a number of these interactions,leveraging the information to identify promising candidate molecules for drug-repurposing.
