Articles publicats (Ciències Mèdiques Bàsiques)

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    Open Access
    The Catalan initiative for the Earth BioGenome Project: contributing local data to global biodiversity genomics.
    (Oxford University Press, 2024-04-17) Corominas, Montserrat; Marquès-Bonet, Tomàs; Arnedo, Miquel A.; Bayés, Mònica; Belmonte, Jordina; Escrivà, Hector; Fernández, Rosa; Gabaldón, Toni; Garnatje, Teresa; Germain i Otzet, Josep; Niell, Manel; Palero, Ferran; Pons, Joan; Puigdomènech, Pere; The Catalan Initiative for the Earth BioGenome Pro; Arroyo, Vanesa; Cuevas-Caballé, Cristian; Ferrer Obiol, Joan; Gut, Ivo; Gut, Marta; Hidalgo, Oriane; Izquierdo-Arànega, Guillem; Pérez-Sorribes, Laia; Righi, Emilio; Riutort, Marta; Vallès, Joan; Rozas, Julio; Alioto, Tyler; Guigó, Roderic
    The Catalan Initiative for the Earth BioGenome Project (CBP) is an EBP-affiliated project network aimed at sequencing the genome of the >40 000 eukaryotic species estimated to live in the Catalan-speaking territories (Catalan Linguistic Area, CLA). These territories represent a biodiversity hotspot. While covering less than 1% of Europe, they are home to about one fourth of all known European eukaryotic species. These include a high proportion of endemisms, many of which are threatened. This trend is likely to get worse as the effects of global change are expected to be particularly severe across the Mediterranean Basin, particularly in freshwater ecosystems and mountain areas. Following the EBP model, the CBP is a networked organization that has been able to engage many scientific and non-scientific partners. In the pilot phase, the genomes of 52 species are being sequenced. As a case study in biodiversity conservation, we highlight the genome of the Balearic shearwater Puffinus mauretanicus, sequenced under the CBP umbrella.
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    Open Access
    Modeling the effect of daytime duration on the biosynthesis of terpenoid precursors
    (Frontiers Media, 2024-01-11) Basallo, Oriol; Lucido, Abel; Sorribas Tello, Albert; Marin-Sanguino, Alberto; Vilaprinyo Terré, Ester; Martinez, Emilce; Eleiwa, Abderrahmane; Alves, Rui
    Terpenoids are valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical industries. Biosynthesis of these chemicals relies on polymerization of Isopentenyl di-phosphate (IPP) and/or dimethylallyl diphosphate (DMAPP) monomers, which plants synthesize using a cytosolic mevalonic acid (MVA) pathway and a plastidic methyleritritol-4-phosphate (MEP) pathway. Circadian regulation affects MVA and MEP pathway activity at three levels: substrate availability, gene expression of pathway enzymes, and utilization of IPP and DMAPP for synthesizing complex terpenoids. There is a gap in understanding the interplay between the circadian rhythm and the dynamics and regulation of the two pathways. In this paper we create a mathematical model of the MVA and MEP pathways in plants that incorporates the effects of circadian rhythms. We then used the model to investigate how annual and latitudinal variations in circadian rhythm affect IPP and DMAPP biosynthesis. We found that, despite significant fluctuations in daylight hours, the amplitude of oscillations in IPP and DMAPP concentrations remains stable, highlighting the robustness of the system. We also examined the impact of removing circadian regulation from different parts of the model on its dynamic behavior. We found that regulation of pathway substrate availability alone results in higher sensitivity to daylight changes, while gene expression regulation alone leads to less robust IPP/DMAPP concentration oscillations. Our results suggest that the combined circadian regulation of substrate availability, gene expression, and product utilization, along with MVA- and MEP-specific regulatory loops, create an optimal operating regime. This regime maintains pathway flux closely coupled to demand and stable across a wide range of daylight hours, balancing the dynamic behavior of the pathways and ensuring robustness in response to cellular demand for IPP/DMAPP.
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    Open Access
    Surrogate endpoints in phase III randomized trials of advanced gastroesophageal cancer: A systematic review and meta-analysis
    (Elsevier, 2024) Veas Rodríguez, Joel; Prieto, Ana; Vilaprinyo Terré, Ester; Bonet, Marta; Diez, Marc; Salud Salvia, Maria Antonieta; Montal Roura, Robert
    Overall survival (OS) is the most meaningful endpoint in clinical trials. However, owing to their limitations, surrogate endpoints are commonly used and validation studies are required to assess their reliability. Analysis of phase III randomized controlled trials (RCTs) of advanced gastroesophageal cancer (AGC) with > 100 patients, correlation coefficients (r), and determination coefficients (R²) between OS and surrogates were evaluated through meta-analyses. Progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR) were examined to determine their correlations with OS. Analysis of 65 phase III RCTs (29,766 subjects) showed a moderate correlation between PFS/TTP and OS (r = 0.77, R² = 0.59), while ORR correlation was low (r = 0.56, R² = 0.31). Excluding immunotherapy trials improved the PFS/TTP and OS correlations (r = 0.83, R² = 0.70). These findings suggest the potential use of PFS/TTP in AGC phase III investigations, disregarding the use of ORR as a surrogate endpoint.
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    Open Access
    Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment
    (Taylor & Francis, 2024) Aguareles, José; Villares Fernández, Paula; Forné Izquierdo, Carles; Martí-Ballesteros, Eva María; Pradillo Fernández, Virginia; Sotres-Fernandez, Gabriel; Fuente-Burguera, Adolfo de la; Navarro-San Francisco, Carolina; Buzon-Martín , Luis Miguel; García-Delangue, Teresa; Aiello, Francesco Tommaso; Carnevali-Ruiz, Daniel; Lloris, Raquel; Luepke-Estefan, Xavier Erik; López-Martín, José Antonio; Jimeno, José María; García-Casas, Ana; Guisado-Vasco, Pablo
    Objective To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. Design We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. Results Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. Conclusions Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population. KEY POINTS Haematological patients face an increased risk for severe COVID-19. Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients. Persistent viral replication is increased in immunocompromised patients. Plitidepsin does not lead to new serious adverse events in immunocompromised patients.
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    Open Access
    Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer
    (Elsevier, 2024) Vrede, Stephanie W.; Van Weelden, Willem Jan; Bulten, Johan; Gilks, C. Blake; Teerenstra, Steven; Huvila, Jutta; Matias-Guiu, Xavier; Gil-Moreno, Antonio; Asberger, Jasmin; Sweegers, Sanne; van der Putten, Louis J. M.; Küsters-Vandevelde, Heidi V. N; Reijnen, Casper; Colás, Eva; Hausnerova, Jitka; Weinberger, Vit; Snijders, Marc P. L. M.; Vinklerova, Petra; Ravaggi, Antonella; Odicino, Franco; Bignotti, Eliana; McAlpine, Jessica N.; Kruitwagen, Roy; Pijnenborg, Johanna M. A.
    Objective: The prognostic relevance of hormonal biomarkers in endometrial cancer (EC) has been well-established. A refined three-tiered risk model for estrogen receptor (ER)/progesterone receptor (PR) expression was shown to improve prognostication. This has not been evaluated in relation to the molecular subgroups. This study aimed to evaluate the ER/PR expression within the molecular subgroups in EC. Methods: A retrospective multicenter cohort study was performed and data from the European Network for Individualized Treatment centers and Vancouver, Canada were used. ER/PR immunohistochemical expression was grouped as: ER/PR 0-10 %, 20-80 % or 90-100 %. Molecular subgroups were determined with full next-generation sequencing or combined with immunohistochemistry: POLEmut, mismatch repair deficient (MMRd), p53mut and no-specific molecular profile (NSMP). Results: A total of 739 patients were included (median follow-up 5.0 years). Tumors were classified as POLEmut in 9.1 %(N = 67), MMRd in 27.6 %(N = 204), p53mut in 20.8 %(N = 154) and NSMP in 42.5 %(N = 314). Among all molecular subgroups, patients with ER/PR 90-100 % expression revealed the best disease-specific survival (DSS). Within p53mut, PR 90-100 % expression showed a 5-year DSS of 100.0 %. ER expression is prognostic more relevant in MMRd and NSMP tumors while PR expression in p53mut and NSMP tumors. Across all molecular subgroups, PR 0-10 %, p53mut, lympho-vascular space invasion and FIGO stage III-IV remained independently prognostic for reduced DSS Whereas PR 90-100 % and POLEmut remained independently prognostic for improved DSS. Conclusion: We demonstrated that ER/PR expression remain prognostically relevant within the molecular subgroups, and that a three-tiered cutoff refines prognostication. These data support incorporating routine evaluation of ER/PR expression in clinical practice.