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Diabetic cardiomyopathy:Importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis

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World Journal of Diabetes 2024年第8期15卷 1659-1662页

作者： Lu Cai Yi Tan md Shahidul Islam michael Horowitz Kupper A Wintergerst Pediatric Research Institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Department of Medicine University of AdelaideAdelaide 5005Australia Pediatric Research Institute Division of EndocrinologyDepartment of PediatricsWendy Novak Diabetes InstituteNorton Children’s HospitalUniversity of LouisvilleLouisvilleKY 40202United States

Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively ***,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and *** direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific *** thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific *** editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent *** clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.

关键词： Diabetic cardiomyopathy Nucleotide oligomerization domain NOD-like receptor protein 3 inflammasome Cardiac cell death Pyroptosis

Impact of cancer diagnosis on life expectancy by area-level socioeconomic groups in New South Wales, Australia: a population-based study

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Cancer Biology & Medicine 2024年第8期21卷 692-702页

作者： md Mijanur Rahman michael David David Goldsbury Karen Canfell Kou Kou Paramita Dasgupta Peter Baade Xue Qin Yu The Daffodil Centre The University of SydneyA Joint Venture with Cancer Council NSWSydneyNSW 1340Australia School of Medicine and Dentistry Griffith UniversityGold CoastQLD 4222Australia Cancer Council Queensland BrisbaneQLD 4006Australia

Objective: Improvement in cancer survival over recent decades has not been accompanied by a narrowing of socioeconomic disparities. This study aimed to quantify the loss of life expectancy(LOLE) resulting from a cancer diagnosis and examine disparities in LOLE based on area-level socioeconomic status(SES).Methods: Data were collected for all people between 50 and 89 years of age who were diagnosed with cancer, registered in the NSW Cancer Registry between 2001 and 2019, and underwent mortality follow-up evaluations until December 2020. Flexible parametric survival models were fitted to estimate the LOLE by gender and area-level SES for 12 common ***: Of 422,680 people with cancer, 24% and 18% lived in the most and least disadvantaged areas, respectively. Patients from the most disadvantaged areas had a significantly greater average LOLE than patients from the least disadvantaged areas for cancers with high survival rates, including prostate [2.9 years(95% CI: 2.5±3.2 years) vs. 1.6 years(95% CI: 1.3±1.9 years)] and breast cancer [1.6 years(95% CI: 1.4±1.8 years) vs. 1.2 years(95% CI: 1.0±1.4 years)]. The highest average LOLE occurred in males residing in the most disadvantaged areas with pancreatic [16.5 years(95% CI: 16.1±16.8 years) vs. 16.2 years(95% CI: 15.7±16.7 years)] and liver cancer [15.5 years(95% CI: 15.0±16.0 years) vs. 14.7 years(95% CI: 14.0±15.5 years)]. Females residing in the least disadvantaged areas with thyroid cancer [0.9 years(95% CI: 0.4±1.4 years) vs. 0.6 years(95% CI: 0.2±1.0 years)] or melanoma [0.9 years(95% CI: 0.8±1.1 years) vs. 0.7 years(95% CI: 0.5±0.8 years)] had the lowest average ***: Patients from the most disadvantaged areas had the highest LOLE with SES-based differences greatest for patients diagnosed with cancer at an early stage or cancers with higher survival rates, suggesting the need to prioritise early detection and reduce treatment-related barriers and survivorship challenges to improve life expec

关键词： Cancer diagnosis life expectancy loss of life expectancy area-level socioeconomic status flexible parametric model

Surgical or medical treatment of obesity-associated type 2 diabetesan increasing clinical conundrum

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World Journal of Diabetes 2024年第10期15卷 2036-2040页

作者： Ryan J Jalleh Karen L Jones md Shahidul Islam Lu Cai michael Horowitz Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health University of Adelaide Endocrine and Metabolic Unit Royal Adelaide HospitalAdelaide 5000South AustraliaAustralia Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Pediatric Research Institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States

In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GLP-1RA)therapy in the management of type 2 diabetes(T2D)associated with *** surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GLP-1RAs in these groups is predictably *** older individuals(age>65 years),both bariatric surgery and GLP-1RA therapy improve cardiovascular ***-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GLP-1RAs and,paradoxically,there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial *** trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.

关键词： Glucagon-like peptide-1 Glucagon-like peptide-1 receptor agonist Obesity Diabetes Weight loss Bariatric surgery Metabolic surgery Hypoglycemia

Impact of surgical management of upper tract urothelial cancer in octogenarians:A population-based study

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Current Urology 2024年第3期18卷 225-231页

作者： Shu Wang michael Phelan Mohummad Minhaj Siddiqui Division of Urology Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMDUSA Veterans Affairs Maryland Healthcare System BaltimoreMDUSA

Background Upper tract urothelial carcinoma(UTUC)is an aggressive disease with a high progression *** standardmanagement for this disease is *** sparing nonradical surgery is an alternative therapeutic *** men with limited life expectancy,the potential harm of UTUC progression must be weighed against surgical morbidity and mortality,and thus,more conservative approaches may be *** study aims to investigate the comparative benefits of radical and conservative surgical management in patients older than 80 years with localized *** and methods A search was conducted in the Surveillance,Epidemiology,and End Results database for patients older than 80 years who were diagnosed with localized(T1–2N0M0)cancer in the renal pelvis or ureter as the only malignancy from 2004 to *** were divided into 3 therapeutic groups:no surgery,local intervention(ie,local tumor excision or segmented ureterectomy),and radical surgery(nephroureterectomy).Demographic and cancer-related parameter data were *** regression analysis was conducted to investigate predictors for surgical ***-Meier curves and Cox regression were used to analyze survival *** Data from 774 patients were analyzed,including 205 in the no-surgery group,181 in the local intervention group,and 388 in the radical surgery ***,African American patients with T1 stage disease were less likely to receive surgical *** surgically treated patients,renal pelvic tumors,and high-grade and T2 stage disease were associated with radical *** treated patients had a longer median overall survival(OS)than in those treated nonsurgically(13,35,and 47 months in no-surgery,local intervention,and radical surgery groups,respectively;p<0.001).Although surgically treated patients demonstrated higher 5-year OS(8.8%[no surgery],23.2%[local intervention],and 23.5%[radical surgery],p<0.001)and 5-year disease-specif

关键词： Older adults Surgery Surveillance,Epidemiology,and End Results Survival Upper tract urothelial carcinoma

Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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Journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： Benjamin T.Schumacher michael J.LaMonte Andrea Z.LaCroix Eleanor M.Simonsick Steven P.Hooker Humberto Parada Jr. John Bellettiere Arun Kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and Biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of California San Diego Moores Cancer Center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

Background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction ***:The Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:Measured VO_(2max)is a strong predictor of *** ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms Epidemiology Mortality

The role of selective serotonin reuptake inhibitors and tricyclic antidepressants in addressing reduction of Meniere's disease burden:A scoping review

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第3期10卷 206-212页

作者： Alexander A.Missner Mana Sheykhsoltan Amir Hakimi michael Hoa Georgetown University School of Medicine WashingtonDistrict of ColumbiaUSA Department of Otolaryngology-Head and Neck Surgery Georgetown University Medical CenterWashingtonDistrict of ColumbiaUSA Auditory Development and Restoration Program National Institute on Deafness and Other Communication DisordersNational Institutes of HealthBethesdaMarylandUSA

Objective:To assess the effect of selective serotonin reuptake inhibitors(SSRIs)and tricyclic antidepressants(TCAs)in reducing vertigo,tinnitus,and hearing loss among patients with Meniere's disease(md).Data Sources:The following databases were utilized in this scoping review:Ovid Medline,PubMed-NCBI,CINAHL,Cochrane Library,Web of Science,and ***:Studies were identified through the following search phrases:"serotonin specific reuptake inhibitors"OR"tricyclic antidepressants"AND"Meniere's disease."References from included manuscripts were examined for possible inclusion of additional ***:The literature search yielded 23 results,which were screened by three independent *** studies and three duplicates were *** examination of references from the included studies yielded two additional publications.A total of four published studies assessing SSRIs and TCAs among 147 patients with md were ultimately *** studies described significant reductions in vertigo attack frequency among patients treated with either SSRIs or TCAs compared to their pretreatment *** studies assessed the drugs'effects on hearing,of which none found a significant difference among patients treated with SSRIs or *** study found a significant decrease in patient-reported tinnitus following treatment with TCAs or SSRIs compared to their pretreatment ***:Data exploring SSRIs and TCAs among patients with md suggests that these medications may reduce the frequency of tinnitus and vertigo,although there was significant heterogeneity in outcome *** remains a need for larger-scale prospective studies that emphasize objective data to evaluate their effective-ness in reducing common md symptoms.

关键词： aural fullness clinical trials Meniere's disease scoping review sensorineural hearing loss serotonin specific reuptake inhibitors tricyclic antidepressants vertigo

Neural network reactive force field for C,H,N,and O systems

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npj Computational Materials 2021年第1期7卷 69-78页

作者： Pilsun Yoo michael Sakano Saaketh Desai md Mahbubul Islam Peilin Liao Alejandro Strachan School of Materials Engineering and Birck Nanotechnology Center Purdue UniversityWest LafayetteIN 47907USA Department of Mechanical Engineering Wayne State UniversityDetroitMI 48202USA

Reactive force fields have enabled an atomic level description of a wide range of phenomena,from chemistry at extreme conditions to the operation of electrochemical devices and *** significant insight and semi-quantitative understanding have been drawn from such work,the accuracy of reactive force fields limits quantitative *** developed a neural network reactive force field(NNRF)for CHNO systems to describe the decomposition and reaction of the high-energy nitramine 1,3,5-trinitroperhydro-1,3,5-triazine(RDX).NNRF was trained using energies and forces of a total of 3100 molecules(11,941 geometries)and 15 condensed matter systems(32,973 geometries)obtained from density functional theory calculations with semi-empirical corrections to dispersion *** training set is generated via a semi-automated iterative procedure that enables refinement of the NNRF until a desired accuracy is *** root mean square(RMS)error of NNRF on a testing set of configurations describing the reaction of RDX is one order of magnitude lower than current state of the art potentials.

关键词： network field reactive

Recent therapeutic targets for the prevention and management of diabetic complications

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世界糖尿病杂志:英文版(电子版) 2023年第9期14卷 1330-1333页

作者： md Shahidul Islam Lu Cai michael Horowitz Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Pediatric Research Institute University of LouisvilleLouisvilleKY 40202United States Department of Medicine University of AdelaideAdelaide 5005Australia

Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature *** some diabetic complications have decreased in the developed world,the majority are still prevalent,with an increasing trend in the developing *** used therapies are mainly‘glucocentric’,focusing on the optimization of glycemic control to prevent,delay or manage diabetes-associated complications-other common comorbidities,such as dyslipidemia and hypertension are often *** a number of novel therapeutic approaches have been reported recently,some of them have not received comparable attention in relation to either further studies or potential clinical *** editorial briefly discusses some recent therapeutic approaches to the prevention and management of diabetes and its associated complications,as well as potential directions for future research and development in this area.

关键词： Diabetic complications Oxidative stress Phytochemicals Zinc Silent information regulator 1 FOXO Micro RNA

Potential therapeutic targets for the prevention of diabetic nephropathy:Glycyrrhetinic acid

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World Journal of Diabetes 2023年第12期14卷 1717-1720页

作者： Lu Cai michael Horowitz md Shahidul Islam Pediatric Research Institute Department of PediatricsUniversity of LouisvilleLouisvilleKY 40202United States Department of Medicine University of AdelaideAdelaide 5005Australia Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa

Uncontrolled hyperglycemia or poorly managed disease increases the propensityfor a number of diabetes-related complications targeting major organs includingthe heart, eyes, and kidney. Although the mechanisms by which diabetes inducescardiovascular diseases include oxidative stress and inflammation, when insulinresistance remains the key to the pathogenesis, as implicated in the two reviews inthis issue. This editorial mainly comments on the potential preventive applicationof glycyrrhetinic acid (or 18β-GA) in relation to diabetic nephropathy. The therapeuticor preventive effects of 18β-GA, as a hydrolytic product of glycy-rrhizicacid that is a component of licorice, have been appreciated in other disorders, buthave received much less attention in relation to diabetic complications. A study inthis issue has identified 18β-GA as a therapeutic for preventing diabeticnephropathy and provides evidence to support efficacy in cultured human renaltubule cells in vitro. Although it represents a pilot study, the observations supporta new therapeutic approach that warrants further ex-ploration.

关键词： Insulin resistance Diabetic cardiomyopathy Diabetic nephropathy Glycyrrhetinic acid Licorice Chinese herbal remedy