Semántica funcional para lógicas temporales X modales. Definibilidad y Teoremas de completitud

Este trabajo está enmarcado en un área de conocimiento teórico, concretamente en el campo de la Lógica Formal como parte de los Fundamentos Matemáticos de la Computación. Sin embargo, su motivación ha partido de un área de conocimiento aplicado como la búsqueda de lógicas adecuadas para la especificación y control de procesos y sistemas multiagentes. Las lógicas introducidas permiten la especificación y control de procesos paralelos y el comportamiento de distintos agentes conectados en red. La investigación llevada a cabo por nuestro grupo de investigación GIMAC (Grupo de Investigación en herramientas matemáticas para la Computación) hasta la fecha de inicio de este trabajo, cuyo objetivo puede ser descrito como: "El diseño de una nueva metodología de demostración automática de teoremas que contribuya al uso real de software deductivo y, en definitiva, al uso de la Lógica en Computación" y, concretamente, los estudiso realizados en el grupo en aspectos tanto teóricos como aplicativos de las lógicas modales y temporales, y siendo conscientes de que las aplicaciones reclaman la integración de distintas lógicas, planteamos lógica adecuada a las aplicaciones anteriormente señaladas una lógica temporal x modal. Consideramos como aspectos destacado y novedosos en la investigación: El estudio de la definibilidad de las propiedades destacadas de clases de funciones tales como: totalidad, sobreyectividad, inyectividad, crecimiento, componibilidad, sin necesidad de hacer uso de la lógica de segundo orden. Deseamos destacar que nuestro trabajo ha tenido un punto de partida diferente a la de los trabajos existentes en la bibliografía en los que encontramos contemplada la combinación de tiempo y modalidad y en los que se abordan cuestiones filosóficas tales como el determinismo, la teoría de la acción, la causalidad, los condicionales, etc. Ver, por ejemplo, [Aqvist(1999)], [Belnap and Perloff)1990)], [Bel

Closure Structures as fixed points of some Galois connections.

The starting point of this work is a published paper where the fuzzy powerset of a fuzzy lattice A, the set of isotone mappings on A and the set of isotone total relations on A were proved to be related by three fuzzy Galois connections such that fuzzy closure systems, fuzzy closure operators and the so called strong fuzzy closure relations are fixed points. The final part of that paper studied the commutativity of the diagrams formed by these mappings.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Fuzzy Closure Structures as Formal Concepts II

This paper is the natural extension of Fuzzy Closure Structures as Formal Concepts. In this paper we take into consideration the concept of closure system which is not dealt with in the previous one. Hence, a connection must be found between fuzzy ordered sets and a crisp ordered set. This problem is two-fold, the core of the fuzzy orders can be considered in order to complete the ensemble, or the crisp order can be fuzzified. Both ways are studied in the paper. The most interesting result is, similarly to the previous paper, that closure systems are formal concepts of these Galois connections as well.Funding for open access charge: Universidad de Málaga / CBUA This research is partially supported by the State Agency of Research (AEI), the Spanish Ministry of Science, Innovation, and Universities (MCIU), the European Social Fund (FEDER), the Junta de Andalucía (JA), and the Universidad de Málaga (UMA) through the FPU19/01467 (MCIU) internship, the project VALID (PID2022-140630NB-I00 funded by MCIN/ AEI/10.13039/501100011033) and the research projects with reference PGC2018-095869-B-I00, PID2021-127870OB-I00, (MCIU/AEI/FEDER, UE) and UMA18-FEDERJA-001 (JA/ UMA/ FEDER, UE)

Fuzzy closure structures as formal concepts

Galois connections seem to be ubiquitous in mathematics. They have been used to model solutions for both pure and application-oriented problems. Throughout the paper, the general framework is a complete fuzzy lattice over a complete residuated lattice. The existence of three fuzzy Galois connections (two antitone and one isotone) between three specific ordered sets is proved in this paper. The most interesting part is that fuzzy closure systems, fuzzy closure operators and strong fuzzy closure relations are formal concepts of these fuzzy Galois connections.This research is partially supported by the State Agency of Research (AEI), the Spanish Ministry of Science, Innovation and Universities (MCIU), the European Social Fund (FEDER), the Junta de Andalucía (JA), and the Universidad de Málaga (UMA) through the FPU19/01467 (MCIU) internship and the research projects with reference PGC2018-095869-B-I00, TIN2017-89023-P, PID2021-127870OB-I00 (MCIU/AEI/FEDER, UE) and UMA18-FEDERJA-001 (JA/ UMA/ FEDER, UE). Funding for open access charge: Universidad de Málaga / CBU

Fuzzy relational Galois connections between fuzzy transitive digraphs

We present a fuzzy version of the notion of relational Galois connection between fuzzy transitive directed graphs (fuzzy T-digraphs) on the specific setting in which the underlying algebra of truth values is a complete Heyting algebra. The components of such fuzzy Galois connection are fuzzy relations satisfying certain reasonable properties expressed in terms of the so-called full powering. Moreover, we provide a necessary and sufficient condition under which it is possible to construct a right adjoint for a given fuzzy relation between a fuzzy T-digraph and an unstructured set.This research is partially supported by the State Agency of Research (AEI), the Spanish Ministry of Science, Innovation and Universities (MCIU), the European Social Fund (FEDER), the Junta de Andalucía (JA), and the Universidad de Málaga (UMA) through the research projects with reference PGC2018-095869-B-I00, PID2021-127870OB-I00, (MCIU/AEI/FEDER, UE) and UMA18-FEDERJA-001 (JA/ UMA/ FEDER, UE). B. De Baets was supported by the Flemish Government under the “Onderzoeksprogramma Artificiële Intelligentie (AI) Vlaanderen” programme. Funding for open access charge: Universidad de Málaga / CBU

Bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer

Este artículo ha sido publicado en Oncology Basel. Esta versión tiene Licencia Creative Commons CC-BY-NC-ND No puedo enviar el postprint porque no lo tienen disponible o no quieren facilitarmelo, en su lugar he aportado en la descripción del envió dos e mail en los cuales la editorial me da permiso por escrito para su depósito como puede ver en los mimos Adjunto e mails, si tiene ustd alguna otra sugerencia para poder hacer deposito por favor hagamelo saber 2º e mail: Dear Alfonso, Our reply is the written permission to deposit the article in the university’s repository – please find it attached once again. Kind regards, Veronika 1º e mail Veronika Duhovnikova Key Account Manager, Academic & Research Markets +41 61 306 12 43 [email protected] Dear Alfonso, Thank you for your email. As to your query, we are pleased to inform you that Karger permits authors to archive their pre-prints (i.e. pre-peer review) or post-prints (i.e. accepted manuscript after peer review but before production) on their personal or their institution’s internal website. In addition, authors may post their accepted manuscripts in public Open Access repositories and scientific networks (e.g. ResearchGate or Mendeley) no earlier than 12 months following the publication of the publisher’s versions. For all self-archiving options, the posted manuscripts must be - used for non-commercial purposes only - linked to the final version on Karger Publishers - include the following statement: ‘This is the peer-reviewed but unedited manuscript version of the following article: [insert full citation, e.g. Oncology 1 December 2010; 79 (1-2): 98–104, (DOI: 10.1159/000320602)]. The final, published version is available at [https://karger.com/ocl/article-abstract/79/1-2/98/328844/Bevacizumab-plus-Low-Dose-Metronomic-Oral?redirectedFrom=fulltext].’ For papers published online first with a DOI number only, full citation details must be added as soon as the paper is published in its final version. This is important to ensure that citations can be credited to the article. It is the author’s responsibility to fulfil these requirements. Further information about Karger’s Self-Archiving Policy can be found on the Karger website https://karger.com/pages/rights-and-permissions ‘How can I share it?’ and on SherpaRomeo Welcome to Sherpa Romeo - v2.sherpa. Please feel free to contact us again, if you need any further information. Kind regards, Veronika Veronika Duhovnikova Key Account Manager, Academic & Research Markets +41 61 306 12 43 [email protected]: To retrospectively assess the efficacy and safety of bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Patients and Methods: Patients with recurrent ovarian cancer and prior treatment with platinum- and taxanebased chemotherapy were included. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks plus oral cyclophosphamide 50 mg daily until disease progression or unacceptable toxicity. Response rates (RR) were determined according to RECIST criteria and by monitoring the CA 125 serum tumor marker according to Rustin’s criteria.The endpoints were progression-free survival (PFS), RR, overall survival (OS), and safety. Results: Thirty-eight patients were treated; 79% were platinum resistant and 21% were platinum sensitive. The median number of previous treatments was 4 (range 1–8). Seventy-nine percent of patients had received more than 2 previous lines of treatment. Eightyone percent of patients had received gemcitabine, 76% liposomal doxorubicin, and 50% topotecan. A median of 8 (range 1–70) cycles of bevacizumab were administered. The overall RR was a complete response (CR) in 3 patients (8.1%), a partial response (PR) in 12 (32.4%), and stable disease (SD) 6 6 months in 3 (8.1%). The median PFS and OS were 4.5 and 10.7 months, respectively. Thirty-nine percent of patients were progression free for at least 6 months. In an exploratory analysis there was a significant relation of prior platinum response and performance status with the risk of progression.Grade 3–4 toxicities included anemia (1), hypertension (2), hematuria (1), arterial thrombosis in the leg (1), dyspnea (1), and intestinal fistulae (1). There were no cases of gastrointestinal perforation (GIP) or treatment-related deaths. Conclusion: The combination of bevacizumab and metronomic cyclophosphamide was active and well-tolerated in heavily pretreated patients with recurrent ovarian cancer

Comprehensive and systematic characterization of multi-functionalized cisplatin nano-conjugate: from the chemistry and proteomic biocompatibility to the animal model

Background Nowadays, nanoparticles (NPs) have evolved as multifunctional systems combining different custom anchorages which opens a wide range of applications in biomedical research. Thus, their pharmacological involvements require more comprehensive analysis and novel nanodrugs should be characterized by both chemically and biological point of view. Within the wide variety of biocompatible nanosystems, iron oxide nanoparticles (IONPs) present mostly of the required features which make them suitable for multifunctional NPs with many biopharmaceutical applications. Results Cisplatin-IONPs and different functionalization stages have been broadly evaluated. The potential application of these nanodrugs in onco-therapies has been assessed by studying in vitro biocompatibility (interactions with environment) by proteomics characterization the determination of protein corona in different proximal fluids (human plasma, rabbit plasma and fetal bovine serum),. Moreover, protein labeling and LC–MS/MS analysis provided more than 4000 proteins de novo synthetized as consequence of the nanodrugs presence defending cell signaling in different tumor cell types (data available via ProteomeXchanges with identified PXD026615). Further in vivo studies have provided a more integrative view of the biopharmaceutical perspectives of IONPs. Conclusions Pharmacological proteomic profile different behavior between species and different affinity of protein coating layers (soft and hard corona). Also, intracellular signaling exposed differences between tumor cell lines studied. First approaches in animal model reveal the potential of theses NPs as drug delivery vehicles and confirm cisplatin compounds as strengthened antitumoral agents

Prevention, Diagnosis and Management of Post-Surgical Mediastinitis in Adults Consensus Guidelines of the Spanish Society of Cardiovascular Infections (SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES)

Prevention, Diagnosis and Management of Post-Surgical Mediastinitis in Adults Consensus Guidelines of the Spanish Society of Cardiovascular Infections (SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES) doctors and radiologists. Despite the clinical and economic consequences of sternal wound infections, to date, there are no specific guidelines for the prevention, diagnosis and management of mediastinitis based on a multidisciplinary consensus. The purpose of the present document is to provide evidencebased guidance on the most effective diagnosis and management of patients who have experienced or are at risk of developing a post-surgical mediastinitis infection in order to optimise patient outcomes and the process of care. The intended users of the document are health care providers who help patients make decisions regarding their treatment, aiming to optimise the benefits and minimise any harm as well as the workload.Funding: J.M. Miró was a recipient of a personal 80:20 research grant from IDIBAPS during the period 2017–2021

Tracking the antibody immunome in sporadic colorectal cancer by using antigen self-assembled protein arrays

© 2021 by the authors.Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) “Una manera de hacer Europa” and Junta Castilla-León (COVID19 grant COV20EDU/00187). Fundación Solórzano FS/38-2017. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. CNPq-National Council for Scientific and Technological Development (Brazil) (306258/2019-6) and FAPERJ-Foundation for Research Support of Rio de Janeiro State for the financial support (E-26/201.670/2017 and 210.379/2018). M. González-González is supported by MINECOPTA2019-017870-I.A. Landeira-Viñuela is supported by VIII Centenario-USAL PhD Program. P.J.-V. is supported by JCYL PhD Program and scholarship JCYL-EDU/601/2020. P.D. and E.B. are supported by a JCYL-EDU/346/2013 Ph.D. scholarship

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD