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Optogenetic inhibition of medial prefrontal cortex projections to the nucleus accumbens core and methyl supplementation via L-Methionine attenuates cocaine-primed reinstatement

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Integrative Zoology 2018年第6期13卷 795-803页

作者： katherine n.wright Amanda M.DOSSAT Caroline E.STROnG Lindsay L.SAILER Samantha M.PAVLOCK Mohamed KABBAJ Department of Biomedical Sciences and Program in neuroscience Florida State UniversityTallahasseeFloridaUSA national Institute on Drug Abuse BaltimoreMarylandUSA Department of Biomedical Sciences College of MedicineFlorida State UniversityTallahasseeFloridaUSA

DnA methylation has been identified as a powerful and activity-dependent regulator of changes in the brain that may underlie neuroadaptations in response to various types of stimuli,including exposure to drugs of ***,the medial prefrontal cortex(mPFC)projections to the nucleus accumbens(nAc)are critically important for reinstated cocaine-seeking in a rodent model of cocaine *** circuitry undergoes several epigenetic modifications following cocaine exposure,including changes in DnA methylation that are associated with drug-seeking *** have previously shown that methyl supplementation via L-Methionine(MET)administration attenuates cocaine-seeking behavior and reverses expression and methylation patterns of the immediate early gene c-fos,suggesting that MET may act by altering the excitability of this circuitry during cocaine *** the current study,male rats were microinjected with an adeno-associated virus overexpressing halorhodopsin in the mPFC,optical fibers were surgically implanted into the nAc,and the rats were given injections of MET *** underwent acquisition of cocaine self-administration(0.75 mg/kg/infusion,2-h sessions)followed by extinction training in the absence of drug-paired *** reinstatement tests were conducted:cue-induced reinstatement without optogenetic manipulations and cocaine-primed reinstatement with optogenetic inhibition of mPFC-to-nAc *** were no group differences before the cocaine-primed reinstatement session,and all groups showed robust cue-induced *** rats treated with MET and rats that received mPFC-to-nAc inhibition showed an abolishment of cocaine-primed reinstatement,suggesting that systemic methyl supplementation may act through this critical circuity.

关键词： cocaine-primed reinstatement corticolimbic DnA methylation methionine optogenetics

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A REDUCED ORDER SCHWARZ METHOD FOR nOnLInEAR MULTISCALE ELLIPTIC EQUATIOnS BASED On TWO-LAYER nEURAL nETWORKS

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Journal of Computational Mathematics 2024年第2期42卷 570-596页

作者： Shi Chen Zhiyan Ding Qin Li Stephen J.wright Mathematics Department University of Wisconsin-MadisonMadisonWI 53706USA Department of Mathematics University of California-BerkeleyBerkeley CA 94720USA Mathematics Department and Discovery Institute University of Wisconsin-Madison MadisonWI 53706USA Computer Sciences Department University of WisconsinMadisonWI 53706USA

neural networks are powerful tools for approximating high dimensional data that have been used in many contexts,including solution of partial differential equations(PDEs).We describe a solver for multiscale fully nonlinear elliptic equations that makes use of domain decomposition,an accelerated Schwarz framework,and two-layer neural networks to approximate the boundary-to-boundarymap for the subdomains,which is the key step in the Schwarz ***,the boundary-to-boundary map requires solution of boundary-value elliptic problems on each *** leveraging the compressibility of multiscale problems,our approach trains the neural network offline to serve as a surrogate for the usual implementation of the boundary-to-boundary *** method is applied to a multiscale semilinear elliptic equation and a multiscale p-Laplace *** both cases we demonstrate significant improvement in efficiency as well as good accuracy and generalization performance.

关键词： nonlinear homogenization Multiscale elliptic problem neural networks Do-main decomposition

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Disaster Awareness and Preparedness Among Older Adults in Canada Regarding Floods, Wildfires, and Earthquakes

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International Journal of Disaster Risk Science 2024年第2期15卷 198-212页

作者： Evalyna Bogdan Rachel Krueger Julie wright Kyle Woods Shaieree Cottar School of Administrative Studies Disaster and Emergency Management ProgramYork UniversityTorontoOntario M3J 1P3Canada Department of Geography and Environmental Management University of WaterlooWaterlooOntario N2L 3G1Canada Partners for Action Faculty of EnvironmentUniversity of WaterlooWaterlooOntario N2L 3G1Canada

Older adults are significantly impacted by natural hazards and disasters that are exacerbated by climate change. Understanding their awareness and preparedness is essential for enhancing disaster resilience. This study investigated the attitudes, actions, and recommendations of older adults regarding natural hazards that pose risks in their geographic area—specifically floods, wildfires, and/or earthquakes in Canada. Methods for this study included survey and focus groups with older adults(n = 161 and n = 10, respectively) and other high-risk groups from across Canada, that are vulnerable to these natural hazards. The main findings from this study are that current awareness and preparedness among older adults is low, though stronger perceptions of risks are associated with risks specific to geographic locations where respondents live. Several barriers, such as hazard vulnerability misperceptions, cost-related reasons, and lack of hazard awareness have resulted in low awareness and preparedness among these populations. The two main recommendations arising from this research are:(1) improve awareness and preparedness with tailor-made emergency preparedness materials for older adults;and(2) adopt community-based approaches to disaster preparedness through existing community groups to strengthen social connections with a focus on locally specific hazards. The findings from this research can be applied to other hazards, including heatwaves and pandemics.

关键词： Canada Community-based disaster risk management Disaster awareness and preparedness Disaster resilience natural hazards Older adults

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nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

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World Journal of Psychiatry 2024年第1期14卷 159-178页

作者： Renee J Dufault katherine M Adler David O Carpenter Steven G Gilbert Raquel A Crider College of Graduate Health Studies A.T.Still UniversityKirksvilleMO 63501United States Department of Research Food Ingredient and Health Research InstituteNaalehuHI 96772United States Department of Health Sciences University of New HavenWest HavenCT 06516United States Institute for Health and the Environment School of Public HealthState University of New YorkAlbanyNY 12222United States Department of Research Institute of Neurotoxicology and Neurological DisordersSeattleWA 98105United States Department of Statistics Food Ingredient and Health Research InstituteNaalehuHI 96772United States

BACKGROUnD Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their *** may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics *** To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food *** The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ***-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)*** test group participated in the six-week online nutritional epigenetics tutorial,while the control group did *** efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention *** intake scores were derived for both ultra-processed and whole/organic *** sample t-tests were conducted to determine any differences in mean diet scores within each *** There was a significant difference in the diet scores of the test group between the pre-and post-intervention *** parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the

关键词： Epigenomics Parenteral nutrition Autism Attention deficit/hyperactivity disorder Ultra-processed foods Heavy metals

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Creation and validation of a novel low-cost dry lab for early resident training and assessment of robotic prostatectomy technical proficiency

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Current Urology 2024年第2期18卷 133-138页

作者： Kevin Kunitsky Abhishek Venkataramana katherine E.Fero Jorge Ballon Jacob Komberg Robert Reiter Wayne Brisbane Institute of Urologic Oncology Department of UrologyDavid Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Charles E.Schmidt College of Medicine Florida Atlantic UniversityBoca RatonFLUSA

Purpose:To evaluate the preliminary validity and acceptability of a low-cost low-fidelity robotic surgery dry lab for training and assessing residents’technical proficiency with key robotic radical prostatectomy *** and methods:Three standardized inanimate tasks were created to simulate the radical prostatectomy steps of posterior dissection,neurovascular bundle release,and urethrovesical *** trainees and faculty at a single institution completed and evaluated each dry lab *** validity was evaluated by comparing task completion times and Global Evaluative Assessment of Robotic Skills scores across four participant cohorts:medical students(n=5),junior residents(n=5),senior residents(n=5),and attending surgeons(n=7).Content validity,face validity,and acceptabilitywere evaluated through a posttask survey using a 5-point Likert ***:There was a significant difference in the individual and composite task completion times and Global Evaluative Assessment of Robotic Skills scores across all participant cohorts(all pn terms of its content validity and acceptability for use in residency ***,model realism,compared with human tissue,was poorly *** dry lab production cost was less than US$***:This low-cost procedure-specific dry lab demonstrated evidence of content validity,construct validity,and acceptability for simulating key robotic prostatectomy technical steps and can be used to augment robot-assisted laparoscopic prostatectomy surgical training.

关键词： Robotic surgery education Radical prostatectomy Simulation Dry laboratory Validation

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Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

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neural Regeneration Research 2025年第2期20卷 574-586页

作者： Olivier Kerdiles Méryl-Farelle Oye Mintsa Mi-mba katherine Coulombe Cyntia Tremblay VincentÉmond Martine Saint-Pierre Clémence Rouxel Line Berthiaume Pierre Julien Francesca Cicchetti Frédéric Calon Facultéde pharmacie UniversitéLaval1050 Avenue de la MédecineQuebecQCCanada Axe neuroscience Centre de recherche du CHU de Québec-UniversitéLaval(Pavillon CHUL)2705 Boulevard LaurierQuebecQCCanada Institute of nutrition and Functional Foods QuebecQCCanada Optinutribrain International Associated Laboratory(nutrineuro FranceINAFCanada)QuebecQCCanada Axe Endocrinologie et néphrologie Centre de recherche du CHU de Québec-UniversitéLavalQuebecQCCanada Département de Médecine Facultéde MédecineUniversitéLavalQuebecQCCanada Département de Psychiatrie et neurosciences Facultéde MédecineQuebecQCCanada

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after *** that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic ***,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal *** weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 *** this period,the animals had access to a running wheel,which they could use or *** acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars ***,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned *** to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned *** present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

关键词： 6-hydroxydopamine dopamine dopamine transporter exercise neurorestoration Parkinson’s disease polyunsaturated fatty acids omega-3

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Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2487-2503页

作者： Carlos A Castaneda Miluska Castillo Luis A Bernabe Joselyn Sanchez Matteo Fassan katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy Ruiz Juvenal Sanchez Fernando Barreda Daniel Valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa Hugo Fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio J Flores Luis Taxa Faculty of Health Sciences Universidad Cientifica del SurLima 15038Peru GECO PERU Grupo de Estudios Clinicos Oncologicos del PeruLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Human Medicine Universidad Ricardo PalmaLima 15039Peru Department of Medicine Surgical Pathology&Cytopathology UnitUniversity of PaduaPadua 35121Italy Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Specialties Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Regional de Enfermedades Neoplasicas del NorteTrujillo 13001Peru Faculty of Human Medicine Universidad Privada Antenor OrregoTrujillo 13008Peru Department of Surgery Instituto Regional de Enfermedades Neoplasicas del SurArequipa 04002Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Epidemiology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unidad de Investigación Básica y Traslacional Oncosalud-AUNALima 15038Peru Faculty of Medicine Universidad San Martin de PorresLima 15008Peru

BACKGROUnD The influence of Helicobacter-pylori(***)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively *** of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive *** To determine the rates of deficient mismatch-repair(dMMR),HER2-status and *** infection and their association with TIL levels in *** Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)*** density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).*** infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of *** dMMR was found in 34.4%,HER2+in 5%and ***-positive in 55.7%of *** IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(Pntestinal-histology(Pnd no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)***2-was associated with high IT-CD8(P=0.009).*** was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).COnCLUSIOn TIL levels were related to dMMR and *** CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关键词： Lymphocytes Macrophages Gastric cancer Helicobacter pylori HER2 Mismatch repair

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用地面磁测法检测隐伏沙金矿床

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地球物理学进展 1989年第2期4卷 55-64页

作者： E.J.Schwarz n.wright 林邦佐

本文提出了一种检测河流沉积物内隐伏磁铁矿矿床的方法。模型研究结果指出,非磁性基质内磁铁矿含量为0.5%的比较小的平板型矿体(厚1m,宽10m)可以使用一台灵敏的(0.1nT)磁力仪进行地面磁测来检测。沿垂直于河流走向而与基岩走向(或航磁... 详细信息

本文提出了一种检测河流沉积物内隐伏磁铁矿矿床的方法。模型研究结果指出,非磁性基质内磁铁矿含量为0.5%的比较小的平板型矿体(厚1m,宽10m)可以使用一台灵敏的(0.1nT)磁力仪进行地面磁测来检测。沿垂直于河流走向而与基岩走向(或航磁异常走向)成某种角度的测线进行测量,结果发现被测剖面上的总场强和垂直梯度异常基本上都在沿河流走向或河谷方向上被拉长了,这说明异常源是隐伏在河流沉积物内磁铁矿含量较高的矿体。对此进一步的证据是(1)在河流和强磁性蛇纹石地域交切处出现较高的总磁场强度和垂直“梯度”异常。(2)原始冰碛物(冰砾泥)上方无高频异常。(3)功率谱上出现某些特性。河流沉积物内比较大的磁铁矿富集体很可能含有最集中的重系列经济矿物,诸如金子。因此最感兴趣的隐伏沙金探测区域可以从地面详细磁测图或直升机低高程磁测图中选取。

关键词：磁测航磁异常河流沉积物探测区域重矿物交切磁力仪平板型磁法勘探磁化率

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对单颗粒黑云母^(40)Ar/^(39)Ar分析得出的热历史的新认识

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地震地质译丛 1994年第4期16卷 57-63页

作者： n.wright 李齐

1.引言在阐明地球的复杂的物理演化过程中,一个重要部分是对它的热历史的准确认识。应用Dodson(1973)的封闭温度的理论,利用^(40)Ar/^(39)Ar 测年技术研究了区域冷却历史。为了把温度与测量的同位素年龄联系起来,这个理论要求测定扩散参... 详细信息

1.引言在阐明地球的复杂的物理演化过程中,一个重要部分是对它的热历史的准确认识。应用Dodson(1973)的封闭温度的理论,利用^(40)Ar/^(39)Ar 测年技术研究了区域冷却历史。为了把温度与测量的同位素年龄联系起来,这个理论要求测定扩散参数,因为扩散参数控制着所测矿物样品的 Ar 的自然丢失。虽然^(40)Ar/^(39)Ar 年龄可以高精度地测量出。但测定扩散参数却不是简单的。

关键词：黑云母颗粒氩40 氩39 同位素

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Resilience, the 6th Vital Sign: Conceptualizing, Contextualizing, and Operationalizing All Six Vital Signs

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Health 2024年第7期16卷 657-673页

作者： Rose E. Constantino Betty J. Braxter Chi Ching Vivian Hui Larissa C. Allen Lillian J. Wolfe katherine H. Endres Jezyl Cempron Cutamora Laurence L. Garcia Daisy R. Palompon Kathleen Thimsen Brayden n. Kameg Margarete L. Zalon Department of Health and Community Systems School of Nursing University of Pittsburgh Pittsburgh PA USA Undergraduate Affairs School of Nursing University of Pittsburgh Pittsburgh PA USA The Hong Kong Polytechnic University Hong Kong China School of nursing Adjunct Faculty at the University of Pittsburgh Pittsburgh PA USA School of nursing University of Pittsburgh Pittsburgh PA USA Department of Health Promotion and Development School of Nursing University of Pittsburgh Pittsburgh PA USA College of nursing Cebu Normal University Cebu City Philippines School of nursing University of Nevada Las Vegas USA Department of Health and Community Systems University of Pittsburgh PA USA Department of nursing University of Scranton Scranton PA USA

There are five vital signs that healthcare providers assess: temperature, pulse, respiration, blood pressure, and pain. normal levels for the five vital signs are published by the American Heart Association, and other specialty organizations, however, the sixth vital sign (resilience) which adopts the measure of immune resilience is suggested in this paper. Resilience is the ability of the immune system to respond to attacks and defend effectively against infections and inflammatory stressors, and psychological resilience is the capacity to resist, adapt, recover, thrive, and grow from a challenge or a stressor. Individuals with better optimal immune resilience had better health outcomes than those with minimal immune resilience. The purpose of this paper is to conceptualize, contextualize, and operationalize all six vital signs. We suggest measuring resilience subjectively and objectively. Subjectively, use a 5-item guided interview revised from the Connor-Davidson Resilience Scale (CDRC), a scale of 10 items. The revised CDRC scale is a 5-item scale. The scale is rated on a 5-point Likert scale from 0 (not true) to 4 (true all the time). The total score ranges from 0 to 20, with higher total scores indicating greater resilience. The scale demonstrated good construct validity and internal consistency (α = 0.85) during the development of the scale. The CD-RISC had a good Cronbach’s alpha level of 0.85. The Revised CD-RISC can be completed in 2 - 4 minutes. To measure resilience objectively, we suggest using Immune Resilience (IR) levels, the level of resilience to preserve and/or rapidly restore immune resilience functions that promote disease resistance and control inflammation and other inflammatory stress. IR levels are gauged with two peripheral blood metrics that quantify the balance between CD8 and CD4 T-cell levels and gene expression signatures tracking longevity-associated immunocompetence and mortality- or entropy-associated inflammation. IR deregulation i

关键词： Conceptualization Contextualization Operationalization Body Temperature Pulse Respiration Blood Pressure Pain Resilience

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