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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

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Further understanding of mechanisms involved in liver cancer chemoresistance

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Hepatoma research 2017年第1期3卷 22-26页

作者： Oscar Briz Maria J.perez Jose J.G.Marin Department of Physiology and Pharmacology University of Salamanca37007 SalamancaSpain

An important limitation for the success of chemotherapy in the treatment of primary liver cancer (hepatocellular carcinoma,hepatoblastoma and cholangiocarcinoma) is the marked efficacy of mechanisms of chemoresistance (MOC).These have been previously classified into five groups depending on whether they result in:a reduced drug uptake or enhanced drug export (MOC-1);poor intracellular activation of prodrugs or higher inactivation of active drugs (MOC-2);changes in the molecular targets that impairs the action of the drug by increasing the activity of the metabolic route to be inhibited or stimulating alternative routes (MOC-3);ability of tumor cells to repair drug-induced modifications in the target molecule,usually DNA (MOC-4);and the activation or inhibition of intracellular signaling pathways that lead to a change in the balance between proand anti-apoptotic factors favoring tumor cell survival (MOC-5).Nevertheless,novel information appeared over the last few years has recommended to consider two additional groups,MOC-6 and MOC-7,based on changes in tumor microenvironment,mainly hypoxia and acidity,and epithelial-mesenchymal transition,*** contribute to the defensive armamentaria developed or enhanced in liver cancer cells to resist the pharmacological attack,which accounts for a negligible beneficial effect of commonly used antitumor drugs and only a modest response to novel targeted therapies based on tyrosine kinase inhibitors,such as ***,further advances are urgently needed to better understand the molecular and cellular bases of the chemoresistant barrier and help scientists in this field to develop new tools able to overcome cancer cell defenses.

关键词： Chemotherapy cholangiocarcinoma hepatoblastoma hepatocellular carcinoma tumor environment epithelial-mesenchymal transition

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Diagnostic and prognostic value of cardiac imaging in amyloidosis

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World Journal of Cardiology 2020年第12期12卷 599-614页

作者： rafael Vidal-perez raquel Vázquez-García Gonzalo Barge-Caballero Alberto Bouzas-Mosquera rafaela Soler-Fernandez Jose Maria Larrañaga-Moreira Maria Generosa Crespo-Leiro Jose Manuel Vazquez-rodriguez Servicio de Cardiología Unidad de Imagen y Función CardíacaComplexo Hospitalario Universitario A Coruña(CHUAC)Santiago de Compostela 15706A CoruñaSpain Servicio de Cardiología Complexo Hospitalario Universitario A Coruña(CHUAC)A Coruña 15006A CoruñaSpain Servicio de Cardiología Complexo Hospitalario Universitario A CoruñaUnidad de Insuficiencia Cardiaca Avanzada y Trasplante CardiacoInstituto de Investigación Biomédica de A Coruña(INIBIC)Centro de Investigación Biomédica en Red(CIBERCV)-Instituto de Salud Carlos IIIA Coruña 15006A CoruñaSpain

Amyloidosis is an infiltrative disease caused by extracellular protein deposition that has accumulated a lot of scientific production in recent *** types of amyloidosis can affect the *** amyloidosis and light chain amyloidosis are the two most common types of cardiac *** entities have a poor prognosis,so accurate diagnostic techniques are imperative for determining an early therapeutic *** advances in cardiac imaging and diagnostic strategies show that these tools are safe and can avoid the use of invasive diagnostic techniques to histological confirmation,such as endomyocardial *** performed a review on the diagnostic and prognostic implications of different cardiac imaging techniques in cardiac *** mainly focus on reviewing echocardiography,cardiac magnetic resonance,computed tomography and nuclear imaging techniques and the different safety measurements that can be done with each of them.

关键词： Cardiac imaging techniques Transthyretin cardiac amyloidosis Immunoglobulin light-chain amyloidosis Echocardiography Magnetic resonance imaging Nuclear imaging

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呆萌的黑啄木鸟

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飞碟探索 2017年第9期 4-4页

作者： carlos perez Naval

黑啄木鸟是一种大型啄木鸟，是啄木鸟中最大的一种，叫声很难听，飞行也很笨拙。照片的拍摄者只有9岁，他从5岁开始学习摄影，不到10岁就获得了多项国际摄影大奖。

关键词：啄木鸟摄影艺术艺术评论作品欣赏

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Bing仍是搜索竞争关键

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软件世界 2009年第10期 26-26页

作者： Juan carlos perez 赵军

在搜索引擎市场上，雅虎不但与谷歌公司展开用户的争夺，而且未来搜索技术的合作伙伴微软公司也是对手之一。

关键词：搜索引擎竞争微软公司合作伙伴搜索技术雅虎

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Thermal response to Heat in Buildings with Green Covers for Tropical Climate： Green Facades and Green roofs

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Journal of Civil Engineering and Architecture 2016年第8期10卷 919-931页

作者： Nuria perez Gallardo Gustavo Zen de Figueiredo Neves Adriano rogerio Bruno Tech Francisco Arthur da Silva Vecchia School of Engineering University of S6o Paulo S6o Carlos 13566-590 Brazil

The main aims of this paper were to study and demonstrate the benefits the plant systems can provide indoors in a critical heat day. This study proposed an experimental method to try to understand the thermal response to heat of four different systems： a prototype called control （no vegetation） and three with different combinations of vegetation （green roofs and green facades） installed in a tropical climate region. The experiments were developed in four test cells with dimensions 2.0 m × 2.50 m× 2.71 m. Measurements of internal surface temperatures and internal air temperatures were collected with the use of specific equipment, a data logger （Cr1000, Campbell Scientific Inc.）, connected with two multiplexers 32 channels （416AM Campbell Scientific Inc.）. Data were recorded over a year and a critical day heat was selected, which was September 24, *** results show that the use of plant systems in buildings establishes a passive technique in reducing energy consumption because of the high incidence of summer solar radiation which is reduced and simultaneously, it maintains thermal internal conditions more pleasant than external ones, because of the best thermal behaviour, which was observed in the test cell with vegetation on both roofs and facades. The biggest difference between maximum internal air temperatures registered was 2 ℃.

关键词： Green facades green roof thermal comfort bioclimatic architecture.

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The effect of broadening the definition of generalized anxiety disorder on healthcare resource utilization and related costs in outpatient psychiatric clinics

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Open Journal of Psychiatry 2013年第1期3卷 158-167页

作者： José M. Olivares José L. Carrasco Enrique álvarez María perez Vanessa López-Gómez Javier rejas Department of Psychiatry Hospital de la Santa Creu i San Pau Universitat Autónoma de Barcelona Centro de Investigación Biomédica En Red de SAlud Mental (CIBERSAM) Barcelona Spain Department of Psychiatry Hospital Meixoeiro Complejo Hospitalario Universitario Vigo Spain Department of Psychiatry Instituto de Investigación Sanitaria Hospital Clínico San Carlos Centro de Investigación Biomédica En Red de SAlud Mental (CIBERSAM) Madrid Spain Health Economics and Outcomes research Department Pfizer S.L.U. Madrid Spain Medical Unit Pfizer S.L.U. Madrid Spain

Background: Patients with generalized anxiety disorder (GAD) are among the highest users of healthcare resources. The broadening of the DSM-IV criteria for GAD has been a subject of controversy in the literature, but its consequences have not been analyzed to date. Objective: The purpose of this study was to analyze how the broadening of the DSM-IV criteria affects healthcare resource utilization and related costs. Methods: A multicentre, prospective, observational study was conducted in randomly selected outpatient psychiatric clinics between October 2007 and April 2008. Patients diagnosed according to DSM-IV or broader criteria (1 month of excessive or non-excessive worry and only 2 associated DSM-IV symptoms) for the first time were consecutively enrolled. Socio-demographic data, healthcare resources and corresponding costs were collected over a 6-month period. results: A total of 3549 patients were systematically recruited, 1815 in the DSM-IV criteria group (DG) and1264 inthe broad criteria group (BG). Treatments prescribed were similar for antidepressants in both groups (77.0% in the DG vs. 75.3% in the BG, p = 0.284), and slightly higher in the DG for benzodiazepines (71.5% vs. 67.2% respectively, p = 0.011) and anticonvulsants (72.1% vs. 67.0% respectively, p = 0.002). Healthcare resource utilization was statistically reduced to a similar extent in both groups as a consequence of treatment, yielding a reduction in the cost of illness of €1196 (SD = 1158) and €1112 (SD = 874) respectively;p = 0.304, over a 6-month period. Conclusion: The broadening of the GAD criteria could lead to earlier diagnosis not necessarily associated with an increase in healthcare resource utilization or costs to the National Health System in the six-month follow-up.

关键词： Generalized Anxiety Disorder Diagnosis DSM-IV Criteria Healthcare resource Utilization Costs

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ABTL0812 enhances antitumor effect of paclitaxel and reverts chemoresistance in triple-negative breast cancer models

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Cancer Communications 2022年第6期42卷 567-571页

作者： Emma Polonio-Alcala Sònia Solé-Sánchez Pau Munoz-Guardiola Elisabet Megías-roda Héctor.perez-Montoyo Marc Yeste-Velasco Jose Alfón Jose Miguel Lizcano Carles Domènech Santiago ruiz-Martínez Teresa Puig New Therapeutic Targets Laboratory(TargetsLab)-Oncology Unit Department of Medical SciencesUniversity of GironaGirona 17003Spain Product Process and Production Engineering Research Group(GREP)Department of Mechanical Engineering and Industrial ConstructionUniversity of GironaGirona 17003Spain Ability Pharmaceuticals SLCerdanyola del VallesBarcelona 08290Spain Protein Kinases and Signal Transduction Laboratory Department de Bioquimica i Biologia Molecular and Institut de NeurocienciesUniversitat Autonoma de BarcelonaBellaterraBarcelona 08193Spain

Dear Editor,Triple-negative breast cancer(TNBC)accounts for 20%of all breast carcinomas and lacks a validated targeted therapy;thus,currently,cytotoxic chemotherapy is the treatment of choice[1].Compared with other breast cancer types,patientswith TNBCare younger,have larger tumors,a higher risk of metastasis,and a higher rate of recurrence[2].Among all the subtypes described by Lehmann et al.[3],mesenchymal-like and mesenchymal stem-like(MSL)subtypes had the lowest 5-year distant metastasis-free survival rates.

关键词： ABTL0812 TrIB3 Autophagy Breast Cancer Targeted Therapy Chemoresistance

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Social media in cardiology:reasons to learn how to use it

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World Journal of Cardiology 2019年第10期11卷 217-220页

作者： rafael Vidal-perez Jose Juan Gómez de Diego Julia Grapsa ricardo Fontes-Carvalho Jose ramon Gonzalez-Juanatey Heart Failure Unit Cardiology DepartmentHospital Clinico Universitario de SantiagoSantiago de Compostela 15706A CorunaSpain Centro de Investigación Biomédica en red de Enfermedades Cardiovasculares SpainSantiago de Compostela 15706A CorunaSpain Cardiovascular Institute Hospital Universitario San CarlosMadrid 28040Spain Cardiology Department St Bartholomew HospitalBarts Health TrustLondon EC1A 7BEUnited Kingdom Cardiology Department Centro Hospitalar GaiaUniversity of PortoPorto 4434-502Portugal

Social media has changed the way we learn,educate,and interact with our *** dynamic nature of social media and their immediate availability through our portable devices(smartphones,tablets,smartwatches,etc.)is quickly transforming the way we participate in *** scope of these digital tools is broad as they deal with many different aspects:Teaching and learning,case discussion,congresses coverage,peer to peer interaction,research are examples worth *** scientific societies considered more innovative,are promoting these tools between their *** new concepts need to be known by the cardiologists to stay updated,as countless information is moving rapidly through these *** summarize the main reasons why learning how to use these tools to be part of the conversation is essential for the cardiologist in training or fully stablished.

关键词： Social media Cardiology Congress Learning Teaching Interaction Cardiovascular diseases Impact Factor Portable devices Smartphone Tablet

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

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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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