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Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

World Journal of Gastroenterology 2015年第6期21卷 1749-1758页

作者： Raymond A Isidro Myrella L Cruz Angel A Isidro axel Baez axel arroyo William A González-Marqués Carmen González-Keelan Esther A Torres Caroline B Appleyard Department of Physiology and Pharmacology Ponce School of Medicine and Health Sciences Ponce Department of Pathology Ponce School of Medicine and Health Sciences Ponce Department of Anatomy Ponce School of Medicine and Health Sciences Ponce Departments of Pathology and Laboratory Medicine University of Puerto Rico School of Medicine Department of Medicine University of Puerto Rico School of Medicine

AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and colorectal neoplasia tissues from Puerto Ricans.METHODS:Tissues from patients with IBD,colitisassociated colorectal cancer(CAC),sporadic dysplasia,and sporadic colorectal cancer(CRC),as well as normal controls,were identified at several centers in Puerto Rico.Archival formalin-fixed,paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R,p EGFR,Cox-2,and VDR.Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a4-point scale that assessed intensity of staining.Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia,in addition to the areas of cancer,within each tissue.Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test.The mean scores for normal tissues and tissues with IBD,dysplasia,CRC,and CAC were calculatedand statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test.Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient.Data are presented as mean±SE.RESULTS:On average,patients with IBD were younger(34.60±5.81)than normal(63.20±6.13,P<0.01),sporadic dysplasia(68.80±4.42,P<0.01),sporadic cancer(74.80±4.91,P<0.001),and CAC(57.50±5.11,P<0.05)patients.NK-1R in cancer tissue(sporadic CRC,1.73±0.34;CAC,1.57±0.53)and sporadic dysplasia(2.00±0.45)were higher than in normal tissues(0.73±0.19).p EGFR was significantly increased in sporadic CRC(1.53±0.43)and CAC(2.25±0.47)when compared to normal tissue(0.07±0.25,P<0.05,P<0.001,respectively).Cox-2 was significantly increased in sporadic colorectal cancer(2.20±0.23 vs 0.80±0.37 for normal tissues,P<0.05

关键词： Colitis Colon cancer Dysplasia Neurokinin Vitamin

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Septic shock due to Capnocytophaga canimorsus treated with IgM-enriched immunoglobulin as adjuvant therapy in an immunocompetent woman

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Journal of Intensive Medicine 2024年第2期4卷 265-268页

作者： Josephine Braunsteiner Stephanie Siedler Dominik Jarczak Stefan Kluge axel Nierhaus Department of Intensive Care Medicine University Medical Centre Hamburg-EppendorfHamburgGermany

Background Capnocytophaga canimorsus(C.canimorsus)belongs to the family Flavobacteriaceae.It is a facultative anaerobic Gram-negative bacillus and belongs to the normal oral microbiota of some mammals,such as cats and dogs.Transmission to humans can occur through the skin after skin abrasion caused by a scratch or a bite.[1]Based on polymerase chain reaction(PCR)analysis,C.canimorsus is present in saliva in 70%-74%of dogs and 55%-57%of cats.

关键词： belongs enriched scratch

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Large-scale Discrete Element Modelling of In-situ Direct Shear and Plate Load Tests on Granular Soils

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Journal of Earth Science 2024年

作者： Zhichun Lu Shan Dong Guodong Liu Marcos arroyo Xingwei Ren China University of Geosciences Associate Professor China University of Geosciences Changjiang Institute of Survey Planning Design and Research Universitat Politécnica de Catalunya (UPC)

This study unveils a novel and potentially economical particulate discrete element modeling (DEM) technique for large-scale simulation of in-situ direct shear tests (DST) and plate load tests， aimed at accurately determining the shear strength and bearing capacity of granular soil foundations， and exploring the key factors influencing these properties. To overcome the limitations associated with the oversimplification of particle shapes， this work introduces an innovative contact model based on the Hertz contact mechanism that incorporates rolling resistance， enhancing the model’s ability to simulate realistic particle interactions. Guided by Prandtl’s foundation bearing-capacity theory， the dimensions of the foundation model for the DST and plate load tests were meticulously calculated to reflect realistic conditions. DEM simulations showed the peak friction angle from in-situ DST to be consistently lower than laboratory DST， due to a smaller dilatation angle， while proposed loading methods for plate load tests established linear relationships between the foundation’s ultimate bearing capacity and its dimensions， also defining the capacity envelope. Crucially， this study highlights a crucial finding: in-situ direct shear tests (DST) conducted under high normal stress may lead to foundation failure， indicating that excessive normal stress should be avoided to ensure the accuracy of in-situ shear test data and its subsequent applicability in engineering design.

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Physical activity and amyloid beta in middle-aged and older adults:A systematic review and meta-analysis

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Journal of Sport and Health Science 2024年第2期13卷 133-144页

作者： María Rodriguez-Ayllon Patricio Solis-Urra Cristina arroyo-ávila Miriam álvarez-Ortega Pablo Molina-García Cristina Molina-Hidalgo Manuel Gómez-Río Belinda Brown Kirk I.Erickson Irene Esteban-Cornejo Department of Epidemiology Erasmus University Medical Center RotterdamRotterdamGD 3015the Netherlands Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18071Spain Faculty of Education and Social Sciences Universidad Andres BelloVina del Mar 2531015Chile Department of Nuclear Medicine Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain Physical Medicine and Rehabilitation Service Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain Department of Psychology University of PittsburghPittsburghPA 15260USA Centre for Healthy Ageing Health Futures InstituteMurdoch UniversityMurdochWA 6150Australia School of Medical and Health Sciences Edith Cowan UniversityJoondalupWA 6027Australia Advent Health Research Institute Neuroscience Institute OrlandoOrlandoFL 32803USA Physiopathology of Obesity and Nutrition Research Center(CIBERobn) Institute of Health Carlos Ⅲ(ISCⅢ)Madrid 28029Spain

Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels modulation.We aimed to explore the relationship between physical activity and Aβin middle-aged and older adults.Methods:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,2022.Studies were eligible if they included physical activity and Aβdata in adults aged 45 years or older.Multi-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβlevels.Results:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and blood.Higher physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older adults.However,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies.In observational studies,higher levels of physical activity were positively associated with Aβonly in CSF.Therefore,further research is needed to understand the modulating role of physical act

关键词： Aging Cognitive impairment Dementia Exercise PET

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NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno Michael K.E.Schafer Sudena Wang Michael J.Schmeisser axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathoph

关键词： calcium EF hand mitochondria nervous system signal transduction

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Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 386-397页

作者： Vilma Pacheco-Barcia Sara Custodio-Cabello Fatima Carrasco-Valero Magda Palka-Kotlowska axel Mariño-Mendez Alberto Carmona-Bayonas Javier Gallego A J Muñoz Martín Paula Jimenez-Fonseca Luis Cabezon-Gutierrez Department of Medical Oncology Hospital Universitario de TorrejonMadrid 28850Spain Department of Internal Medicine Hospital Universitario de TorrejonMadrid 28850Spain Department of Medical Oncology Hospital Universitario Central de AsturiasOviedo 33011Spain Department of Medical Oncology Hospital Universitario Morales MeseguerUniversity of MurciaMurcia 30001Spain Department of Medical Oncology Hospital General Universitario de ElcheElche 03202Spain Department of Medical Oncology Hospital General Universitario Gregorio MarañónUniversidad Complutense MadridMadrid 28007Spain Universidad Francisco de Vitoria Madrid 28223Spain

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not

关键词： Pancreatic cancer Nutrition Prognostic factor Inflammation Advanced cancer Systemic inflammatory response index Weight loss

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High-rate metal-free MXene microsupercapacitors on paper substrates

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Carbon Energy 2024年第5期6卷 94-104页

作者： Han Xue Po‐Han Huang Lee‐Lun Lai Yingchun Su axel Strömberg Gaolong Cao Yuzhu Fan Sergiy Khartsev Mats Göthelid Yan‐Ting Sun Jonas Weissenrieder Kristinn BGylfason Frank Niklaus Jiantong Li School of Electrical Engineering and Computer Science KTH Royal Institute of TechnologyStockholmSweden School of Engineering Sciences KTH Royal Institute of TechnologyStockholmSweden

MXene is a promising energy storage material for miniaturized microbatteries and microsupercapacitors(MSCs).Despite its superior electrochemical performance,only a few studies have reported MXene-based ultrahigh-rate(>1000 mV s^(−1))on-paper MSCs,mainly due to the reduced electrical conductance of MXene films deposited on paper.Herein,ultrahigh-rate metal-free on-paper MSCs based on heterogeneous MXene/poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)(PEDOT:PSS)-stack electrodes are fabricated through the combination of direct ink writing and femtosecond laser scribing.With a footprint area of only 20 mm^(2),the on-paper MSCs exhibit excellent high-rate capacitive behavior with an areal capacitance of 5.7 mF cm^(−2)and long cycle life(>95%capacitance retention after 10,000 cycles)at a high scan rate of 1000 mV s^(−1),outperforming most of the present on-paper MSCs.Furthermore,the heterogeneous MXene/PEDOT:PSS electrodes can interconnect individual MSCs into metal-free on-paper MSC arrays,which can also be simultaneously charged/discharged at 1000 mV s^(−1),showing scalable capacitive performance.The heterogeneous MXene/PEDOT:PSS stacks are a promising electrode structure for on-paper MSCs to serve as ultrafast miniaturized energy storage components for emerging paper electronics.

关键词： direct ink writing femtosecond laser scribing MXene on-paper microsupercapacitors PEDOT:PSS ultrahigh rate capability

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Work Ability Index and Work Ability Score: A Comparation between both Scores in a Persistent COVID-19 Cohort

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Occupational Diseases and Environmental Medicine 2024年第1期12卷 49-57页

作者： Carmen Muñoz-Ruiperez Diego Alvaredo Rodrigo Daniel arroyo-Sánchez Juan Francisco Álvarez Zarallo Ignacio Sánchez-Arcilla Conejo José Lorenzo Bravo Grande Department of Occupational Health Hospital Universitario 12 de Octubre Madrid Spain Instituto de Investigación Biomédica Hospital 12 de Octubre (Imas12) Madrid Spain Department of Occupational Health Hospital Universitario Virgen Macarena Andalucía Sevilla Spain Department of Occupational Health Hospital Universitario Gregorio Mara&#241ón Madrid Spain Department of Occupational Health Complejo Asistencial Universitario de Salamanca Castilla y León Salamanca Spain

Aims: The present study aims to compare the assessment of work ability based on the use of the Work Ability Index (WAI) with another questionnaire base only on the use of WAI’s first item, termed as the “Work Ability Score” (WAS). Study design: A cohort of 384 Spanish workers included in a Post COVID-19 condition or persistent COVID-19 multicenter research was utilized. Place and Duration of Study: This cohort was enlisted in four hospitals (Hospital Universitario 12 de Octubre, Madrid;Hospital Universitario Virgen Macarena, Sevilla, Andalucía;Hospital Universitario Gregorio Marañón, Madrid and Complejo Asistencial Universitario de Salamanca, Castilla y León), since 2021 until 2022. Methodology: 384 Spanish workers (176 men and 208 women;aged 20 to 70 years) with Post COVID-19 condition or persistent COVID-19 were included. Descriptive analysis of primary scores was conducted. Given the non-normal distribution of data, the Mann-Whitney and Kruskal-Wallis tests were employed. Spearman and Kendall correlations were employed to assess the relationship between WAI and WAS, also used weighted Kappa to estimate the degree agreement between WAI and WAS. Logistic regression models were utilized to study determinants influencing WAI and WAS, categorized as poor or moderate. Results: WAI had an average score of 32.98 (SD = 10.28), whereas WAS had an average of 5.95 (SD = 2.77). Significant differences were observed in both WAI and WAS across the same variables. Strong and statistically significant correlations were evident between WAI and WAS (rs = 0.83, p < 0.001). All the variables used in the logistic regression model (gender, the sector employment, and previous chronic diseases) were statistically significant in both questionnaires. Conclusion: WAS questionnaire could be used as a tool for reliable assessment of work ability among Spanish workers with Post COVID-19 condition or Persistent CO-VID-19.

关键词： Work Ability Index Work Ability Score Post COVID-19 Condition Occupational Health Occupational Medicine

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Innovation in pathogenesis and management of aortic aneurysm

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World Journal of Experimental Medicine 2024年第2期14卷 35-45页

作者： Maryam Barkhordarian Hadrian Hoang-Vu Tran Aiswarya Menon Sai Priyanka Pulipaka Izage Kianifar Aguilar axel Fuertes Shraboni Dey Angel Ann Chacko Tanni Sethi Ayrton Bangolo Simcha Weissman Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States

Aortic aneurysm(AA)refers to the persistent dilatation of the aorta,exceeding three centimeters.Investigating the pathophysiology of this condition is important for its prevention and management,given its responsibility for more than 25000 deaths in the United States.AAs are classified based on their location or morphology.various pathophysiologic pathways including inflammation,the immune system and atherosclerosis have been implicated in its development.Inflammatory markers such as transforming growth factorβ,interleukin-1β,tumor necrosis factor-α,matrix metalloproteinase-2 and many more may contribute to this phenomenon.Several genetic disorders such as Marfan syndrome,Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease.Recent years has seen the investigation of novel management of AA,exploring the implication of different immune suppressors,the role of radiation in shrinkage and prevention,as well as minimally invasive and newly hypothesized surgical methods.In this narrative review,we aim to present the new contributing factors involved in pathophysiology of AA.We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.

关键词： Aortic aneurysm Abdominal aneurysm Thoracic aneurysm Immunotherapy Surgical management Pathophysiology Inflammation and molecular pathways

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Vegetation cover and occurrence of salamanders in the western Mediterranean

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Integrative Zoology 2022年第3期17卷 456-467页

作者： Daniel ESCORIZA axel HERNANDEZ GRECO Institute of Aquatic EcologyUniversity of GironaGironaSpain Department of Environmental Sciences Faculty of Sciences and TechnicsUniversity Pasquale Paoli of CorsicaCorteFrance

The Mediterranean region possesses a rich diversity of salamanders,which also exhibit a high degree of ecological diversification.It is assumed that the presence of salamanders is dependent on the level of vegetation cover in terrestrial habitats,but the strength of this association is likely to vary among species.In this study,we investigated the patterns of habitat utilization for Mediterranean salamanders based on 589 records of 33 species.We tested the hypothesis that the association between salamander presence and vegetation density varies among genera or reproductive modes(i.***.terrestrial vs aquatic).The results show that vegetation cover has similar influences on terrestrial and aquatic groups but important differences are identified for lotic and lentic aquatic species.Our findings also indicate that the aquatic lotic,terrestrial,and small-body species deviate significantly from that expected from the background range of variation.

关键词： amphibian conservation habitat remote sensing salamander

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