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
BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals w...BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals with echocardiographic measures in TJA patients.METHODS The study comprised 110 TJA patients who had a recent history of high chromium,cobalt or titanium concentrations.Patients underwent two-dimensional,three-dimensional,Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations.Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations(exposure)with echocardiographic measures(outcome).RESULTS Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume(estimate 5.09;95%CI:0.02-10.17)as well as left atrial and right ventricular dilation,particularly in men but no changes in cardiac function.Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain(estimate 0.38;95%CI:0.70 to 0.06)and cardiac index(estimate 0.08;95%CI,-0.15 to-0.01).CONCLUSION Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients.Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.展开更多
BACKGROUND Smartwatches have become readily accessible tools for detecting atrial fibrillation(AF).There remains limited data on how they affect psychosocial outcomes and engagement in older adults.We examine the heal...BACKGROUND Smartwatches have become readily accessible tools for detecting atrial fibrillation(AF).There remains limited data on how they affect psychosocial outcomes and engagement in older adults.We examine the health behavior outcomes of stroke survivors prescribed smartwatches for AF detection stratified by age.METHODS We analyzed data from the Pulsewatch study,a randomized controlled trial that enrolled patients(≥50 years)with a history of stroke or transient ischemic attack and CHA2DS2-VASc≥2.Intervention participants were equipped with a cardiac patch monitor and a smartwatch-app dyad,while control participants wore the cardiac patch monitor for up to 44 days.We evaluated health behavior parameters using standardized tools,including the Consumer Health Activation Index,the Generalized Anxiety Disorder questionnaire,the 12-Item Short Form Health Survey,and wear time of participants categorized into three age groups:Group 1(ages 50-60),Group 2(ages 61-69),and Group 3(ages 70-87).We performed statistical analysis using a mixedeffects repeated measures linear regression model to examine differences amongst age groups.RESULTS Comparative analysis between Groups 1,2 and 3 revealed no significant differences in anxiety,patient activation,perception of physical health and wear time.The use of smartwatch technology was associated with a decrease in perception of mental health for Group 2 compared to Group 1(β=-3.29,P=0.046).CONCLUSION Stroke survivors demonstrated a willingness to use smartwatches for AF monitoring.Importantly,among these study participants,the majority did not experience negative health behavior outcomes or decreased engagement as age increased.展开更多
This study utilizes the Dynamic Conditional Correlation-Generalized Autoregressive Conditional Heteroskedasticity (DCC-GARCH) model to investigate the dynamic relationship between Chinese and U.S. stock markets amid t...This study utilizes the Dynamic Conditional Correlation-Generalized Autoregressive Conditional Heteroskedasticity (DCC-GARCH) model to investigate the dynamic relationship between Chinese and U.S. stock markets amid the COVID-19 pandemic. Initially, a univariate GARCH model is developed to derive residual sequences, which are then used to estimate the DCC model parameters. The research reveals a significant rise in the interconnection between the Chinese and U.S. stock markets during the pandemic. The S&P 500 index displayed higher sensitivity and greater volatility in response to the pandemic, whereas the CSI 300 index showed superior resilience and stability. Analysis and model estimation suggest that the market’s dependence on historical data has intensified and its sensitivity to recent shocks has heightened. Predictions from the model indicate increased market volatility during the pandemic. While the model is proficient in capturing market trends, there remains potential for enhancing the accuracy of specific volatility predictions. The study proposes recommendations for policymakers and investors, highlighting the importance of improved cooperation in international financial market regulation and investor education.展开更多
The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Fin...The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Finite difference method is incorporated to simulate the problem. The numerical results are compared with square duct channel for different parametric effect. It is observed that the flow rate is increased in cylindrical channel compared to square duct channel for the increasing value of pressure gradient, porosity and permeability. On the contrary, the flow rate is decreased in square duct channel compared to cylindrical channel for increasing value of viscosity. Flow rate in both channels is analyzed and compared for non-porous medium also. It is observed that flow rate is increased very high in cylindrical channel compared to square duct channel for both medium.展开更多
BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on...BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on fungal infection within a medical intensive liver unit(MILU),particularly in relation to acute on chronic liver failure.AIM To investigate the impact of fungal infections among critically ill patients with advanced liver disease,and compare outcomes to those of patients with bacterial infections.METHODS From our prospective registry of MILU patients from 2018-2022,we included 27 patients with culture-positive fungal infections and 183 with bacterial infections.We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts.Data was extracted through chart review.RESULTS All fungal infections were due to Candida species,and were most frequently blood isolates.Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,P<0.001).The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,P=0.02).Patients in the fungal cohort had increased use of vasopressors(96%vs 70%,P=0.04),mechanical ventilation(96%vs 65%,P<0.001),and dialysis due to acute kidney injury(78%vs 52%,P=0.014).On MILU admission,the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation(108 vs 91,P=0.003),Acute Physiology Score(86 vs 65,P=0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,P=0.041).There was no significant difference in the rate of central line use preceding culture(52%vs 40%,P=0.2).Patients with fungal infection had higher rate of transplant hold placement,and lower rates of transplant;however,differences did not achieve statistical significance.CONCLUSION Mortality was worse among patients with fungal infections,likely attributable to severe ACLF development.Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.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
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 National Institutes of Health,No.R01HL147155 and No.R01AG060920.
文摘BACKGROUND There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty(TJA)patients.AIM To determine the association of commonly used implant metals with echocardiographic measures in TJA patients.METHODS The study comprised 110 TJA patients who had a recent history of high chromium,cobalt or titanium concentrations.Patients underwent two-dimensional,three-dimensional,Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations.Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations(exposure)with echocardiographic measures(outcome).RESULTS Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume(estimate 5.09;95%CI:0.02-10.17)as well as left atrial and right ventricular dilation,particularly in men but no changes in cardiac function.Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain(estimate 0.38;95%CI:0.70 to 0.06)and cardiac index(estimate 0.08;95%CI,-0.15 to-0.01).CONCLUSION Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients.Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.
基金funded by R01HL137734 from the National Heart,Lung,and Blood Institutesupported by F30HL149335 from the National Heart,Lung,and Blood Institute+3 种基金supported by NIH grant 2T32HL 120823supported by K23HL161432 from the National Heart,Lung,and Blood Institutesupported by R01 HL137734supported by R01HL126911,R01HL137734,R01HL137794,R01HL135219,R01HL136660,U54HL143541,and 1U01HL146382 from the National Heart,Lung,and Blood Institute.
文摘BACKGROUND Smartwatches have become readily accessible tools for detecting atrial fibrillation(AF).There remains limited data on how they affect psychosocial outcomes and engagement in older adults.We examine the health behavior outcomes of stroke survivors prescribed smartwatches for AF detection stratified by age.METHODS We analyzed data from the Pulsewatch study,a randomized controlled trial that enrolled patients(≥50 years)with a history of stroke or transient ischemic attack and CHA2DS2-VASc≥2.Intervention participants were equipped with a cardiac patch monitor and a smartwatch-app dyad,while control participants wore the cardiac patch monitor for up to 44 days.We evaluated health behavior parameters using standardized tools,including the Consumer Health Activation Index,the Generalized Anxiety Disorder questionnaire,the 12-Item Short Form Health Survey,and wear time of participants categorized into three age groups:Group 1(ages 50-60),Group 2(ages 61-69),and Group 3(ages 70-87).We performed statistical analysis using a mixedeffects repeated measures linear regression model to examine differences amongst age groups.RESULTS Comparative analysis between Groups 1,2 and 3 revealed no significant differences in anxiety,patient activation,perception of physical health and wear time.The use of smartwatch technology was associated with a decrease in perception of mental health for Group 2 compared to Group 1(β=-3.29,P=0.046).CONCLUSION Stroke survivors demonstrated a willingness to use smartwatches for AF monitoring.Importantly,among these study participants,the majority did not experience negative health behavior outcomes or decreased engagement as age increased.
文摘This study utilizes the Dynamic Conditional Correlation-Generalized Autoregressive Conditional Heteroskedasticity (DCC-GARCH) model to investigate the dynamic relationship between Chinese and U.S. stock markets amid the COVID-19 pandemic. Initially, a univariate GARCH model is developed to derive residual sequences, which are then used to estimate the DCC model parameters. The research reveals a significant rise in the interconnection between the Chinese and U.S. stock markets during the pandemic. The S&P 500 index displayed higher sensitivity and greater volatility in response to the pandemic, whereas the CSI 300 index showed superior resilience and stability. Analysis and model estimation suggest that the market’s dependence on historical data has intensified and its sensitivity to recent shocks has heightened. Predictions from the model indicate increased market volatility during the pandemic. While the model is proficient in capturing market trends, there remains potential for enhancing the accuracy of specific volatility predictions. The study proposes recommendations for policymakers and investors, highlighting the importance of improved cooperation in international financial market regulation and investor education.
文摘The steady flow behavior in terminal bronchus of human lung for cylindrical channel of porous medium has been studied. The governing equations have been solved analytically and numerically for cylindrical channel. Finite difference method is incorporated to simulate the problem. The numerical results are compared with square duct channel for different parametric effect. It is observed that the flow rate is increased in cylindrical channel compared to square duct channel for the increasing value of pressure gradient, porosity and permeability. On the contrary, the flow rate is decreased in square duct channel compared to cylindrical channel for increasing value of viscosity. Flow rate in both channels is analyzed and compared for non-porous medium also. It is observed that flow rate is increased very high in cylindrical channel compared to square duct channel for both medium.
文摘BACKGROUND Due to development of an immune-dysregulated phenotype,advanced liver disease in all forms predisposes patients to sepsis acquisition,including by opportunistic pathogens such as fungi.Little data exists on fungal infection within a medical intensive liver unit(MILU),particularly in relation to acute on chronic liver failure.AIM To investigate the impact of fungal infections among critically ill patients with advanced liver disease,and compare outcomes to those of patients with bacterial infections.METHODS From our prospective registry of MILU patients from 2018-2022,we included 27 patients with culture-positive fungal infections and 183 with bacterial infections.We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts.Data was extracted through chart review.RESULTS All fungal infections were due to Candida species,and were most frequently blood isolates.Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort(93%vs 52%,P<0.001).The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure(ACLF)(90%vs 64%,P=0.02).Patients in the fungal cohort had increased use of vasopressors(96%vs 70%,P=0.04),mechanical ventilation(96%vs 65%,P<0.001),and dialysis due to acute kidney injury(78%vs 52%,P=0.014).On MILU admission,the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation(108 vs 91,P=0.003),Acute Physiology Score(86 vs 65,P=0.003),and Model for End-Stage Liver Disease-Sodium scores(86 vs 65,P=0.041).There was no significant difference in the rate of central line use preceding culture(52%vs 40%,P=0.2).Patients with fungal infection had higher rate of transplant hold placement,and lower rates of transplant;however,differences did not achieve statistical significance.CONCLUSION Mortality was worse among patients with fungal infections,likely attributable to severe ACLF development.Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.
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.
