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A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles

Nano Research 2016年第2期9卷 537-548页

作者： Sara Capolla Nelly Mezzaroba Sonia Zorzet Claudio Tripodo Ramiro Mendoza-Maldonado Marilena Granzotto Francesca Vita Ruben Spretz Gustavo Larsen Sandra Noriega eduardo mansilla Michele Dal Bo Valter Gattei Gabriele Pozzato Luis Nunez Paolo Macor Department of Life Sciences University of Trieste 34127 Trieste Italy Department of Human Pathology University of Palermo 90133 Sicilia Italy Molecular Oncology Unit National Laboratory Consorzio Interuniversitatio per le Biotecnologie (CIB) 34012 Trieste Italy Dipartimento Universitario Clinico di Scienze mediche Chirurgiche e della Salute University of Trieste 34149 Trieste Italy LNK Chemsolutions LLC Lincoln NE 68521 USA Bio-Target Inc. Chicago IL 60637 USA Centro Unico Coordinador de Ablacion e Implante Provincia de Buenos Aires (C.U.CA.I.B.A.) Ministry of Health La Plata Buenos AiresArgentina Clinical and Experimental Onco-Hematology Unit Centro di Riferimento Oncologico Istituto di Ricerca e Cura a Carattere Scientifico(I.R.C.C.S.) 33081 Aviano Italy Callerio Foundation Onlus Institutes of Biological Researches 34127 Trieste Italy

Current approaches for the treatment of chronic lymphocytic leukemia （CLL） have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term side- effects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant ceils. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanopartides coated with an anti-CD20 *** first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated]deleted leukemia cells expressing a low amount of CD20, but also circulating primary ceils isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders.

关键词： chronic lymphocytic leukemia immune targeted nanoparticles treatment xenograft model

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Macrolide-Clarithromycin Task-Force for the Treatment and Prophylaxis of Covid-19 as a Single Agent

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Pharmacology & Pharmacy 2020年第6期11卷 85-104页

作者： eduardo mansilla Ricardo Rangel Martínez Gustavo Horacio Marín Idiberto Zotarelli Filho Elsa Rivas Jaime Rivas Katherine Athayde Teixeira de Carvalho Mohammad Reza Dayer Alí Samadikuchaksaraei Internal Medicine School of Medical Sciences UNLP La Plata Argentina ExomePharma Ciudad de México DF México Pharmacology School of Medical Sciences UNLP La Plata Argentina Faceres Medical School Sao José do Rio Preto Sao Paulo Brazil Intensive Care Units-Hospital de la Amistad Perú Corea II Santa Rosa and Salvador University Hospital Piura Perú Intensive Care Unit Hospital de la Amistad Perú Corea II Santa Rosa Piura Perú Pequeno Príncipe Faculty & Pelé Pequeno Príncipe Institute Curitiba Paraná Brazil Department of Biology Faculty of Science Shahid Chamran University of Ahvaz Ahvaz Iran Department of Tissue Engineering & Regenerative Medicine Iran University of Medical Sciences Tehran Iran

SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.

关键词： COVID-19 Macrolides Clarithromycin Single Agent Therapy Prophylaxis

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Cadaveric bone marrow mesenchymal stem cells:first experience treating a patient with large severe burns

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Burns & Trauma 2015年第2期3卷 74-82页

作者： eduardo mansilla Gustavo H.Marín Mirta Berges Silvia Scafatti Jaime Rivas Andrea Núñez Martin Menvielle Roberto Lamonega Cecilia Gardiner Hugo Drago Flavio Sturla Mercedes Portas Silvia Bossi Maria Victoria Castuma Sandra Peña Luengas Gustavo Roque Karina Martire Jose Maria Tau Gabriel Orlandi Adrian Tarditti Tissue Engineering Regenerative Medicine and Cell Therapies LaboratoryCUCAIBAProvince of Buenos Aires Ministry of HealthTransplantation ProgramLa PlataProvince of Buenos AiresArgentina Burns and Plastic Surgery Department San Martín HospitalProvince of Buenos Aires Ministry of HealthLa PlataProvince of Buenos AiresArgentina Burns Hospital Buenos Aires CityArgentina Department of Chemistry Mayaguez CampusUniversity of Puerto RicoMayaguezPuerto RicoUSA.

Background:In January 2005,Rasulov et *** published"First experience in the use of bone marrow mesenchymal stem cells(MSCs)for the treatment of a patient with deep skin burns".Here,we present the first ever treated patient with cadaveric bone marrow mesenchymal stem cells(CMSCs)in the history of ***:A young man,who severely burned 60%of his total body surface with 30%of full-thickness burns while working with a grass trimmer that exploded,was involved in the *** were obtained from the bone marrow of a cadaver donor in a routine procurement procedure of CUCAIBA,the Province of Buenos Aires,Argentina,Ministry of Health,Transplantation Agency,cultured,expanded,and applied on the burned surfaces using a fibrin spray after early ***:So far,our preliminary experience and our early results have been very impressive showing an outstanding safety data as well as some impressive good results in the use of ***:Based on al this,we think that improvements in the use of stem cells for burns might be possible in the near future and a lot of time as well as many lives could be saved by many other research teams all over the *** will probably be a real scientific opportunity in Regenerative Medicine as well as in Transplantation.

关键词： Burns Cadaveric Transplantation Skin regeneration Mesenchymal stem cells

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Pesticides in a temperate coastal lagoon in southwest Europe (Ria de Aveiro, Portugal) – Risk assessment and acute assays with Artemia and Daphnia

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Emerging Contaminants 2024年第2期10卷 40-56页

作者： Maria João Rocha eduardo Rocha Laboratory of Histology and Embryology Department of MicroscopyICBAS-School of Medicine and Biomedical SciencesUniversity of Porto(U.Porto)Portugal Team of Animal Morphology and Toxicology Interdisciplinary Centre of Marine and Environmental Research(CIIMAR/CIMAR)U.PortoPortugal

The Ria de Aveiro lagoon has been considered one of the most important Southern European long-term monitoring sites(LTER-site)concerning climate change and anthropogenic ***,studies concerning pesticide contamination herein are few and mostly ***,56 pesticides dissolved in the aqueous phase(DAP)and suspended particulate matter(SPM)were examined to fill the knowledge gap,considering the hydrophobic nature of most evaluated *** samples were taken seasonally from eight sites,and both DAP and SPM fractions were analysed by gas-chromatography-mass *** annual average concentrations of fungicides,herbicides and insecticides were≈57 ng/L,≈409 ng/L and≈1058 ng/L in DAP and≈7μg/g,≈28μg/g and≈67μg/g in *** pesticides and the excessive phosphate concentrations suggest that the lagoon's water quality may be hazardous to biota and *** were identified as the most threatened trophic level using deterministic risk assessment,with chlorpyriphos and chlorfenvinphos being the primary *** experiments with Artemia and Daphnia supported the suppositions.

关键词： Coastal lagoon Invertebrate bioassays Risk evaluation Waterborne pesticides

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Impact of low alcohol consumption in the natural history of cirrhosis

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 161-164页

作者： David Marti-Aguado eduardo Vilar-Gomez Digestive Disease Department Clinic University HospitalINCLIVA Health Research InstituteValenciaSpain Division of Gastroenterology and Hepatology Department of MedicineIndiana University School of MedicineIndianapolisINUSA

Alcohol-related liver disease(ALD)and metabolic dysfunction-associated steatotic liver disease(MASLD)are the most common causes of chronic liver disease worldwide(1).Daily alcohol consumption thresholds(<20 g/day for women and<30 g/day for men)are used to arbitrarily differentiate MASLD from ALD(2).However,“safe”levels of alcohol intake are difficult to define because of wide variations in the factors that contribute to its susceptibility and multiple effect *** MASLD,conflicting results on whether light alcohol intake is detrimental or beneficial.

关键词： Compensated cirrhosis alcohol consumption mortality hepatic decompensation

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How far have we come?Review of main public policies to reduce landslide impacts in Brazil

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Journal of Mountain Science 2024年第9期21卷 2891-2904页

作者： Bianca Carvalho VIEIRA Tiago Damas MARTINS Telma Mendes da SILVA Joséeduardo BONINI Department of Geography University of São PauloAvenida Professor Lineu Prestes 05508-000Brazil Cities Institute Federal University of São PauloAvenida Jacu-Pêssego 08260-001Brazil Department of Geography Federal University of Rio de JaneiroAvenida Athos da Silveira Ramos 21941-916Brazil

During the rainy season in Brazil,landslides can have catastrophic consequences,including loss of life,damage to urban infrastructure and significant economic ***,more than eight million people in Brazil live in disaster-prone *** objective of this article is to present a chronological review of the principal policies and programmes at the national,state,and municipal levels,with an emphasis on their key actions aimed at mitigating the impact of disasters related to natural hazards,particularly *** analysis was based on official records of public policies from the national,state,and municipal *** results show that several initiatives were initially developed at the local and regional ***,it was not until the late 1980s that a comprehensive organisation of civil protection at the national level emerged as a response *** is possible to highlight three phases(understanding,coexistence,and prevention)of institutional action focused on risk management in the face of *** the growing knowledge of risk scenarios,disasters continue to occur in Brazil on an annual basis,revealing several obstacles to reducing their impact,particularly given the social and economic disparities between Brazilian regions and the applicability of public policies that must overcome the limitations of each municipality.

关键词： Disasters Risk Mitigation Prevention Legislation Civil Defense Natural Hazards

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Assembly structures of coastal woody species of eastern South America:Patterns and drivers

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Plant Diversity 2024年第5期46卷 611-620页

作者： eduardo Vinícius da Silva Oliveira Myrna Friederichs Landim Sidney F.Gouveia Graduate Program in Ecology and Conservation Federal University of SergipeSão CristovãoSergipeBrazil National Institute of Science and Technology Ecology Evolution and Conservation of Biodiversity(INCT-EECBio)GoiâniaGoiasBrazil Department of Biology Federal University of SergipeSão CristóvãoSergipeBrazil Department of Ecology Federal University of SergipeSão CristóvãoSergipeBrazil

Tropical regions have provided new insights into how ecological communities are *** dry coastal communities,water stress has been hypothesized to determine plant assembly structure by favoring preadapted lineages from neighboring ecosystems,consistent with functional ***,it is unclear whether this hypothesis is sufficient to explain how coastal communities in tropical ecosystems are ***,we test whether water stress or other factors drive community assembly in woody plant communities across the coastal zone of Brazil,a tropical *** characterized functional and phylogenetic structures of these communities and determined the underlying environmental factors(e.g.,water stress,historical climate stability,edaphic constraints,and habitat heterogeneity)that drive their community *** of coastal woody species show geographically varied patterns,including stochastic arrangements,clustering,and overdispersion of species relative to their traits and phylogenetic *** complexity,water vapor pressure,and soil nutrient availability best explained the gradient in the functional *** deficit,water vapor pressure,and soil organic carbon were the best predictors of variation in phylogenetic *** results support the water-stress conservatism hypothesis on functional and phylogenetic structure,as well as the effect of habitat heterogeneity on functional structure and edaphic constraints on functional and phylogenetic *** effects are associated with increased phenotypic and phylogenetic divergence of woody plant assemblages,which is likely mediated by abiotic filtering and niche opportunities,suggesting a complex pattern of ecological assembly.

关键词： Brazil Completeness Clustering Restinga vegetation Water constraints

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BSN:The First Light Curve Analysis of the Total Eclipse Binary System EL Tuc

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Research in Astronomy and Astrophysics 2024年第10期24卷 66-75页

作者： Elham Sarvari eduardo Fernández Lajús Atila Poro Independent researcher TehranIran Instituto de Astrofísica de La Plata(CCT La Plata-CONICET-UNLP) La PlataArgentina BSN Project &Astronomy Department of the Raderon AI Lab.BurnabyBCCanada

We conducted the first light curve study of the binary star EL Tuc within the Binary Systems of South and North project's *** photometric observations were made using standard multiband BVR_cI_c filters at an observatory in *** presented a new ephemeris for EL Tuc and a linear fit to the O–C diagram,utilizing our extracted times of minima and additional *** employed the PHysics Of Eclipsing BinariEs Python code and the Markov chain Monte Carlo approach for the system's light curve *** target system's light curve solution required a cold starspot on the hotter *** conclude that EL Tuc is a total contact binary system with a low mass ratio of q=0.172±0.002,an orbital inclination of i=83°.74±0°.40,and a fillout factor of f=53.7%±1.6%.We used the P-a relationship and the Gaia Data Release 3 parallax method to determine the absolute parameters of EL Tuc to compare the precision of our *** system was classified as W-type based on the mass and effective temperature of the companion *** positions of the systems were depicted on the M-L,M-R,T-M,and *** relationship between the spectroscopic and photometric mass ratios of binaries was discussed.

关键词： (stars:)binaries:eclipsing stars:individual(EL Tuc) line:identification

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Hyperparameter optimization of YOLOv8 for smoke and wildfire detection:Implications for agricultural and environmental safety

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Artificial Intelligence in Agriculture 2024年第2期12卷 109-126页

作者： Leo Ramos Edmundo Casas eduardo Bendek Cristian Romero Francklin Rivas-Echeverría Kauel Inc. Menlo Park(Silicon Valley)CA 94025USA Computer Vision Center Universitat Autònoma de BarcelonaBellaterra 08193Spain Faculty of Engineering University of DeustoBilbao 48007Spain Jet Propulsion Laboratory NASAPasadenaCA 91109USA

In this study,we extensively evaluated the viability of the state-of-the-art YOLOv8 architecture for object detec-tion tasks,specifically tailored for smoke and wildfire identification with a focus on agricultural and environmen-tal *** available versions of YOLOv8 were initially fine-tuned on a domain-specific dataset that included a variety of scenarios,crucial for comprehensive agricultural ***‘large’version(YOLOv8l)was se-lected for further hyperparameter tuning based on its performance *** model underwent a detailed hyperparameter optimization using the One Factor At a Time(OFAT)methodology,concentrating on key param-eters such as learning rate,batch size,weight decay,epochs,and *** from the OFAT study were used to define search spaces for a subsequent Random Search(RS).The final model derived from RS demon-strated significant improvements over the initial fine-tuned model,increasing overall precision by 1.39%,recall by 1.48%,F1-score by 1.44%,mAP@0.50 by 0.70%,and mAP@0.50:0.95 by 5.09%.We validated the enhanced model's efficacy on a diverse set of real-world images,reflecting various agricultural settings,to confirm its ro-bustness in detecting smoke and *** results underscore the model's reliability and effectiveness in scenar-ios critical to agricultural safety and environmental *** work,representing a significant advancement in the field of fire and smoke detection through machine learning,lays a strong foundation for fu-ture research and solutions aimed at safeguarding agricultural areas and natural environments.

关键词： Agricultural safety Wildfire detection Smoke detection Object detection Computer vision YOL

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How inflammation influences psychiatric disease

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World Journal of Psychiatry 2024年第3期14卷 342-349页

作者： eduardo Ferat-Osorio JoséLuis Maldonado-García Lenin Pavón División de Investigación Clínica de la Coordinación de Investigación en Salud Instituto Mexicano del Seguro SocialMexico City 06720Mexico Departamento de Bioquímica Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoCoyoacán 04510Ciudad de MéxicoMexico Departamento de Inmunología Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalMexico City 11340Mexico Laboratorio de Psicoinmunología Instituto Nacional de Psiquiatría Ramón de la Fuente MuñizMexico City 14370Mexico

Recent studies highlight the strong correlation between infectious diseases and the development of neuropsychiatric *** this editorial,we comment on the article“Anti-infective therapy durations predict psychological stress and laparoscopic surgery quality in pelvic abscess patients”by Zhang et al,published in the recent issue of the World Journal of Psychiatry 2023;13(11):*** discussion highlighted the potential consequences of anxiety,depression,and psychosis,which are all linked to bacterial,fungal,and viral infections,which are relevant to the impact of inflammation on the sequelae in mental health as those we are observing after the coronavirus disease 2019 *** focus specifically on the immune mechanisms triggered by inflammation,the primary contributor to psychiatric ***,pathophysiological mechanisms such as organ damage,post-injury inflammation,and infectioninduced endocrine alterations,including hypocortisolism or autoantibody formation,significantly contribute to the development of chronic low-grade inflammation,promoting the emergence or development of psychiatric alterations in susceptible *** inflammation can have long-term effects on patients,a multidisciplinary treatment plan can avoid complications and debilitating health issues,and it is crucial to recognize and address the mental health implications.

关键词： Inflammation infection Depression Pelvic inflammatory disease Psychiatric complication

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