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Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism:WLB-73502,an analgesic with improved efficacy and safety profile compared to strong opioids

24th International Papillomavirus Conference and Clinical Workshop

作者： luz del carmen alarcon-romero Elba Reyes-Maldonado Berenice Illades-Aguiar Eugenia Flores-Alfaro Amafia Vences Velazquez Gloria Fernondez-Tilapa Esther Ivonne Lopez-Bayghen Ethel A Garcia-Latorre Patricia romero Neri Victor Gabriel Hernandez Chavez Marco Antonio Teron-Porcayo Escuela Nacional de Ciencias Biologicas IPNMexicoD.F.Facultad de Ciencias Quimico BiologicasUniversidad Autonoma de GuerreroChilpancingo.GuerreroMexico Escuela Nacional de Ciencias Biologicas IPNMexicoD.F Facultad de Ciencias Quimico Biologicas Universidad Autonoma de GuerreroChilpancingo.GuerreroMexico Facultad de Ciencias Quimico Biologicas Universidad Autonoma de GuerreroChilpancingo.GuerreroMexico Escuela Nacional de Ciencias Biologicas IPNMexicoD.F.Facultad de Ciencias Quimico BiologicasUniversidad Autonoma de GuerreroChilpancingo.GuerreroMexico Escuela Nacional de Ciencias Biologicas IPNMexicoD.F.Facultad de Ciencias Quimico BiologicasUniversidad Autonoma de GuerreroChilpancingo.GuerreroMexico Depatamento de Genetica y Biologia Molecular CIVESTAV-IPNMexicoD.F Escuela Nacional de Ciencias Biologicas IPNMexicoD.F Clinica de Displasias ChilpancingoGuerreroMexico Departamento de Anatomia patologica Hospital de Cardiologia Centro Medico Nacional Siglo XXI del IMSSMexicoD.F Instituto Estatal de Cancerologia‘Dr Arturo Beltran Ortega’ AcapulcoGuerreroMexico

＜正＞Background:Expression of the high-risk human papillomavirus（hr-hpv）e7-gene replicating epithelial cells results in disruption of the prb-e2f complex and degradation of prb This leads to strong overexpression o...

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Acta Pharmaceutica Sinica B 2023年第1期13卷 82-99页

作者： Alba Vidal-Torres Begoña Fernández-Pastor Mónica García Eva Ayet Anna Cabot Javier Burgueño Xavier Monroy Bertrand Aubel Xavier Codony luz romero Rosalía Pascual Maria Teresa Serafini Gregorio Encina carmen Almansa Daniel Zamanillo Manuel Merlos JoséMiguel Vela WeLab Barcelona Parc Cientific de BarcelonaBarcelona 08028Spain

Opioids are the most effective painkillers,but their benefit-risk balance often hinder their therapeutic ***-73502 is a dual,bispecific compound that binds sigma-1(S1R)and mu-opioid(MOR)***-73502 is an antagonist at the *** behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificantβ-arrestin-2 recruitment,thus demonstrating low intrinsic efficacy on MOR at both signalling *** its partial MOR agonism,WLB-73502exerted full antinociceptive efficacy,with potency superior to morphine and similar to oxycodone against nociceptive,inflammatory and osteoarthritis pain,and superior to both morphine and oxycodone against neuropathic ***-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive *** to morphine and oxycodone,tolerance to its antinociceptive effect did not develop after repeated 4-week ***,contrary to opioid comparators,WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy,and it was devoid of proemetic effect(retching and vomiting)in ferrets at potentially effective ***-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

关键词： WLB-73502 Sigma-1 receptor Mu-opioid receptor Biased agonist Analgesic activity Chronic pain Neuropathic pain Safety

Cost Optimisation for Minimizing the Visual Impact of Ornamental Stone Quarrying. A Case Study in Murcia Region

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Journal of Geoscience and Environment Protection 2018年第2期6卷 74-88页

作者： José Molina-Ruiz María José Martínez-Sánchez carmen Pérez-Sirvent Mari luz García-Lorenzo María luz Tudela-Serrano Department of Geography Faculty of Geography University of Murcia Campus de la Merced Murcia Spain Department of Agricultural Chemistry Geology and Pedology Faculty of Chemistry University of Murcia Campus de Espinardo Murcia Spain Department of Mineralogy and Petrology Faculty of Geology University Complutense of Madrid Madrid Spain

Quarrying of ornamental stone has adverse effects that are both visual and environmental. This paper aims to develop a methodology for minimising the costs associated with reducing the visual impact of ornamental stone quarrying. This study uses digital topographical maps of the study zone and a GPS and GIS application to calculate the extent of the area affected by quarrying activities for each altitude designated in the work plan and to calculate the extent of the potential visual impact. The results obtained applying the proposed methodology for the selected area suggested that the potential visual impact is minimal for an altitude of 520 metres, this being the optimal point for the observer. When altitude increases, the potential visual impact increases and the optimal point for the observer diminishes until the highest impact altitude (740 m) is readied. The optimal point that the exploitation should reach is that at which the values of the diagram generated by the (%) area of potential visual impact and area of exploitation (%) intersect. The methodology allows the optimal altitude to be determined for mining exploitations and helps assess the viability of a given exploitation from an environmental point of view.

关键词： Restoration Costs Ornamental Stone Visual Impact Limestone Quarrying

Detection of KRAS G12D in colorectal cancer stool by droplet digital PCR

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World Journal of Gastroenterology 2017年第39期23卷 7087-7097页

作者： Susana Olmedillas-López Dennis César Lévano-Linares carmen Laura Aúz Alexandre luz Vega-Clemente Edurne León Sánchez Alejandro Villagrasa Jaime Ruíz-Tovar Mariano García-Arranz Damián García-Olmo Foundation Health Research Institute-Fundación Jiménez Díaz University Hospital Department of Surgery School of Medicine Universidad Autónoma de Madrid Department of Surgery Rey Juan Carlos University Hospital Department of Pathology Fundación Jiménez Díaz University Hospital Department of Biomedicine and Biotechnology Universidad de Alcalá Department of Surgery Fundación Jiménez Díaz University Hospital

AIMTo assess KRAS G12D mutation detection by droplet digital PCR (ddPCR) in stool-derived DNA from colorectal cancer (CRC) *** this study, tumor tissue and stool samples were collected from 70 patients with stage I-IV CRC diagnosed by preoperative biopsy. KRAS mutational status was determined by pyrosequencing analysis of DNA obtained from formalin-fixed paraffin-embedded (FFPE) tumor tissues. The KRAS G12D mutation was then analyzed by ddPCR in FFPE tumors and stool-derived DNA from patients with this point mutation. Wild-type (WT) tumors, as determined by pyrosequencing, were included as controls; analysis of FFPE tissue and stool-derived DNA by ddPCR was performed for these patients as *** the total 70 patients included, KRAS mutations were detected by pyrosequencing in 32 (45.71%), whereas 38 (54.29%) had WT tumors. The frequency of KRAS mutations was higher in left-sided tumors (11 located in the right colon, 15 in the left, and 6 in the rectum). The predominant point mutation was KRAS G12D (14.29%, n = 10), which was more frequent in early-stage tumors (I-IIA, n = 7). In agreement with pyrosequencing results, the KRAS G12D mutation was detected by ddPCR in FFPE tumor-derived DNA, and only a residual number of mutated copies was found in WT controls. The KRAS G12D mutation was also detected in stool-derived DNA in 80% of all fecal samples from CRC patients with this point *** is a reliable and sensitive method to analyze KRAS G12D mutation in stool-derived DNA from CRC patients, especially at early stages. This non-invasive approach is potentially applicable to other relevant biomarkers for CRC management.

关键词： Droplet digital PCR KRAS Stool Formalin-fixed paraffin-embedded Pyrosequencing Colorectal cancer

Diversity and host assemblage of avian haemosporidians in different terrestrial ecoregions of Peru

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Current Zoology 2022年第1期68卷 27-40页

作者： luz GARCIA-LONGORIA Jaime MURIEL Sergio MAGALLANES Zaira Hellen VILLA-GALARCE Leonila RICOPA Wilson Giancarlo INGA-DIAZ Esteban FONG Daniel VECCO Cesar GUERRA-SALDANA Teresa SALAS-RENGIFO Wendy FLORES-SAAVEDRA Kathya ESPINOZA Carlos MENDOZA Blanca SALDANA Manuel GONZALEZ-BLAZQUEZ Henry GONZALES-PINEDO Charlene LUJAN-VEGA Carlos Alberto del AGUILA Yessica VILCA-HERRERA Carlos Alberto PINEDA carmen REATEGUI Jorge Manuel CARDENAS-CALLIRGOS JoseAlberto IANNACONE Jorge Luis MENDOZA Ravinder NMSEHGAL Alfonso MARZAL Departamento de Anatomia Biologia Celular y ZoologiaUniversidad de ExtremaduraBadajoz E-506071Spain Molecular Ecology and Evolution Lab Department of BiologyLund UniversitySolvegatan 37SE-22362 LundSweden Instituto Pirenaico de Ecologıa-IPE(CSIC) Avda.Nuestra Senora de la Victoria 16Jaca 22700Spain DIRESA Direccion Regional de SaludLoreto 16001Peru Departamento Academico de Microbiologia y Parasitologia.Facultad de Ciencias Biologicas Universidad Nacional de la Amazonia PeruanaIquitos 16001Peru Facultad de Ciencias Agropecuarias Universidad Alas PeruanasLima 15823Peru EverGreen Institute-San Rafael Distrito de IndianaLoreto 16200Peru Observatorio de Aves Loreto(LBO) Distrito de San JuanLoreto 16008Peru Centro Urku de Estudios Amazonicos Tarapoto 22200Peru Servicio Nacional de Areas Naturales Protegidas por el Estado 15036Peru Sanidad Animal-Facultad de Zootecnia Universidad Nacional Agraria La MolinaLima 15012Peru Laboratorio de Microbiologia Facultad de Medicina Veterinaria y ZootecniaUniversidad CientUfica del SurLima 15067Peru Laboratorio de Analisis Clinico Moraleslab SAC MoralesSan Martin 22201Peru Asociacion Ecosistemas Andinos(ECOAN) Cuzco 08002Peru Pharmacology and Toxicology Graduate Group University of CaliforniaDavisDA 95616USA Global Health Initiative Wabash CollegeCrawfordsvilleIN 47933USA Facultad de Ciencias Biologicas Universidad Nacional Mayor de San MarcosLima 15081Peru Facultad de Medicina Veterinaria Universidad Nacional Hermilio ValdizanHuanuco10160Peru Asociacion Peruana de Helmintologia e Invertebrados Afines Lima 15054Peru Laboratorio de Ecologia y Biodiversidad Animal Universidad Nacional Federico VillarrealEl AgustinoLima 15007Peru Laboratorio de Invertebrados Universidad Ricardo Palma-Santiago de SurcoLima 15537Peru Department of Biology San Francisco State UniversitySan FranciscoCA 94132USA

Characterizing the diversity and structure of host–parasite communities is crucial to understandingtheir eco-evolutionary *** and related haemosporidian parasites are responsible forfitness loss and mortality in bird species ***,despite exhibiting the greatest ornithologicalbiodiversity,avian haemosporidians from Neotropical regions are quite ***,we analyze the genetic diversity of bird haemosporidian parasites(Plasmodium andHaemoproteus)in 1,336 individuals belonging to 206 bird species to explore for differences in diversityof parasite lineages and bird species across 5 well-differentiated Peruvian *** 70 different haemosporidian lineages infecting 74 bird *** showed that 25 out ofthe 70 haplotypes had not been previously ***,we also identified 81 new host–parasite interactions representing new host records for these haemosporidian *** outcomesrevealed that the effective diversity(as well as the richness,abundance,and Shannon–Weaver index)for both birds and parasite lineages was higher in Amazon basin ***,we also showed that ecoregions with greater diversity of bird species also had highparasite richness,hence suggesting that host community is crucial in explaining parasite *** parasites were found in ecoregions with lower bird diversity,implying that the abundanceand richness of hosts may shape the exploitation strategy followed by haemosporidian *** outcomes reveal that Neotropical region is a major reservoir of unidentified *** studies analyzing host distribution and specificity of these parasites inthe tropics will provide important knowledge about phylogenetic relationships,phylogeography,and patterns of evolution and distribution of haemosporidian parasites.

关键词： Amazonia avian malaria generalist parasite habitat specificity Haemoproteus Plasmodium specialist parasite

Pyonephrosis as a sign of sarcomatoid carcinoma of the renal pelvis

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世界临床病例杂志 2014年第6期2卷 215-218页

作者： Sergio Fernández-Pello Victoria Venta Iván González Rodrigo Gil carmen luz Menéndez Department of Urology Cabuenes Hospital33394 GijonSpain Department of Pathology Cabuenes Hospital33394 GijonSpain

We report the case of an urgent nephrectomy because of a pyonephrosis and sepsis due to an unsuspected sarcomatoid transitional cell carcinoma, an infrequent subtype with a bad oncological prognosis. We present a 58-year-old man assessed by internal medicine for a general syndrome and weakness many months previously. A pyonephrotic kidney was observed at abdominal computed tomography in the context of septic shock, without suspecting the underlying cause. The pathology report described a sarcomatoid transitional cell carcinoma. Sarcomatoid transitional cell carcinoma is an invasive and infrequent subtype of urothelial tumors. The symptoms are often the same as other renal masses; however, in this case, sepsis and pyonephrosis were the rare initial symptoms.

关键词： Urothelial carcinoma Renal pelvis Sarcomatoid

Lymph node non-Hodgkin's lymphoma incidentally discovered during a nephrectomy for renal cell carcinoma

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World Journal of Clinical Cases 2013年第3期1卷 121-123页

作者： Sergio Fernandez-Pello Luis Rodriguez Villamil Ivan Gonzalez Rodriguez Victoria Venta Javier Cuervo carmen luz Menéndez Urology Department Cabuenes Hospital33203 GijónSpain Pathology Department Cabuenes Hospital33203 GijónSpain

We report the case of a left laparoscopic nephroureterectomy with the incidental discovery of a non-Hodgkin's lymphoma in one of the lymph nodes of the renal hilum. A laparoscopic nephroureterectomy was decided on for a 64-year-old man. Renal cell carcinoma in the kidney and one lymph node of the renal hilum with non-Hodgkin's lymphoma was found. Chemotherapy was not started for the lymphoma discovery. There are no signs of relapse after two years of follow up. Coexistence in the same patient is an extremely rare condition. We review the literature about this issue to clarify this association.

关键词： Renal cell carcinoma Lymphoma Nephrectomy

Taphonomic characterisation of tooth marks of extinct Eurasian carnivores through geometric morphometrics

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Science Bulletin 2022年第16期67卷 1644-1648,M0003,M0004页

作者： José Yravedra Lloyd Austin Courtenay Darío Herranz-Rodrigo Gonzalo Linares-Matás Juan JoséRodríguez-Alba Verónica Estaca-Gómez carmen luzón Alexia Serrano-Ramos MiguelÁngel Maté-González JoséAntonio Solano Diego González-Aguilera Juan Manuel Jiménez-Arenas Department of Prehistory Ancient History and ArchaeologyComplutense University of MadridMadrid 28040Spain C.A.I.Archaeometry and Archaeological Analysis Complutense UniversityMadrid 28040Spain Grupo de Investigación Ecosistemas Cuaternarios Complutense UniversityMadrid 28040Spain Grupo de Investigación Arqueología Prehistórica Complutense UniversityMadrid 28040Spain Museo Primeros Pobladores de Europa‘Josep Gibert’ Orce 18858Spain Department of Cartographic and Land Engineering Higher Polytechnic School of AvilaUniversity of SalamancaAvila 05003Spain School of Archaeology St.Hugh’s CollegeUniversity of OxfordOxford 01865United Kingdom History and Arts Doctoral Program University of GranadaGranada 18071Spain Escuela Técnica Superior de Ingenieros en Topografía Geodesia y Cartografía.Universidad Politécnica de MadridMadrid 28031Spain Department of Prehistory and Archaeology University of GranadaGranada 18071Spain

Determining the cause and nature of the postmortem processes that living organisms experience is one of the main common issues faced by forensic experts,zooarchaeologists,palaeontologists,and other *** are among the most destructive agents that can interact with a corpse,since their feeding behaviour can lead to very extensive alterations,complicating the diagnostic identification of which carnivore species was responsible for the death of an individual,a livestock unit,or the formation of a fossil *** though some currently available techniques enable forensic experts to undertake a differential diagnosis of carnivore agency from corpse examination.

关键词：几何形态测量学埋藏特征有蹄类动物齿痕几何形态学机器学习分类预测多变量分析

Metastatic hormone-sensitive prostate cancer:How should it be treated?

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World Journal of Clinical Oncology 2021年第2期12卷 43-49页

作者： Fernando López-Campos carmen González-San Segundo Antonio JoséConde-Moreno Felipe Couñago Department of Radiation Oncology Hospital Universitario Ramón y CajalMadrid 28034Spain Department of Radiation Oncology HGU Gregorio MarañonComplutense UniversityMadrid 28007Spain Department of Radiation Oncology Hospital Universitario y Politécnico La Fe.CEU Cardenal Herrera UniversityValencia 46026Spain Department of Radiation Oncology Hospital Universitario Quirón Salud MadridHospital La LuzUniversidad Europea de Madrid(UEM)Madrid 28223Spain

The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent *** classic treatment approach for these patients—androgen-deprivation therapy alone—is now considered *** randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival and quality of life—for treatments that combine androgen-deprivation therapy with docetaxel,abiraterone acetate,enzalutamide,apalutamide,and/or radiotherapy to the primary *** a result,these approaches are now included in treatment guidelines and considered standard of ***,the different treatment strategies have not been directly compared,and thus treatment selection remains at the discretion of the individual physician or,ideally,a multidisciplinary *** the range of available treatment approaches with varying toxicity profiles,treatment selection should be individualized based on the patient’s clinical characteristics and preferences,which implies active patient participation in the decision-making *** the present document,we discuss the changing landscape of the management of patients with metastatic hormonesensitive prostate cancer in the context of several recently-published landmark randomized *** addition,we discuss several unresolved issues,including the optimal sequencing of systemic treatments and the incorporation of local treatment of the primary tumour and metastases.

关键词： Metastatic hormone-sensitive prostate cancer Androgen-receptor signaling inhibitors Abiraterone acetate Enzalutamide Apalutamide Docetaxel