Fundación Pública Andaluza Progreso y Salud

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  • Publication
    How should medicines reimbursement work? The views of Spanish experts.
    (Cambridge University Press, 2025-01-30) Rejon-Parrilla, Juan Carlos; Epstein, David; Pérez-Troncoso, Daniel; Espin, Jaime; [Rejon-Parrilla,JC] Health Technology Assessment Area (AETSA), Andalusian Public Foundation Progress and Health (FPS), Seville, Spain.; [Espín,J] Andalusian School of Public Health, Granada, Spain.; [Espín,J] Instituto de Investigación Biosanitaria ibs., Granada, Spain.; [Espín,J] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.; Spanish Ministry of Science and Innovation/National Research Agency MCIN/AEI/10.13039/501100011033
    Although the criteria that support reimbursement decisions for medicines are often set by legislation, as is the case in Spain, in many cases neither the definition nor the measurement methods for these criteria are provided. Our goal was to elicit the views of a large sample of Spanish technical specialists on how to evaluate each one of the criteria that inform pricing and reimbursement decisions in Spain. Professionals from various stakeholder groups involved in health economics, health technology assessment, and industry participated in a survey. Participants recommended that reimbursement decisions should take specific account of unmet medical need and rare diseases. Health benefit should be measured using quality-adjusted life-years. There should be an explicit cost-effectiveness threshold, and this threshold should take account of population groups and special situations.
  • Publication
    Vol. 30, nº 05. Mapeado de líneas y grupos de I+D+I en salud pública en Andalucía: área de vigilancia y sistemas inteligentes.
    (Consejería de Salud y Consumo, 2025-01-31) Servicio de Vigilancia y Salud Laboral
    Enfermedades de Declaración Obligatoria por provincias. Semana 04/2025 y acumulado desde la semana 01/2025. Datos provisionales. Incluye además el artículo titulado “Mapeado de líneas y grupos de I+D+I en salud pública en Andalucía: área de vigilancia y sistemas inteligentes”, de “Cristina Medina Prado, Virginia Nieto Guerrero y Belén Jiménez Ojeda”.
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    Discovery of Pancreatic Adenocarcinoma Biomarkers by Untargeted Metabolomics.
    (2020-04-18) Martín-Blázquez, Ariadna; Jiménez-Luna, Cristina; Díaz, Caridad; Martínez-Galán, Joaquina; Prados, Jose; Vicente, Francisca; Melguizo, Consolación; Genilloud, Olga; Pérez Del Palacio, José; Caba, Octavio
    Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, with a 5-year survival rate of less than 5%. In fact, complete surgical resection remains the only curative treatment. However, fewer than 20% of patients are candidates for surgery at the time of presentation. Hence, there is a critical need to identify diagnostic biomarkers with potential clinical utility in this pathology. In this context, metabolomics could be a powerful tool to search for new robust biomarkers. Comparative metabolomic profiling was performed in serum samples from 59 unresectable PDAC patients and 60 healthy controls. Samples were analyzed by using an untargeted metabolomics workflow based on liquid chromatography, coupled to high-resolution mass spectrometry in positive and negative electrospray ionization modes. Univariate and multivariate analysis allowed the identification of potential candidates that were significantly altered in PDAC patients. A panel of nine candidates yielded excellent diagnostic capacities. Pathway analysis revealed four altered pathways in our patients. This study shows the potential of liquid chromatography coupled to high-resolution mass spectrometry as a diagnostic tool for PDAC. Furthermore, it identified novel robust biomarkers with excellent diagnostic capacities.
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    Generation and Evaluation of Novel Biomaterials Based on Decellularized Sturgeon Cartilage for Use in Tissue Engineering.
    (2021-07-04) Ortiz-Arrabal, Olimpia; Carmona, Ramón; García-García, Óscar-Darío; Chato-Astrain, Jesús; Sánchez-Porras, David; Domezain, Alberto; Oruezabal, Roke-Iñaki; Carriel, Víctor; Campos, Antonio; Alaminos, Miguel
    Because cartilage has limited regenerative capability, a fully efficient advanced therapy medicinal product is needed to treat severe cartilage damage. We evaluated a novel biomaterial obtained by decellularizing sturgeon chondral endoskeleton tissue for use in cartilage tissue engineering. In silico analysis suggested high homology between human and sturgeon collagen proteins, and ultra-performance liquid chromatography confirmed that both types of cartilage consisted mainly of the same amino acids. Decellularized sturgeon cartilage was recellularized with human chondrocytes and four types of human mesenchymal stem cells (MSC) and their suitability for generating a cartilage substitute was assessed ex vivo and in vivo. The results supported the biocompatibility of the novel scaffold, as well as its ability to sustain cell adhesion, proliferation and differentiation. In vivo assays showed that the MSC cells in grafted cartilage disks were biosynthetically active and able to remodel the extracellular matrix of cartilage substitutes, with the production of type II collagen and other relevant components, especially when adipose tissue MSC were used. In addition, these cartilage substitutes triggered a pro-regenerative reaction mediated by CD206-positive M2 macrophages. These preliminary results warrant further research to characterize in greater detail the potential clinical translation of these novel cartilage substitutes.
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    Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: a joint publication from the AABB and the International Society for Cell & Gene Therapy.
    (Cytotherapy, 2019-07-12) Bieback, Karen; Fernandez-Muñoz, Beatriz; Pati, Shibani; Schäfer, Richard
    Fetal bovine serum (FBS) is used as a growth supplement in a wide range of cell culture applications for cell-based research and therapy. However, as a xenogenic product, FBS can potentially transmit prions and adventitious viruses as well as induce undesirable immunologic reactions. In addition, the use of bovine fetuses for FBS production raises concerns as society looks for ways to replace animal testing and reduce the use of animal products for scientific purposes, in particular for the manufacture of clinical products intended for human use. Until chemically defined media are available for these purposes, human platelet lysate (hPL) has been introduced as an attractive alternative for replacing FBS as a cell culture supplement. hPL is a human product that can be produced from outdated platelets avoiding ethical, medical and animal welfare concerns. An increasing number of studies demonstrate that hPL can promote cell growth similarly or even better than FBS in specific cell types. Due to increasing interest in hPL, the AABB and the International Society of Cell Therapy (ISCT) established a joint working group to address its potential. With this article, we aim to present an overview of hPL, identifying the gaps in information on how hPL is produced and tested and the barriers to its translational use in the production of clinical-grade cell therapy products.
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    Efficacy of Fosfomycin and Its Combination With Aminoglycosides in an Experimental Sepsis Model by Carbapenemase-Producing Klebsiella pneumoniae Clinical Strains.
    (2021-03-26) Cebrero-Cangueiro, Tania; Labrador-Herrera, Gema; Pascual, Álvaro; Díaz, Caridad; Rodríguez-Baño, Jesús; Pachón, Jerónimo; Del Palacio, José P; Pachón-Ibáñez, María E; Conejo, M Carmen
    Carbapenemase-producing Klebsiella pneumoniae infections are an increasing global threat with scarce and uncertain treatment options. In this context, combination therapies are often used for these infections. The bactericidal and synergistic activity of fosfomycin plus amikacin and gentamicin was studied trough time-kill assays against four clonally unrelated clinical isolates of carbapenemase-producing K. pneumoniae, VIM-1, VIM-1 plus DHA-1, OXA-48 plus CTXM-15, and KPC-3, respectively. The efficacy of antimicrobials that showed synergistic activity in vitro against all the carbapenemase-producing K. pneumoniae were tested in monotherapy and in combination, in a murine peritoneal sepsis model. In vitro, fosfomycin plus amikacin showed synergistic and bactericidal effect against strains producing VIM-1, VIM-1 plus DHA-1, and OXA-48 plus CTX-M-15. Fosfomycin plus gentamicin had in vitro synergistic activity against the strain producing KPC-3. In vivo, fosfomycin and amikacin and its combination reduced the spleen bacterial concentration compared with controls groups in animals infected by K. pneumoniae producing VIM-1 and OXA-48 plus CTX-M-15. Moreover, amikacin alone and its combination with fosfomycin reduced the bacteremia rate against the VIM-1 producer strain. Contrary to the in vitro results, no in vivo efficacy was found with fosfomycin plus amikacin against the VIM-1 plus DHA-1 producer strain. Finally, fosfomycin plus gentamicin reduced the bacterial concentration in spleen against the KPC-3 producer strain. In conclusion, our results suggest that fosfomycin plus aminoglycosides has a dissimilar efficacy in the treatment of this severe experimental infection, when caused by different carbapenemase-producing K. pneumoniae strains. Fosfomycin plus amikacin or plus gentamycin may be useful to treat infections by OXA-48 plus CTX-M-15 or KPC-3 producer strains, respectively.
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    A Clinical Decision Support System (KNOWBED) to Integrate Scientific Knowledge at the Bedside: Development and Evaluation Study.
    (2021-03-10) Martinez-Garcia, Alicia; Naranjo-Saucedo, Ana Belén; Rivas, Jose Antonio; Romero Tabares, Antonio; Marín Cassinello, Ana; Andrés-Martín, Anselmo; Sánchez Laguna, Francisco José; Villegas, Roman; Pérez León, Francisco De Paula; Moreno Conde, Jesús; Parra Calderón, Carlos Luis
    The evidence-based medicine (EBM) paradigm requires the development of health care professionals' skills in the efficient search of evidence in the literature, and in the application of formal rules to evaluate this evidence. Incorporating this methodology into the decision-making routine of clinical practice will improve the patients' health care, increase patient safety, and optimize resources use. The aim of this study is to develop and evaluate a new tool (KNOWBED system) as a clinical decision support system to support scientific knowledge, enabling health care professionals to quickly carry out decision-making processes based on EBM during their routine clinical practice. Two components integrate the KNOWBED system: a web-based knowledge station and a mobile app. A use case (bronchiolitis pathology) was selected to validate the KNOWBED system in the context of the Paediatrics Unit of the Virgen Macarena University Hospital (Seville, Spain). The validation was covered in a 3-month pilot using 2 indicators: usability and efficacy. The KNOWBED system has been designed, developed, and validated to support clinical decision making in mobility based on standards that have been incorporated into the routine clinical practice of health care professionals. Using this tool, health care professionals can consult existing scientific knowledge at the bedside, and access recommendations of clinical protocols established based on EBM. During the pilot project, 15 health care professionals participated and accessed the system for a total of 59 times. The KNOWBED system is a useful and innovative tool for health care professionals. The usability surveys filled in by the system users highlight that it is easy to access the knowledge base. This paper also sets out some improvements to be made in the future.
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    The Role of Exosomes Derived From Mesenchymal Stromal Cells in Dermatology.
    (2021-04-07) Quiñones-Vico, María I; Sanabria-de la Torre, Raquel; Sánchez-Díaz, Manuel; Sierra-Sánchez, Álvaro; Montero-Vílchez, Trinidad; Fernández-González, Ana; Arias-Santiago, Salvador
    The skin is the largest organ of the human body and its main functions include providing protection from external harmful agents, regulating body temperature, and homeostatic maintenance. Skin injuries can damage this important barrier and its functions so research focuses on approaches to accelerate wound healing and treat inflammatory skin diseases. Due to their regenerative and immunomodulatory properties, mesenchymal stromal cells (MSCs) have been reported to play a significant role in skin repair and regeneration. However, it seems that the secretome of these cells and exosomes in particular may be responsible for their functions in skin regeneration and the immunomodulation field. The present review aims to gather the available information about the role of MSC-derived exosomes for both in vitro and in vivo models of different skin conditions and to highlight the need for further research in order to overcome any limitations for clinical translation.
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    Untargeted metabolomics to identify novel biomarkers of pancreatic cancer
    (Elsevier, 2020-09-01) Caba, O.; Jimenez-Luna, C.; Martin-Blazquez, A.; Martinez-Galan, J.; Perez Del Palacio, J.; Melguizo, C.; Diaz, C.; Dieguez, C.; Vicente, F.; Genilloud, O.; Martin-Ruiz, J. L.; Prados, J.; [Caba, O.] Univ Granada, Dept Anat & Embryol, Granada, Spain; [Jimenez-Luna, C.] Univ Granada, Inst Biopathol & Regenerat Med, Granada, Spain; [Prados, J.] Univ Granada, Inst Biopathol & Regenerat Med, Granada, Spain; [Martin-Blazquez, A.] Fdn MEDINA, Ctr Excelencia Invest Medicamentos Innovadores An, Granada, Spain; [Perez Del Palacio, J.] Fdn MEDINA, Ctr Excelencia Invest Medicamentos Innovadores An, Granada, Spain; [Melguizo, C.] Fdn MEDINA, Ctr Excelencia Invest Medicamentos Innovadores An, Granada, Spain; [Diaz, C.] Fdn MEDINA, Ctr Excelencia Invest Medicamentos Innovadores An, Granada, Spain; [Vicente, F.] Fdn MEDINA, Ctr Excelencia Invest Medicamentos Innovadores An, Granada, Spain; [Genilloud, O.] Fdn MEDINA, Ctr Excelencia Invest Medicamentos Innovadores An, Granada, Spain; [Martinez-Galan, J.] Univ Hosp Virgen de las Nieves, Med Oncol, Granada, Spain; [Dieguez, C.] Univ Hosp San Cecilio, Gastroenterol, Granada, Spain; [Martin-Ruiz, J. L.] Univ Hosp San Cecilio, Gastroenterol, Granada, Spain; Junta de Andalucia
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    Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.
    (BioMed Central Ltd., 2021-11-20) Axfors, Cathrine; Janiaud, Perrine; Schmitt, Andreas M; Van't Hooft, Janneke; Smith, Emily R; Haber, Noah A; Abayomi, Akin; Abduljalil, Manal; Abdulrahman, Abdulkarim; Acosta-Ampudia, Yeny; Aguilar-Guisado, Manuela; Al-Beidh, Farah; Alejandria, Marissa M; Alfonso, Rachelle N; Ali, Mohammad; AlQahtani, Manaf; AlZamrooni, Alaa; Anaya, Juan-Manuel; Ang, Mark Angelo C; Aomar, Ismael F; Argumanis, Luis E; Averyanov, Alexander; Baklaushev, Vladimir P; Balionis, Olga; Benfield, Thomas; Berry, Scott; Birocco, Nadia; Bonifacio, Lynn B; Bowen, Asha C; Bown, Abbie; Cabello-Gutierrez, Carlos; Camacho, Bernardo; Camacho-Ortiz, Adrian; Campbell-Lee, Sally; Cao, Damon H; Cardesa, Ana; Carnate, Jose M; Castillo, German Jr J; Cavallo, Rossana; Chowdhury, Fazle R; Chowdhury, Forhad U H; Ciccone, Giovannino; Cingolani, Antonella; Climacosa, Fresthel Monica M; Compernolle, Veerle; Cortez, Carlo Francisco N; Costa Neto, Abel; D'Antico, Sergio; Daly, James; Danielle, Franca; Davis, Joshua S; De Rosa, Francesco Giuseppe; Denholm, Justin T; Denkinger, Claudia M; Desmecht, Daniel; Diaz-Coronado, Juan C; Diaz Ponce-Medrano, Juan A; Donneau, Anne-Françoise; Dumagay, Teresita E; Dunachie, Susanna; Dungog, Cecile C; Erinoso, Olufemi; Escasa, Ivy Mae S; Estcourt, Lise J; Evans, Amy; Evasan, Agnes L M; Fareli, Christian J; Fernandez-Sanchez, Veronica; Galassi, Claudia; Gallo, Juan E; Garcia, Patricia J; Garcia, Patricia L; Garcia, Jesus A; Garigliany, Mutien; Garza-Gonzalez, Elvira; Gauiran, Deonne Thaddeus V; Gaviria García, Paula A; Giron-Gonzalez, Jose-Antonio; Gomez-Almaguer, David; Gordon, Anthony C; Gothot, Andre; Grass Guaqueta, Jeser Santiago; Green, Cameron; Grimaldi, David; Hammond, Naomi E; Harvala, Heli; Heralde, Francisco M; Herrick, Jesica; Higgins, Alisa M; Hills, Thomas E; Hines, Jennifer; Holm, Karin; Hoque, Ashraful; Hoste, Eric; Ignacio, Jose M; Ivanov, Alexander V; Janssen, Maike; Jennings, Jeffrey H; Jha, Vivekanand; King, Ruby Anne N; Kjeldsen-Kragh, Jens; Klenerman, Paul; Kotecha, Aditya; Krapp, Fiorella; Labanca, Luciana; Laing, Emma; Landin-Olsson, Mona; Laterre, Pierre-François; Lim, Lyn-Li; Lim, Jodor; Ljungquist, Oskar; Llaca-Díaz, Jorge M; Lopez-Robles, Concepcion; Lopez-Cardenas, Salvador; Lopez-Plaza, Ileana; Lucero, Josephine Anne C; Lundgren, Maria; Macias, Juan; Maganito, Sandy C; Malundo, Anna Flor G; Manrique, Ruben D; Manzini, Paola M; Marcos, Miguel; Marquez, Ignacio; Martinez-Marcos, Francisco Javier; Mata, Ana M; McArthur, Colin J; McQuilten, Zoe K; McVerry, Bryan J; Menon, David K; Meyfroidt, Geert; Mirasol, Ma Angelina L; Misset, Benoît; Molton, James S; Mondragon, Alric V; Monsalve, Diana M; Moradi Choghakabodi, Parastoo; Morpeth, Susan C; Mouncey, Paul R; Moutschen, Michel; Müller-Tidow, Carsten; Murphy, Erin; Najdovski, Tome; Nichol, Alistair D; Nielsen, Henrik; Novak, Richard M; O'Sullivan, Matthew V N; Olalla, Julian; Osibogun, Akin; Osikomaiya, Bodunrin; Oyonarte, Salvador; Pardo-Oviedo, Juan M; Patel, Mahesh C; Paterson, David L; Peña-Perez, Carlos A; Perez-Calatayud, Angel A; Perez-Alba, Eduardo; Perkina, Anastasia; Perry, Naomi; Pouladzadeh, Mandana; Poyato, Inmaculada; Price, David J; Quero, Anne Kristine H; Rahman, Md M; Rahman, Md S; Ramesh, Mayur; Ramirez-Santana, Carolina; Rasmussen, Magnus; Rees, Megan A; Rego, Eduardo; Roberts, Jason A; Roberts, David J; Rodriguez, Yhojan; Rodriguez-Baño, Jesus; Rogers, Benjamin A; Rojas, Manuel; Romero, Alberto; Rowan, Kathryn M; Saccona, Fabio; Safdarian, Mehdi; Santos, Maria Clariza M; Sasadeusz, Joe; Scozzari, Gitana; Shankar-Hari, Manu; Sharma, Gorav; Snelling, Thomas; Soto, Alonso; Tagayuna, Pedrito Y; Tang, Amy; Tatem, Geneva; Teofili, Luciana; Tong, Steven Y C; Turgeon, Alexis F; Veloso, Januario D; Venkatesh, Balasubramanian; Ventura-Enriquez, Yanet; Webb, Steve A; Wiese, Lothar; Wikén, Christian; Wood, Erica M; Yusubalieva, Gaukhar M; Zacharowski, Kai; Zarychanski, Ryan; Khanna, Nina; Moher, David; Goodman, Steven N; Ioannidis, John P A; Hemkens, Lars G; Laura and John Arnold Foundation
    Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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    Genome-wide association study identifies 30 loci associated with bipolar disorder.
    (2019-05-01) Stahl, Eli A; Breen, Gerome; Forstner, Andreas J; McQuillin, Andrew; Ripke, Stephan; Trubetskoy, Vassily; Mattheisen, Manuel; Wang, Yunpeng; Coleman, Jonathan R I; Gaspar, Héléna A; de Leeuw, Christiaan A; Steinberg, Stacy; Pavlides, Jennifer M Whitehead; Trzaskowski, Maciej; Byrne, Enda M; Pers, Tune H; Holmans, Peter A; Richards, Alexander L; Abbott, Liam; Agerbo, Esben; Akil, Huda; Albani, Diego; Alliey-Rodriguez, Ney; Als, Thomas D; Anjorin, Adebayo; Antilla, Verneri; Awasthi, Swapnil; Badner, Judith A; Bækvad-Hansen, Marie; Barchas, Jack D; Bass, Nicholas; Bauer, Michael; Belliveau, Richard; Bergen, Sarah E; Pedersen, Carsten Bøcker; Bøen, Erlend; Boks, Marco P; Boocock, James; Budde, Monika; Bunney, William; Burmeister, Margit; Bybjerg-Grauholm, Jonas; Byerley, William; Casas, Miquel; Cerrato, Felecia; Cervantes, Pablo; Chambert, Kimberly; Charney, Alexander W; Chen, Danfeng; Churchhouse, Claire; Clarke, Toni-Kim; Coryell, William; Craig, David W; Cruceanu, Cristiana; Curtis, David; Czerski, Piotr M; Dale, Anders M; de Jong, Simone; Degenhardt, Franziska; Del-Favero, Jurgen; DePaulo, J Raymond; Djurovic, Srdjan; Dobbyn, Amanda L; Dumont, Ashley; Elvsåshagen, Torbjørn; Escott-Price, Valentina; Fan, Chun Chieh; Fischer, Sascha B; Flickinger, Matthew; Foroud, Tatiana M; Forty, Liz; Frank, Josef; Fraser, Christine; Freimer, Nelson B; Frisén, Louise; Gade, Katrin; Gage, Diane; Garnham, Julie; Giambartolomei, Claudia; Pedersen, Marianne Giørtz; Goldstein, Jaqueline; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Green, Melissa J; Greenwood, Tiffany A; Grove, Jakob; Guan, Weihua; Guzman-Parra, José; Hamshere, Marian L; Hautzinger, Martin; Heilbronner, Urs; Herms, Stefan; Hipolito, Maria; Hoffmann, Per; Holland, Dominic; Huckins, Laura; Jamain, Stéphane; Johnson, Jessica S; Juréus, Anders; Kandaswamy, Radhika; Karlsson, Robert; Kennedy, James L; Kittel-Schneider, Sarah; Knowles, James A; Kogevinas, Manolis; Koller, Anna C; Kupka, Ralph; Lavebratt, Catharina; Lawrence, Jacob; Lawson, William B; Leber, Markus; Lee, Phil H; Levy, Shawn E; Li, Jun Z; Liu, Chunyu; Lucae, Susanne; Maaser, Anna; MacIntyre, Donald J; Mahon, Pamela B; Maier, Wolfgang; Martinsson, Lina; McCarroll, Steve; McGuffin, Peter; McInnis, Melvin G; McKay, James D; Medeiros, Helena; Medland, Sarah E; Meng, Fan; Milani, Lili; Montgomery, Grant W; Morris, Derek W; Mühleisen, Thomas W; Mullins, Niamh; Nguyen, Hoang; Nievergelt, Caroline M; Adolfsson, Annelie Nordin; Nwulia, Evaristus A; O'Donovan, Claire; Loohuis, Loes M Olde; Ori, Anil P S; Oruc, Lilijana; Ösby, Urban; Perlis, Roy H; Perry, Amy; Pfennig, Andrea; Potash, James B; Purcell, Shaun M; Regeer, Eline J; Reif, Andreas; Reinbold, Céline S; Rice, John P; Rivas, Fabio; Rivera, Margarita; Roussos, Panos; Ruderfer, Douglas M; Ryu, Euijung; Sánchez-Mora, Cristina; Schatzberg, Alan F; Scheftner, William A; Schork, Nicholas J; Shannon Weickert, Cynthia; Shehktman, Tatyana; Shilling, Paul D; Sigurdsson, Engilbert; Slaney, Claire; Smeland, Olav B; Sobell, Janet L; Søholm Hansen, Christine; Spijker, Anne T; St Clair, David; Steffens, Michael; Strauss, John S; Streit, Fabian; Strohmaier, Jana; Szelinger, Szabolcs; Thompson, Robert C; Thorgeirsson, Thorgeir E; Treutlein, Jens; Vedder, Helmut; Wang, Weiqing; Watson, Stanley J; Weickert, Thomas W; Witt, Stephanie H; Xi, Simon; Xu, Wei; Young, Allan H; Zandi, Peter; Zhang, Peng; Zöllner, Sebastian; eQTLGen Consortium; BIOS Consortium; Adolfsson, Rolf; Agartz, Ingrid; Alda, Martin; Backlund, Lena; Baune, Bernhard T; Bellivier, Frank; Berrettini, Wade H; Biernacka, Joanna M; Blackwood, Douglas H R; Boehnke, Michael; Børglum, Anders D; Corvin, Aiden; Craddock, Nicholas; Daly, Mark J; Dannlowski, Udo; Esko, Tõnu; Etain, Bruno; Frye, Mark; Fullerton, Janice M; Gershon, Elliot S; Gill, Michael; Goes, Fernando; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Hougaard, David M; Hultman, Christina M; Jones, Ian; Jones, Lisa A; Kahn, René S; Kirov, George; Landén, Mikael; Leboyer, Marion; Lewis, Cathryn M; Li, Qingqin S; Lissowska, Jolanta; Martin, Nicholas G; Mayoral, Fermin; McElroy, Susan L; McIntosh, Andrew M; McMahon, Francis J; Melle, Ingrid; Metspalu, Andres; Mitchell, Philip B; Morken, Gunnar; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Myers, Richard M; Neale, Benjamin M; Nimgaonkar, Vishwajit; Nordentoft, Merete; Nöthen, Markus M; O'Donovan, Michael C; Oedegaard, Ketil J; Owen, Michael J; Paciga, Sara A; Pato, Carlos; Pato, Michele T; Posthuma, Danielle; Ramos-Quiroga, Josep Antoni; Ribasés, Marta; Rietschel, Marcella; Rouleau, Guy A; Schalling, Martin; Schofield, Peter R; Schulze, Thomas G; Serretti, Alessandro; Smoller, Jordan W; Stefansson, Hreinn; Stefansson, Kari; Stordal, Eystein; Sullivan, Patrick F; Turecki, Gustavo; Vaaler, Arne E; Vieta, Eduard; Vincent, John B; Werge, Thomas; Nurnberger, John I; Wray, Naomi R; Di Florio, Arianna; Edenberg, Howard J; Cichon, Sven; Ophoff, Roel A; Scott, Laura J; Andreassen, Ole A; Kelsoe, John; Sklar, Pamela; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
    Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P 
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    Human Neural Stem Cells for Cell-Based Medicinal Products.
    (2021-09-09) Fernandez-Muñoz, Beatriz; Garcia-Delgado, Ana Belen; Arribas-Arribas, Blanca; Sanchez-Pernaute, Rosario
    Neural stem cells represent an attractive tool for the development of regenerative therapies and are being tested in clinical trials for several neurological disorders. Human neural stem cells can be isolated from the central nervous system or can be derived in vitro from pluripotent stem cells. Embryonic sources are ethically controversial and other sources are less well characterized and/or inefficient. Recently, isolation of NSC from the cerebrospinal fluid of patients with spina bifida and with intracerebroventricular hemorrhage has been reported. Direct reprogramming may become another alternative if genetic and phenotypic stability of the reprogrammed cells is ensured. Here, we discuss the advantages and disadvantages of available sources of neural stem cells for the production of cell-based therapies for clinical applications. We review available safety and efficacy clinical data and discuss scalability and quality control considerations for manufacturing clinical grade cell products for successful clinical application.
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    Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development
    (Mdpi, 2021-10-18) Millan-Esteban, David; Pena-Chilet, Maria; Garcia-Casado, Zaida; Manrique-Silva, Esperanza; Requena, Celia; Banuls, Jose; Lopez-Guerrero, Jose Antonio; Rodriguez-Hernandez, Aranzazu; Traves, Victor; Dopazo, Joaquin; Viros, Amaya; Kumar, Rajiv; Nagore, Eduardo; [Millan-Esteban, David] Univ Catolica Valencia San Vicente Martir, Sch Med, Valencia 46001, Spain; [Nagore, Eduardo] Univ Catolica Valencia San Vicente Martir, Sch Med, Valencia 46001, Spain; [Millan-Esteban, David] Fdn Inst Valenciano Onco, Mol Biol Lab, Valencia 46009, Spain; [Garcia-Casado, Zaida] Fdn Inst Valenciano Onco, Mol Biol Lab, Valencia 46009, Spain; [Lopez-Guerrero, Jose Antonio] Fdn Inst Valenciano Onco, Mol Biol Lab, Valencia 46009, Spain; [Pena-Chilet, Maria] Hosp Virgen Rocio, Fdn Progreso & Salud, Clin Bioinformat Area, Seville 41013, Spain; [Dopazo, Joaquin] Hosp Virgen Rocio, Fdn Progreso & Salud, Clin Bioinformat Area, Seville 41013, Spain; [Pena-Chilet, Maria] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Bioinformat Rare Dis BiER, Seville 41013, Spain; [Dopazo, Joaquin] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Bioinformat Rare Dis BiER, Seville 41013, Spain; [Pena-Chilet, Maria] Hosp Virgen Rocio, Inst Biomed Seville IBIS, Computat Syst Med, Seville 41013, Spain; [Requena, Celia] Hosp Virgen Rocio, Inst Biomed Seville IBIS, Computat Syst Med, Seville 41013, Spain; [Dopazo, Joaquin] Hosp Virgen Rocio, Inst Biomed Seville IBIS, Computat Syst Med, Seville 41013, Spain; [Manrique-Silva, Esperanza] Fdn Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain; [Rodriguez-Hernandez, Aranzazu] Fdn Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain; [Nagore, Eduardo] Fdn Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain; [Banuls, Jose] Hosp Gen Univ Alicante, El Inst Invest Sanitari & Biomed Alicante ISABIAL, Dept Dermatol, Alicante 03010, Spain; [Traves, Victor] Fdn Inst Valenciano Oncol, Dept Pathol Anat, Valencia 46009, Spain; [Dopazo, Joaquin] Hosp Virgen Rocio, Fdn Progreso & Salud ELIXIRes, Seville 41013, Spain; [Viros, Amaya] Univ Manchester, Canc Res UK Manchester Inst, Skin Canc & Aging Lab, Manchester SK10 4TG, Lancs, England; [Kumar, Rajiv] Deutsch Krebsforschungzentrum, Div Funct Genome Anal, D-69120 Heidelberg, Germany; [Kumar, Rajiv] Czech Acad Sci, Inst Expt Med, Dept Mol Biol Canc, Prague 14220, Czech Republic; [Kumar, Rajiv] Heidelberg Univ, Inst Med Biometry & Informat, D-69117 Heidelberg, Germany; Ministerio de Ciencia e Innovacion-Instituto de Salud Carlos III; Asociacion Espanola Contra el Cancer-Valencia through "Ayudas predoctorales en Oncologia" grant; European Academy of Dermatology and Venereology
    According to the divergent pathway model, cutaneous melanoma comprises a nevogenic group with a propensity to melanocyte proliferation and another one associated with cumulative solar damage (CSD). While characterized clinically and epidemiologically, the differences in the molecular profiles between the groups have remained primarily uninvestigated. This study has used a custom gene panel and bioinformatics tools to investigate the potential molecular differences in a thoroughly characterized cohort of 119 melanoma patients belonging to nevogenic and CSD groups. We found that the nevogenic melanomas had a restricted set of mutations , with the prominently mutated gene being BRAF. The CSD melanomas , in contrast, showed mutations in a diverse group of genes that included NF1, ROS1, GNA11, and RAC1. We thus provide evidence that nevogenic and CSD melanomas constitute different biological entities and highlight the need to explore new targeted therapies .
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    COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.
    (EMBO Press, 2021-10-19) Ostaszewski, Marek; Niarakis, Anna; Mazein, Alexander; Kuperstein, Inna; Phair, Robert; Orta-Resendiz, Aurelio; Singh, Vidisha; Aghamiri, Sara Sadat; Acencio, Marcio Luis; Glaab, Enrico; Ruepp, Andreas; Fobo, Gisela; Montrone, Corinna; Brauner, Barbara; Frishman, Goar; Monraz-Gomez, Luis Cristobal; Somers, Julia; Hoch, Matti; Kumar-Gupta, Shailendra; Scheel, Julia; Borlinghaus, Hanna; Czauderna, Tobias; Schreiber, Falk; Montagud, Arnau; Ponce-de-Leon, Miguel; Funahashi, Akira; Hiki, Yusuke; Hiroi, Noriko; Yamada, Takahiro G; Dräger, Andreas; Renz, Alina; Naveez, Muhammad; Bocskei, Zsolt; Messina, Francesco; Börnigen, Daniela; Fergusson, Liam; Conti, Marta; Rameil, Marius; Nakonecnij, Vanessa; Vanhoefer, Jakob; Schmiester, Leonard; Wang, Muying; Ackerman, Emily E; Shoemaker, Jason E; Zucker, Jeremy; Oxford, Kristie; Teuton, Jeremy; Kocakaya, Ebru; Summak, Gökçe Yağmur; Hanspers, Kristina; Kutmon, Martina; Coort, Susan; Eijssen, Lars; Ehrhart, Friederike; Balaya-Rex, Devasahayam Arokia ; Slenter, Denise; Martens, Marvin; Pham, Nhung; Haw, Robin; Jassal, Bijay; Matthews, Lisa; Orlic-Milacic, Marija; Senff-Ribeiro, Andrea; Rothfels, Karen; Shamovsky, Veronica; Stephan, Ralf; Sevilla, Cristoffer; Varusai, Thawfeek; Ravel, Jean-Marie; Fraser, Rupsha; Ortseifen, Vera; Marchesi, Silvia; Gawron, Piotr; Smula, Ewa; Heirendt, Laurent; Satagopam, Venkata; Wu, Guanming; Riutta, Anders; Golebiewski, Martin; Owen, Stuart; Goble, Carole; Hu, Xiaoming; Overall, Rupert W; Maier, Dieter; Bauch, Angela; Gyori, Benjamin M; Bachman, John A; Vega, Carlos; Grouès, Valentin; Vazquez, Miguel; Porras, Pablo; Licata, Luana; Iannuccelli, Marta; Sacco, Francesca; Nesterova, Anastasia; Yuryev, Anton; de-Waard, Anita; Turei, Denes; Luna, Augustin; Babur, Ozgun; Soliman, Sylvain; Valdeolivas, Alberto; Esteban-Medina, Marina; Peña-Chilet, Maria; Rian, Kinza; Helikar, Tomáš; Puniya, Bhanwar Lal; Modos, Dezso; Treveil, Agatha; Olbei, Marton; De-Meulder, Bertrand; Ballereau, Stephane; Dugourd, Aurelien; Naldi, Aurelien; Noël, Vincent; Calzone, Laurence; Sander, Chris; Demir, Emek; Korcsmaros, Tamas; Freeman, Tom C; Auge, Franck; Beckmann, Jacques S; Hasenauer, Jan; Wolkenhauer, Olaf; Wilighagen, Egon L; Pico, Alexander R; Evelo, Chris T; Gillespie, Marc E; Stein, Lincoln D; Hermjakob, Henning; D'Eustachio, Peter; Saez-Rodriguez, Julio; Dopazo, Joaquin; Valencia, Alfonso; Kitano, Hiroaki; Barillot, Emmanuel; Auffray, Charles; Balling, Rudi; Schneider, Reinhard; Marie Curie Actions; European Commission; COVID-19 Disease Map Community
    We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
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    Author Correction: COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms.
    (2020-07-17) Ostaszewski, Marek; Mazein, Alexander; Gillespie, Marc E; Kuperstein, Inna; Niarakis, Anna; Hermjakob, Henning; Pico, Alexander R; Willighagen, Egon L; Evelo, Chris T; Hasenauer, Jan; Schreiber, Falk; Dräger, Andreas; Demir, Emek; Wolkenhauer, Olaf; Furlong, Laura I; Barillot, Emmanuel; Dopazo, Joaquin; Orta-Resendiz, Aurelio; Messina, Francesco; Valencia, Alfonso; Funahashi, Akira; Kitano, Hiroaki; Auffray, Charles; Balling, Rudi; Schneider, Reinhard
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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    Fostering improvement in social centres for integrated care through a certification process
    (Ubiquity press ltd, 2019-01-01) Castellano Zurera, Ma del Mar; Rodriguez Benavente, Ana; Herrera Usagre, Manuel; Reyes Alcazar, Victor; Palop Del Rio, Angela; Torres Olivera, Antonio; [Castellano Zurera, Ma del Mar] Andalusian Agcy Healthcare Qual, Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Rodriguez Benavente, Ana] Andalusian Agcy Healthcare Qual, Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Herrera Usagre, Manuel] Andalusian Agcy Healthcare Qual, Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Reyes Alcazar, Victor] Andalusian Agcy Healthcare Qual, Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Palop Del Rio, Angela] Andalusian Agcy Healthcare Qual, Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Torres Olivera, Antonio] Andalusian Agcy Healthcare Qual, Agencia Calidad Sanitaria Andalucia, Seville, Spain
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    Willingness to Pay for Government-Approved Mobile Health Applications and mHealth Social Acceptability In Spain
    (Oxford univ press, 2018-09-01) Herrera-Usagre, M.; Buiza, B.; Reyes-Alcazar, V.; Escobar, A.; [Herrera-Usagre, M.] Univ Pablo de Olavide, Andalusian Agcy Healthcare Qual, Seville, Spain; [Buiza, B.] Andalusian Agcy Healthcare Qual, Seville, Spain; [Reyes-Alcazar, V.] Andalusian Agcy Healthcare Qual, Strateg Planning, Seville, Spain; [Escobar, A.] Andalusian Agcy Healthcare Qual, Digital Environm, Seville, Spain
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    Use and assessment of mobile health applications by health professionals in Andalusia to improve healthcare continuity and communication
    (Ubiquity press ltd, 2019-01-01) Gonzalez, Belen Sotillos; Reyes Alcazar, Victor; Ferrero Alvarez-Rementeria, Javier; Santana Lopez, Vicente; Vazquez Vazquez, Marta; Herrera Usagre, Manuel; Torres Olivera, Antonio; [Gonzalez, Belen Sotillos] Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Reyes Alcazar, Victor] Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Ferrero Alvarez-Rementeria, Javier] Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Santana Lopez, Vicente] Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Vazquez Vazquez, Marta] Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Herrera Usagre, Manuel] Agencia Calidad Sanitaria Andalucia, Seville, Spain; [Torres Olivera, Antonio] Agencia Calidad Sanitaria Andalucia, Seville, Spain
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    DOME: recommendations for supervised machine learning validation in biology.
    (2021) Walsh, Ian; Fishman, Dmytro; Garcia-Gasulla, Dario; Titma, Tiina; Pollastri, Gianluca; ELIXIR Machine Learning Focus Group; Harrow, Jennifer; Psomopoulos, Fotis E; Tosatto, Silvio C E