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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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Plant triterpenoid saponins function as susceptibility factors to promote the pathogenicity of Botrytis cinerea

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Molecular Plant 2024年第7期17卷 1073-1089页

作者： Francisco J.Escaray Amelia Felipo-Benavent Cristian J.Antonelli Begona Balaguer maria pilar Lopez-Gresa Pablo Vera Instituto de Biologia Molecular y Celular de Plantas Universidad Politecnica de Valencia-C.S.l.CCiudad Politecnica de la InnovacionEdificio 8Eacceso GIngeniero Fausto Elios/n46022ValenciaSpain

The gray mold fungus Botrytis cinerea is a necrotrophic pathogen that causes diseases in hundreds of plant species,including high-value *** polyxenous nature and pathogenic success are due to its ability to perceive host signals in its *** this study,we found that laticifer cells of Euphorbia lathyris are a source of susceptibility factors required by *** to cause ***,poor-in-latex(pil)mutants,which lack laticifer cells,show full resistance to this pathogen,whereas lot-of-latex mutants,which produce more laticifer cells,are *** S factors are triterpenoid saponins,which are widely distributed natural products of vast structural *** downregulation of laticifer-specific oxydosqualene cyclase genes,which encode the first committed step enzymes for triterpene and,therefore,saponin biosynthesis,conferred disease resistance to ***,the Medicago truncatula Iha-1 mutant,compromised in triterpenoid saponin biosynthesis,showed enhanced ***,the application of different purified triterpenoid saponins pharmacologically complemented the diseaseresistant phenotype ofpil and hla-1 mutants and enhanced disease susceptibility in different plant *** found that triterpenoid saponins function as plant cues that signal transcriptional reprogramming in ***,leading to a change in its growth habit and infection strategy,culminating in the abundant formation of infection cushions,the multicellular appressoria apparatus dedicated to plant penetration and biomass destruction in *** together,these results provide an explanation for how plant triterpenoid saponins function as disease susceptibility factors to promote *** pathogenicity.

关键词： Euphorbia lathyris laticifer cell latex appressorium infection cushion necrotrophic fungi

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Intense pulsed light‑based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops

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Eye and Vision 2024年第2期10卷 12-21页

作者： Jose maria Martinez‑de‑la‑Casa Carlos Oribio‑Quinto Almudena Milans‑del‑Bosch pilar Perez‑Garcia Laura Morales‑Fernandez Javier Garcia‑Bella Jose Manuel Benitez‑del‑Castillo Julian Garcia‑Feijoo David P.Pinero Ophthalmology Unit Department of Ophthalmology and ORLFaculty of MedicineHospital Clinico San-CarlosUniversidad Complutense de MadridInstituto de Investigacion Sanitaria del Hospital Clinico San-Carlos(IdISSC)28040 MadridSpain Department of Immunology Ophthalmology and ORLSchool of MedicineInstituto de Investigaciones Oftalmologicas Ramon CastroviejoUniversidad Complutense de MadridMadridSpain Department of Optics Pharmacology and AnatomyUniversity of AlicanteAlicanteSpain

Background:Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40%to 59%of these patients *** current study was aimed at evaluating the potential clinical benefit of an intense pulsed light(IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop *** our knowledge,this is the first series analyzing the therapeutic effect of this treatment option in this type of ***:This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye *** patients received four sessions of IPL treatment using the Optima IPL system(Lumenis,Yokneam,Israel)adjusted to the official optimized Lumenis *** in symptomatology,corneal staining,conjunctival hyperemia,non-invasive break-up time(NIBUT),tear osmolarity,tear meniscus height(TMH),meiboscore and meibomian gland expressibility was analyzed after ***:Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires[ocular surface disease index(OSDI),standard patient evaluation of eye dryness(SPEED)and symptom assessment questionnaire in dry eye(SANDE)]as well as with the visual analogue scale(P<0.001).Mean change in OSDI was−15.0±11.3.A significant reduction was found after treatment in the corneal staining score(P<0.001).A significant reduction was found in tear film meniscus height(P=0.012),as well as in tear film osmolarity(P=0.001).A significant reduction was also found in meibomian gland expressibility(P=0.003),changing the percentage of grade 3 eyes from 44.4%before IPL to 17.2%after ***:IPL therapy combined with meibomian gland expression(MGX)seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface diseas

关键词： Glaucoma Intense pulsed light Dry eye Meibomian glands

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Clinical outcomes and complications of single anastomosis duodenal-ileal bypass with sleeve gastrectomy:A 2-year follow-up study in Bogotá,Colombia

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World Journal of Clinical Cases 2023年第21期11卷 5035-5046页

作者： Andres Ospina Jaramillo Angie Carolina Riscanevo Bobadilla mariana Ospina Espinosa Alvaro Valencia Humberto Jiménez maria del pilar Montilla Velásquez maria Bastidas Department of General Surgery Clínica Reina SofiaColsanitasBogotáD.C 110151Colombia Department of General Surgery Fundación Universitaria SanitasBogotáD.C 11162Colombia Department of General Surgery Universidad del RosarioBogotá110151Colombia Department of Epidemiology Fundación Universitaria SanitasBogotá110151Colombia

BACKGROUND The global prevalence of obesity has increased over the past 40 years,and bariatric surgery has proven to be the most effective therapy for long-term weight *** principles are based on modifying the brain-gut axis by altering the gastrointestinal anatomy and affecting the function of gastrointestinal hormones,thereby modifying satiety *** anastomosis duodeno-ileal bypass with sleeve gastrectomy(SADI-S)combines both techniques and has become an alternative to gastric bypass and biliopancreatic diversion procedures for treating severe obesity and associated metabolic diseases in selected *** To describe the outcomes and complications of *** We retrospectively analyzed the data of patients who underwent SADI-S laparoscopically at the Clínica Reina Sofía in Bogotá,*** study assessed the therapeutic effectiveness of SADI-S in terms of short-term preoperative clinical characteristics,postoperative complications,comorbidities,nutritional deficiencies,and intraoperative complications during a 2-year *** Sixty-one patients with a mean body mass index(BMI)of 50±7.1 kg/m2 underwent laparoscopic *** mean operative time and hospital stays were 143.8±42 min and 2.3±0.8 d,*** mean follow-up period was 18 mo,and the mean BMI decreased to 28.5±12.2 kg/*** excess BMI loss was 41.8%±13.5%,and the weight loss percentage was 81.1%±17.0%.Resolution of obesity-related comorbidities,including type 2 diabetes mellitus,hypertension,dyslipidemia,and obstructive sleep apnea,was achieved and defined as complete or partial *** intraoperative complications were ***-term complications were observed in four(6.8%)***,larger studies with longer follow-up periods are required to draw definitive *** SADI-S has a low intraoperative and postoperative complication rate and is effective for weight loss and improving obesity-related comorbidities,including hyperte

关键词： Extreme obesity Bariatric surgery Body mass index Metabolic syndrome Cardiovascular diseases Complications

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Selective Fetal Growth Restriction in Monochorionic Diamniotic Twins: Diagnosis and Management

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Maternal-Fetal Medicine 2022年第4期4卷 268-275页

作者： Alicia Mazer Zumaeta maria Mar Gil Miguel Rodriguez-Fernandez pilar Carretero JoséHector Ochoa maria Cristina Casanova Francisca Sonia Molina Department of Obstetrics and Gynecology Hospital Universitario Clinico San CecilioGranada 18016Spain Department of Obstetrics and Gynecology Hospital Matemo Provincial Dr.Raul Felipe LuciniCordoba 500oArgentina Diagnus SA Prenatal Diagnosis and Fetal Medicine CenterCordoba 5000Argentina Obstetrics and Gynecology Department Hospital Universitario de TorrejonTorrejon de Ardoz 28223MadridSpain School of Medicine Universidad Francisco de VitoriaPozuelo de Alarcon 28223MadridSpain Instituto de Investigacion Biosanitaria lbs.GRANADA Granada 18016Spain

Selective fetal growth restriction (sFGR) is a severe condition that complicates 10% to 15% of all monochorionic diamniotic (MCDA) twin pregnancies. Pregnancies complicated with sFGR are at high risk of intrauterine demise or adverse perinatal outcome for the twins. Three clinical types have been described according to the umbilical artery (UA) Doppler pattern observed in the smaller twin: type I, when the UA Doppler is normal;type II, when there is persistent absent or reversed end-diastolic blood flow in the UA Doppler;and type III, when there is intermittent absent and/or reversed end-diastolic blood flow in the UA Doppler. Clinical evolution and management options mainly depend on the type of sFGR. Type I is usually associated with a good prognosis and is managed conservatively. There is no consensus on the management of types II and III, but in earlier and more severe presentations, fetal interventions such as selective laser photocoagulation of placental anastomoses or selective fetal cord occlusion of the smaller twin may be considered. This review aims to provide updated information about the diagnosis, evaluation, follow-up, and management of sFGR in MCDA twin pregnancies.

关键词： Twins Monochorionic diamniotic twins Selective fetal growth restriction Birthweight discordance Fetal therapy Placenta

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S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte cultures by a c-Jun N-terminal kinase activity-independent mechanism

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World Journal of Gastroenterology 2006年第12期12卷 1895-1904页

作者： maria del pilar Cabrales-Romero Lucrecia Márquez-Rosado Samia FatteI-Fazenda Cristina Trejo-solis Evelia Arce-Popoca Leticia Alemán-Lazarini Saúl Villa-Trevineo Department of Cell Biology Centro de Investigacién y Estudios Avanzados IPN Av. IPN No. 2508 México DF México Department of Neuroimmunology Instituto National de Neurologia y Neurocirugia MVS Insurgentes Sur 3877 Col La Fama DF México

AIM:To determine the role of c-Jun N-terminal kinase(JNK)activity in ethanol-induced apoptosis and themodulation of this signaling cascade by S-Adenosyl-methionine(AdoMet).METHODS:Primary hepatocyte cultures werepretreated with 100 μmol/L SP600125,a selective JNKinhibitor,1 mL/L DMSO or 4 mmol/L AdoMet and thenexposed to 100 mmo/L *** apoptosiswas determined by the TUNEL and DNA ladder *** activity and its inhibition by SP600125 and AdoMetwere determined by Western blot analysis of c-junphosphorylation and Bid ***600125 andAdoMet effects on the apoptotic signaling pathway weredetermined by Western blot analysis of cytochrome crelease and pro-caspase 3 *** AdoMeteffect on glutathione levels was measured by Ellman'smethod and reactive oxygen species(ROS)generationby cell ***:The exposure of hepatocytes to ethanolinduced JNK activation,c-jun phosphorylation,Bidfragmentation,cytochrome c release and pro-caspase 3cleavage;these effects were diminished by SP600125,and caused a significant decrease in ethanol-inducedapoptosis(P<0.05).AdoMet exerted an antioxidanteffect maintaining glutathione levels and decreasing ROSgeneration,without a significant effect on JNK activity,and prevented cytochrome c release and pro-caspase 3cleavage. CONCLUSION:The JNK signaling cascade is a keycomponent of the proapoptotic signaling pathwayinduced by *** activation may be independentfrom ROS generation,since AdoMet which exertedantioxidant properties did not have a significant effect onJNK *** pathway modulator agents and AdoMetmay be components of promising therapies for alcoholicliver disease(ALD)treatment.

关键词：蛋氨酸甲硫氨酸乙醇细胞调亡肝细胞酶活性

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Coronavirus disease-2019 and the intestinal tract:An overview

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World Journal of Gastroenterology 2021年第13期27卷 1255-1266页

作者： Gabriela Gama Freire Alberca Rosa Liliana solis-Castro maria Edith solis-Castro Ricardo Wesley Alberca Department of Microbiology Institute of Biomedical Sciences-University of São PauloSão Paulo 05508-000Brazil Departamento Académico de Biología Bioquímica Facultad de Ciencias de la SaludUniversidad Nacional de TumbesPampa Grande 24000TumbesPeru Departamento Académico de Medicina Humana Facultad de Ciencias de la SaludUniversidad Nacional de TumbesPampa Grande 24000TumbesPeru Laboratorio de Dermatologia e Imunodeficiencias(LIM-56) Departamento de DermatologiaFaculdade de Medicina FMUSPUniversidade de São PauloSão Paulo 01246-903Brazil

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) infection can progress to a severe respiratory and systemic disease named coronavirus disease–2019(COVID-19). The most common symptoms are fever and respiratory discomfort. Nevertheless, gastrointestinal infections have been reported, with symptoms such as diarrhea, nausea, vomiting, abdominal pain, and lack of appetite. Importantly, SARS-CoV-2 can remain positive in fecal samples after nasopharyngeal clearance. After gastrointestinal SARS-CoV-2 infection and other viral gastrointestinal infections, some patients may develop alterations in the gastrointestinal microbiota. In addition, some COVID-19 patients may receive antibiotics, which may also disturb gastrointestinal homeostasis. In summary, the gastrointestinal system, gut microbiome, and gut-lung axis may represent an important role in the development, severity, and treatment of COVID-19. Therefore, in this review, we explore the current pieces of evidence of COVID-19 gastrointestinal manifestations, possible implications, and interventions.

关键词： COVID-19 SARS-CoV-2 Gastrointestinal Microbiota Antibiotics

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Effect of asphalt thin beams mixed with three nominal maximum aggregate sizes in the bending beam rheometer on the prediction of thermal properties of bituminous material

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Frontiers of Structural and Civil Engineering 2017年第1期11卷 1-7页

作者： Chun-Hsing HO maria Francisca Martinez GONZALEZ Cristina pilar Martin LINARES Department of Civil Engineering Construction Management and Environmental Engineering Northern Arizona UniversityFlagstaff Arizona 86001 USA

The objective of this research is to evaluate an impact of asphalt mixture beams with varying sizes of aggregate in the Bending Beam Rheometer （BBR） for testing/predicting thermal cracking properties of asphalt pavements. The BBR test has following benefits： the equipment is cheaper, it uses smaller specimens, faster conditioning, easier availability for quality control, easier to manage, etc. However some concerns have been raised： some consider that the size of the aggregate may affect the test＇s results; the other concern is that such small beams cannot represent the whole properties of the asphalt pavement. To address these criticisms, imaging techniques, statistical analysis, and viscoelastic modeling are used. Asphalt thin beams prepared with three different nominal maximum aggregate size （NMAS）（12.5mm, 9.5 mm, and 4.75 mm） were tested at three different temperatures （-18℃, -24℃, and -30℃）. Based on results from statistical analyses and viscoelasticity, the ratio of asphalt binders and voids and stiffness differences among the three NMAS specimens are not significant, meaning that the impact of asphalt thin beams prepared with the three NMAS on the prediction of thermal cracking is minimal and can be neglected.

关键词： bending beam rheometer thin beams thermal cracking

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Ultra-compact on-chip slot Bragg grating structure for small electric field detection

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Photonics Research 2017年第3期5卷 212-218页

作者： WENTAO QIU HUIHUI LU FADI ISSAM BAIDA maria-pilar BERNAL Guangdong Provincial Key Laboratory of Optical Fiber Sensing and Communications Department of Optoelectronic EngineeringJinan University Département d'Optique P.M.Duffieux Institut FEMTO-STUMR 6174 CNRS Université Bourgogne Franche-Comté

In this paper, we present an ultra-compact 1D photonic crystal(Ph C) Bragg grating design on a thin film lithium niobate slot waveguide(SWG) via 2D-and 3D-FDTD simulations. 2D-FDTD simulations are employed to tune the photonic bandgap(PBG) size, PBG center, cavity resonance wavelength, and the whole size of Ph C. 3DFDTD simulations are carried out to model the real structure by varying different geometrical parameters such as SWG height and Ph C size. A moderate resonance quality factor Q of about 300 is achieved with a Ph C size of only 0.5 μm× 0.7 μm× 6 μm. The proposed slot Bragg grating structure is then exploited as an electric field(E-field) sensor. The sensitivity is analyzed by 3D-FDTD simulations with a minimum detectable E-field as small as 23 m V∕m. The possible fabrication process of the proposed structure is also discussed. The compact size of the proposed slot Bragg grating structure may have applications in on-chip E-field sensing, optical filtering, etc.

关键词： of nm FDTD in PBG for

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Effect of initial material bulk density and easily-degraded organic matter content on temperature changes during composting of cucumber stalk

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Journal of Environmental Sciences 2019年第6期31卷 306-315页

作者： Ruixue Chang Qiuyue Guo Qing Chen maria pilar Bernal Qian Wang Yanming Li College of Resource and Environmental Science China Agricultural University Department of Soil and Water Conservation and Organic Waste Management Centro Edafologia y Biologia Applicada del SeguraCSIC

To inactivate the potentially pathogenic microorganisms and safely utilize vegetable waste compost, ultra-high temperatures(> 70°C) should be maintained during the composting without having an inhibitory effect on maturity. This study investigated the influence of bulk density(part 1) and easily-degraded organic matter content(EDOMC, part 2) on temperature evolution during vegetable waste composting: Part 1: corn straw with different particle sizes was used to achieve different bulk densities in the composting material(BD1–BD3); Part 2: partial or total substitution of the corn straw by corn starch was carried out to obtain different EDOMC(ED1–ED4). The composting experiments were conducted in a labscale reactor(1.75 kg material) and lasted for 30 d. Temperature and CO2 emission were recorded daily, and the organic matter, lignocellulose, microbial activity, germination index(GI) and C/N of the samples were measured at different stages. The highest temperature(65.7°C) in part 1 occurred in the treatment with the bulk density of 0.35 g/cm3, which also had the longest thermophilic phase. Bulk density was found to seriously influence the utilization efficiency of O2 and heat transfer through materials, rather than heat production from organic matter degradation. In experiment part 2, the highest temperature was obtained with EDOMC of 45%(71.4°C). Therefore, adjusting the bulk density to 0.35 g/cm3 and the easily-degraded organic matter content of the initial material to 45% was the best combination for reaching temperatures above 70°C during composting, with no inhibitory effect on the maturity of the compost product.

关键词： Compost 70℃ Vegetable waste Bulk density Easily-degraded organic matter con tent Cucumber stalk

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