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Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage:Comparative analytical study of physicochemical quality attributes

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Journal of Pharmaceutical Analysis 2020年第6期10卷 532-545页

作者： Natalia Navas Jesús Hermosilla Anabel Torrente-lopez jose Hernandez-Jimenez jose Cabeza Raquel Perez-Roblesa Antonio Salmeron-garcía Department of Analytical Chemistry Science Faculty/Biomedical Research Institute ibs.GranadaUniversity of GranadaGranadaE-18071Spain UGC Farmacia Hospitalaria Biomedical Research Institute ibs.Granada.Hospital Universitario San Cecilio de GranadaGranadaE-18012Spain

COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many *** studies suggest that cytokine storms(interleukins)may play an important role in severe cases of *** key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality ***(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS *** investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical *** has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug ***,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of *** is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.

关键词： COVID-19 Tocilizumab Critical quality attributes IV and SC medicines

An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair

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Regenerative Biomaterials 2019年第6期6卷 335-347页

作者： Filippo Cipriani Blanca Arino Palao Israel Gonzalez de Torre Aurelio Vega Castrillo Hector jose Aguado Hernandez Matilde Alonso Rodrigo Angel jose Alvarez Barcia Ana Sanchez Veronica garcıa Diaz Monica lopez Pena jose Carlos Rodriguez-Cabello Technical Proteins Nanobiotechnology S.L. Paseo Belen 9AValladolid 47011Spain Departamento de traumatologıa Hospital Clınico de ValladolidAv.Ramon y Cajal 3Valladolid 47003Spain Bioforge University of Valladolid CIBER-BBNPaseo de Belen 19Valladolid 47011Spain SIBA-UVA:servicio investigacion y bienestar animal University of ValladolidC/Plaza de Santa Cruz 8Valladolid 47002Spain Instituto de Biologıa y Genetica Molecular(IBGM) Universidad de Valladolid y CSICCalle Sanz y Fores 3Valladolid 47003Spain Facultad de veterinaria Campus UniversitarioAvda.Carballo Calero s/nLugo 27002Spain

The aim of this study was to evaluate injectable,in situ cross-linkable elastin-like recombinamers(ELRs)for osteochondral *** the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells(rMSCs)were tested for the regeneration of critical subchondral defects in 10 New Zealand ***,cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4months for histological and gross evaluation of features of biomaterial performance,including integration,cellular infiltration,surrounding matrix quality and the new matrix in the *** both approaches helped cartilage regeneration,the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration,whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline *** conclusion,the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.

关键词： biopolymer animal test cartilage bone

Nonlinear parabolic predator-prey coupled system with convection

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International Journal of Biomathematics 2021年第2期14卷 83-118页

作者： jose Luis Diaz Palencia Mariano Fernandez lopez University Foundation San Pablo CEU Spain

The aim of this work is to provide a formulation of two related nonlinear diffusive convective models in the form of coupled reaction-absorption ***,the postulated models are studied with an analytical *** on,numerical evidences are considered to account for a precise *** problem(P)analyzed is of the form:ut=δΔu+c⋅∇u+v^(n),vt=ϵΔv+c⋅∇v−um,n,m∈(0,1),u_(0)(x),v_(0)(x)>0∈L^(1)_(loc)(RN)∩L^(∞)(R^(N)).(0.1)Afterwards,a related problem P_(T)is studied:ut=δΔu+c⋅∇u−v^(n)(u−d),vt=ϵΔv+c⋅∇v−u^(m)v,n,m∈(0,1),u_(0)(x),v_(0)(x)>0∈L^(1)_(loc)(R^(N))∩L^(∞)(R^(N)).(0.2)The principal aspects for analysis are related to the existence and the derivation of particular solutions to reproduce the dynamic of the interacting *** the problem PT,we make use of the TW approach to study existence of solutions and precise evolution of *** that the term predator is used to refer to an invasive behavior,while the term prey is used for the invaded species.

关键词： Nonlinearity reaction absorption coupled system diffusion,traveling waves

Land-use change and windstorms legacies drove the recolonization dynamics of laurel forests in Tenerife, Canary islands

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Forest Ecosystems 2023年第1期10卷 113-124页

作者： Vicente Rozas Maria A.garcia-lopez jose M.Olano Gabriel Sanguesa-Barreda Miguel garcia-Hidalgo Susana Gomez-Gonzalez Roberto lopez-Rubio jose M.Fernandez-Palacios Ignacio garcia-Gonzalez Laura Lozano-lopez Paula garcia-Gonzalez Ana I.garcia-Cervigon EiFAB-iuFOR Universidad de ValladolidCampus Duques de Soria42004SoriaSpain Departamento de Biologia-IVAGRO Universidad de CadizCampus Rio San Pedro11510Puerto RealSpain Center for Climate and Resilience Research(CR)2 Blanco Encalada 20028370449SantiagoChile Area de Biodiversidad y Conservacion Universidad Rey Juan Carlosc/Tulipan s/n28933MostolesSpain Grupo de Ecologia y Biogeografia Insular Universidad de La Laguna38206La LagunaTenerifeSpain BIOAPLIC Departamento de BotanicaEscola Politecnica Superior de EnxenariaCampus TerraUniversidade de Santiago de CompostelaLugo27002Spain

Laurel forests are quite relevant for biodiversity conservation and are among the island ecosystems most severely damaged by human *** the past,Canary laurel forests have been greatly altered by logging,livestock and *** remains of laurel forests are currently protected in the Canary Islands(Spain).However,we miss basic information needed for their restoration and adaptive management,such as tree longevity,growth potential and responsiveness to natural and anthropogenic *** dendrochronological methods,we studied how forest dynamic is related to land-use change and windstorms in two well-preserved laurel forests on Tenerife *** cores were collected from over 80 trees per stand at three stands per *** used ring-width series to estimate tree ages and calculate annual basal area increments(BAI),cumulative diameter increases,and changes indicative of released and suppressed *** tree species were found in all stands,with Laurus novocanariensis,Ilex canariensis and Morella faya being the most common *** some individuals were over 100 years old,61.8%-88.9% of the trees per stand established between 1940 and 1970,coinciding with a post-war period of land abandonment,rural exodus and the onset of a tourism *** trees have shown growth rates larger than 1 cm diameter per year and most species have had increasing BAI trends over the past *** growth releases occurred after windstorms at both sites,but the effects of windstorms were site-dependent,with the 1958 storm affecting mainly the eastern tip of the island(Anaga massif)and the 1991 storm the western tip(Teno massif).Given the great ability of laurel forest trees to establish after land use cessation and to increase growth after local disturbances such as windstorms,passive restoration may be sufficient to regenerate this habitat in currently degraded areas.

关键词： Canary islands Dendroecology Disturbance Forest structure Macaronesia Management cessation Tree rings

Different Roles of Microalloying in Thin Slab Direct Rolling Technologies

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Journal of Iron and Steel Research International 2011年第S1期18卷 459-465页

作者： Rodriguez-Ibabe jose M Uranga Pello lopez Beatriz CEIT and Tecnun (Univ.of Navarra) P M.Lardizabal 1520018-San SebastianBasque CountrySpain

HSLA steels constitute one of the main types of steels produced worldwide by Thin Slab Direct Rolling technologies (TSDR).Among microalloying elements,the most widely used are V,Nb and *** elements play different roles during the austenite evolution in *** austenite conditioning before transformation,the limitations in the total reduction that can be applied in TSDR technologies need to be considered when composition/process parameters are *** this context,whereas an important number of studies have been focused on Nb microalloyed grades,a less systematic analysis has been performed concerning the role of vanadium on austenite *** paper analyzes these singularities taking into account different process parameter conditions,such as total reduction and initial rolling temperature.

关键词： thin slab direct rolling microalloyed steels vanadium niobium austenite conditioning

Secreted protein acidic and rich in cysteine(SPARC)induces epithelial-mesenchymal transition,enhancing migration and invasion,and is associated with high Gleason score in prostate cancer

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Asian Journal of Andrology 2019年第6期21卷 557-564页

作者： Fernanda lopez-Moncada Maria jose Torres Enrique A Castellon Hector R Contreras Department of Basic and Clinic Oncology Faculty of Medic泊eUniversity of ChileSantiago 8389100Chile

Secreted protein acidic and rich in cysteine(SPARC)is a matricellular protein highly expressed in bone tissue that acts as achemoattractant factor promoting the arrival of prostate cancer(PCa)cells to the bone ***,the contribution of SPARCduring the early stages of tumor progression remains *** this study,we show that SPARC is highly expressed in PCa tissueswith a higher Gleason *** stable knockdown and overexpression of SPARC in PC3 and LNCaP cells,respectively,here wedem on strate that en doge nous SPARC induces the epithelial-mesenchymal tran sition(EMT),decreasing E-cadheri n and cytokeratin18 and increasing N-cadheri n and vime ***,SPARC in duces the expression of EMT regulatory tran scription factors Snailfamily transcriptional repressor 1(Snail),Snail family transcriptional repressor 2(Slug),and zinc finger E-box binding homeobox 1(Zeb1).In addition,SPARC knockdown in PC3 cells decreases migration and invasion in vitro,without modifying cell *** results indicate that SPARC might facilitate tumor progression by modifying the cellular phenotype in cancer cells.

关键词： epithelial-mesenchymal transition invasion migration prostate cancer secreted protein acidic and rich in cysteine(SPARC)

Unsupervised full-color cellular image reconstruction through disordered optical fiber

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Light(Science & Applications) 2023年第6期12卷 1091-1102页

作者： Xiaowen Hu Jian Zhao jose Enrique Antonio-lopez Rodrigo Amezcua Correa Axel Schülzgen CREOL The College of Optics and PhotonicsUniversity of Central FloridaOrlandoFL 32816USA The Picower Institute for Learning and Memory Massachusetts Institute of TechnologyCambridgeMA 02139USA

Recent years have witnessed the tremendous development of fusing fiber-optic imaging with supervised deep learning to enable high-quality imaging of hard-to-reach ***,the supervised deep learning method imposes strict constraints on fiber-optic imaging systems,where the input objects and the fiber outputs have to be collected in *** unleash the full potential of fiber-optic imaging,unsupervised image reconstruction is in ***,neither optical fiber bundles nor multimode fibers can achieve a point-to-point transmission of the object with a high sampling density,as is a prerequisite for unsupervised image *** recently proposed disordered fibers offer a new solution based on the transverse Anderson ***,we demonstrate unsupervised full-color imaging with a cellular resolution through a meter-long disordered fiber in both transmission and reflection *** unsupervised image reconstruction consists of two *** the first stage,we perform a pixel-wise standardization on the fiber outputs using the statistics of the *** the second stage,we recover the fine details of the reconstructions through a generative adversarial *** image reconstruction does not need paired images,enabling a much more flexible calibration under various *** new solution achieves full-color high-fidelity cell imaging within a working distance of at least 4 mm by only collecting the fiber outputs after an initial *** imaging robustness is also demonstrated when the disordered fiber is bent with a central angle of 60°.Moreover,the cross-domain generality on unseen objects is shown to be enhanced with a diversified object set.

关键词： fiber optical image

Survival after pulmonary metastasectomy in colorectal cancer patients:does a history of resected liver metastases worsen the prognosis?A literature review

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Cancer Biology & Medicine 2017年第3期14卷 281-286页

作者： Jon Zabaleta Borja Aguinagalde Iker lopez Arantza Fernandez-Monge jose M.Izquierdo jose I.Emparanza Thoracic surgery service Hospital UniversitarioDonostiaGipuzkoa 20014Spain

Objective: To assess the impact of past liver metastases on the survival duration of patients who are undergoing surgery for lung ***: We conducted a review of literature published from 2007 to 2014. The studies were identified by searching Pub Med,MEDLINE, and Embase and were supplemented by a manual search of the references listed by the retrieved studies. The following search terms were used: lung metastasectomy, pulmonary metastasectomy, lung metastases, and lung metastasis. We selected retrospective and prospective studies published from 2007 to 2014 on patients with lung metastases from colorectal cancer and were undergoing surgery with curative intent. We excluded reviews, studies that focused on surgical techniques, patients who were treated non-surgically, analyses of specific subgroups of patients, and those that did not report follow-up of the patients undergoing ***: We identified 28 papers that assessed survival after lung metastases, 21 of which were mostly retrospective studies that identified previous liver metastases to explore their impact on patient survival. In more than half of the papers analyzed(63.2%),patients with a history of resected liver metastases had a lower survival rate than those who did not have such a history, and the difference was statistically significant in eight of these studies. However, data were presented differently, and authors reported mean survival time, survival rates, or hazard ***: A history of liver metastases seems to be a negative prognostic factor, but the individual data need to undergo a meta-analysis.

关键词： Lung metastasis liver colorectal cancer review

Warm Forged Medium Carbon V Steel

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Journal of Iron and Steel Research International 2011年第S1期18卷 822-826页

作者： Carlos garcia-Mateo Beatriz lopez jose Maria Rodriguez-Ibabe MATERALIA Research Group.Department of Physical Metallurgy Centro Nacional de Investigaciones Metalúrgicas (CENIM-CSIC)Avda.Gregorio del Amo 8.E-28040MadridSpain CEIT and TECNUM (University of Navarra) Po Manuel de Lardizabal 15San SebastianE-20018Basque ContrySpain

Nowadays there is a continuous demand,particularly from the automotive industry,for cheaper,lighter and more reliable *** is not surprising then that steel research has been focused during the last decades in new qualities and *** paper is dealing with the use of vanadium microalloyed steels on one of those new processes,warm *** its low precipitation temperature and its recognised ability to strengthen steel microstructures via austenite grain growth control,precipitation hardening and interference of the static recrystallization process,vanadium in microalloyed steels seem to be an appropriate candidate for warm forging.

关键词： warm forging vanadium microalloyed steels