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Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression,anxiety and psychosis

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World journal of Psychiatry 2022年第2期12卷 308-322页

作者： Ana Paula Michelin michael h j maes Thitiporn Supasitthumrong Chusak Limotai Andressa Keiko Matsumoto Laura de Oliveira Semeão joão Victor de Lima Pedrão Estefânia Gastaldello Moreira Buranee Kanchanatawan Décio Sabbatini Barbosa health Sciences Center State University of LondrinaLondrina 86038-440Brazil Department of Psychiatry Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Department of Psychiatry Medical University of PlovdivPlovdiv 4004Bulgaria IMPACT Strategic Research Center Deakin UniversityGeelong 3220Australia Chulalongkorn Comprehensive Epilepsy Center of Excellence King Chulalongkorn Memorial HospitalThe Thai Red Cross SocietyBangkok 10330Thailand Division of Neurology Department of MedicineFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand

BACKGROUND Temporal lobe epilepsy(TLE)is the most common focal epilepsy subtype in adults and is frequently accompanied by depression,anxiety and *** in total paraoxonase 1(PON1)status may occur in TLE and these psychiatric *** To examine PON1 status,namely Q192R PON1 genotypes and PON1 enzymatic activities,in *** We recruited 40 normal controls and 104 TLE patients,27 without comorbidities and 77 with comorbidities including mood disorders(n=25),anxiety disorders(n=27)and psychosis(n=25).RESULTS Four-(chloromethyl)phenyl acetate hydrolysis(CMPAase)and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis(MTS)with and without psychiatric comorbidities than those in normal *** areas under the receiver operating characteristic curve of CMPAase were 0.893(0.037)for TLE and 0.895(±0.037)for *** least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity(Phopathology(Phich were both mediated by lowered CMPAase activity,while arylesterase activity was not *** severity of TLE was significantly associated with psychopathology ***,PON1 CMPAase activity was inversely associated with Mini Mental State Examination *** The severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype,which are mediated by reduced CMPAase *** PON1 status plays a key role in the pathophysiology of TLE,MTS and psychiatric comorbidities by increasing the risk of oxidative ***1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

关键词： Antioxidants Oxidative stress Neuroimmune Major depression Mood disorders Affective disorders

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Universal hyperthermal Model for Mass Extinctions

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journal of Earth Science 2024年第2期35卷 704-707页

作者： michael j.Benton Paleobiology Research Group School of Earth SciencesUniversity of BristolLife Sciences BuildingTyndall AvenueBristolBS81TQUK

INTRODUCTION Earth scientists have long sought universal features of past extinction *** can be argued that each past extinction event was a singularity,caused by combinations of circumstances that are unique in each case,and therefore that the search for common causes is ***,a key feature of the uniformitarian approach to geology is that past processes are the same as modern-day processes and,with that in mind,earth scientists are keen to use their knowledge to contribute some understanding to the study of the present and future climate crisis.

关键词： extinction singularity Extinction

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harnessing naturally occurring mutations for T-cell therapy:a potential new avenue to enhance treatment efficacy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1799-1801页

作者： michael hiltensperger jürgen Ruland Kilian Schober Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und HygieneFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany Institute of Clinical Chemistry and Pathobiochemistry School of MedicineTechnical University of MunichMunichGermany TranslaTUM Center for Translational Cancer ResearchTechnical University of MunichMunichGermany German Cancer Consortium(DKTK) HeidelbergGermany German Center for Infection Research(DZIF) partner site MunichMunichGermany FAU Profile Center Immunomedicine Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Garcia et *** a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rejection and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.

关键词： cancer potential

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The quasi-Gramian solution of a non-commutative extension of the higher-order nonlinear Schr?dinger equation

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Communications in Theoretical Physics 2024年第3期76卷 51-61页

作者： h W A Riaz j Lin Department of Physics Zhejiang Normal UniversityJinhua 321004China

The nonlinear Schr?dinger(NLS)equation,which incorporates higher-order dispersive terms,is widely employed in the theoretical analysis of various physical *** this study,we explore the non-commutative extension of the higher-order NLS *** treat real or complex-valued functions,such as g_(1)=g_(1)(x,t)and g_(2)=g_(2)(x,t)as non-commutative,and employ the Lax pair associated with the evolution equation,as in the commutation *** derive the quasi-Gramian solution of the system by employing a binary Darboux *** soliton solutions are presented explicitly within the framework of *** visually understand the dynamics and solutions in the given example,we also provide simulations illustrating the associated ***,the solution can be used to study the stability of plane waves and to understand the generation of periodic patterns within the context of modulational instability.

关键词： integrable systems Darboux transformation solitons

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Dietary fibre effects and the interplay with exogenous carbohydrases in poultry nutrition

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Animal Nutrition 2024年第1期16卷 231-240页

作者： michael R.Bedford Birger Svihus Aaron j.Cowieson AB Vista Feed Ingredients Ltd Norwegian University of Life Sciences DSM Nutritional Products

A comprehensive understanding of the role of dietary fibre in non-ruminant animal production is elusive. Equivocal and conflated definitions of fibre coupled with significant analytical complexity,interact with poorly defined host and microbiome relationships. Dietary fibre is known to influence gut development, feed intake and passage rate, nutrient absorption, microbiome taxonomy and function, gut p h, endogenous nutrient loss, environmental sustainability, animal welfare and more. Whilst significant gaps persist in our understanding of fibre in non-ruminant animal production, there is substantial interest in optimizing the fibre fraction of feed to induce high value phenotypes such as improved welfare,live performance and to reduce the environmental footprint of animal production systems. In order to achieve these aspirational goals, it is important to tackle dietary fibre with the same level of scrutiny as is currently done for other critical nutrient classes such as protein, minerals and vitamins. The chemical,mechanical and nutritional role of fibre must be explored at the level of monomeric sugars, oligosaccharides and polysaccharides of varying molecular weight and decoration, and this must be in parallel to standardisation of analytical tools and definitions for speciation. To further complicate subject, exogenous carbohydrases recognise dietary fibre as a focal substrate and have varying capacity to generate lower molecular weight carbohydrates that interact differentially with the host and the enteric microbiome. This short review article will explore the interactive space between dietary fibre and exogenous carbohydrases and will include their nutritional and health effects with emphasis on functional development of the gut, microbiome modulation and host metabolism.

关键词： Fibre Carbohydrase Nutrition Microbiome Gastro-intestinal development Feed

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Convexification of hybrid AC-DC Optimal Power Flow with Line-Commutated Converters

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CSEE journal of Power and Energy Systems 2024年第2期10卷 617-628页

作者： hongyuan Liang Zhigang Li j.h.Zheng Q.h.Wu School of Electric Power Engineering South China University of TechnologyGuangzhou 510641China

Line-commutated converter (LCC)-based high-voltage DC (hVDC) systems have been integrated with bulk AC power grids for interregional transmission of renewable power. The nonlinear LCC model brings additional nonconvexity to optimal power flow (OPF) of hybrid AC-DC power grids. A convexification method for the LCC station model could address such nonconvexity but has rarely been discussed. We devise an equivalent reformulation for classical LCC station models that facilitates second-order cone convex relaxation for the OPF of LCC-based AC-DC power grids. We also propose sufficient conditions for exactness of convex relaxation with its proof. Equivalence of the proposed LCC station models and properties, exactness, and effectiveness of convex relaxation are verified using four numerical simulations. Simulation results demonstrate a globally optimal solution of the original OPF can be efficiently obtained from relaxed model.

关键词： AC-DC power system convex relaxation linecommutated converter optimal power flow second-order cone programming

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Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold jenifer Murphy-Smith Chee h.Ng David Mischoulon Gerard j.Byrne Chad A.Bousman Con Stough michael Berk jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression Clinical and Research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia Departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Psychiatry the University of MelbourneMelbourne 3052Australia Centre for human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical health and Clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental health the University of MelbourneParkville 3052Australia NICM health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPh1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical Psychiatry

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Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson j.michael Taylor University of Cincinnati College of Medicine CincinnatiOHUSA Department of Pediatrics University of CincinnatiCincinnatiOHUSA Department of Neurology and Rehabilitation Medicine University of CincinnatiCincinnatiOHUSA Division of Pediatric Rehabilitation Medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA Division of Neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric *** inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric *** goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain *** queried PubMed to identify literature published from database inception thro ugh june 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined *** on preselected search criteria,340 unique papers we re selected for title and abstra ct ***-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the *** adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive *** children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited *** additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age *** its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain injury

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Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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World journal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： jeffrey A Lowell michael j Farber Keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States Preclinical Studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined *** et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this *** importance of controlled trials should be stressed in establishing new treatment *** prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy

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Observability Analysis of Integrated Electricity and heating Systems with Thermal Quasi-dynamics in Pipelines

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CSEE journal of Power and Energy Systems 2024年第3期10卷 1145-1158页

作者： Zhigang Li Wenjian Zheng junbo Zhao j.h.Zheng Q.h.Wu School of Electric Power Engineering South China University of TechnologyGuangzhou 510641China Fuzhou Changle District Power Supply Company of State Grid Fujian Electric Power Co. Ltd.Fuzhou 350000China Department of Electrical and Computer Engineering University of ConnecticutStorrsCT 06269USA CSEE IEEE

Observability analysis(OA)is vital to obtaining the available input measurements of state estimation(SE)in an integrated electricity and heating system(IEhS).Considering the thermal quasi-dynamics in pipelines,the measurement equations in heating systems are dependent on the estimated results,leading to an interdependency between OA and *** OA methods require measurement equations be known exactly before SE is performed,and they are not applicable to *** bridge this gap,a scenario-based OA scheme for IEhSs is devised that yields reliable analysis results for a predefined set of time-delay scenarios to cope with this *** its core procedure,the observable state identification and observability restoration are formulated in terms of integer linear *** tests are conducted to demonstrate the validity and superiority of the proposed formulation.

关键词： Integrated electricity and heating system measurement observability analysis state estimation thermal quasi-dynamics

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