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Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

World Journal of Stem Cells 2016年第11期8卷 376-383页

作者： Sonia Labrador-Velandia maría luz alonso-alonso Sara Alvarez-Sanchez Jorge González-Zamora Irene Carretero-Barrio José Carlos Pastor Iván Fernandez-Bueno Girish Kumar Srivastava Instituto Universitario de Oftalmobiología Aplicada Universidad de Valladolid 47011 Valladolid Spain Facultad de Medicina Universidad de Valladolid 47005 Valladolid Spain Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León 47011 Valladolid Spain Red Temática de Investigación Cooperativa Sanitaria del Instituto de Salud Carlos Ⅲ. Oftared 28029 Madrid Spain Hospital Clínico Universitario de Valladolid 47003 Valladolid Spain

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

关键词： Mesenchymal stem cells Cell therapy Optic nerve diseases Clinical trials Retinal diseases

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Initial host-pathogen interactions explained by the Organism Prearranged Recognition Theory: fundamental role of saccharides

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Life Research 2024年第3期7卷 9-23页

作者： luz P.Blanco Systemic Autoimmunity Branch National Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of HealthBethesdaUSA

Herein based on literature available a hypothesis is provided about molecular basis for initial events in establishment *** hypothesis asserts that:"recognition and interaction that occur between organisms is *** are membrane receptors with or without soluble components derived from the respective organisms that bridge specific interactions".Organisms'prearranged recognition theory(OPRT)can be specifically applied to host-microbe interactions where most microbes are coated(opsonised)by soluble components(opsonins)from the host,but there are also some microbes that can bypass host opsonization expressing receptors for the host cells or secreting host’s opsonin-like *** receptors involved in organism's interactions,their specificity and repertoire depend on saccharides from glycoproteins,glycolipids,and polysaccharides(glycans)which are abundant extracellular *** in OPRT is possible to explain species-specific interactions and several other phenomena,such as hyper-infectivity,tissue tropism,differential sensitivity to disease depending on type O-blood,and tumoral cell *** lipid raft domain in cellular membrane is proposed as the main location where interactions will trigger cellular *** scientific and biotechnology applications and alternative routes to modify organism's interactions and consequences are *** is a novel hypothesis regarding the degree to which an organism's interactions are prearranged and the role of saccharides epitopes.

关键词： Species-specificity saccharides extracellular-matrix host-pathogen antibodies

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Simulated rainfall in Brazil:An alternative for assesment of soil surface processes and an opportunity for technological development

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International Soil and Water Conservation Research 2024年第1期12卷 29-42页

作者： Camila Calazans da Silva luz Wilk Sampaio de Almeida Adilson Pacheco de Souza Nivaldo Schultz Jamil Alexandre Ayach Anache Daniel Fonseca de Carvalho Postgraduate Program in Agronomy-Soil Sciences Federal Rural University of Rio de JaneiroSeropédicaRJBrazil Agronomy Department Federal Institute of EducationScience and Technology of RondôniaAriquemesROBrazil Federal University of Mato Grosso SinopMTBrazil Federal Rural University of Rio de Janeiro SeropédicaRJBrazil Federal University of Mato Grosso do Sul Campo GrandeMSBrazil

Rainfall simulators(RS)have been used,above all,to evaluate hydrological processes related to soil water infiltration,surface runoff and soil *** allow repeatability of rain application with different precipitation intensities in field and/or laboratory conditions and should produce events with physical characteristics similar to natural *** this manuscript,we carried out a bibliometric and scientometric analysis of studies with simulated rainfall in Brazil to assess the temporal evolution of publications,the main topics addressed and the degree of technological development of the *** searched for the terms“rainfall simulator”OR“simulated rainfall”AND“Brazil”in the Scopus,Web of Science,SciELO and Google Scholar *** found 143 articles published in the last 37 years(1985-2022).Our findings indicate that the main research areas covered in papers are soil erosion(57.34%),soil water infiltration(24.47%),nutrient losses(9.8%)and RS development and calibration/assessment(8.39%).In recent years,the number of published papers in international high-impact factor journals has *** of the papers(49.65%)refer to studies carried out by institutions located in the south and southeast regions of ***,there is a large gap of studies on simulated rainfall in other regions of Brazil,where important biomes such as the Cerrado,Amazon,Caatinga,and their transitions are *** study informs research priorities on soil erosion under simulated rainfall and provides a bibliographic database that can assist in more detailed future analyses.

关键词： Rainfall simulator Soil and water losses Soil water infiltration Bibliometrics Scientific review

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A Tutorial on Federated Learning from Theory to Practice:Foundations,Software Frameworks,Exemplary Use Cases,and Selected Trends

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 824-850页

作者： M.Victoria luzón Nuria Rodríguez-Barroso Alberto Argente-Garrido Daniel Jiménez-López Jose M.Moyano Javier Del Ser Weiping Ding Francisco Herrera Department of Software Engineering Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Computer Science and Artificial Intelligence Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Communications Engineering University of the Basque Country(UPV/EHU)and also with TECNALIABasque Research&Technology Alliance(BRTA)Spain School of Information Science and Technology Nantong UniversityNantong 226019China

When data privacy is imposed as a necessity,Federated learning(FL)emerges as a relevant artificial intelligence field for developing machine learning(ML)models in a distributed and decentralized *** allows ML models to be trained on local devices without any need for centralized data transfer,thereby reducing both the exposure of sensitive data and the possibility of data interception by malicious third *** paradigm has gained momentum in the last few years,spurred by the plethora of real-world applications that have leveraged its ability to improve the efficiency of distributed learning and to accommodate numerous participants with their data *** virtue of FL,models can be learned from all such distributed data sources while preserving data *** aim of this paper is to provide a practical tutorial on FL,including a short methodology and a systematic analysis of existing software ***,our tutorial provides exemplary cases of study from three complementary perspectives:i)Foundations of FL,describing the main components of FL,from key elements to FL categories;ii)Implementation guidelines and exemplary cases of study,by systematically examining the functionalities provided by existing software frameworks for FL deployment,devising a methodology to design a FL scenario,and providing exemplary cases of study with source code for different ML approaches;and iii)Trends,shortly reviewing a non-exhaustive list of research directions that are under active investigation in the current FL *** ultimate purpose of this work is to establish itself as a referential work for researchers,developers,and data scientists willing to explore the capabilities of FL in practical applications.

关键词： Data privacy distributed machine learning federated learning software frameworks

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Camalote Grass (Paspalum fasciculatum Willd) as a Sustainable Raw Material for the Production of Lignocellulosic Ethanol

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Journal of Sustainable Bioenergy Systems 2024年第2期14卷 23-33页

作者： maría luz May-Reyes Cintya Valerio-Cárdenas Gloria Ivette Bolio-López Manuel Mateo Hernández-Villegas Miguel Ángel Velázquez-Carmona Patricia De la Cruz-Burelo Research and Postgraduate Coordination Universidad Popular de la Chontalpa Crdenas Tabasco Mexico

The current trend of replacing a percentage of gasoline with ethanol has promoted the development of new processes for its production from lignocellulosic biomass. This work reports the production of ethanol from the Camalote grass (Paspalum fasciculatum Willd). The lignocellulosic biomass was subjected to acid hydrolysis at 125C and 15 psi with H2SO4 concentrations at 5%, 10%, and 20%, obtaining an average of reducing sugars (pentoses and hexoses) from the hydrolyzed juice with 12.3%, 10%, and 17% Brix, respectively. The sugars were fermented using yeast of the Saccharomyces cerevisiae at 30C for 48 hours. Finally, the ethanol was distilled at 78C, and the average yields were obtained through analysis of variance with a 95% confidence level. The values indicate that there is a significant difference (p > 0.05), the Tukey study shows that all the % v/v averages are different from each other. For H2SO4 concentration at 5% (10.33 ± 2), H2SO4 at 10% (9.33 ± 1.8), and H2SO4 at 20% (6.33 ± 2). The acidity analysis for the ethanol obtained from each treatment gave a value of 1.8 mg/L of acetic acid in all cases.

关键词： Lignocellulosic Ethanol Lignocellulosic Biomass Camalote Grass Acid Hydrolysis Energy Crops

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New avenues for the treatment of immunotherapy-resistant pancreatic cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： Luis Guilherme de Oliveira Silva Fabian Fellipe Bueno Lemos marcel Silva luz Samuel Luca Rocha Pinheiro mariana dos Santos Calmon Gabriel Lima Correa Santos Gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases ***,due to its complexity,it ranks 7th in the list of the most lethal cancers *** pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and *** in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,*** this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy *** is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive *** to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as *** this way,finding new strategies that make it possible to manipulate resistance mechanisms is ***,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC ***,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating thi

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation Combined immunotherapy

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Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy

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World Journal of Gastroenterology 2024年第6期30卷 579-598页

作者： Fabian Fellipe Bueno Lemos Caroline Tianeze de Castro marcel Silva luz Gabriel Reis Rocha Gabriel Lima Correa Santos Luís Guilherme de Oliveira Silva mariana Santos Calmon Cláudio Lima Souza Ana Carla Zarpelon-Schutz Kádima Nayara Teixeira Dulciene maria de Magalhães Queiroz Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Instituto de Saúde Coletiva Universidade Federal da BahiaSalvador 40110040BahiaBrazil Campus Toledo Universidade Federal do ParanáToledo 85919-899ParanáBrazil Laboratory of Research in Bacteriology UFMGBelo Horizonte 30130-100Minas GeraisBrazil

BACKGROUND Helicobacter pylori(***)infection has been well-established as a significant risk factor for several gastrointestinal *** urea breath test(UBT)has emerged as a leading non-invasive method for detecting *** numerous studies confirming its substantial accuracy,the reliability of UBT results is often compromised by inherent *** findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of *** *** To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for *** infection in adult patients with *** We conducted an independent search of the PubMed/MEDLINE,EMBASE,and Cochrane Central databases until April *** search included diagnostic accuracy studies that evaluated at least one of the index tests(^(13)C-UBT or ^(14)C-UBT)against a reference *** used the QUADAS-2 tool to assess the methodo-logical quality of the *** utilized the bivariate random-effects model to calculate sensitivity,specificity,positive and negative test likelihood ratios(LR+and LR-),as well as the diagnostic odds ratio(DOR),and their 95%confidence *** conducted subgroup analyses based on urea dosing,time after urea administration,and assessment *** investigate a possible threshold effect,we conducted Spearman correlation analysis,and we generated summary receiver operating characteristic(SROC)curves to assess ***,we visually inspected a funnel plot and used Egger’s test to evaluate publication *** both as reliable diagnostic tools in clinical *** In summary,our study has demonstrated that ^(13)C-UBT has been found to outperform the ^(14)C-UBT,making it the preferred diagnostic ***,our results emphasize the significance of carefully considering urea dosage,assessment timing,and measurement techniques for both tests to enh

关键词： Helicobacter pylori Urea breath test Diagnosis Diagnostic test accuracy Meta-analysis

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Submicroscopic 11p13 deletion including the elongator acetyltransferase complex subunit 4 gene in a girl with language failure, intellectual disability and congenital malformations: A case report

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World Journal of Clinical Cases 2020年第21期8卷 5296-5303页

作者： Jaime Toral-Lopez luz maría González Huerta Olga Messina-Baas Sergio A Cuevas-Covarrubias Departamento de Genética Medica Centro Medico EcatepecISSEMYMEcatepec 55000México Programa de Maestría y Doctorado en Ciencias Médicas Odontológicas y de la Salud/Hospital Infantil de MéxicoUniversidad Nacional Autónoma de MéxicoMéxico 06720México Departamento de Biología Molecular Hospital General de MéxicoCuauhtémoc 06720México Departamento de Oftalmología Hospital General de MéxicoCuauhtémoc 06720México Genetica Hospital General de MéxicoCuauhtémoc 06726Mexico Sergio A Cuevas-CovarrubiasPrograma de Maestría y Doctorado en Ciencias MédicasOdontológicas y de la SaludUniversidad Nacional Autónoma de MéxicoMéxico 06720Mexico

BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the ***,treatment is only rehabilitation and surgery for cleft lip and *** SUMmarY The proband was a 2-years-8-months-old *** history was negative for congenital malformations or intellectual *** patient had microcephaly,upward-slanting palpebral fissures,depressed nasal bridge,bulbous nose and bilateral cleft lip and *** magnetic resonance imaging showed cortical atrophy and band *** motor and intellectual development is delayed.A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene(ELP4)and a loss of heterozygosity in Xq25-q26.3 were *** There is no treatment for the ELP4 deletion caused by a submicroscopic 11p3 *** describe a second case of deletion of the ELP4 gene without aniridia,which confirms the association between ELP4 gene with several defects and absence of this ocular *** clinical data in the deletion of the ELP4 gene as cleft palate,facial dysmorphism,and changes at level brain could be associated to this gene or be part of the effect of the recessives genes involved in the loss of heterozygosity region of Xq25-26.3.

关键词： Submicroscopic 11p13 deletion Elongator acetyltransferase complex subunit 4 gene Language failure Intellectual disability Congenital malformations Case report

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Immune pathway through endometriosis to ovarian cancer

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World Journal of Clinical Oncology 2024年第4期15卷 496-522页

作者： mariana Santos Calmon Fabian Fellipe Bueno Lemos marcel Silva luz Samuel Luca Rocha Pinheiro Luis Guilherme de Oliveira Silva Gabriel Lima Correa Santos Gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine *** disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic *** endometriosis is a benign disease,it shares several characteristics with invasive *** support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic *** is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and ***,the carcinogenic pathways between both pathologies remain poorly *** studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and *** article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their *** recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

关键词： Ovarian neoplasms Endometriosis Endometriosis-associated ovarian cancers Immune response Immunotherapy

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Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation

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World Journal of Gastroenterology 2020年第34期26卷 5101-5117页

作者： David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao martina Pagano Laura Mosca Maider Bizkarguenaga marina Serrano-Macia Mikel Azkargorta marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan martijn van Liempd Felix M Goni Cristina alonso maría luz martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato Precision Medicine and Metabolism Laboratory Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160BizkaiaSpain CIBERehd-Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas Madrid 28029Spain Department of Precision Medicine University of Campania"Luigi Vanvitelli"Naples 80138Italy Liver Disease Laboratory Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain Proteomics Platform Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain OWL Metabolomics Derio 48160Spain Instituto Biofisika(UPV/EHU CSIC)Leioa 48940SpainDepartamento de Bioquímica y Biología MolecularUniversidad del País VascoLeioa 48940Spain Pre-clinical and Chemistry Manufacturing and ControlsGalmed PharmaceuticalsTel Aviv 6578317Israel Metabolomics Platform Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain Division of Digestive and Liver Diseases Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of *** a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic *** To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with *** Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 ***,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled *** the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 *** metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related *** Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in *** translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA ***,liver metabolomic analysis showed

关键词： Nonalcoholic fatty liver disease Steatohepatitis Methionine and choline deficient diet Tricarboxylic acid cycle Hemoglobin A1c Stearoyl-CoA desaturase 1

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