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1. Random Forest-Based Prediction of Stroke Outcome

Author

Fernandez-Lozano, Carlos, Hervella, Pablo, Mato-Abad, Virginia, Rodriguez-Yanez, Manuel, Suarez-Garaboa, Sonia, Lopez-Dequidt, Iria, Estany-Gestal, Ana, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Rodriguez-Yanez, Santiago, and Iglesias-Rey, Ramon

Subjects
Computer Science - Machine Learning
Abstract

We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3 months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity. In conclusion, machine learning algorithms RF can be effectively used in stroke patients for long-term outcome prediction of mortality and morbidity., Comment: 12 pages, 5 figures

Published
2024
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2. Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke

Author

Pérez-Mato, María, Dopico-López, Antonio, Akkoc, Yunus, López-Amoedo, Sonia, Correa-Paz, Clara, Candamo-Lourido, María, Iglesias-Rey, Ramón, López-Arias, Esteban, Bugallo-Casal, Ana, da Silva-Candal, Andrés, Bravo, Susana B., Chantada-Vázquez, María del Pilar, Arias, Susana, Santamaría-Cadavid, María, Estany-Gestal, Ana, Zaghmi, Ahlem, Gauthier, Marc A., Gutiérrez-Fernández, María, Martin, Abraham, Llop, Jordi, Rodríguez, Cristina, Almeida, Ángeles, Migliavacca, Martina, Polo, Ester, Pelaz, Beatriz, Gozuacik, Devrim, El Yamani, Naouale, SenGupta, Tanima, Rundén-Pran, Elise, Vivancos, José, Castellanos, Mar, Díez-Tejedor, Exuperio, Sobrino, Tomás, Rabinkov, Aharon, Mirelman, David, Castillo, José, and Campos, Francisco

Published
2024
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4. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Author

Dehghan, Abbas, Heath, Adam S., Morrison, Alanna C., Reiner, Alex P., Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M., Hayward, Caroline, Ward-Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P., Tregouet, David A., Mook-Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W., Leebeek, Frank W.G., Rosendaal, Frits R., Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A., Bressler, Jan, Huffman, Jennifer E., Rotter, Jerome I., Yao, Jie, Wilson, James F., Bis, Joshua C., Hahn, Julie M., Desch, Karl C., Wiggins, Kerri L., Díez-Ahijado, Laia, Raffield, Laura M., Bielak, Lawrence F., Yanek, Lisa R., Kleber, Marcus E., Sabater-Lleal, Maria, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Conomos, Matthew P., Liu, Melissa, Brown, Michael R., Jhun, Min-A, Chen, Ming-Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L., Peyser, Patricia A., Elliot, Paul, de Vries, Paul S., Wei, Peng, Wild, Philipp S., Morange, Pierre E., van der Harst, Pim, Yang, Qiong, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M., Cox, Simon R., Trompet, Stella, Felix, Stephan B., Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Gallego-Fabrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martin-Campos, Jesús M., Sobrino, Tomás, Castillo, José, Millán, Mònica, Muñoz-Narbona, Lucía, López-Cancio, Elena, Ribó, Marc, Alvarez-Sabin, Jose, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan F., Segura, Tomas, Serrano-Heras, Gemma, Marti-Fabregas, Joan, Freijo-Guerrero, Marimar, Moniche, Francisco, Castellanos, Maria del Mar, and Fernández-Cadenas, Israel

Published
2024
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9. The systemic impact of non‐surgical treatment of peri‐implantitis with or without adjunctive systemic metronidazole: Secondary analysis of a randomized clinical trial.

Author

Liñares, Antonio, Dopico, Jose, Blanco, Carlota, Pico, Alex, Sobrino, Tomás, Blanco, Juan, and Leira, Yago

Abstract

Objectives: The aim of this study was to evaluate the systemic effect of non‐surgical peri‐implantitis treatment (NSPIT) with or without the administration of systemic metronidazole. Methods: In this secondary analysis from a previously published clinical trial (NCT03564301), peri‐implantitis patients were randomized into two groups: test, receiving NSPIT plus 500 mg of oral systemic metronidazole three times a day for 7 days (n = 10); and control group, receiving NSPIT plus placebo (n = 11). Serum samples were obtained at baseline, 3 and 6 months after therapy to determine levels of inflammatory biomarkers, lipid fractions and complete blood counts. Results: Both treatment modalities produced improvements in clinical and radiographic parameters. After 6 months from NSPIT, a substantial reduction in C‐reactive protein (6.9 mg/dL; 95% CI: 3.7 to 9.9, p <.001) and low‐density lipoprotein cholesterol (21.8 mg/dL; 95% CI: −6.9 to 50.5, p =.013) as well as a modest increase in neutrophils counts (0.4 × 103/μL; 95% CI: −0.4 to 1.1, p =.010) was observed in the control group while the test group showed a significant reduction of TNF‐α (110.1; 95% CI: 38.9 to 181.4, p =.004). Conclusions: NSPIT showed a short‐term beneficial systemic effect regardless of adjunctive use of systemic metronidazole. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Sex-Stratified Genome-Wide Association Study in the Spanish Population Identifies a Novel Locus for Lacunar Stroke.

Author

Cárcel-Márquez, Jara, Muiño, Elena, Gallego-Fabrega, Cristina, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martín-Campos, Jesús M., Sobrino, Tomás, Campos, Francisco, Castillo, José, Freijo, Marimar, Francisco Arenillas, Juan, Obach, Victor, Álvarez-Sabín, José, Molina, Carlos A., Ribó, Marc, Jiménez-Conde, Jordi, Roquer, Jaume, Muñoz-Narbona, Lucia, and Lopez-Cancio, Elena

Published
2024
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14. Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation

Author

Milbank, Edward, Dragano, Nathalia R. V., González-García, Ismael, Garcia, Marcos Rios, Rivas-Limeres, Verónica, Perdomo, Liliana, Hilairet, Grégory, Ruiz-Pino, Francisco, Mallegol, Patricia, Morgan, Donald A., Iglesias-Rey, Ramón, Contreras, Cristina, Vergori, Luisa, Cuñarro, Juan, Porteiro, Begoña, Gavaldà-Navarro, Aleix, Oelkrug, Rebecca, Vidal, Anxo, Roa, Juan, Sobrino, Tomás, Villarroya, Francesc, Diéguez, Carlos, Nogueiras, Rubén, García-Cáceres, Cristina, Tena-Sempere, Manuel, Mittag, Jens, Carmen Martínez, M., Rahmouni, Kamal, Andriantsitohaina, Ramaroson, and López, Miguel

Published
2021
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16. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Author

National Heart, Lung, and Blood Institute (US), Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Gallego-Fabrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martin-Campos, Jesús M, Sobrino, Tomás, Castillo, José, Millán, Mònica, Muñoz-Narbona, Lucía, López-Cancio, Elena, Ribó, Marc, Álvarez-Sabín, José, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan F., Segura, Tomás, Serrano-Heras, Gemma, Marti-Fabregas, Joan, Freijo-Guerrero, Marimar, Moniche, Francisco, Castellanos, Maria Del Mar, Morrison, Alanna C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, Sabater-Lleal, Maria, National Heart, Lung, and Blood Institute (US), Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Gallego-Fabrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martin-Campos, Jesús M, Sobrino, Tomás, Castillo, José, Millán, Mònica, Muñoz-Narbona, Lucía, López-Cancio, Elena, Ribó, Marc, Álvarez-Sabín, José, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan F., Segura, Tomás, Serrano-Heras, Gemma, Marti-Fabregas, Joan, Freijo-Guerrero, Marimar, Moniche, Francisco, Castellanos, Maria Del Mar, Morrison, Alanna C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, and Sabater-Lleal, Maria

Abstract

[Background] Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient’s prognosis., [Objectives] To investigate the association between genetically determined natural hemostatic factors’ levels and increased risk of HT after r-tPA treatment., [Methods] Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT., [Results] Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10−11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10−10; rs1421067 (CHD9), P = 1.81 × 10−14; and rs34780449, near ROBO1 gene, P = 1.64 × 10−8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10−14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [−0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05)., [Conclusion] We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed.

Published
2024

17. dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe

Author

Universidad de Sevilla. Departamento de Biología Celular, Agencia Estatal de Investigación. España, Instituto de Salud Carlos III, Rodrigues, Joana S., Chenlo, Miguel, Bravo, Susana B., Pérez Romero, Sihara, Suárez Fariña, María, Sobrino, Tomás, Sanz Pamplona, Rebeca, González Prieto, Román, Álvarez, Clara V., Universidad de Sevilla. Departamento de Biología Celular, Agencia Estatal de Investigación. España, Instituto de Salud Carlos III, Rodrigues, Joana S., Chenlo, Miguel, Bravo, Susana B., Pérez Romero, Sihara, Suárez Fariña, María, Sobrino, Tomás, Sanz Pamplona, Rebeca, González Prieto, Román, and Álvarez, Clara V.

Abstract

The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA–directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.

Published
2024

18. PSEN2 Mutations May Mimic Frontotemporal Dementia: Two New Case Reports and a Review.

Author

Minguillón Pereiro, Anxo Manuel, Quintáns Castro, Beatriz, Ouro Villasante, Alberto, Aldrey Vázquez, José Manuel, Cortés Hernández, Julia, Aramburu-Núñez, Marta, Arias Gómez, Manuel, Jiménez Martín, Isabel, Sobrino, Tomás, and Pías-Peleteiro, Juan Manuel

Subjects
ALZHEIMER'S disease, FRONTOTEMPORAL dementia, WHITE matter (Nerve tissue), CEREBROSPINAL fluid, GENETIC mutation
Abstract

Background: Monogenic Alzheimer's disease (AD) has severe health and socioeconomic repercussions. Its rarest cause is presenilin 2 (PSEN2) gene mutations. We present two new cases with presumed PSEN2-AD with unusual clinical and neuroimaging findings in order to provide more information on the pathophysiology and semiology of these patients. Methods: Women aged 69 and 62 years at clinical onset, marked by prominent behavioral and language dysfunction, progressing to severe dementia within three years were included. The complete study is depicted. In addition, a systematic review of the PSEN2-AD was performed. Results: Neuroimaging revealed pronounced frontal white matter hyperintensities (WMH) and frontotemporal atrophy/hypometabolism. The genetic study unveiled PSEN2 variants: c.772G>A (p.Ala258Thr) and c.1073-2_1073-1del. Both cerebrospinal fluid (CSF) and experimental blood biomarkers shouldered AD etiology. Conclusions: Prominent behavioral and language dysfunction suggesting frontotemporal dementia (FTD) may be underestimated in the literature as a clinical picture in PSEN2 mutations. Thus, it may be reasonable to include PSEN2 in genetic panels when suspecting FTDL. PSEN2 mutations may cause striking WMH, arguably related to myelin disruption induced by amyloid accumulation. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Autotaxin as a novel biomarker of migraine

Author

Ouro, Alberto, primary, Castro-Mosquera, Mónica, additional, Leira, Yago, additional, Rodríguez-Arrizabalaga, Mariña, additional, Debasa-Mouce, Manuel, additional, Romaus-Sanjurjo, Daniel, additional, Aramburu-Nuñez, Marta, additional, Iglesias-Rey, Ramón, additional, Casas, Josefina, additional, Lema, Isabel, additional, Castillo, José, additional, Leira, Rogelio, additional, and Sobrino, Tomás, additional

Published
2024
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23. Systemic biomarker associated with poor outcome after futile reperfusion

Author

Hervella, Pablo, primary, Sampedro‐Viana, Ana, additional, Rodríguez‐Yáñez, Manuel, additional, López‐Dequidt, Iria, additional, Pumar, José M., additional, Mosqueira, Antonio J., additional, Fernández‐Rodicio, Sabela, additional, Bazarra‐Barreiros, Marcos, additional, Serena, Joaquín, additional, Silva‐Blas, Yolanda, additional, Gubern‐Merida, Carme, additional, Rey‐Aldana, Daniel, additional, Cinza, Sergio, additional, Campos, Francisco, additional, Sobrino, Tomás, additional, Castillo, José, additional, Alonso‐Alonso, Maria Luz, additional, and Iglesias‐Rey, Ramón, additional

Published
2024
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30. Random forest-based prediction of stroke outcome

Author

Fernandez-Lozano, Carlos, Hervella, Pablo, Mato-Abad, Virginia, Rodríguez-Yáñez, Manuel, Suárez-Garaboa, Sonia, López-Dequidt, Iria, Estany-Gestal, Ana, Sobrino, Tomás, Campos, Francisco, Castillo, José, Rodríguez-Yáñez, Santiago, and Iglesias-Rey, Ramón

Published
2021
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34. Precision Medicine for Blood Glutamate Grabbing in Ischemic Stroke.

Author

Hervella, Pablo, Sampedro-Viana, Ana, Fernández-Rodicio, Sabela, Rodríguez-Yáñez, Manuel, López-Dequidt, Iria, Pumar, José M., Mosqueira, Antonio J., Bazarra-Barreiros, Marcos, Abengoza-Bello, María Teresa, Ortega-Espina, Sara, Ouro, Alberto, Pérez-Mato, María, Campos, Francisco, Sobrino, Tomás, Castillo, José, Alonso-Alonso, Maria Luz, and Iglesias-Rey, Ramón

Subjects
ISCHEMIC stroke, ASPARTATE aminotransferase, GLUTAMIC acid, INDIVIDUALIZED medicine, TUMOR necrosis factors, PEARSON correlation (Statistics), BLOOD-brain barrier
Abstract

Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood–brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient's functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson's correlation coefficient: −0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson's correlation coefficients: −0.299; p < 0.001 vs. −0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28–0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69–0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Differential blood-based biomarkers of subcortical and deep brain small vessel disease.

Author

Hervella, Pablo, Alonso-Alonso, Maria Luz, Sampedro-Viana, Ana, Rodríguez-Yáñez, Manuel, López-Dequidt, Iria, Pumar, José M., Ouro, Alberto, Romaus-Sanjurjo, Daniel, Campos, Francisco, Sobrino, Tomás, Castillo, José, Leira, Yago, and Iglesias-Rey, Ramón

Subjects
CEREBRAL small vessel diseases, LACUNAR stroke, PATHOGENESIS, ALZHEIMER'S disease, BIOMARKERS
Abstract

Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Design: Prospective case–control study involving 120 patients with imaging-confirmed LS and a 120 control group. Methods: We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aβ1–40, Aβ1–42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aβ1–40 and Aβ1–42 were significantly lower in patients with deep LS (p < 0.0001). Aβ1–42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001). Conclusion: The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome

Author

Heitsch, Laura, Ibanez, Laura, Carrera, Caty, Binkley, Michael M., Strbian, Daniel, Tatlisumak, Turgut, Bustamante, Alejandro, Ribó, Marc, Molina, Carlos, Dávalos, Antoni, López-Cancio, Elena, Muñoz-Narbona, Lucia, Soriano-Tárraga, Carol, Giralt-Steinhauer, Eva, Obach, Victor, Slowik, Agnieszka, Pera, Joanna, Lapicka-Bodzioch, Katarzyna, Derbisz, Justyna, Sobrino, Tomás, Castillo, José, Campos, Francisco, Rodríguez-Castro, Emilio, Arias-Rivas, Susana, Segura, Tomas, Serrano-Heras, Gemma, Vives-Bauza, Cristófol, Díaz-Navarro, Rosa, Tur, Silva, Jimenez, Carmen, Martí-Fàbregas, Joan, Delgado-Mederos, Raquel, Arenillas, Juan, Krupinski, Jerzy, Cullell, Natalia, Torres-Aguila, Nuria P., Muiño, Elena, Cárcel-Márquez, Jara, Moniche, Francisco, Cabezas, Juan A., Ford, Andria L., Dhar, Rajat, Roquer, Jaume, Khatri, Pooja, Jiménez-Conde, Jordi, Fernandez-Cadenas, Israel, Montaner, Joan, Rosand, Jonathan, Cruchaga, Carlos, and Lee, Jin-Moo

Published
2021
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38. Association of periodontitis with cognitive decline and its progression: Contribution of blood‐based biomarkers of Alzheimer's disease to this relationship

Author

Carballo, Álvaro, primary, López‐Dequidt, Iria, additional, Custodia, Antía, additional, Botelho, João, additional, Aramburu‐Núñez, Marta, additional, Machado, Vanessa, additional, Pías‐Peleteiro, Juan Manuel, additional, Ouro, Alberto, additional, Romaus‐Sanjurjo, Daniel, additional, Vázquez‐Vázquez, Laura, additional, Jiménez‐Martín, Isabel, additional, Aguiar, Pablo, additional, Rodríguez‐Yáñez, Manuel, additional, Aldrey, José Manuel, additional, Blanco, Juan, additional, Castillo, José, additional, Sobrino, Tomás, additional, and Leira, Yago, additional

Published
2023
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39. Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

Author

Martínez-Sánchez, Noelia, Seoane-Collazo, Patricia, Contreras, Cristina, Varela, Luis, Villarroya, Joan, Rial-Pensado, Eva, Buqué, Xabier, Aurrekoetxea, Igor, Delgado, Teresa C., Vázquez-Martínez, Rafael, González-García, Ismael, Roa, Juan, Whittle, Andrew J., Gomez-Santos, Beatriz, Velagapudi, Vidya, Tung, Y.C. Loraine, Morgan, Donald A., Voshol, Peter J., Martínez de Morentin, Pablo B., López-González, Tania, Liñares-Pose, Laura, Gonzalez, Francisco, Chatterjee, Krishna, Sobrino, Tomás, Medina-Gómez, Gema, Davis, Roger J., Casals, Núria, Orešič, Matej, Coll, Anthony P., Vidal-Puig, Antonio, Mittag, Jens, Tena-Sempere, Manuel, Malagón, María M., Diéguez, Carlos, Martínez-Chantar, María Luz, Aspichueta, Patricia, Rahmouni, Kamal, Nogueiras, Rubén, Sabio, Guadalupe, Villarroya, Francesc, and López, Miguel

Published
2017
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45. Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke

Author

Torres-Aguila, Nuria P., Carrera, Caty, Giese, Anne-Katrine, Cullell, Natalia, Muiño, Elena, Cárcel-Márquez, Jara, Gallego-Fabrega, Cristina, González-Sánchez, Jonathan, del Mar Freijo, María, Álvarez-Sabín, José, Molina, Carlos, Ribó, Marc, Jimenez-Conde, Jordi, Roquer, Jaume, Sobrino, Tomás, Campos, Francisco, Castillo, José, Muñoz-Narbona, Lucia, Lopez-Cancio, Elena, Dàvalos, Antoni, Diaz-Navarro, Rosa, Tur, Silvia, Vives-Bauza, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Krupinski, Jerzy, Delgado-Mederos, Raquel, Martí-Fàbregas, Joan, Heitsch, Laura, Ibañez, Laura, Cruchaga, Carlos, Rost, Natalia S., Montaner, Joan, Lee, Jin-Moo, and Fernandez-Cadenas, Israel

Published
2019
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49. Organotypic Hippocampal Slice Cultures from Adult Tauopathy Mice and Theragnostic Evaluation of Nanomaterial Phospho-TAU Antibody-Conjugates

Author

Kemppainen, Susanna, primary, Huber, Nadine, additional, Willman, Roosa-Maria, additional, Zamora, Ana, additional, Mäkinen, Petra, additional, Martiskainen, Henna, additional, Takalo, Mari, additional, Haapasalo, Annakaisa, additional, Sobrino, Tomás, additional, González Gómez, Manuel Antonio, additional, Piñeiro, Yolanda, additional, Rivas, José, additional, Himmelreich, Uwe, additional, and Hiltunen, Mikko, additional

Published
2023
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50. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Author

Gallego-Fábrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullel, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martín-Campos, Jesús M., Sobrino, Tomás, Castillo, José, Millán, Mónica, Muñoz-Narbona, Lucía, López-Cancio Martínez, Elena, Ribó, Marc, Álvarez-Sabín, José, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan, Segura, Tomás, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Freijo Guerrero, María del Mar, Moniche Álvarez, Francisco, Castellanos, María del Mar, Morrison, Alana C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, Sabater-Lleal, María, Gallego-Fábrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullel, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martín-Campos, Jesús M., Sobrino, Tomás, Castillo, José, Millán, Mónica, Muñoz-Narbona, Lucía, López-Cancio Martínez, Elena, Ribó, Marc, Álvarez-Sabín, José, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan, Segura, Tomás, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Freijo Guerrero, María del Mar, Moniche Álvarez, Francisco, Castellanos, María del Mar, Morrison, Alana C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, and Sabater-Lleal, María

Abstract

[Abstract] Background: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis. Objectives: To investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment. Methods: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT. Results: Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10-11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10-10; rs1421067 (CHD9), P = 1.81 × 10-14; and rs34780449, near ROBO1 gene, P = 1.64 × 10-8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10-14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [-0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05). Conclusion: We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT

Published
2023

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