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Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui Ling He Jing Wang Regenerative Medicine Program Ottawa Hospital Research InstituteOttawaONCanada Department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada Department of Pediatrics and Medicine Johns Hopkins Medical SchoolBaltimoreMDUSA Department of Cellular and Molecular Medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

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Optimizing oncolytic virus design:a“Swiss army knife”approach to create a systemically delivered therapeutic

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1791-1792页

作者： Carolina S.Ilkow John Cameron Bell ottawa hospital Research Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper published in Nature Biotechnology,Chen et al.1 describe a multiplex oncolytic virus platform that coupled with adoptive T cell therapy could solve the problem of repeat,systemic delivery of virus based *** is widely accepted that multi-targeted therapeutic approaches attacking several facets of cancer biology are necessary to effectively deal with the tumor heterogeneity that exists within and between patients.

关键词： therapeutic al. targeted

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A Bayesian model calibration framework for stochastic compartmental models with both time-varying and timeinvariant parameters

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Infectious Disease Modelling 2024年第4期9卷 1224-1249页

作者： Brandon Robinson Philippe Bisaillon Jodi D.Edwards Tetyana Kendzerska Mohammad Khalil Dominique Poirel Abhijit Sarkar Department of Civil and Environmental Engineering Carleton UniversityOttawaON K1S 5B6Canada School of Epidemiology and Public Health University of Ottawa and University of Ottawa Heart InstituteOttawaOntarioCanada ICES OttawaOntarioCanada the ottawa hospital Research Institute OttawaOntarioCanada Department of Medicine Faculty of MedicineDivision of RespirologyUniversity of OttawaOttawaOntarioCanada Quantitative Modeling&Analysis Department Sandia National LaboratoriesLivermoreCAUSA Department of Mechanical and Aerospace Engineering Royal Military College of CanadaKingstonONCanada

We consider state and parameter estimation for compartmental models having both timevarying and time-invariant *** this manuscript,we first detail a general Bayesian computational framework as a continuation of our previous ***,this framework is specifically tailored to the susceptible-infectious-removed(SIR)model which describes a basic mechanism for the spread of infectious diseases through a system of coupled nonlinear differential *** SIR model consists of three states,namely,the susceptible,infectious,and removed *** coupling among these states is controlled by two parameters,the infection rate and the recovery *** simplicity of the SIR model and similar compartmental models make them applicable to many classes of infectious ***,the combined assumption of a deterministic model and time-invariance among the model parameters are two significant impediments which critically limit their use for long-term *** tendency of certain model parameters to vary in time due to seasonal trends,non-pharmaceutical interventions,and other random effects necessitates a model that structurally permits the incorporation of such time-varying *** to this,is the need for a robust mechanism for the estimation of the parameters of the resulting model from *** this end,we consider an augmented state vector,which appends the time-varying parameters to the original system states whereby the time evolution of the time-varying parameters are driven by an artificial noise process in a standard *** between time-varying and time-invariant parameters in this fashion limits the introduction of artificial dynamics into the system,and provides a robust,fully Bayesian approach for estimating the timeinvariant system parameters as well as the elements of the process noise covariance *** computational framework is implemented by leveraging the robustness of the Markov chain Mont

关键词： Time-varying parameter estimation Bayesian inference Stochastic compartmental models

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Evaluating the efficacy of immunotherapy in gastric cancer:Insights from immune checkpoint inhibitors

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World Journal of Gastroenterology 2024年第32期30卷 3726-3729页

作者： Yu-Nuo Yang Li-Sheng Wang Yan-Qi Dang Guang Ji Institute of Digestive Diseases Longhua HospitalChina-Canada Center of Research for Digestive DiseasesShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Biochemistry University of OttawaOttawa K1H 8M5ONCanada

The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influenced by various *** manuscript identified sarcopenia and myosteatosis as independent prognostic factors impacting the outcomes of GC patients treated with ***,this study introduced a visual predictive model to estimate the prognosis of GC *** confirmed by further studies,this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.

关键词： Gastric cancer Immune checkpoint inhibitors Sarcopenia Myosteatosis Prediction model

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How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

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Journal of Sport and Health Science 2024年第4期13卷 537-547页

作者： Jacqueline Josee van Ierssel Olivia Galea Kirsten Holte Caroline Luszawski Elizabeth Jenkins Jennifer O’Neil Carolyn A Emery Rebekah Mannix Kathryn Schneider Keith Owen Yeates Roger Zemek Children’s hospital of Eastern Ontario Research Institute OttawaON K1H 8L1Canada The Centre for Health Activity and Rehabilitation ResearchUniversity of OtagoDunedin 9016New Zealand Sport Injury Prevention Research Centre Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada Alberta Children’s hospital Research Institute University of Calgary CalgaryAB T2N 1N4Canada Hotchkiss Brain Institute University of CalgaryCalgaryAB T2N 4N1Canada Department of Psychology University of CalgaryCalgaryAB T2N 1N4Canada g Faculty of MedicineUniversity of OttawaOttawaON K1H 8M5Canada School of Rehabilitation Sciences University of OttawaOttawaON K1H 8M5Canada Bruyere Research Institute OttawaON K1N 5C8Canada Departments of Pediatrics and Emergency Medicine Harvard Medical SchoolBostonMA 02115USA Departments of Pediatrics and Emergency Medicine University of OttawaOttawaON K1H 8M5Canada

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following ***:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May *** reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)*** information was sought my study authors where reporting was *** of bias(ROB)was assessed with the Cochrane ROB-2 *** examining non-pharmacological interventions following ***:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck *** scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified *** completeness improved after TIDieR and CERT publication,but p

关键词： Concussion Intervention Randomized controlled trial Systematic review

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Impact of frailty on outcomes of elderly patients undergoing percutaneous coronary intervention: A systematic review and metaanalysis

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World Journal of Clinical Cases 2024年第1期12卷 107-118页

作者： Shi-Shi Wang Wang-Hao Liu Department of Emergency Medicine Huzhou Third Municipal HospitalThe Affiliated Hospital of Huzhou UniversityHuzhou 313000Zhejiang ProvinceChina Department of Geriatrics Huzhou Third Municipal Hospitalthe Affiliated Hospital of Huzhou UniversityHuzhou 313000Zhejiang ProvinceChina

BACKGROUND Frailty is a common condition in elderly patients who receive percutaneous coronary intervention(PCI).However,how frailty affects clinical outcomes in this group is *** To assess the link between frailty and the outcomes,such as in-hospital complic-ations,post-procedural complications,and mortality,in elderly patients *** The PubMed/MEDLINE,EMBASE,Cochrane Library,and Web of Science databases were screened for publications up to August *** primary outcomes assessed were in-hospital and all-cause mortality,major adverse cardiovascular events(MACEs),and major *** Newcastle-ottawa Scale was used for quality *** Twenty-one studies with 739693 elderly patients undergoing PCI were *** was consistently associated with adverse *** patients had significantly higher risks of in-hospital mortality[risk ratio:3.45,95%confidence interval(95%CI):1.90-6.25],all-cause mortality[hazard ratio(HR):2.08,95%CI:1.78-2.43],MACEs(HR:2.92,95%CI:1.85-4.60),and major bleeding(HR:4.60,95%CI:2.89-7.32)compared to non-frail *** Frailty is a pivotal determinant in the prediction of risk of mortality,development of MACEs,and major bleeding in elderly individuals undergoing percutaneous coronary intervention.

关键词： Frailty Elderly Percutaneous coronary intervention Systematic review Meta-analysis

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Examining the effects of voluntary avoidance behaviour and policy-mediated behaviour change on the dynamics of SARS-CoV-2:A mathematical model

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Infectious Disease Modelling 2024年第3期9卷 701-712页

作者： Gabrielle Brankston David N.Fisman Zvonimir Poljak Ashleigh R.Tuite Amy L.Greer Department of Population Medicine University of GuelphCanada Dalla Lana School of Public Health University of TorontoCanada Centre for Immunization Readiness Public Health Agency of CanadaOttawaOntarioCanada

Background Throughout the SARS-CoV-2 pandemic,policymakers have had to navigate between recommending voluntary behaviour change and policy-driven behaviour change to mitigate the impact of the *** individuals will voluntarily engage in self-protective behaviour when there is an increasing infectious disease risk,the extent to which this occurs and its impact on an epidemic is not *** This paper describes a deterministic disease transmission model exploring the impact of individual avoidance behaviour and policy-mediated avoidance behaviour on epidemic outcomes during the second wave of SARS-CoV-2 infections in Ontario,Canada(September 1,2020 to February 28,2021).The model incorporates an information feedback function based on empirically derived behaviour data describing the degree to which avoidance behaviour changed in response to the number of new daily cases *** Voluntary avoidance behaviour alone was estimated to reduce the final attack rate by 23.1%,the total number of hospitalizations by 26.2%,and cumulative deaths by 27.5%over 6 months compared to a counterfactual scenario in which there were no interventions or avoidance behaviour.A provincial shutdown order issued on December 26,2020 was estimated to reduce the final attack rate by 66.7%,the total number of hospitalizations by 66.8%,and the total number of deaths by 67.2%compared to the counterfactual *** Given the dynamics of SARS-CoV-2 in a pre-vaccine era,individual avoidance behaviour in the absence of government action would have resulted in a moderate reduction in disease however,it would not have been sufficient to entirely mitigate transmission and the associated risk to the population in *** action during the second wave of the COVID-19 pandemic in Ontario reduced infections,protected hospital capacity,and saved lives.

关键词： Mathematical modelling COVID-19 SARS-CoV-2 Human behaviour

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Is recovery enhancement after gastric cancer surgery really a safe approach for elderly patients?

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1334-1343页

作者： Zi-Wei Li Xiao-Juan Luo Fei Liu Xu-Rui Liu Xin-Peng Shu Yue Tong Quan Lv Xiao-Yu Liu Wei Zhang Dong Peng Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Endoscopy Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400012China

BACKGROUND This study aimed to evaluate the safety of enhanced recovery after surgery(ERAS)in elderly patients with gastric cancer(GC).AIM To evaluate the safety of ERAS in elderly patients with *** The PubMed,EMBASE,and Cochrane Library databases were used to search for eligible studies from inception to April 1,*** mean difference(MD),odds ratio(OR)and 95%confidence interval(95%CI)were pooled for *** quality of the included studies was evaluated using the Newcastle-ottawa Scale *** used Stata(V.16.0)software for data *** This study consists of six studies involving 878 elderly *** analyzing the clinical outcomes,we found that the ERAS group had shorter postoperative hospital stays(MD=-0.51,I2=0.00%,95%CI=-0.72 to-0.30,P=0.00);earlier times to first flatus(defecation;MD=-0.30,I²=0.00%,95%CI=-0.55 to-0.06,P=0.02);less intestinal obstruction(OR=3.24,I2=0.00%,95%CI=1.07 to 9.78,P=0.04);less nausea and vomiting(OR=4.07,I2=0.00%,95%CI=1.29 to 12.84,P=0.02);and less gastric retention(OR=5.69,I2=2.46%,95%CI=2.00 to 16.20,P=0.00).Our results showed that the conventional group had a greater mortality rate than the ERAS group(OR=0.24,I2=0.00%,95%CI=0.07 to 0.84,P=0.03).However,there was no statistically significant difference in major complications between the ERAS group and the conventional group(OR=0.67,I2=0.00%,95%CI=0.38 to 1.18,P=0.16).CONCLUSION Compared to those with conventional recovery,elderly GC patients who received the ERAS protocol after surgery had a lower risk of mortality.

关键词： Enhanced recovery after surgery Gastric cancer Elderly Mortality

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Public health importance of light intensity physical activity

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Journal of Sport and Health Science 2024年第5期13卷 674-675页

作者： Robert Ross Ian Janssen Mark S.Tremblay School of Kinesiology and Health Studies Queen’s UniversityKingstonON K7L 3N6Canada School of Medicine Division of Endocrinology and MetabolismQueen’s UniversityKingstonON K7L 3N6Canada Healthy Active Living and Obesity Research Group Children’s Hospital of Eastern Ontario Research InstituteOttawaON K1H 8L1Canada Department of Pediatrics University of OttawaOttawaON K1H 8L1Canada

*** intensity physical activity(PA)benefits health PA guidelines worldwide recommend that adults accumulate 150 min of moderate intensity or 75 min of vigorous intensity PA(moderate-to-vigorous PA(MVPA))weekly to achieve health benefits.1-3 Absent from these guidelines are recommendations for light intensity PA(LPA,e.g.,walking at a leisurely pace of 3 km/h or less,equivalent to 1.5-2.9 metabolic equivalents).

关键词： intensity light benefits

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Poor oral health was associated with higher risk of gastric cancer: Evidence from 1431677 participants

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 585-595页

作者： Fei Liu Shi-Jun Tang Zi-Wei Li Xu-Rui Liu Quan Lv Wei Zhang Dong Peng Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Pediatric Dentistry Stomatological Hospital of Guizhou Medical UniversityGuizhou 550000Guizhou ProvinceChina

BACKGROUND In recent years,the association between oral health and the risk of gastric cancer(GC)has gradually attracted increased ***,in terms of GC incidence,the association between oral health and GC incidence remains *** is reported to increase the risk of ***,some studies have shown that periodontitis has no effect on the risk of ***,the present study aimed to assess whether there is a relationship between oral health and the risk of *** To assess whether there was a relationship between oral health and the risk of *** Five databases were searched to find eligible studies from inception to April 10,***-ottawa Scale score was used to assess the quality of included *** quality of cohort studies and case-control studies were evaluated separately in this *** of GC were described by odds ratio(OR)and 95%confidence interval(CI).Funnel plot was used to represent the publication bias of included *** performed the data analysis by StataSE *** A total of 1431677 patients from twelve included studies were enrolled for data analysis in this *** to our analysis,we found that the poor oral health was associated with higher risk of GC(OR=1.15,95%CI:1.02-1.29;I2=59.47%,P=0.000.01),gingivitis(OR=1.19,95%CI:0.71-1.67;I2=0.00%,P>0.01),dentures(OR=1.27,95%CI:0.63-1.19;I2=68.79%,P>0.01),or tooth brushing(OR=1.25,95%CI:0.78-1.71;I2=88.87%,P>0.01)had no influence on the risk of ***,patients with periodontitis(OR=1.13,95%CI:1.04-1.23;I2=0.00%,P<0.01)had a higher risk of *** Patients with poor oral health,especially periodontitis,had a higher risk of *** should be concerned about their oral *** oral health might reduce the risk of GC.

关键词： Oral health Tooth loss Periodontitis Gastric cancer Risk factor

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