المؤلفون: Juan J Cáceres, Alberto Paccanaro

المصدر: PLoS Computational Biology, Vol 15, Iss 7, p e1007078 (2019)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Network medicine approaches have been largely successful at increasing our knowledge of molecularly characterized diseases. Given a set of disease genes associated with a disease, neighbourhood-based methods and random walkers exploit the interactome allowing the prediction of further genes for that disease. In general, however, diseases with no known molecular basis constitute a challenge. Here we present a novel network approach to prioritize gene-disease associations that is able to also predict genes for diseases with no known molecular basis. Our method, which we have called Cardigan (ChARting DIsease Gene AssociatioNs), uses semi-supervised learning and exploits a measure of similarity between disease phenotypes. We evaluated its performance at predicting genes for both molecularly characterized and uncharacterized diseases in OMIM, using both weighted and binary interactomes, and compared it with state-of-the-art methods. Our tests, which use datasets collected at different points in time to replicate the dynamics of the disease gene discovery process, prove that Cardigan is able to accurately predict disease genes for molecularly uncharacterized diseases. Additionally, standard leave-one-out cross validation tests show how our approach outperforms state-of-the-art methods at predicting genes for molecularly characterized diseases by 14%-65%. Cardigan can also be used for disease module prediction, where it outperforms state-of-the-art methods by 87%-299%.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1553-734XTest; https://doaj.org/toc/1553-7358Test

الوصول الحر: https://doaj.org/article/922a5da61aac4c49ad1cab49c7d05910Test

المؤلفون: Leonardo Lorente, María M Martín, Agustín F González-Rivero, Mónica Argueso, Luis Ramos, Jordi Solé-Violán, Juan J Cáceres, Alejandro Jiménez, Juan M Borreguero-León

المصدر: PLoS ONE, Vol 10, Iss 3, p e0121739 (2015)

مصطلحات موضوعية: Medicine, Science

الوصف: There have been found apoptotic changes in brain tissue samples from animals and humans after a traumatic brain injury (TBI). The protein cytokeratin 18 (CK-18), present in epithelial cells, is cleaved by the action of caspases during apoptosis, and the resulting fragments are released into the blood as caspase-cleaved CK (CCCK)-18. Circulating levels of CCCK-18, as biomarker of apoptosis, have been determined in patients with different processes; however, it has not been explored in TBI patients. Thus, the objective of this study was to determine whether there is an association between serum CCCK-18 levels and mortality and whether such levels could be used as a biomarker to predict outcomes in TBI patients.A prospective, observational, multicenter study carried out in six Spanish Intensive Care Units. We included patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9; and were excluded those patients with Injury Severity Score (ISS) in non-cranial aspects higher than 9. We measured serum CCCK-18 levels at admission. The end-point of the study was 30-day mortality.Surviving patients (n = 73) showed lower serum CCCK-18 levels (P = 0.003) than non-survivors (n = 27). On ROC analysis, the area under the curve (AUC) for serum CCCK-18 levels as predictor of 30-day mortality was 0.69 (95% CI = 0.59-0.78; P = 0.006). We found in survival analysis that patients with serum CCCK-18 higher than 201 u/L had higher 30-day mortality than patients with lower levels (Hazard ratio = 3.9; 95% CI = 1.81-8.34; P

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4379106?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/7f4190790ea4425db94944bf1905bb14Test

المؤلفون: Leonardo Lorente, María M Martín, Patricia López, Luis Ramos, José Blanquer, Juan J Cáceres, Jordi Solé-Violán, Jorge Solera, Judith Cabrera, Mónica Argueso, Raquel Ortiz, María L Mora, Santiago Lubillo, Alejandro Jiménez, Juan M Borreguero-León, Agustín González, Josune Orbe, José A Rodríguez, José A Páramo

المصدر: PLoS ONE, Vol 9, Iss 4, p e94370 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: ObjectiveMatrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play a role in neuroinflammation after brain trauma injury (TBI). Previous studies with small sample size have reported higher circulating MMP-2 and MMP-9 levels in patients with TBI, but no association between those levels and mortality. Thus, the aim of this study was to determine whether serum TIMP-1 and MMP-9 levels are associated with mortality in patients with severe TBI.MethodsThis was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. Patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Serum levels of TIMP-1, MMP-9 and tumor necrosis factor (TNF)-alpha, and plasma levels of tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 plasma were measured in 100 patients with severe TBI at admission. Endpoint was 30-day mortality.ResultsNon-surviving TBI patients (n = 27) showed higher serum TIMP-1 levels than survivor ones (n = 73). We did not find differences in MMP-9 serum levels. Logistic regression analysis showed that serum TIMP-1 levels were associated 30-day mortality (OR = 1.01; 95% CI = 1.001-1.013; P = 0.03). Survival analysis showed that patients with serum TIMP-1 higher than 220 ng/mL presented increased 30-day mortality than patients with lower levels (Chi-square = 5.50; P = 0.02). The area under the curve (AUC) for TIMP-1 as predictor of 30-day mortality was 0.73 (95% CI = 0.624-0.844; PConclusionsThe most relevant and new findings of our study, the largest series reporting data on TIMP-1 and MMP-9 levels in patients with severe TBI, were that serum TIMP-1 levels were associated with TBI mortality and could be used as a prognostic biomarker of mortality in TBI patients.

وصف الملف: electronic resource

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24728097/?tool=EBITest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/50f32a47f7eb45859415c83de83ba427Test

المؤلفون: Sergio Toledo, David Caballero, Edgar Maqueda, Juan J. Cáceres, Marco Rivera, Raúl Gregor, Patrick Wheeler

المصدر: Energies; Volume 15; Issue 20; Pages: 7801

مصطلحات موضوعية: control strategies, matrix converters, predictive control strategies, review protocol, systematic literature review, types of matrix converters

الوصف: Power electronic devices play an important role in energy conversion. Among the options, matrix converters, in combination with predictive control, represent a good alternative for the power conversion stage. Although several reviews have been undertaken on this topic, they have been conducted in a non-systematic manner, without indicating how the studies considered were chosen. This paper presents results from a systematic literature review on predictive control applied to matrix converters that included 142 primary papers, which were selected after applying a defined protocol with clear inclusion and exclusion criteria. The study provides a detailed classification of predictive control methods and strategies applied to different matrix converter topologies. Research findings require to be understood in combination to develop a common understanding of the topic and ensure that future research effort is based on solid premises. In light of this, this study identifies and characterizes different predictive control techniques and matrix converter topologies through systematic literature review. The results of the review indicate that interest in the area is increasing. A number of open questions in the field are discussed.

وصف الملف: application/pdf

العلاقة: https://dx.doi.org/10.3390/en15207801Test

الإتاحة: https://doi.org/10.3390/en15207801Test

المؤلفون: Leonardo Lorente, María M Martín, Antonia Pérez-Cejas, Luis Ramos-Gómez, Jordi Solé-Violan, Juan J Cáceres, Alejandro Jiménez, Agustín F González-Rivero

المصدر: World Journal of Critical Care Medicine. 12:63-70

مصطلحات موضوعية: General Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::28645a506b0e5fc050d621d674c6d3e6Test
https://doi.org/10.5492/wjccm.v12.i2.63Test

المؤلفون: Leonardo, Lorente, María M, Martín, Antonia, Pérez-Cejas, Carmen, Ferrer-Moure, Luis, Ramos-Gómez, Jordi, Solé-Violán, Juan J, Cáceres, Alejandro, Jiménez, Agustín F, González-Rivero

المصدر: Expert Review of Molecular Diagnostics. 22:1117-1121

مصطلحات موضوعية: Genetics, Molecular Medicine, Molecular Biology, Pathology and Forensic Medicine

الوصف: Fas is a major receptor for cell death by apoptosis. Higher blood concentrations of soluble Fas (sFas) have been reported in patients with ischemic stroke compared to control subjects. The aim of this study was to explore the existence or not of an association between blood sFas concentrations and mortality in patients with ischemic stroke.This study included patients admitted to Intensive Care Units with severe and malignant middle cerebral artery infarction (MCAI), defined as acute infarction, in more than 50% of this territory on computed tomography and less than 9 points on the Glasgow Coma Scale (GCS). Serum sFas levels were determined at the time of diagnosis of MMCAI.Non-surviving severe MMCAI patients (n = 27) showed lower platelet count (p = 0.004), higher serum sFas (p 0.001), and lower GCS (p = 0.001) compared to surviving patients (n = 27). Multiple logistic regression found an association of serum sFas levels and mortality at 30 days (OR = 1.015; 95% CI = 1.002-1.027; p = 0.02) after control for CGS and platelet count.The main novelty of our study was the existence of an association between high blood sFas concentrations and mortality in patients with ischemic stroke.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bee816ca80bfacc7657d8a950fc24081Test
https://doi.org/10.1080/14737159.2022.2165913Test

المؤلفون: Leonardo Lorente, María M. Martín, Antonia Pérez-Cejas, Agustín F González-Rivero, Rafael Sabatel, Luis Ramos, Mónica Argueso, Jordi Solé-Violán, Juan J. Cáceres, Alejandro Jiménez, Victor García-Marín

المصدر: Brain Sciences; Volume 10; Issue 3; Pages: 132

مصطلحات موضوعية: CCCK-18, patients, cerebral infarction, prognosis, mortality

الوصف: Objective: Caspase-cleaved cytokeratin (CCCK)-18 could appear in blood during apoptosis. In two different studies, on day 1 of cerebral infarction and at 72 h of cerebral infarction, respectively, higher circulating CCCK-18 levels were found in non-surviving than in surviving patients. The objective of this study was to analyze the ability of these levels to predict mortality at any time during the first week of cerebral infarction. Methods: Patients with malignant middle cerebral artery infarction (MMCAI) were included and the diagnosis criteria were the presence, observed in a computed tomography, of an acute cerebral infarction in at least 50% of this territory and midline shift, and an acute neurological deterioration with a Glasgow Coma Scale ≤ 8. Serum CCCK-18 levels at days 1, 4 and 8 of MMCAI were determined. Results: Serum concentrations of CCCK-18 at days 1, 4 and 8 of MMCAI were higher in non-surviving (n = 34) than in surviving patients (n = 34). Serum CCCK-18 concentrations at days 1, 4 and 8 of MMCAI had an area under curve (95% CI) used to predict a 30-day mortality of 0.83 (0.72 –0.91; p < 0.001), 0.78 (0.65–0.89; p < 0.001) and 0.82 (0.68–0.92; p < 0.001). Conclusions: The novel finding is that serum levels of CCCK-18 levels at any time after the first week of MMCAI could help predict 30-day mortality.

وصف الملف: application/pdf

العلاقة: https://dx.doi.org/10.3390/brainsci10030132Test

الإتاحة: https://doi.org/10.3390/brainsci10030132Test

المؤلفون: Leonardo Lorente, María M. Martín, Antonia Pérez-Cejas, Agustín F. González-Rivero, Pedro Abreu-González, Luis Ramos, Mónica Argueso, Jordi Solé-Violán, Juan J. Cáceres, Alejandro Jiménez, Victor García-Marín

المصدر: Brain Sciences; Volume 10; Issue 2; Pages: 110

مصطلحات موضوعية: total antioxidant capacity, traumatic brain injury, patients, mortality, prognosis

الوصف: Objective: Oxidation is involved in secondary brain injury after traumatic brain injury (TBI). Increased concentrations of total antioxidant capacity (TAC) in blood at the time of admission for TBI have been found in non-surviving patients. The main objective of this study was to determine the role of serum TAC levels at any time during the first week of TBI for the prediction of early mortality. Methods: Isolated (<10 points in non-cranial aspects of Injury Severity Score) and severe (<9 points in Glasgow Coma Scale) TBI patients were included. Serum TAC concentrations at days 1, 4, and 8 of TBI were determined. The end-point study was 30-day mortality. Results: Higher serum TAC levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.002) of TBI were found in non-surviving (n = 34) than in surviving patients (n = 90). The area under curve (95% Confidence Interval) for prediction of 30-day mortality by serum TAC concentrations at days 1, 4, and 8 of TBI were 0.79 (0.71–0.86; p < 0.001), 0.87 (0.79–0.93; p < 0.001), and 0.76 (0.67–0.84; p = 0.006) respectively. Conclusions: The novelty of our study was the ability to predict 30-day mortality by serum TAC concentrations at any time during the first week of TBI.

وصف الملف: application/pdf

العلاقة: https://dx.doi.org/10.3390/brainsci10020110Test

الإتاحة: https://doi.org/10.3390/brainsci10020110Test

المؤلفون: Joanna C. Dawes, Philip Webster, Barbara Iadarola, Claudia Garcia-Diaz, Marian Dore, Bruce J. Bolt, Hamlata Dewchand, Gopuraja Dharmalingam, Alex P. McLatchie, Jakub Kaczor, Juan J. Caceres, Alberto Paccanaro, Laurence Game, Simona Parrinello, Anthony G. Uren

المصدر: Mobile DNA, Vol 11, Iss 1, Pp 1-16 (2020)

مصطلحات موضوعية: Genomics, Genetics, Mutagenesis, Retroviruses, Integration site cloning, QH426-470

الوصف: Background Ligation-mediated PCR protocols have diverse uses including the identification of integration sites of insertional mutagens, integrating vectors and naturally occurring mobile genetic elements. For approaches that employ NGS sequencing, the relative abundance of integrations within a complex mixture is typically determined through the use of read counts or unique fragment lengths from a ligation of sheared DNA; however, these estimates may be skewed by PCR amplification biases and saturation of sequencing coverage. Results Here we describe a modification of our previous splinkerette based ligation-mediated PCR using a novel Illumina-compatible adapter design that prevents amplification of non-target DNA and incorporates unique molecular identifiers. This design reduces the number of PCR cycles required and improves relative quantitation of integration abundance for saturating sequencing coverage. By inverting the forked adapter strands from a standard orientation, the integration-genome junction can be sequenced without affecting the sequence diversity required for cluster generation on the flow cell. Replicate libraries of murine leukemia virus-infected spleen samples yielded highly reproducible quantitation of clonal integrations as well as a deep coverage of subclonal integrations. A dilution series of DNAs bearing integrations of MuLV or piggyBac transposon shows linearity of the quantitation over a range of concentrations. Conclusions Merging ligation and library generation steps can reduce total PCR amplification cycles without sacrificing coverage or fidelity. The protocol is robust enough for use in a 96 well format using an automated liquid handler and we include programs for use of a Beckman Biomek liquid handling workstation. We also include an informatics pipeline that maps reads, builds integration contigs and quantitates integration abundance using both fragment lengths and unique molecular identifiers. Suggestions for optimizing the protocol to other target DNA sequences are ...

العلاقة: https://doi.org/10.1186/s13100-020-0201-4Test; https://doaj.org/toc/1759-8753Test; https://doaj.org/article/cdb46adc21fd43509b19e5cc6b2b40e7Test

الإتاحة: https://doi.org/10.1186/s13100-020-0201-4Test
https://doaj.org/article/cdb46adc21fd43509b19e5cc6b2b40e7Test

المؤلفون: Leonardo Lorente, María M. Martín, Agustín F. González-Rivero, Antonia Pérez-Cejas, Pedro Abreu-González, Rafael Sabatel, Luis Ramos-Gómez, Mónica Argueso, Jordi Solé-Violán, Juan J. Cáceres, Alejandro Jiménez, Victor García-Marín

المصدر: Journal of Integrative Neuroscience, Vol 19, Iss 3, Pp 501-506 (2020)

مصطلحات موضوعية: total antioxidant capacity|prognosis|ischemic stroke|blood-brain barrier, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: It has been previously established that total antioxidant capacity concentrations of blood on the first day of ischemic stroke could predict mortality. Therefore, our study objective was to determine whether total antioxidant capacity concentrations in the blood during the first week of a cerebral infarction could help predict mortality. We included severe and malignant middle cerebral artery infarction patients (affecting 50% or more of the territory in computed tomography and a score of nine or fewer points in the Glasgow Coma Scale). Serum total antioxidant capacity concentrations were determined on days first, fourth, and eighth of the diagnosis of a malignant middle cerebral artery infarction. Higher serum total antioxidant capacity concentrations at first (P< 0.001), fourth (P< 0.001), and eighth (P = 0.003) day were found in non-surviving patients than in surviving ones. Serum total antioxidant capacity concentrations on first, fourth and eighth day of malignant middle cerebral artery infarction had an area under curve (95% Confidence Intervals) for 30-day mortality prediction of 0.86 (0.75-0.93; P<0.001), 0.87 (0.74-0.95; P< 0.001) and 0.79 (0.64-0.90; P = 0.004)), respectively. Thus, the potential use of serum total antioxidant capacity concentrations at any time during the first 7 days of a severe malignant middle cerebral artery infarction without thrombectomy to predict mortality was the main novel finding of our study.

العلاقة: https://jin.imrpress.com/fileup/1757-448X/PDF/1601435795072-842286317.pdfTest; https://doaj.org/toc/1757-448XTest; https://doaj.org/article/44ecbe70b2694cc78c07435d6ded28e9Test

الإتاحة: https://doi.org/10.31083Test/j.jin.2020.03.101
https://doaj.org/article/44ecbe70b2694cc78c07435d6ded28e9Test