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Mesenchymal stem cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration

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Neural Regeneration Research 2024年第1期19卷 49-54页

作者： Ye Xiong Asim Mahmood Michael Chopp Department of Neurosurgery Henry Ford HospitalDetroitMIUSA Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.

关键词： biomarkers extracellular vesicles functional outcome mesenchymal stem/stromal cells neuroinflammation neuroplasticity neuroprotection traumatic brain injury

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Reflections on four decades of physical activity epidemiology

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Journal of Sport and Health Science 2024年第5期13卷 608-610页

作者： Barbara Sternfeld David R.Jacobs Jr. Division of Research Kaiser Permanente Northern CaliforniaOaklandCA 94610USA Division of Epidemiology and Community Health School of Public HealthUniversity of MinnesotaMinneapolisMN 55454USA

In 1985,Public Health Reports published a series of papers prepared for a workshop sponsored by the Centers for Disease Control and Prevention(CDC).1 Building on the seminal work of Jeremy Morris and Ralph Paffenbarger Jr.,who were among the first to use epidemiological methods to study physical activity(PA),2,3 the workshop itself was the result of a growing scientific understanding of the importance of“physical fitness and exercise for improving the health of the public”.

关键词： semi workshop Ralph

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A Bayesian Mixture Model Approach to Disparity Testing

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Applied Mathematics 2024年第3期15卷 214-234页

作者： Gary C. McDonald Department of Mathematics and Statistics Oakland University Rochester USA

The topic of this article is one-sided hypothesis testing for disparity, i.e., the mean of one group is larger than that of another when there is uncertainty as to which group a datum is drawn. For each datum, the uncertainty is captured with a given discrete probability distribution over the groups. Such situations arise, for example, in the use of Bayesian imputation methods to assess race and ethnicity disparities with certain insurance, health, and financial data. A widely used method to implement this assessment is the Bayesian Improved Surname Geocoding (BISG) method which assigns a discrete probability over six race/ethnicity groups to an individual given the individual’s surname and address location. Using a Bayesian framework and Markov Chain Monte Carlo sampling from the joint posterior distribution of the group means, the probability of a disparity hypothesis is estimated. Four methods are developed and compared with an illustrative data set. Three of these methods are implemented in an R-code and one method in WinBUGS. These methods are programed for any number of groups between two and six inclusive. All the codes are provided in the appendices.

关键词： Bayesian Improved Surname and Geocoding (BISG) Mixture Likelihood Function Posterior Distribution Metropolis-Hastings Algorithms Random Walk Chain Independence Chain Gibbs Sampling WinBUGS

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Comparison of Block Design Nonparametric Subset Selection Rules Based on Alternative Scoring Rules

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Applied Mathematics 2024年第5期15卷 355-389页

作者： Gary C. McDonald Sajidah Alsaeed Department of Mathematics and Statistics Oakland University Rochester MI USA

This article compares the size of selected subsets using nonparametric subset selection rules with two different scoring rules for the observations. The scoring rules are based on the expected values of order statistics of the uniform distribution (yielding rank values) and of the normal distribution (yielding normal score values). The comparison is made using state motor vehicle traffic fatality rates, published in a 2016 article, with fifty-one states (including DC as a state) and over a nineteen-year period (1994 through 2012). The earlier study considered four block design selection rules—two for choosing a subset to contain the “best” population (i.e., state with lowest mean fatality rate) and two for the “worst” population (i.e., highest mean rate) with a probability of correct selection chosen to be 0.90. Two selection rules based on normal scores resulted in selected subset sizes substantially smaller than corresponding rules based on ranks (7 vs. 16 and 3 vs. 12). For two other selection rules, the subsets chosen were very close in size (within one). A comparison is also made using state homicide rates, published in a 2022 article, with fifty states and covering eight years. The results are qualitatively the same as those obtained with the motor vehicle traffic fatality rates.

关键词： Order Statistics Rank Scoring Methods Probability of a Correct Selection Subset Size Motor Vehicle Traffic Fatality Rates Homicide Rates Asymptotic Distributions

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Enhancing Renewable Energy Integration:A Gaussian-Bare-Bones Levy Cheetah Optimization Approach to Optimal Power Flow in Electrical Networks

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1339-1370页

作者： Ali S.Alghamdi Mohamed A.Zohdy Saad Aldoihi Department of Electrical Engineering College of EngineeringMajmaah UniversityAl-Majmaah11952Saudi Arabia Electrical and Computer Engineering Department Oakland UniversityRochesterMI48309USA Institute of Earth and Space Science King Abdulaziz City for Science and Technology(KACST)Riyadh11442Saudi Arabia Computer Science and Systems Engineering Institute Polytechnique de ParisPalaiseau CedexFrance

In the contemporary era,the global expansion of electrical grids is propelled by various renewable energy sources(RESs).Efficient integration of stochastic RESs and optimal power flow(OPF)management are critical for network optimization.This study introduces an innovative solution,the Gaussian Bare-Bones Levy Cheetah Optimizer(GBBLCO),addressing OPF challenges in power generation systems with stochastic RESs.The primary objective is to minimize the total operating costs of RESs,considering four functions:overall operating costs,voltage deviation management,emissions reduction,voltage stability index(VSI)and power loss mitigation.Additionally,a carbon tax is included in the objective function to reduce carbon emissions.Thorough scrutiny,using modified IEEE 30-bus and IEEE 118-bus systems,validates GBBLCO’s superior performance in achieving optimal solutions.Simulation results demonstrate GBBLCO’s efficacy in six optimization scenarios:total cost with valve point effects,total cost with emission and carbon tax,total cost with prohibited operating zones,active power loss optimization,voltage deviation optimization and enhancing voltage stability index(VSI).GBBLCO outperforms conventional techniques in each scenario,showcasing rapid convergence and superior solution quality.Notably,GBBLCO navigates complexities introduced by valve point effects,adapts to environmental constraints,optimizes costs while considering prohibited operating zones,minimizes active power losses,and optimizes voltage deviation by enhancing the voltage stability index(VSI)effectively.This research significantly contributes to advancing OPF,emphasizing GBBLCO’s improved global search capabilities and ability to address challenges related to local minima.GBBLCO emerges as a versatile and robust optimization tool for diverse challenges in power systems,offering a promising solution for the evolving needs of renewable energy-integrated power grids.

关键词： Renewable energy integration optimal power flow stochastic renewable energy sources gaussian-bare-bones levy cheetah optimizer electrical network optimization carbon tax optimization

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Phrenic nerve block: the key to managing acute biliary pain?

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World Journal of Emergency Medicine 2024年第1期15卷 62-63页

作者： Michael Shalaby Joshua Luftig Department of Emergency Medicine and Critical Care Herbert Wertheim College of Medicine at Florida International UniversityMiami 33199USA Advanced Emergency Ultrasound Mount Sinai Medical CenterMiami Beach 33140USA Department of Emergency Medicine Highland HospitalAlameda Health SystemOakland 94602USA

Over the past two decades,the USA has witnessed a steep rise in the incidence of acute cholecystitis(AC),[1]even among children,[2]with over 200,000 cases annually.[3]Patients with AC often present to the emergency department(ED)experiencing severe distress,with most describing their pain level as“intolerable.”[4]Furthermore,there is usually a considerable delay before surgery,with a median time from diagnosis of AC to surgery of 28.5 h,[5]and a substantial percentage of patients wait as long as 10 d.[6]Prolonged delays before surgery lead to increased opioid use,which is associated with extended hospital stays and higher rates of readmission after cholecystectomy.[7]Furthermore,opioids can lead to vomiting,respiratory depression,delirium,and ultimately addiction.[8]We propose a novel regional anesthesia technique for managing AC:right phrenic nerve blockade.This method could offer improved pain control and a more favorable risk profile in selected patients when compared to current ED practices.

关键词： pain anesthesia diagnosis

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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by prom

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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Edge Impulse Based ML-Tensor Flow Method for Precise Prediction of Remaining Useful Life (RUL) of EV Batteries

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Journal of Power and Energy Engineering 2024年第6期12卷 1-15页

作者： Tarik Hawsawi Mohamed Zohdy Department of Electrical and Computer Engineering Oakland University Rochester USA Department of Electronic Technology Technical Vocational Training Corporation Dammam KSA

Electric Vehicle (EV) adoption is rapidly increasing, necessitating efficient and precise methods for predicting EV charging requirements. The early and precise prediction of the battery discharging status is helpful to avoid the complete discharging of the battery. The complete discharge of the battery degrades its lifetime and requires a longer charging duration. In the present work, a novel approach leverages the Edge Impulse platform for live prediction of the battery status and early alert signal to avoid complete discharging. The proposed method predicts the actual remaining useful life of batteries. A powerful edge computing platform utilizes Tensor Flow-based machine learning models to predict EV charging needs accurately. The proposed method improves the overall lifetime of the battery by the efficient utilization and precise prediction of the battery status. The EON-Tuner and DSP processing blocks are used for efficient results. The performance of the proposed method is analyzed in terms of accuracy, mean square error and other performance parameters.

关键词： Electric Vehicle EV Charging Machine Learning Lifetime Edge Computing

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CT Thresholds for Spinal Bone Mineral Attenuation to Prioritize Eligible Older Women for Osteoporosis Screening

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Open Journal of Radiology 2024年第2期14卷 92-101页

作者： Seo Yeon K. Orite Bryn Higuchi Hyo-Chun Yoon Lana H. Gimber St. Elizabeths Medical Center Brighton MA USA university of California Irvine CA USA Kaiser Permanente Division of Research Oakland CA USA Department of Diagnostic Imaging Hawaii Permanente Medical Group Honolulu HI USA

Introduction: Computed tomography (CT) measurements of bone mineral attenuation may be a useful means to identify older women who should be prioritized for bone mineral density screening. Methods: We compared bone mineral attenuation as measured in the L1 vertebra of CT studies to the results of dual-energy x-ray absorptiometry (DEXA) studies to determine what CT attenuation thresholds might yield a reasonable combination of sensitivity and specificity for the detection of osteoporosis. The study was limited to women between the ages of 65 and 75 years who had a DEXA study and a CT that included the L1 or adjacent vertebra performed within 3 years of the DEXA study. Results: There were 1226 women in this study, of whom 452 (38%) had osteoporosis based on a T-score ≤ −2.5 by DEXA. There were 830 CT studies performed with contrast and 396 studies which were performed without contrast. There was a statistically significant difference in the mean HU of those studies performed without contrast compared to those with contrast (unenhanced mean 103 HU versus 125 HU, p < 0.001). Different CT attenuation thresholds provided the most appropriate combination of sensitivity and specificity for the detection of osteoporosis when comparing CT studies performed without or with IV contrast and when all the CT data were used in aggregate. Conclusion: Different thresholds appear necessary when using the mean CT vertebral attenuation to identify older women for preferential referral for DEXA studies.

关键词： Osteoporosis Bone Mineral Attenuation CT Threshold

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Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions

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World Journal of Hepatology 2024年第1期16卷 17-32页

作者： Yash R Shah Hassam Ali Angad Tiwari David Guevara-Lazo Natalia Nombera-Aznaran Bhanu Siva Mohan Pinnam Manesh Kumar Gangwani Harishankar Gopakumar Amir H Sohail SriLakshmiDevi Kanumilli Ernesto Calderon-Martinez Geetha Krishnamoorthy Nimish Thakral Dushyant Singh Dahiya Department of Internal Medicine Trinity Health Oakland/Wayne State UniversityPontiacMI 48341United States Division of Gastroenterology and Hepatology East Carolina University/Brody School of MedicineGreenvilleNC 27858United States Department of Internal Medicine Maharani Laxmi Bai Medical CollegeJhansi 284001India Faculty of Medicine Universidad Peruana Cayetano HerediaLima 15102Peru Department of Internal Medicine John H.Stroger Hospital of Cook CountyChicagoIL 60612United States Department of Internal Medicine The University of ToledoToledoOH 43606United States Department of Gastroenterology and Hepatology University of Illinois College of Medicine at PeoriaPeoriaIL 61605United States Department of Surgery University of New MexicoAlbuquerqueNM 87106United States Department of Internal Medicine GSL Medical CollegeRajamahendravaram 533296India Department of Internal Medicine Universidad Nacional Autonoma de MexicoCiudad De Mexico 04510Mexico Department of Digestive Diseases and Nutrition University of KentuckyLexingtonKY 40536United States Division of Gastroenterology Hepatology&MotilityThe University of Kansas School of MedicineKansas CityKS 66160United States

Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.

关键词： Hepatic encephalopathy Fecal microbiota transplant Cognitive impairment Liver cirrhosis Chronic liver disease

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