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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： Ana M.López-Estévez Y.Zhang María Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia María J.Vicent Defang Ouyang Dolores Torres María José Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics Laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses Lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(HANAs)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).HANAs composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed HANAs’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of HANAs technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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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 *** To study the prognostic significance of SIRI and weight loss in metastatic pancreatic *** 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 *** pilot study sought to analyze the association between weight loss and inflammatory status as defined by *** cohort stems from a proof-of-concept pilot study conducted at one of the coordinating *** with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were *** index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation *** study evaluated associations between overall survival(OS),SIRI and weight *** A total of 50 patients were included.66%of these patients were male and the median age was 66 *** sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple *** 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 *** difference was statistically significant(P<0.000).For pat

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

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Refractive outcomes after V4c Toric collamer lens implantation over 1y of follow-up

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1322-1330页

作者： Humberto Carreras-Díaz Josefina Reñones de Abajo María del Rosario Carreras-Díaz Amalia Lorente-Velázquez Vithas Eurocanarias Las Palmas de Gran Canaria 35004Spain University Hospital of Girona Doctor Josep Trueta Gerona 17007Spain Departament of Optometry and Vision Faculty of Optics and OptometryComplutense University of MadridMadrid 28040Spain

AIM:To evaluate refractive outcomes and corneal astigmatism changes after Toric implantable collamer lens with a central port(V4c T-ICL)implantation over 1y of ***:A retrospective study was performed including 50 eyes of 50 patients that underwent V4c T-ICL ***(UDVA)and corrected(CDVA)distance visual acuities,refraction,refractive and corneal astigmatism changes and corneal coupling correction were evaluated preoperatively,1 and 12mo *** analysis was used for astigmatism *** of adjustment(CAdj)was calculated for corneal coupling ***:The mean UDVA achieved was 0.03 logMAR at 1mo and remained unchanged throughout the whole follow-up(P=0.193).At the last visit,84%of the eyes achieved a CDVA of 0.00 logMAR or *** spherical equivalent refraction(SEQ),96%of eyes were ranges of±1.00 D and 84%of them within±0.50 ***,94%of eyes had a remaining refractive cylinder within±1.00 D and 78%of them within±0.50 ***,SEQ and refractive cylinder,remain stable over the postoperative follow-up(P=1.000 and P=0.660,respectively).In terms of surgically induced astigmatism(SIA),no statistically significant differences were found over the follow-up(P=0.102)and under correction was found with a correction index lower than the unit at each visit.A keratometric astigmatism induced of 0.59±0.53(vector mean:0.26×73º)D was reached at the last *** significant changes in terms of corneal astigmatism orientation were reported over post-surgery visits(P=0.129 and P=0.097 at 1 and 12mo respectively).No clinical significance was found for CAdj on with-the-rule *** postoperative complications resulting from the surgery were ***:Refractive outcomes suggest that the V4c T-ICL implantation for correction of myopic astigmatism was satisfactory in terms of effectiveness,safety,and stability during 1y of *** astigmatism induced by the incision around 0.5 D is achieved

关键词： V4c Toric collamer lens corneal astigmatism surgically induced astigmatism corneal coupling

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High-temperature tribological performance of functionally graded Stellite 6/WC metal matrix composite coatings manufactured by laser-directed energy deposition

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Friction 2024年第3期12卷 522-538页

作者： Marta OSTOLAZA Alaitz ZABALA Jon Inaki ARRIZUBIETA Iñigo LLAVORI Nagore OTEGI Aitzol LAMIKIZ Department of Mechanical Engineering University of the Basque Country UPV/EHUPlaza Torres Quevedo 1Bilbo 48013Spain Faculty of Engineering Mechanics and Industrial ProductionMondragon UnibertsitateaLoramendi 4Mondragon 20500Spain

Wear-driven tool failure is one of the main hurdles in the *** issue can be addressed through surface coating with ceramic-reinforced metal matrix ***,the maximum ceramic content is limited by *** this work,the tribological behaviour of the functionally graded WC-ceramic-particlereinforced Stellite 6 coatings is *** that end,the wear resistance at room temperature and 400°C is ***,the tribological analysis is supported by crack sensitivity and hardness evaluation,which is of utmost importance in the processing of composite materials with *** indicate that functionally graded materials can be employed to increase the maximum admissible WC content,hence improving the tribological behaviour,most notably at high ***,a shift from abrasive to oxidative wear is observed in high-temperature wear testing.

关键词： friction coating metal matrix composite functionally graded materials high temperature laserdirected energy deposition

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Pollen analysis reveals the effects of uncovered interactions,pollen-carrying structures,and pollinator sex on the structure of wild bee-plant networks

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Insect Science 2024年第3期31卷 971-988页

作者： Clément Tourbez Carmelo Gómez-Martínez MiguelÁngel Gonzalez-Estévez Amparo Lazaro Mediterranean Institute for Advanced Studies(UIB-CSIC) Global Change Research GroupEsporlesBalearic IslandsSpain Department of Biology Ecology AreaUniversity of the Balearic/slandsPalmaSpain

Pollination networks are increasingly used to model the complexity of interactions between pollinators and flowering plants in *** methods exist to sample these interactions,with direct observations of plant-pollinator contacts in the field being by far the most *** the identification of pollen carried by pollinators allows uncovering interactions and increasing sample sizes,the methods used to build pollen-transport networks are variable and their effect on network structure remains *** understand how interaction sampling influences the structure of networks,we analyzed the pollen found on wild bees from eight communities across Mallorca Island and investigated the differences in pollen loads between bee body parts(scopa ***)and *** then assessed how these differences,as well as the uncovered interactions not detected in the field,influenced the structure of wild bee-plant *** identified a higher quantity and diversity of pollen in the scopa than in the rest of the female body,but these differences did not lead to differences in structure between plant-pollination(excluding scopa pollen)and bee-feeding interaction(including scopa pollen)***,networks built with pollen data were richer in plant species and interactions and showed lower modularity and specialization(H2'),and higher nestedness than visitation networks based on field *** interactions with plants were stronger compared to those of males,although not ***,females were more generalist(low d')and tended to be more central in interaction networks,indicating their more key role structuring pollination networks in comparison to *** study highlights the importance of palynological data to increase the resolution of networks,as well as to understand important ecological questions such as the differences between plant-pollination and bee-feeding interaction networks,and the role of sexes in pollination.

关键词： palynology pollen-transport networks pollination role of bee sexes sampling methodology visitation networks

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Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2233-2240页

作者： Joaquina Martínez-Galán Cristina Jiménez-Luna Isabel Rodriguez Elisabeth Maza Carlos García-Collado Antonio Rodríguez-Fernández Javier Luis López-Hidalgo Octavio Caba Department of Medical Oncology Virgen de las Nieves University HospitalGranada 18014Spain Instituto de Investigación Biosanitaria Ibs.GranadaGranada 18012Spain Institute of Biopathology and Regenerative Medicine(IBIMER) University of GranadaGranada 18016Spain Pharmacogenetics Unit Virgen de las Nieves University HospitalGranada 18014Spain Department of Medicina Nuclear Virgen de las Nieves University HospitalGranada 18014Spain Department of Anatomía Patológica Virgen de las Nieves University HospitalGranada 18014Spain

BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival *** is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor *** describe a case of metastatic PDAC effectively treated with *** SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus *** nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung *** immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor *** patient showed a complete metabolic response that was maintained throughout the *** patient continues to be disease-free at 5.6 years since the start of *** These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic *** our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative *** studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.

关键词： Pancreatic ductal adenocarcinoma Lung cancer Immunotherapy Pembrolizumab Programmed cell death protein-1 Case report

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Developing kNN forest data imputation for Catalonia

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Journal of Forestry Research 2024年第4期35卷 142-155页

作者： Timo Pukkala Núria Aquilué Ariadna Just Jordi Corbera Antoni Trasobares Forest Science and Technology Centre of Catalonia(CTFC) Crta.de St.Llorençde MorunysKm 225280 SolsonaSpain Cartographic and Geological Institute of Catalonia(ICGC) 08038 BarcelonaSpain

The combined use of LiDAR(Light Detection And Ranging)scanning and field inventories can provide spatially continuous wall-to-wall information on forest *** information can be used in many ways in forest mapping,scenario analyses,and forest manage-ment *** study aimed to find the optimal way to obtain continuous forest data for Catalonia when using kNN imputation(kNN stands for“k nearest neighbors”).In this method,data are imputed to a certain location from k field-measured sample plots,which are the most similar to the location in terms of LiDAR metrics and topographic *** multidimensional Euclidean distance was used as the similarity *** study tested two different methods to optimize the distance *** first method optimized,in the first step,the set of LiDAR and topographic variables used in the measure,as well as the transformations of these *** weights of the selected variables were optimized in the second *** other method optimized the variable set as well as their transformations and weights in one single *** two-step method that first finds the variables and their transfor-mations and subsequently optimizes their weights resulted in the best imputation *** the study area,the use of three to five nearest neighbors was *** and latitude turned out to be the most important variables when assessing the similarity of two locations of Catalan forests in the context of kNN data *** optimal distance measure always included both LiDAR metrics and topographic *** study showed that the optimal similarity measure may be different for different ***,it was suggested that kNN data imputation should always be started with the optimization of the measure that is used to select the k nearest neighbors.

关键词： Forest inventory Differential evolution Simulated annealing LiDAR

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Game changer:How Janus kinase inhibitors are reshaping the landscape of ulcerative colitis mana

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World Journal of Gastroenterology 2024年第35期30卷 3942-3953页

作者： Antonio M Caballero-Mateos Guillermo Arturo Cañadas-de la Fuente Department of Gastroenterology and Hepatology San Cecilio University HospitalGranada 18014Spain Department of Nursing Faculty of Health SciencesUniversity of GranadaGranada 18004Spain

Recent advancements in the treatment landscape of ulcerative colitis(UC)have ushered in a new era of possibilities,particularly with the introduction of Janus kinase(JAK)-signal transducer and activator of transcription *** novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory *** approved JAK inhibitors(JAKis),such as tofacitinib,filgotinib,and upadacitinib,clinicians now have powerful tools to modulate immune responses and gene expression,potentially revolutionizing the treatment algorithm for *** trials have demonstrated the efficacy of JAKis in inducing and maintaining remission,presenting viable options for patients who have failed conventional ***-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy,particularly in patients with aggressive disease phenotypes or refractory to biologic *** rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC,offering timely relief for patients with active disease and facilitating personalized treatment *** safety concerns,including cardiovascular risks and infections,ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.

关键词： Ulcerative colitis Janus kinase inhibitors Filgotinib Tofacitinib Upadacitinib

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Sperm function, mitochondrial activity and in vivo fertility are associated to their mitochondrial DNA content in pigs

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1550-1558页

作者： Marc Llavanera Yentel Mateo‑Otero Estel Vinolas‑Vergés Sergi Bonet Marc Yeste Unit of Cell Biology Department of BiologyFaculty of SciencesUniversity of GironaGirona ES‑17003Spain Biotechnology of Animal and Human Reproduction(TechnoSperm) Institute of Food and Agricultural TechnologyUniversity of GironaGirona ES‑17003Spain Catalan Institution for Research and Advanced Studies(ICREA) Barcelona ES‑08010Spain

Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNAc) has been reported to be negatively linked to sperm function and fertility. Yet, the association between mtDNAc and sperm function in livestock remains unexplored. For this reason, this study aimed to shed some light on the link between mtDNAc and sperm function and fertilising potential in pigs. A qPCR method for mtDNAc quantification was optimised for pig sperm, and the association of this parameter with sperm motility, kinematics, mitochondrial activity, and fertility was subsequently *** First, the q PCR method was found to be sensitive and efficient for mtDNAc quantification in pig sperm. By using this technique, mtDNAc was observed to be associated to sperm motility, mitochondrial activity and in vivo, but not in vitro, fertility outcomes. Specifically, sperm with low mtDNAc were seen to exhibit greater motility but decreased mitochondrial activity and intracellular reactive oxygen species. Interestingly, samples with lower mtD-NAc showed higher conception and farrowing rates, but similar in vitro fertilisation rates and embryo development, when compared to those with greater *** These findings enrich our comprehension of the association of mtDNAc with sperm biology, and lay the foundation for future research into employing this parameter as a molecular predictor for sperm function and fer-tility in livestock.

关键词： Fertility Mitochondria Motility mtDNA copy number qPCR Sperm

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Federated Network Intelligence Orchestration for Scalable and Automated FL-Based Anomaly Detection in B5G Networks

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Computers, Materials & Continua 2024年第7期80卷 163-193页

作者： Pablo Fernández Saura José M.Bernabé Murcia Emilio García de la Calera Molina Alejandro Molina Zarca Jorge Bernal Bernabé Antonio F.Skarmeta Gómez Department of Information and Communications Engineering University of MurciaMurcia30100Spain University Center of Defense Spanish Air Force AcademySan Javier30720Spain

The management of network intelligence in Beyond 5G(B5G)networks encompasses the complex challenges of scalability,dynamicity,interoperability,privacy,and *** are essential steps towards achieving the realization of truly ubiquitous Artificial Intelligence(AI)-based analytics,empowering seamless integration across the entire Continuum(Edge,Fog,Core,Cloud).This paper introduces a Federated Network Intelligence Orchestration approach aimed at scalable and automated Federated Learning(FL)-based anomaly detection in *** leveraging a horizontal Federated learning approach based on the FedAvg aggregation algorithm,which employs a deep autoencoder model trained on non-anomalous traffic samples to recognize normal behavior,the systemorchestrates network intelligence to detect and prevent *** into a B5G Zero-touch Service Management(ZSM)aligned Security Framework,the proposal utilizes multi-domain and multi-tenant orchestration to automate and scale the deployment of FL-agents and AI-based anomaly detectors,enhancing reaction capabilities against *** proposed FL architecture can be dynamically deployed across the B5G Continuum,utilizing a hierarchy of Network Intelligence orchestrators for real-time anomaly and security threat *** includes FL enforcement operations for interoperability and extensibility,enabling dynamic deployment,configuration,and reconfiguration on *** validation of the proposed solution was conducted through dynamic orchestration,FL,and real-time anomaly detection processes using a practical test *** of key performance metrics,leveraging the 5G-NIDD dataset,demonstrates the system’s capability for automatic and near real-time handling of anomalies and attacks,including real-time network monitoring and countermeasure implementation for mitigation.

关键词： Federated learning 6G orchestration anomaly detection security policy

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