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Phase Ⅱ trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/CDKN2A

Signal Transduction and Targeted Therapy 2023年第11期8卷 5518-5527页

作者： javier Martin-Broto Jeronimo Martinez-Garcia David SMoura Andres Redondo Antonio Gutierrez Antonio Lopez-Pousa javier Martinez-Trufero Isabel Sevilla Roberto Diaz-Beveridge Maria Pilar Solis-Hernandez Amancio Carnero Marco Perez David Marcilla Jesus Garcia-Foncillas Pablo Romero javier Fernandez-Jara Daniel Lopez-Lopez Ivan Arribas Nadia Hindi Health Research Institute-Fundación Jiménez Díaz University Hospital Universidad Autónoma de Madrid(IIS-FJDUAM)28040MadridSpain Medical Oncology Department Fundación Jimenez Diaz University Hospital28040MadridSpain General de Villalba University Hospital 28400MadridSpain Medical Oncology Department University Hospital Virgen de la Arrixaca30120MurciaSpain Department of Medical Oncology Hospital Universitario La Paz-IdiPAZP.Castellana26128046MadridSpain Hematology Department University Hospital Son Espases07120MallorcaSpain Medical Oncology Department Sant Pau Hospital08025BarcelonaSpain Medical Oncology Department University Hospital Miguel Servet50009ZaragozaSpain Investigación Clínica y Traslacional en Cáncer/Instituto de Investigaciones Biomédicas de Malaga(IBIMA)/Hospitales Universitarios Regional y Virgen de la Victoria de Malaga MalagaSpain Medical Oncology Department Hospital Universitari i Politècnic La Fe46026ValenciaSpain Medical Oncology Department Central University Hospital of Asturias33011OviedoSpain Instituto de Biomedicina de Sevilla(IBiS HUVRCSICUS)41013SevillaSpain Pathology Department Virgen del Rocio University Hospital41013SevillaSpain Radiology Department Fundación Jimenez Diaz University Hospital28040MadridSpain Computational Medicine Platform Fundación progreso y salud(FPS)Hospital Virgen del Rocío41013SevilleSpain Bioinformatics in Rare Diseases(BiER).Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER) FPSHospital Virgen del RocioSevillaSpain Universitat de València-ERI-CES 46010ValenciaSpain

Cyclin-dependent kinases 4 and 6(CDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with CDK4 ***4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK *** investigators of this study found that CDK4 overexpression,while not of CDKN2A,was the most consistent predictive factor for palbociclib efficacy in *** adult-type soft-tissue sarcoma,excluding DD-LPS,or bone sarcoma patients,progressing after at least one systemic line,whose tumors overexpressed CDK4,but not CDKN2A at baseline biopsy,were accrued in this single-arm phase II trial(EudraCT number:2016-004039-19).With the main endpoint of a 6-month PFS rate,40%was considered promising in this *** was administered orally at 125 mg/day for 21 days in 28-day cycles.A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening,archival material(141),and screening,baseline biopsy(95).There were 28(29%)with favorable mRNA profiles from 95 screened patients at *** 23 enrolled patients,21 evaluable,the 6-month PFS rate was 29%(95%CI 9–48),and there were 6 patients out of 21 with a PFS longer than 6 *** median PFS and overall survival were 4.2(95%CI 3.6–4.8)and 12(95%CI 8.7–15.4)months,*** research showed a significant correlation between CDK4 mRNA and protein *** was active in a variety of sarcoma subtypes,selected by CDK4/CDKN2A,and deserves further investigation in the sarcoma context.

关键词： CDKN2A sarcoma CDK4

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Globe penetration during loco-regional anesthesia: prevalence and review of cases

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International Journal of Ophthalmology(English edition) 2022年第10期15卷 1683-1690页

作者： Alba Gómez-Benlloch Maximiliano Olivera Jeroni Nadal Gemma Julio javier Elizalde Centro de Oftalmología Barraquer Barcelona 08021Spain Institut Universitari Barraquer Universitat Autònoma de BarcelonaBarcelona 08021Spain School of Medicine Universitat Internacional de CatalunyaBarcelona 08017Spain

AIM: To describe prevalence and different clinical signs and management of cases with penetrating eye injuries during loco-regional anesthesia for ophthalmic surgery. METHODS: A retrospective review of clinical records was carried out, identifying cases of globe penetration secondary to peribulbar anesthesia injection during 5 y activity in Centro de Oftalmología Barraquer. RESULTS: A total of 17 460 needle-based ocular anesthesia procedures were performed in our centre and 4 cases of globe penetration were recorded with an estimated prevalence of 0.024%. Globe penetrations were always detected in the first 24 h after surgery. Vitreous haemorrhage was found in all the cases. Two eyes presented retinal detachment and two eyes choroidal detachment(CD). The initial surgical approach was performed within the first 48 h. Silicone oil was used as tamponade in three eyes and the fourth case remained only with air. Detachments were solved successfully in all the cases. Functional results varied among cases, depending on ocular remarkable antecedent and globe penetration with or without retinal or ***: Prevalence of globe penetration during loco-regional anesthesia is low in our centre. Physicians should consider the possibility of globe penetration in eyes with postoperative atypical appearance after locoregional anesthesia. Immediate B-scan ultrasonography is recommended in suspicious cases with a dense vitreous haemorrhage. An early vitrectomy surgery in conjunction with laser or cryotherapy at the penetration sites is essential for good anatomical and functional results.

关键词： loco-regional anesthesia peribulbar retrobulbar globe penetration retina

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Periprocedural management of hemostatic alterations in patients with cirrhosis and vascular liver disorders: a step forward of the American Association for the Study of Liver Diseases

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Hepatobiliary Surgery and Nutrition 2023年第1期12卷 105-109页

作者： Jose Ignacio Fortea Angela Puente javier Crespo Emilio Fabrega Gastroenterology and Hepatology Department Clinical and Translational Research in Digestive DiseasesValdecilla Research Institute(IDIVAL)Marques de Valdecilla University HospitalSantanderSpain

“Time flies over us,but leaves its shadow behind”(Nathaniel Hawthorne,1860,The Marble Faun).The shadow that separates the latest guidance on vascular liver disorders of the American Association for the Study of Liver Diseases(AASLD)from its former counterpart is 12 years long(1,2).Along the course,several guidelines from different societies have been published on this topic(3-7).As acknowledged in the preamble,the lack of high-quality evidence in the field led the AASLD to commission a guidance from an expert panel based on formal review and analysis of the *** thus differs from other guidelines that perform systematic reviews with explicit methods of searching,selection,and rating the quality of evidence and,if appropriate,meta-analysis on certain clinical questions(2).

关键词： Portal hypertension cirrhosis vascular liver disorders hemostasis bleeding thrombosis

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Turning carbon dots into selenium bearing nanoplatforms with in vitro GPx-like activity and pro-oxidant activity

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Nano Research 2023年第5期16卷 7784-7791页

作者： Laura Perez-Garrido Mariano Ortega-Muñoz Fernando Hernandez-Mateo F.javier Lopez-Jaramillo Francisco Santoyo-Gonzalez Department of Organic Chemistry Biotechnology InstituteSchool of SciencesCampus Fuentenueva snUniversity of Granada18071-GranadaSpain

Selenium(Se)has been defined as the“Janus element”,with one face showing antioxidant activity and the other pro-oxidant *** biological effect of Se depends on both dose and *** nanoparticles are attracting major interest,although their large-scale preparation for biomedical applications is not *** hypothesize that acid anhydride-coated carbon dots(AACD)are an attractive platform for preparing nanoparticles containing chemically defined *** reaction of AA-CD with 3-selenocyanatopropan-1-amine yields carbon dots bearing selenocyanate and carboxylate groups(CD-SeCN)that allow for tuning the ***-SeCN has a Se content of 0.36μmol per mg of nanoparticles,they show the typical photoluminescence of carbon *** selenocyanate groups(SeCN)exhibited glutathione peroxidase-like activity and *** show that antioxidant behavior differs between normal and tumor cells,the evaluation on HEK293 and A549 cells reveals that the toxicity of CD-SeCN depends on dose,time,intracellular glutathione(GSH)*** toxicity of CD-SeCN decreases with the time of incubation and the cell death mechanism switches from necrosis to apoptosis,indicating that CD-SeCN is ***,high levels of intracellular GSH exert a protective *** results support a pharmacological potential in cancers with low levels of intracellular *** use of AA-CD as nanoplatforms is a general strategy that paves the way for the engineering of advanced nanosystems.

关键词： selenium nanoparticles carbon dots glutathione peroxidase-like activity Janus element nanomedicine

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Viability,behavior,and color expression in the offspring of matings between common wall lizard Podarcis muralis color morphs

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Current Zoology 2022年第1期68卷 41-55页

作者： javier ABALOS Guillem PEREZ I DE LANUZA Alicia BARTOLOME Fabien AUBRET Tobias ULLER Enrique FONT Ethology Lab Instituto Cavanilles de Biodiversidad y Biologı´a EvolutivaUniversitat de ValenciaValenciaSpain CIBIO/InBIO Centro de Investigacao em Biodiversidade e Recursos Geneticos da Universidade do PortoPortoPortugal SETE Station d’Ecologie Theorique et ExperimentaleUPR2001Centre National de la Recherche ScientifiqueParisFrance Department of Biology Lund UniversityLundSweden

Color polymorphisms are widely studied to identify the mechanisms responsible for the origin and maintenance of phenotypic variability in *** of the mechanisms of balancing selection currently thought to explain the long-term persistence of polymorphisms are the evolution of alternative phenotypic optima through correlational selection on suites of traits including color and *** of these mechanisms can generate differences in offspring viability and fitness arising from different morph ***,we examined the effect of parental morph combination on fertilization success,embryonic viability,newborn quality,antipredator,and foraging behavior,as well as inter-annual survival by conducting controlled matings in a polymorphic lacertid Podarcis muralis,where color morphs are frequently assumed to reflect alternative phenotypic optima(e.g.,alternative reproductive strategies).Juveniles were kept in outdoor tubs for a year in order to study inter-annual growth,survival,and morph *** agreement with a previous genome-wide association analysis,morph frequencies in the year-old juveniles matched the frequencies expected if orange and yellow expressions depended on recessive homozygosity at 2 separate *** findings also agree with previous literature reporting higher reproductive output of heavy females and the higher overall viability of heavy newborn lizards,but we found no evidence for the existence of alternative breeding investment strategies in female morphs,or morphcombination effects on offspring viability and *** conclude that inter-morph breeding remains entirely viable and genetic incompatibilities are of little significance for the maintenance of discrete color morphs in *** from the Pyrenees.

关键词： alternative breeding strategies color polymorphism controlled matings lizard behavior morph ontogeny newborn viability

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Interaction network between frugivorous birds and zoochorous plants in cloud forest riparian strips immersed in anthropic landscapes

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Avian Research 2022年第3期13卷 311-320页

作者： Omar A.Hernández-Dávila javier Laborde Vinicio J.Sosa Cecilia Díaz-Castelazo Instituto de Ecología A.C.Red de Ecología FunctionalCarretera Antigua a CoatepecNo.351El HayaXalapaVeracruz C.P91073Mexico Instituto de Ecología A.C.Red de Interacciones Multitr oficasCarretera Antigua a CoatepecNo.351El HayaXalapaVer.C.P91073Mexico

Worldwide,tropical montane cloud forest is one of the most important and biodiverse ecosystems;however,it is also one of those most threatened by anthropic *** activities lead to a fragmented,deforested landscape with narrow riparian forest strips immersed in an agricultural matrix dominated by ***,we characterize the interaction network between frugivorous birds and zoochorous plants in riparian strips of cloud forest in deforested landscapes of Central Veracruz,*** characterize the network of this mutualistic interaction,we estimated network-and species-level metrics using the Bipartite R ***,modularity and robustness were used to describe network *** measures of degree,closeness,betweenness centrality and their relative contribution to nestedness were used to determine the importance of each bird/plant species to the network’s *** interaction network has 24 species of birds and 30 species of plants,with low connectance(0.11),low nestedness(11.53),and intermediate but not significant modularity(0.49).The bird species most important to network stability were Chlorospingus flavopectus,Myadestes occidentalis,and Catharus *** most important plants were Conostegia xalapensis,***,and Rubus *** robustness varied from 0.36 to 0.86 and its stability is compromised when species of birds or plants with the highest values of centrality are removed,with plant removal more *** strips of cloud forest crossing deforested areas maintain a relatively rich set of birds that disperse the seeds of many forest plants,thus they are crucial to the preservation of this mutualistic network in anthropic *** stability is severely undermined by the loss of any of the few species—whether birds or plants—with high centrality *** most important plants for this stability are pioneer tree and shrub species that provide food for several bird species,and they

关键词： Frugivory Keystone species Riparian corridors Seed dispersal Vegetation corridors

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Are we ready for telemonitoring inflammatory bowel disease?A review of advances,enablers,and barriers

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World Journal of Gastroenterology 2023年第7期29卷 1139-1156页

作者： javier Del Hoyo Mónica Millán Alejandro Garrido-Marín Mariam Aguas Department of Gastroenterology La Fe University and Polytechnic HospitalValencia 46026Spain Department of Surgery La Fe University and Polytechnic HospitalValencia 46026Spain Health Research Institute La Fe La Fe University and Polytechnic HospitalValencia 46026Spain

This review summarizes the evidence about telemonitoring in patients with inflammatory bowel disease(IBD). To give an overview of the advances performed, as well as the enablers and barriers which favoured/hindered telemonitoring implementation. We performed a literature search in Pub Med, EMBASE, MEDLINE, Cochrane Database, Web of Science and Conference Proceedings. Titles and abstracts published up to September 2022 were screened for a set of inclusion criteria: telemonitoring intervention, IBD as the main disease, and a primary study performed. Ninety-seven reports were selected for full review. Finally, 20 were included for data extraction and critical appraisal. Most studies used telemonitoring combined with tele-education, and programs evolved from home telemanagement systems towards web portals through m Health applications. Web systems demonstrated patients’ acceptance, improvement in quality of life, disease activity and knowledge, with a good cost-effectiveness profile in the short-term. Initially, telemonitoring was almost restricted to ulcerative colitis, but new patient reported outcome measures, home-based tests and mobile devices favoured its expansion to different patients’ categories. However, technological and knowledge advances led to legal, ethical, economical and logistic issues. Standardization of remote healthcare is necessary, to improve the interoperability of systems as well as to address liability concerns and users’ preferences. Telemonitoring IBD is well accepted and improves clinical outcomes at a lower cost in the short-term. Funders, policymakers, providers, and patients need to align their interests to overcome the emerging barriers for its full implementation.

关键词： Inflammatory bowel disease Telemedicine Telemonitoring Information and communication technology Crohn´s disease Ulcerative colitis

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Monitoring gully erosion in the European Union: A novel approach based on the Land Use/Cover Area frame survey (LUCAS)

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International Soil and Water Conservation Research 2022年第1期10卷 17-28页

作者： Pasquale Borrelli Jean Poesen Matthias Vanmaercke Cristiano Ballabio javier Hervas Michael Maerker Simone Scarpa Panos Panagos Department of Earth and Environmental Sciences University of PaviaVia Ferrata127100PaviaItaly Department of Biological Environment Kangwon National UniversityChuncheon24341Republic of Korea Department of Earth and Environmental Sciences KU LeuvenBelgium Faculty of Earth Sciences and Spatial Management Maria-Curie Sklodowska UniversityLublinPoland Departement de Geographie Universite de LiegeLiegeBelgium European Commission Joint Research Centre(JRC)IspraItaly

The European Commission's Thematic Strategy for Soil Protection(COM(2012)46)identified soil erosion as an important threat to European Union's(EU)soil *** erosion is an important but hitherto poorly understood component of this *** we present the results of an unprecedented attempt to monitor the occurrence of gully erosion across the EU and *** integrate a soil erosion module into the 2018 LUCAS Topsoil Survey,which was conducted to monitor the soil health status across the EU and to support actions to prevent soil *** discuss and explore opportunities to further improve this *** 2018 LUCAS Topsoil Survey consisted of soil sampling(0-20 cm depth)and erosion observations conducted in ca.10%(n=24,759)of the 238,077 Land Use/Cover Area frame Survey(LUCAS)2018 in-field survey *** erosion channels were detected for ca.1%(211 sites)of the visited LUCAS Topsoil ***(false positives,2.5%)and omission errors(false negatives,5.6%)were found to be low and at a level that could not compromise the representativeness of the gully erosion ***,the findings indicate that the tested 2018 LUCAS Topsoil in-field gully erosion monitoring system is effective for detecting the incidence of gully *** morphogenesis of the mapped gullies suggests that the approach is an effective tool to map permanent gullies,whereas it appears less effective to detect short-lived forms like ephemeral *** patterns emerging from the LUCAS Topsoil field observations provide new insights on typical gully formation sites across the EU and *** can help to design further targeted research *** extension of this approach to all LUCAS sites of 2022 would significantly enhance our understanding of the geographical distribution of gully erosion processes across the *** every three years,LUCAS soil erosion surveys would contribute to assess the state of gully erosion in the EU over *** will also enable m

关键词： Soil erosion Soil Concentrated flow erosion Google earth Earth observations

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Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients:A systematic review and meta-analysis of randomized controlled trials

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Journal of Sport and Health Science 2023年第2期12卷 147-157页

作者： Antonio García-Hermoso Robinson Ramírez-Vélez javier Díez Arantxa González Mikel Izquierdo Navarrabiomed Public University of Navarra(UPNA)Health Research Institute of Navarra(IdiSNA)University Hospital of NavarraPamplona 310008Spain CIBER of Frailty and Healthy Aging(CIBERFES) Carlos Ⅲ Institute of HealthMadrid 28029Spain Institute for Health Research of Navarra(IDISNA) Pamplona 31008Spain Program of Cardiovascular Diseases Center for Applied Medical ResearchUniversity of NavarraPamplona 31008Spain Centre for Biomedical Research in Cardiovascular Disease Network Carlos Ⅲ Institute of HealthMadrid 28029Spain Departments of Nephrology and Cardiology University of Navarra ClinicPamplona 31008Spain

Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise ***:A systematic search for relevant studies was performed in 3 *** controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and ***:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to *** exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per ***:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

关键词： Adipokines Exercise training Hepatokines Myokines

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All-fiber ellipsometer for nanoscale dielectric coatings

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Opto-Electronic Advances 2023年第10期6卷 31-43页

作者： Jose javier Imas Ignacio R.Matías Ignacio Del Villar Aritz Ozcáriz Carlos Ruiz Zamarreño Jacques Albert Department of Electrical Electronic and Communications EngineeringPublic University of NavarrePamplona 31006Spain Institute of Smart Cities Public University of NavarrePamplona 31006Spain Department of Electronics Carleton UniversityOttawa(Ontario)K1S 5B6Canada.

Multiple mode resonance shifts in tilted fiber Bragg gratings(TFBGs)are used to simultaneously measure the thickness and the refractive index of TiO_(2) thin films formed by Atomic Layer Deposition(ALD)on optical *** is achieved by comparing the experimental wavelength shifts of 8 TFBG resonances during the deposition process with simulated shifts from a range of thicknesses(T)and values of the real part of the refractive index(n).The minimization of an error function computed for each(n,T)pair then provides a solution for the thickness and refractive index of the deposited film and,a posteriori,to verify the deposition rate throughout the process from the time evolution of the wavelength shift *** of the results were carried out with a conventional ellipsometer on flat witness samples deposited simultaneously with the fiber and with scanning electron measurements on cut pieces of the fiber *** final values obtained by the TFBG(n=2.25,final thickness of 185 nm)were both within 4%of the validation *** approach provides a method to measure the formation of nanoscale dielectric coatings on fibers in situ for applications that require precise thicknesses and refractive indices,such as the optical fiber sensor ***,the TFBG can also be used as a process monitor for deposition on other substrates for deposition methods that produce uniform coatings on dissimilar shaped substrates,such as ALD.

关键词： tilted fiber Bragg grating(TFBG) mode transition ellipsometer

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