Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches...Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.展开更多
This study explores free convective heat transfer in an electrically conducting nanofluid flow over a moving semi-infinite flat plate under the influence of an induced magnetic field and viscous dissipation.The veloci...This study explores free convective heat transfer in an electrically conducting nanofluid flow over a moving semi-infinite flat plate under the influence of an induced magnetic field and viscous dissipation.The velocity and magnetic field vectors are aligned at a distance from the plate.The Spectral Relaxation Method(SRM)is used to numerically solve the coupled nonlinear partial differential equations,analyzing the effects of the Eckert number on heat and mass transfer.Various nanofluids containing Cu,Ag,Al_(2)O_(3),and TiO_(2) nanoparticles are examined to assess how external magnetic fields influence fluid behavior.Key parameters,including the nanoparticle volume fraction ϕ,magnetic parameter M,magnetic Prandtl number Prm,and Eckert number Ec,are evaluated for their impact on velocity,induced magnetic field,and heat transfer.Results indicate that increasing the magnetic parameter reduces velocity and magnetic field components in alumina-water nanofluids,while a higher nanoparticle volume fraction enhances the thermal boundary layer.Greater viscous dissipation(Ec)increases temperature,and Al_(2)O_(3) nanofluids exhibit higher speeds than Cu,Ag,and TiO_(2) due to density differences.Silver-water nanofluids,with their higher density,move more slowly.The SRM results closely align with those from Maple,confirming the method’s accuracy.展开更多
Background Using Systematic Assessment of Geriatric Elements in Atrial Fibrillation(SAGE-AF) data, determine how well the rich mix of demographic, clinical history, geriatric assessments, and clinically adjudicated ev...Background Using Systematic Assessment of Geriatric Elements in Atrial Fibrillation(SAGE-AF) data, determine how well the rich mix of demographic, clinical history, geriatric assessments, and clinically adjudicated events can predict two-year survival.Methods Subjects were recruited from participating outpatient practices if they had non-valvular AF, were 65 or over with CHA_(2)DS_(2)-VASc scores of at least 2, and were candidates for anticoagulation. Demographics, clinical history, and geriatric qualities of life were assessed by interview and medical records review using standardized protocols and repeated at one and two years. Events identified were abstracted and submitted for adjudication using standard definitions of events and categories. Nonmortality event categories included hospitalizations(cardiovascular, bleeding, other), bleeding(major, clinically relevant non-major, minor), and seven major adverse cardiovascular events.Results The 1245 subjects experienced 1960 events, primarily hospitalizations(935) and/or bleeding(817);114 subjects(9.2%)died during two years of follow-up. Events initially abstracted to more than one category(172) were combined, resulting in 1788unique incidents. Most subjects had zero or one event(69%) and fewer than 7% had more than 3 types. Most variables were significant in bivariate analysis. Using multiple logistic regression with two-year survival as the outcome variable, the best-fit model included event number and type, number of unique incidents, and number of bleeding events(R^(2) = 0.511, C = 93.1) with sensitivity = 97.9% and specificity = 44.7%.Conclusions Two-year survival was high. This model, if validated, could have major implications for treatment of patients with AF. Patients in the large group with no or one event are at very low risk of death(under 2%). The small group with high risk for further complications, including death, deserve reassessment to determine if this trajectory can be altered.展开更多
Little is known about the inheritance of very low heteroplasmy mitochondria DNA （mtDNA） variations. Even with the development of new next-generation sequencing methods, the practical lower limit of measured heteropl...Little is known about the inheritance of very low heteroplasmy mitochondria DNA （mtDNA） variations. Even with the development of new next-generation sequencing methods, the practical lower limit of measured heteroplasmy is still about 1% due to the inherent noise level of the sequencing. In this study, we sequenced the mitochondrial genome of 44 individuals using Illumina high-throughput sequencing technology and obtained high-coverage mitochondria sequencing data. Our study population contains many mother-offspring pairs. This unique study design allows us to bypass the usual heteroplasmy limitation by analyzing the correlation of mutation levels at each position in the mtDNA sequence between maternally related pairs and non-related pairs. The study showed that very low heteroplasmy variants, down to almost 0.1%, are inherited maternally and that this inheritance begins to decrease at about 0.5%, cor- resnondin to abottleneck of about 200 mtDNA.展开更多
Model of Casson nanofluid flow over a nonlinear shrinking surface is considered.Model of Tiwari and Das is applied to nanofluid comprising of sodium alginate with copper and silver.The governing nonlinear equations in...Model of Casson nanofluid flow over a nonlinear shrinking surface is considered.Model of Tiwari and Das is applied to nanofluid comprising of sodium alginate with copper and silver.The governing nonlinear equations incorporating the effects of the viscous dissipation are transformed into boundary value problems (BVPs) of ordinary differential equations (ODEs) by using appropriate similarity transformations.The resulting equations are converted into initial value problems (IVPs) using the shooting method which are then solved by Runge-Kutta method of fourth order.In order to determine the stability of the dual solutions obtained,stability analysis is performed and discovered that the first (second) solution is stable (unstable) and physically realizable (unrealizable).Both the thickness of the thermal boundary layer as well as temperature increase when the Casson parameter (β) is increased in the second solution.展开更多
正确报告随机对照临床试验(randomized controlled trial,RCT)是严格评价试验结果真实性与有效性的必要前提。含22项条目清单和流程图的CONSORT(Consolidated Standards of Reporting Trials)声明旨在通过改进RCT的报告来解决这一问题...正确报告随机对照临床试验(randomized controlled trial,RCT)是严格评价试验结果真实性与有效性的必要前提。含22项条目清单和流程图的CONSORT(Consolidated Standards of Reporting Trials)声明旨在通过改进RCT的报告来解决这一问题。然而,《CONSORT声明》中没有专门论及那些适用于非药物治疗(如手术、技术干预、仪器设备、康复理疗、心理治疗和行为干预等)临床试验的具体问题。此外,相当多的证据表明非药物临床试验的报告仍然需要改进,因此CONSORT小组针对评估非药物治疗的临床INFORMATION FOR AUTHORS试验制定了《CONSORT扩展声明》。为制定《CONSORT扩展声明》以规范非药物临床试验的报告,33名专家于2006年2月在法国巴黎组织召开了讨论会议,并就此达成了共识。与会者扩充了原有《CONSORT声明》中的11项条目,新增了1项条目,修改并重新制定了报告流程图。为便于充分理解和执行《CONSORT扩展声明》,CONSORT小组通过对文献的回顾编制了这一说明与详述文本,旨在为正确报告非药物临床试验提供范例。本扩展声明,连同《CONSORT声明》以及《CONSORT声明》的其他扩展本,将有助于改进非药物治疗领域RCT的报告。展开更多
AIM: To study the small bowel (SB) mucosa on biopsy in cirrhotic patients with portal hypertension and in non-cirrhotic controls and grade fi ndings according to the Marsh criteria. METHODS: We prospectively enrolled ...AIM: To study the small bowel (SB) mucosa on biopsy in cirrhotic patients with portal hypertension and in non-cirrhotic controls and grade fi ndings according to the Marsh criteria. METHODS: We prospectively enrolled 51 consecutive patients undergoing an upper endoscopy for their routine medical care. Twenty f ive patients with cirrhosis and portal hypertension were compared to 26 controls. We obtained coeliac serology and multiple upper small bowel biopsies on all 51 patients. A GI pathologist interpreted biopsies and graded fi ndings according to the Marsh criteria. We assessed equivalence in Marsh grade between cirrhotic and non-cirrhotic controls using the Mann-Whitney test for equivalence. RESULTS: Gender, ethnicity and age were similar between both groups. Marsh grades were equivalent between the groups. Grade of 0 was present in 96% and grade of 1 was present in 4% of both groups and there was no villus atrophy or decrease in villus/crypt ratio in patients with portal hypertension. CONCLUSION: This study provides evidence for the lack of villus atrophy in patients with cirrhosis and portal hypertension, and supports the continuous reliance on the Marsh criteria when the diagnosis of coeliac disease is to be made in the presence of cirrhosis.展开更多
Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stag...Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer.展开更多
BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopat...BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.展开更多
The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the th...The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the threats, cells have evolved an intricate network, namely DNA damage response(DDR) system that senses and deals with the lesions of DNA.Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues.In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis.We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.展开更多
AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the C...AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.展开更多
BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used ...BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.展开更多
AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis(AH).METHODS: We prospectively recruited patients with cirrhosis ...AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis(AH).METHODS: We prospectively recruited patients with cirrhosis from AH(n = 23) and those with cirrhosis with acute decompensation(AD) from etiologies other than alcohol(n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free survival.RESULTS: A comparison of model for end-stage liver disease(MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD(area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54(0.18, 0.91); P = 0.005], homocitrulline [0.66(0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53(0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers(carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION: Metabolomics plasma analyte levels might be used to diagnose of AH or help predict patient prognoses.展开更多
Background Though engaging patients with atrial fibrillation(AF) in understanding their stroke risk is encouraged by guidelines, little is known regarding AF patients' perceived stroke risk or its relationship wit...Background Though engaging patients with atrial fibrillation(AF) in understanding their stroke risk is encouraged by guidelines, little is known regarding AF patients' perceived stroke risk or its relationship with oral anticoagulation(OAC) use. We aim to identify factors associated with underestimation of stroke risk among older patients with AF and relate this to OAC use. Methods Data are from the ongoing SAGE(Systematic Assessment of Geriatric Elements)-AF study, which included older patients(> 65 years) with non-valvular AF and a CHA2 DS2-VASc score of ≥ 2. Participants reported their perceived risk of having a stroke without OAC. We compared the perceived risk to CHA2 DS2-VASc predicted stroke risk and classified participants as "over" or "under" estimators, and identified factors associated with underestimation of risk using multiple logistic regression. Results The average CHA2 DS2-VASc score of 915 participants(average age: 75 years, 47% female, 86% white) was 4.3 ± 1.6, 43% of participants had discordant predicted and self-reported stroke risks. Among the 376 participants at highest risk(CHA2 DS2-VASc score ≥ 5), 46% of participants underestimated their risk. Older participants(≥ 85 years) were more likely and OAC treated patients less likely to underestimate their risk of developing a future stroke than respective comparison groups. Conclusions A significant proportion of study participants misperceived their stroke risk, mostly by overestimating. Almost half of participants at high risk of stroke underestimated their risk, with older patients more likely to do so. Patients on OAC were less likely to underestimate their risk, suggesting that successful efforts to educate patients about their stroke risk may influence treatment choices.展开更多
Histamine_2-receptor antagonists(H_2RAs) are availableover-the-counter (OTC) for the treatment and prevention of heartburn, but more than occasional, singledose use can lead to rapid development of tachyphylaxis. The ...Histamine_2-receptor antagonists(H_2RAs) are availableover-the-counter (OTC) for the treatment and prevention of heartburn, but more than occasional, singledose use can lead to rapid development of tachyphylaxis. The aim of this review is to assess the publishedevidence regarding the development of tachyphylaxiswith repeat usage of H_2RAs. PubMed and SCOPUS were searched across all years to identify clinical studies thatexamined the development of tachyphylaxis with repeated dosing of H_2RAs. Although a single (first) doseof an H_2RA can be effective for controlling gastric acidand preventing or relieving food-related heartburn, numerous studies confirm that tachyphylaxis, also knownas tolerance, is consistently detected at the first timepoint assessed after the first dose, including the second day and/or second dose. Even if symptom relief isachieved with an H_2RA, it may be due to desensitizationof the esophagus to acid exposure, potentially providingsymptom relief without significantly decreasing esophageal acid exposure. When recommending OTC drugsfor treatment of frequent heartburn, clinicians shouldbe aware of the potential for rapid development oftachyphylaxis in patients who use H_2RAs for 2 or more consecutive days. Even if symptom relief is achieved, it may be due to desensitization of the esophagus to acid by the H_2RA, potentially providing symptom relief without significantly decreasing esophageal acid exposure. Other strategies, such as an OTC proton pump inhibitor, may be needed to optimize management of frequent heartburn.展开更多
BACKGROUND Endoscopic evaluation in diagnosing and managing ulcerative colitis(UC)is becoming increasingly important.Several endoscopic scoring systems have been established,including the Ulcerative Colitis Endoscopic...BACKGROUND Endoscopic evaluation in diagnosing and managing ulcerative colitis(UC)is becoming increasingly important.Several endoscopic scoring systems have been established,including the Ulcerative Colitis Endoscopic Index of Severity(UCEIS)score and Mayo Endoscopic Subscore(MES).Furthermore,the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score for UC has recently been proposed;however,its clinical value remains unclear.AIM To investigate the clinical value of the TIGER score in UC by comparing it with the UCEIS score and MES.METHODS This retrospective study included 166 patients with UC who underwent total colonoscopy between January 2017 and March 2023 at the Affiliated Hospital of Qingdao University(Qingdao,China).We retrospectively analysed endoscopic scores,laboratory and clinical data,treatment,and readmissions within 1 year.Spearman’s rank correlation coefficient,receiver operating characteristic curve,and univariate and multivariable logistic regression analyses were performed using IBM SPSS Statistics for Windows,version 26.0(IBM Corp.,Armonk,NY,United States)and GraphPad Prism version 9.0.0 for Windows(GraphPad Software,Boston,Massachusetts,United States).RESULTS The TIGER score significantly correlated with the UCEIS score and MES(r=0.721,0.626,both P<0.001),showed good differentiating values for clinical severity among mild,moderate,and severe UC[8(4-112.75)vs 210(109–219)vs 328(219–426),all P<0.001],and exhibited predictive value in diagnosing patients with severe UC[area under the curve(AUC)=0.897,P<0.001].Additionally,the TIGER(r=0.639,0,551,0.488,0.376,all P<0.001)and UCEIS scores(r=0.622,0,540,0.494,and 0.375,all P<0.001)showed stronger correlations with laboratory and clinical parameters,including C-reactive protein,erythrocyte sedimentation rate,length of hospitalisation,and hospitalisation costs,than MES(r=0.509,0,351,0.339,and 0.270,all P<0.001).The TIGER score showed the best predictability for patients'recent advanced treatment,including systemic corticosteroids,biologics,or immunomodulators(AUC=0.848,P<0.001)and 1-year readmission(AUC=0.700,P<0.001)compared with the UCEIS score(AUC=0.762,P<0.001;0.627,P<0.05)and MES(AUC=0.684,P<0.001;0.578,P=0.132).Furthermore,a TIGER score of≥317 was identified as an independent risk factor for advanced UC treatment(P=0.011).CONCLUSION The TIGER score may be superior to the UCIES score and MES in improving the accuracy of clinical disease severity assessment,guiding therapeutic decision-making,and predicting short-term prognosis.展开更多
文摘Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.
文摘This study explores free convective heat transfer in an electrically conducting nanofluid flow over a moving semi-infinite flat plate under the influence of an induced magnetic field and viscous dissipation.The velocity and magnetic field vectors are aligned at a distance from the plate.The Spectral Relaxation Method(SRM)is used to numerically solve the coupled nonlinear partial differential equations,analyzing the effects of the Eckert number on heat and mass transfer.Various nanofluids containing Cu,Ag,Al_(2)O_(3),and TiO_(2) nanoparticles are examined to assess how external magnetic fields influence fluid behavior.Key parameters,including the nanoparticle volume fraction ϕ,magnetic parameter M,magnetic Prandtl number Prm,and Eckert number Ec,are evaluated for their impact on velocity,induced magnetic field,and heat transfer.Results indicate that increasing the magnetic parameter reduces velocity and magnetic field components in alumina-water nanofluids,while a higher nanoparticle volume fraction enhances the thermal boundary layer.Greater viscous dissipation(Ec)increases temperature,and Al_(2)O_(3) nanofluids exhibit higher speeds than Cu,Ag,and TiO_(2) due to density differences.Silver-water nanofluids,with their higher density,move more slowly.The SRM results closely align with those from Maple,confirming the method’s accuracy.
文摘Background Using Systematic Assessment of Geriatric Elements in Atrial Fibrillation(SAGE-AF) data, determine how well the rich mix of demographic, clinical history, geriatric assessments, and clinically adjudicated events can predict two-year survival.Methods Subjects were recruited from participating outpatient practices if they had non-valvular AF, were 65 or over with CHA_(2)DS_(2)-VASc scores of at least 2, and were candidates for anticoagulation. Demographics, clinical history, and geriatric qualities of life were assessed by interview and medical records review using standardized protocols and repeated at one and two years. Events identified were abstracted and submitted for adjudication using standard definitions of events and categories. Nonmortality event categories included hospitalizations(cardiovascular, bleeding, other), bleeding(major, clinically relevant non-major, minor), and seven major adverse cardiovascular events.Results The 1245 subjects experienced 1960 events, primarily hospitalizations(935) and/or bleeding(817);114 subjects(9.2%)died during two years of follow-up. Events initially abstracted to more than one category(172) were combined, resulting in 1788unique incidents. Most subjects had zero or one event(69%) and fewer than 7% had more than 3 types. Most variables were significant in bivariate analysis. Using multiple logistic regression with two-year survival as the outcome variable, the best-fit model included event number and type, number of unique incidents, and number of bleeding events(R^(2) = 0.511, C = 93.1) with sensitivity = 97.9% and specificity = 44.7%.Conclusions Two-year survival was high. This model, if validated, could have major implications for treatment of patients with AF. Patients in the large group with no or one event are at very low risk of death(under 2%). The small group with high risk for further complications, including death, deserve reassessment to determine if this trajectory can be altered.
基金supported by the grant from the National Cancer Institute(RO1 CA104666)supported in part by the Vanderbilt-Ingram Cancer Center(P30 CA68485)
文摘Little is known about the inheritance of very low heteroplasmy mitochondria DNA （mtDNA） variations. Even with the development of new next-generation sequencing methods, the practical lower limit of measured heteroplasmy is still about 1% due to the inherent noise level of the sequencing. In this study, we sequenced the mitochondrial genome of 44 individuals using Illumina high-throughput sequencing technology and obtained high-coverage mitochondria sequencing data. Our study population contains many mother-offspring pairs. This unique study design allows us to bypass the usual heteroplasmy limitation by analyzing the correlation of mutation levels at each position in the mtDNA sequence between maternally related pairs and non-related pairs. The study showed that very low heteroplasmy variants, down to almost 0.1%, are inherited maternally and that this inheritance begins to decrease at about 0.5%, cor- resnondin to abottleneck of about 200 mtDNA.
基金Universiti Utara Malaysia (UUM) for the moral and financial support in conducting this research
文摘Model of Casson nanofluid flow over a nonlinear shrinking surface is considered.Model of Tiwari and Das is applied to nanofluid comprising of sodium alginate with copper and silver.The governing nonlinear equations incorporating the effects of the viscous dissipation are transformed into boundary value problems (BVPs) of ordinary differential equations (ODEs) by using appropriate similarity transformations.The resulting equations are converted into initial value problems (IVPs) using the shooting method which are then solved by Runge-Kutta method of fourth order.In order to determine the stability of the dual solutions obtained,stability analysis is performed and discovered that the first (second) solution is stable (unstable) and physically realizable (unrealizable).Both the thickness of the thermal boundary layer as well as temperature increase when the Casson parameter (β) is increased in the second solution.
文摘正确报告随机对照临床试验(randomized controlled trial,RCT)是严格评价试验结果真实性与有效性的必要前提。含22项条目清单和流程图的CONSORT(Consolidated Standards of Reporting Trials)声明旨在通过改进RCT的报告来解决这一问题。然而,《CONSORT声明》中没有专门论及那些适用于非药物治疗(如手术、技术干预、仪器设备、康复理疗、心理治疗和行为干预等)临床试验的具体问题。此外,相当多的证据表明非药物临床试验的报告仍然需要改进,因此CONSORT小组针对评估非药物治疗的临床INFORMATION FOR AUTHORS试验制定了《CONSORT扩展声明》。为制定《CONSORT扩展声明》以规范非药物临床试验的报告,33名专家于2006年2月在法国巴黎组织召开了讨论会议,并就此达成了共识。与会者扩充了原有《CONSORT声明》中的11项条目,新增了1项条目,修改并重新制定了报告流程图。为便于充分理解和执行《CONSORT扩展声明》,CONSORT小组通过对文献的回顾编制了这一说明与详述文本,旨在为正确报告非药物临床试验提供范例。本扩展声明,连同《CONSORT声明》以及《CONSORT声明》的其他扩展本,将有助于改进非药物治疗领域RCT的报告。
文摘AIM: To study the small bowel (SB) mucosa on biopsy in cirrhotic patients with portal hypertension and in non-cirrhotic controls and grade fi ndings according to the Marsh criteria. METHODS: We prospectively enrolled 51 consecutive patients undergoing an upper endoscopy for their routine medical care. Twenty f ive patients with cirrhosis and portal hypertension were compared to 26 controls. We obtained coeliac serology and multiple upper small bowel biopsies on all 51 patients. A GI pathologist interpreted biopsies and graded fi ndings according to the Marsh criteria. We assessed equivalence in Marsh grade between cirrhotic and non-cirrhotic controls using the Mann-Whitney test for equivalence. RESULTS: Gender, ethnicity and age were similar between both groups. Marsh grades were equivalent between the groups. Grade of 0 was present in 96% and grade of 1 was present in 4% of both groups and there was no villus atrophy or decrease in villus/crypt ratio in patients with portal hypertension. CONCLUSION: This study provides evidence for the lack of villus atrophy in patients with cirrhosis and portal hypertension, and supports the continuous reliance on the Marsh criteria when the diagnosis of coeliac disease is to be made in the presence of cirrhosis.
文摘Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer.
文摘BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.
基金supported by the National Natural Science Foundation of China (Grant No.81622035, 81672610, and 81521002)
文摘The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the threats, cells have evolved an intricate network, namely DNA damage response(DDR) system that senses and deals with the lesions of DNA.Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues.In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis.We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.
文摘AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.
文摘BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.
基金Supported by In part by NIH grant R01 HL122283(Brown JM)
文摘AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis(AH).METHODS: We prospectively recruited patients with cirrhosis from AH(n = 23) and those with cirrhosis with acute decompensation(AD) from etiologies other than alcohol(n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free survival.RESULTS: A comparison of model for end-stage liver disease(MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD(area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54(0.18, 0.91); P = 0.005], homocitrulline [0.66(0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53(0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers(carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION: Metabolomics plasma analyte levels might be used to diagnose of AH or help predict patient prognoses.
基金supported by the National Heart,Lung,and Blood Institute(R01HL126911)supported by the NIH Training Grant entitled Transdisciplinary Training in Cardiovascular Research 5T32HL120823-05supported by the National Heart,Lung,and Blood Institute(R01HL137734&R01HL 137794&R01HL13660&R01HL141434&U54HL143541)。
文摘Background Though engaging patients with atrial fibrillation(AF) in understanding their stroke risk is encouraged by guidelines, little is known regarding AF patients' perceived stroke risk or its relationship with oral anticoagulation(OAC) use. We aim to identify factors associated with underestimation of stroke risk among older patients with AF and relate this to OAC use. Methods Data are from the ongoing SAGE(Systematic Assessment of Geriatric Elements)-AF study, which included older patients(> 65 years) with non-valvular AF and a CHA2 DS2-VASc score of ≥ 2. Participants reported their perceived risk of having a stroke without OAC. We compared the perceived risk to CHA2 DS2-VASc predicted stroke risk and classified participants as "over" or "under" estimators, and identified factors associated with underestimation of risk using multiple logistic regression. Results The average CHA2 DS2-VASc score of 915 participants(average age: 75 years, 47% female, 86% white) was 4.3 ± 1.6, 43% of participants had discordant predicted and self-reported stroke risks. Among the 376 participants at highest risk(CHA2 DS2-VASc score ≥ 5), 46% of participants underestimated their risk. Older participants(≥ 85 years) were more likely and OAC treated patients less likely to underestimate their risk of developing a future stroke than respective comparison groups. Conclusions A significant proportion of study participants misperceived their stroke risk, mostly by overestimating. Almost half of participants at high risk of stroke underestimated their risk, with older patients more likely to do so. Patients on OAC were less likely to underestimate their risk, suggesting that successful efforts to educate patients about their stroke risk may influence treatment choices.
文摘Histamine_2-receptor antagonists(H_2RAs) are availableover-the-counter (OTC) for the treatment and prevention of heartburn, but more than occasional, singledose use can lead to rapid development of tachyphylaxis. The aim of this review is to assess the publishedevidence regarding the development of tachyphylaxiswith repeat usage of H_2RAs. PubMed and SCOPUS were searched across all years to identify clinical studies thatexamined the development of tachyphylaxis with repeated dosing of H_2RAs. Although a single (first) doseof an H_2RA can be effective for controlling gastric acidand preventing or relieving food-related heartburn, numerous studies confirm that tachyphylaxis, also knownas tolerance, is consistently detected at the first timepoint assessed after the first dose, including the second day and/or second dose. Even if symptom relief isachieved with an H_2RA, it may be due to desensitizationof the esophagus to acid exposure, potentially providingsymptom relief without significantly decreasing esophageal acid exposure. When recommending OTC drugsfor treatment of frequent heartburn, clinicians shouldbe aware of the potential for rapid development oftachyphylaxis in patients who use H_2RAs for 2 or more consecutive days. Even if symptom relief is achieved, it may be due to desensitization of the esophagus to acid by the H_2RA, potentially providing symptom relief without significantly decreasing esophageal acid exposure. Other strategies, such as an OTC proton pump inhibitor, may be needed to optimize management of frequent heartburn.
基金Clinical Medicine+X Research Project of the Affiliated Hospital of Qingdao University in 2021,No.QDFY+X202101036Qingdao Medical and Health Research Program in 2021,No.2021-WJZD166and Youth Project of Natural Science Foundation of Shandong Province,No.ZR2020QH031.
文摘BACKGROUND Endoscopic evaluation in diagnosing and managing ulcerative colitis(UC)is becoming increasingly important.Several endoscopic scoring systems have been established,including the Ulcerative Colitis Endoscopic Index of Severity(UCEIS)score and Mayo Endoscopic Subscore(MES).Furthermore,the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score for UC has recently been proposed;however,its clinical value remains unclear.AIM To investigate the clinical value of the TIGER score in UC by comparing it with the UCEIS score and MES.METHODS This retrospective study included 166 patients with UC who underwent total colonoscopy between January 2017 and March 2023 at the Affiliated Hospital of Qingdao University(Qingdao,China).We retrospectively analysed endoscopic scores,laboratory and clinical data,treatment,and readmissions within 1 year.Spearman’s rank correlation coefficient,receiver operating characteristic curve,and univariate and multivariable logistic regression analyses were performed using IBM SPSS Statistics for Windows,version 26.0(IBM Corp.,Armonk,NY,United States)and GraphPad Prism version 9.0.0 for Windows(GraphPad Software,Boston,Massachusetts,United States).RESULTS The TIGER score significantly correlated with the UCEIS score and MES(r=0.721,0.626,both P<0.001),showed good differentiating values for clinical severity among mild,moderate,and severe UC[8(4-112.75)vs 210(109–219)vs 328(219–426),all P<0.001],and exhibited predictive value in diagnosing patients with severe UC[area under the curve(AUC)=0.897,P<0.001].Additionally,the TIGER(r=0.639,0,551,0.488,0.376,all P<0.001)and UCEIS scores(r=0.622,0,540,0.494,and 0.375,all P<0.001)showed stronger correlations with laboratory and clinical parameters,including C-reactive protein,erythrocyte sedimentation rate,length of hospitalisation,and hospitalisation costs,than MES(r=0.509,0,351,0.339,and 0.270,all P<0.001).The TIGER score showed the best predictability for patients'recent advanced treatment,including systemic corticosteroids,biologics,or immunomodulators(AUC=0.848,P<0.001)and 1-year readmission(AUC=0.700,P<0.001)compared with the UCEIS score(AUC=0.762,P<0.001;0.627,P<0.05)and MES(AUC=0.684,P<0.001;0.578,P=0.132).Furthermore,a TIGER score of≥317 was identified as an independent risk factor for advanced UC treatment(P=0.011).CONCLUSION The TIGER score may be superior to the UCIES score and MES in improving the accuracy of clinical disease severity assessment,guiding therapeutic decision-making,and predicting short-term prognosis.
