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Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern

Journal of Molecular Cell Biology 2024年第3期16卷 9-23页

作者： Ilaria Frasson Linda Diamante Manuela Zangrossi Elena Carbognin Anna Dalla Pietà Alessandro Penna Antonio Rosato Ranieri Verin Filippo Torrigiani Cristiano Salata Marìa Paula Dizanzo Lorenzo Vaccaro Davide Cacchiarelli sara n.richter Marco Montagner Graziano Martello Department of Molecular Medicine University of PaduaPadua 35121Italy Department of Biology Armenise/Harvard Pluripotent Stem Cell Biology LaboratoryUniversity of PaduaPadua 35131Italy Department of Surgery Oncology and GastroenterologyUniversity of PaduaPadua 35128Italy Veneto Institute of Oncology IOV-IRCCS Padua 35128Italy Department of Comparative Biomedicine and Food Science University of PaduaPadua 35020Italy Telethon Institute of Genetics and Medicine(TIGEM) Armenise/Harvard Laboratory of Integrative GenomicsPozzuoli 80078Italy Department of Translational Medicine University of Naples Federico IINaples 80138Italy School for Advanced Studies Genomics and Experimental Medicine ProgramUniversity of Naples Federico IINaples 80138Italy Microbiology and Virology Unit Padua University HospitalPadua 35128Italy

The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral *** host dependency factors,*** proteins required for viral replication,would help prevent the development of ***,it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host *** this end,we compared three variants of concern and found that the host transcriptional response was conserved,differing only in kinetics and *** regularly interspaced short palindromic repeats screening identified host genes required for each variant during *** of the genes were shared by multiple *** validated our hits with small molecules and repurposed the US Food and Drug Administration-approved *** the drugs were highly active against all the tested variants,including new variants that emerged during the study(Delta and Omicron).Mechanistically,we identified reactive oxygen species production as a key step in early viral *** such as n-acetyl cysteine(nAC)were effective against all the variants in both human lung cells and a humanized mouse *** study supports the use of available antioxidant drugs,such as nAC,as a general and effective anti-COVID-19 approach.

关键词： SARS-CoV-2 variants of concern host dependency factors antivirals n-acetyl cysteine

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Previously undiagnosed Morgagni hernia with bowel perforation detected during repeat screening colonoscopy: A case report

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World Journal of Clinical Cases 2024年第14期12卷 2389-2395页

作者： Said Al Alawi Alan n Barkun sara najmeh Division of Gastroenterology McGill UniversityMontrealQC H4A 3J1Canada Division of Thoracic surgery McGill UniversityMontrealQC H4A 3J1Canada

BACKGROUnD Morgagni hernia(MH)is a form of congenital diaphragmatic hernia(CDH)characterized by an incomplete formation of diaphragm,resulting in the protru-sion of abdominal organs into the thoracic *** estimated incidence of CDH is between 1 in 2000 and 1 in 5000 live births,although the true incidence is *** typically presents in childhood and can be diagnosed either pre-natally or ***,it can also be asymptomatic and carry the risk of developing into a life-threatening condition in *** SUMMARY A 76-year-old female with no history of prior abdominal surgeries presented for an elective colonoscopy for polyp *** the procedure,when approaching the hepatic flexure,the scope could not be advanced further despite multiple *** patient experienced mild abdominal discomfort,leading to the abortion of the *** in the recovery area,she developed increa-sing abdominal pains and *** abdominal imaging revealed her-niation of the proximal transverse colon through a MH into the chest with evi-dence of *** patient underwent laparoscopic urgent colonic resection and primary hernia repair and was discharged uneventfully 2 d *** A MH is a rare condition in adults that can present as a life-threatening compli-cation of colonoscopy,even in patients with a history of uneventful *** case highlights the importance of considering congenital and internal hernias when faced with sudden and unexplained difficulties during *** there is a suspicion of MH,the endoscopist should halt the procedure and immediately obtain abdominal imaging to confirm the diagnosis.

关键词： Bowel perforation Colonoscopy Adverse event Congenital diaphragmatic

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The importance of post-COVID condition phenotypes characterization to decipher the mechanisms underlying this post-viral syndrome

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World Journal of Pediatrics 2024年第6期20卷 633-634页

作者： Jon Izquierdo-Pujol sara Moron-Lopez IrsiCaixa and Institute for Health Science Research Germans Trias i Pujol(IGTP) Can Ruti CampusBadalonaSpain Biomedicine doctoral programme Faculty of BiologyUniversity of BarcelonaBarcelonaSpain CIBERInFEC MadridSpain

The coronavirus disease-19(COVID-19)outbreak,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),was declared a global pandemic in March *** has affected over 700 million people worldwide and resulted in almost 7 million deaths,equating to a 1%mortality *** present,the majority of COVID-19 cases are either asymptomatic or mild,typically resolving within two ***,between 1%and 10%of COVID-19 survivors do not fully recover and experience a post-viral syndrome referred to as"long COVID","post-acute COVID-19 syndrome"(PASC),or"post-COVID condition"(PCC).This post-viral syndrome affects both adult and pediatric ***,most of the studies published to date evaluate the adult population,leaving a gap in our understanding of its impact on children and adolescents.

关键词： acute mortality respiratory

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Development and characterization of 3D-printed electroconductive pHEMA-co-MAA nP-laden hydrogels for tissue engineering

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Bio-Design and Manufacturing 2024年第3期7卷 262-276页

作者： sara De nitto Aleksandra Serafin Alexandra Karadimou Achim Schmalenberger John J.EMulvihill Maurice n.Collins DIBRIS Polytechnic Inter-School Section University of Genoa16126 GenoaItaly School of Engineering Bernal InstituteUniversity of LimerickLimerick V94 T9PXIreland School of natural Sciences Department of Biological SciencesUniversity of LimerickLimerick V94 T9PXIreland Health Research Institute University of LimerickLimerick V94 T9PXIreland AMBER University of LimerickLimerick V94 T9PXIreland

Tissue engineering(TE)continues to be widely explored as a potential solution to meet critical clinical needs for diseased tissue replacement and tissue *** this study,we developed a poly(2-hydroxyethyl methacrylate-co-methacrylic acid)(pHEMA-co-MAA)based hydrogel loaded with newly synthesized conductive poly(3,4-ethylene-dioxythiophene)(PEDOT)and polypyrrole(PPy)nanoparticles(nPs),and subsequently processed these hydrogels into tissue engineered constructs via three-dimensional(3D)*** presence of the nPs was critical as they altered the rheological properties during ***,all samples exhibited suitable shear thinning properties,allowing for the development of an optimized processing window for 3D *** were 3D printed into pre-determined disk-shaped configurations of 2 and 10 mm in height and diameter,*** observed that the nPs disrupted the gel crosslinking efficiencies,leading to shorter degradation times and compressive mechanical properties ranging between 450 and 550 *** conductivity of the printed hydrogels increased along with the nP concentration to(5.10±0.37)×10^(−7)S/*** vitro studies with cortical astrocyte cell cultures demonstrated that exposure to the pHEMA-co-MAA nP hydrogels yielded high cellular viability and proliferation ***,hydrogel antimicrobial studies with staphylococcus epidermidis bacteria revealed that the developed hydrogels affected bacterial *** together,these materials show promise for various TE strategies.

关键词： Conductive nanoparticles Hydroxyethyl methacrylate(HEMA) Ultraviolet(UV)polymerization 3D printing

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SHARE-EnV:A Data Set to Advance Our Knowledge of the Environment−Wellbeing Relationship

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Environment & Health 2024年第2期2卷 95-104页

作者： Catarina Midões Enrica De Cian Giacomo Pasini sara Pesenti Malcolm n.Mistry Department of Economics Ca’Foscari University of Venice30121 VeneziaItaly Institute of Environmental Science and Technology of Universitat Autònoma de Barcelona 08193 Cerdanyola del VallèsBarcelonaSpain European Central Bank 60314 Frankfurt am MainGermany Environment and Health Modelling(EHM)Lab Department of Public HealthEnvironments and SocietyLondon School of Hygiene and Tropical Medicine(LSHTM)London WC1E 7HTUnited Kingdom

Climate change interacts with other environmental stressors and vulnerability *** places and,owing to socioeconomic conditions,some people,are far more at *** data behind current assessments of the environment−wellbeing nexus is coarse and regionally aggregated,when considering multiple regions/groups;or,when granular,comes from ad hoc samples with few *** assess the impacts of climate change,we require data that are granular and comprehensive,both in the variables and population *** build a publicly accessible data set,the SHARE-EnV data set,which fulfills these *** expand on EU representative,individual-level,longitudinal data(the SHARE survey),with environmental exposure information about temperature,radiation,precipitation,pollution,and flood *** illustrate through four simplified multilevel linear regressions,cross-sectional and longitudinal,how full-fledged studies can use SHARE-EnV to contribute to the *** studies would help assess climate impacts and estimate the effectiveness and fairness of several climate adaptation *** surveys can be expanded with environmental information to unlock different research avenues.

关键词： climate change risk environmental impacts climate adaptation population health longitudinal data

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Stabilisation of estuarine sediments with an alkali-activated cement for deep soil mixing applications

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第4期16卷 1398-1410页

作者： Claver Pinheiro sara Rios António Viana da Fonseca nuno Cristelo Centre of Physics of Minho and Porto Universities (CF-UM-UP) Azurém CampusUniversity of MinhoGuimarães4800-058Portugal COnSTRUCT-GEO Faculty of EngineeringUniversity of PortoRua Dr.Roberto FriasPortos/n 4200-465Portugal CQ-VR School of Science and TechnologyUniversity of Trás-os-Montes e Alto DouroVila Real5000-801Portugal

In this work,an alternative alkali-activated cement(AAC)made of ladle slag precursor mixed with sodium hydroxide and sodium silicate has been developed to enhance the bearing capacity of estuarine soils in coastal conditions via deep soil mixing(DSM).The AAC was optimized to use a low reactivity precursor(ladle slag)and to deal with a contaminated high-water content natural sediment cured under *** material performance was analysed by comparison to a mixture made with Portland cement and cured in the same *** and unconfined compressive strength tests as well as seismic waves measurements after 3-,7-,14-and 28-d curing were performed to obtain a relationship between elastic stiffness and strength with curing time for both ***,the AAC mix demonstrated superior strength results,exhibiting almost double flexural and compressive strengths after 28 d compared to the Portland cement *** AAC mix also showed a higher rate of stiffness increase than the Portland cement mix,which has a higher initial stiffness at young ages but lower stiffness *** analysis confirmed that the proposed AAC could effectively immobilise any contaminants from soil or *** effect of curing under stress was analysed in triaxial compression tests and found to be insignificant,indicating that laboratory data obtained without stress curing can represent the material's behaviour in a DSM column,which will cure under the weight of the column.

关键词： Alkaline-activation Steel slag Submerged curing Seismic wave measurements Leachate analysis Curing under stress

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Leveraging Robust Artificial Intelligence for Mechatronic Product Development—A Literature Review

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International Journal of Intelligence Science 2024年第1期14卷 1-21页

作者： Alexander nüßgen René Degen Marcus Irmer Fabian.richter Cecilia Boström Margot Ruschitzka CAD CAM Center Cologne Institute of Automotive Engineering Cologne (IFK) Faculty of Automotive Systems and Production Cologne University of Applied Science Cologne Germany Division of Electricity Department of Electrical Engineering Uppsala University Uppsala Sweden

Mechatronic product development is a complex and multidisciplinary field that encompasses various domains, including, among others, mechanical engineering, electrical engineering, control theory and software engineering. The integration of artificial intelligence technologies is revolutionizing this domain, offering opportunities to enhance design processes, optimize performance, and leverage vast amounts of knowledge. However, human expertise remains essential in contextualizing information, considering trade-offs, and ensuring ethical and societal implications are taken into account. This paper therefore explores the existing literature regarding the application of artificial intelligence as a comprehensive database, decision support system, and modeling tool in mechatronic product development. It analyzes the benefits of artificial intelligence in enabling domain linking, replacing human expert knowledge, improving prediction quality, and enhancing intelligent control systems. For this purpose, a consideration of the V-cycle takes place, a standard in mechatronic product development. Along this, an initial assessment of the AI potential is shown and important categories of AI support are formed. This is followed by an examination of the literature with regard to these aspects. As a result, the integration of artificial intelligence in mechatronic product development opens new possibilities and transforms the way innovative mechatronic systems are conceived, designed, and deployed. However, the approaches are only taking place selectively, and a holistic view of the development processes and the potential for robust and context-sensitive artificial intelligence along them is still needed.

关键词： Artificial Intelligence Mechatronic Product Development Knowledge Management Data Analysis Optimization Human Experts Decision-Making Processes V-Cycle

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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 SIRIng 21 patients with>5%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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Lesser kestrels of the same colony do not overwinter together

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Current Zoology 2024年第4期70卷 505-512页

作者： Jorge Garcia-Macia Munir Chaouni sara Morollon Javier Bustamante Lina Lopez-Ricaurte Juan Martinez-Dalmau Beatriz Rodriguez-Moreno Vicente Urios Grupo de Investigacion Zoologia de Vertebrados Universidad de AlicanteApdo.99E-03080 AlicanteSpain Department of Wetland Ecology Estacion Biologica de Donana(CSIC)C/Americo Vespucio 2641092SevillaSpain GREFA C/MontedelPilarS/NE-28220MajadahondaMadridSpain

Migratory connectivity describes the linkage between breeding and nonbreeding sites,having major ecological implications in birds:1 season influence the success of an individual or a population in the following *** studies on migratory connectivity have used large-scale approaches,often considering regional populations,but fine-scale studies are also necessary to understand colony *** lesser kestrel Falco naumanni,an insectivorous migratory raptor which form colonies during the breeding period,was considered to have strong connectivity based on regional ***,no small-scale studies on migratory connectivity have been ***,we GPS(Global Positioning System)-tracked 40 adult lesser kestrels from 15 different Spanish breeding colonies,estimating the overlap index between home ranges and the distance between their *** was found that lesser kestrels from the same breeding colony placed their nonbreeding areas at 347±281 km(mean±standard deviation)away from each other(range=23-990),and their home ranges over-lapped by 38.4±23.6%.no differences between intra-colony and inter-colony metrics were found,which suggests that lesser kestrels from the same breeding cluster do not overwinter together,but they spread out and mixed independently of the colony belonging throughout the nonbreeding range of the ***,this study highlights the importance of performing connectivity studies using fine-scale approaches.

关键词： Falco naumanni GPS telemetry migratory connectivity nonbreeding raptor spatial ecology wintering.

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