CBR - Contribuições em Revistas Científicas / Contribution to Journals
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- Glucocorticoid-induced arginine vasopressin deficiency and neurohypophyseal T1-hyperintensity transient switch-offPublication . Marques, Pedro; Neto, Lia; Fontes, Luísa; Sapinho, Inês
- Protocol for evaluating ChatGPT in biomedical association generation and verification using a RAG enabled, cross-model majority voting workflowPublication . Hamed, Ahmed Abdeen; Rocha, Luis M.We present a protocol to evaluate ChatGPT’s ability to generate disease-centric biomedical associations. It outlines how we generate the associations, validate the biological entities using biomedical ontologies, and verify associations using literature. The protocol includes a self-consistency strategy to assess generative reliability across ChatGPT models. To address ontology exact-match limitations, we provide a use case performing semantic verification through a workflow enabled by Retrieval-Augmented Generation (RAG) powered by open-source large language models (LLMs). This enables LLMs to establish truth over content generated by other LLMs and expose hallucination.
- Glucocorticoid-induced arginine vasopressin deficiency and neurohypophyseal T1-hyperintensity transient switch-offPublication . Marques, Pedro; Neto, Lia; Fontes, Luísa; Sapinho, Inês
- Protocol for evaluating ChatGPT in biomedical association generation and verification using a RAG enabled, cross-model majority voting workflowPublication . Hamed, Ahmed Abdeen; Rocha, Luis M.We present a protocol to evaluate ChatGPT’s ability to generate disease-centric biomedical associations. It outlines how we generate the associations, validate the biological entities using biomedical ontologies, and verify associations using literature. The protocol includes a self-consistency strategy to assess generative reliability across ChatGPT models. To address ontology exact-match limitations, we provide a use case performing semantic verification through a workflow enabled by Retrieval-Augmented Generation (RAG) powered by open-source large language models (LLMs). This enables LLMs to establish truth over content generated by other LLMs and expose hallucination.
- Urinary-free cortisol-based thresholds for differentiating ACTH-dependent Cushing: a Spanish validation studyPublication . Biagetti, Betina; Marques, Pedro; Soto-Moreno, Alfonso; García-Centeno, Rogelio; González-Fernández, Laura; Garcia, María Dolores Ollero; Echarri, Ana Irigaray; Cardona-Arias, Andres; Rodríguez, Maria Dolores Moure; Paja, Miguel; Castro, Ana; Valero, Lucía Manzano; Guerrero-Pérez, Fernando; Lamas, Cristina; Lázaro, Victoria Alcázar; Gracia, Paola; Sanchis-Pascual, David; ÁLvarez-Escolá, Cristina; Lozano-Aida, Claudia; Hanzu, Felicia A.; Araujo-Castro, MartaContext: Differentiating ectopic ACTH secretion (EAS) from Cushing disease (CD) remains one of the most challenging steps in the diagnostic workup of ACTH-dependent Cushing syndrome (CS). Urinary-free cortisol (UFC) expressed as times above the upper limit of normal (ULN) has been proposed as a simple, noninvasive discriminator, but external validation in independent populations is lacking. Objective: To validate the diagnostic performance of UFC × ULN for distinguishing EAS from CD and explore complementary biochemical markers, including late-night salivary cortisol (LNSC × ULN) and hypokalemia. Design, Setting, and Participants Multicenter retrospective study from the Spanish Cushing Registry including 269 patients with ACTH-dependent Cushing’s syndrome (208 CD, 61 EAS) diagnosed and managed in tertiary referral centers. Main Outcome Measures: Diagnostic accuracy of UFC × ULN and LNSC × ULN for discriminating EAS from CD, expressed as area under the ROC curve (AUC), sensitivity, specificity, and predictive value. Results: EAS patients were older (median 59.0 vs 44.9 years; P < .001) and showed higher UFC × ULN (16.6 vs 3.6; P < .001) and LNSC × ULN (9.3 vs 1.5; P < .001). UFC × ULN and LNSC × ULN achieved excellent discriminative performance (AUC 0.90 and 0.92). No EAS occurred with UFC × ULN < 3 × ULN, while 40.5% of patients with UFC ≥ 10 × ULN had EAS. The combination of severe hypercortisolism (UFC ≥ 10 × ULN and LNSC ≥ 9 × ULN) plus hypokalemia identified 75% of EAS with 98% specificity. Conclusion: UFC × ULN thresholds reliably stratify the probability of EAS vs CD. Severe hypercortisolism and hypokalemia strongly predict EAS, supporting a pragmatic diagnostic approach that prioritizes whole-body imaging in high-risk patients and pituitary-centered evaluation in mild cases.
- Dynamics and ecology of a multistage expansion of Oropouche virus in BrazilPublication . Tegally, Houriiyah; Dellicour, Simon; Poongavanan, Jenicca; Mavian, Carla; Dor, Graeme; Fonseca, Vagner; Tagliamonte, Massimiliano S.; Dunaiski, Marcel; Moir, Monika; Wilkinson, Eduan; Albuquerque, Carlos Frederico Campelo de; Frutuoso, Livia C. V.; Holmes, Edward C.; Baxter, Cheryl; Lessells, Richard; Kraemer, Moritz U. G.; Lourenco, José; Alcantara, Luiz Carlos Junior; Oliveira, Tulio de; Giovanetti, MartaIn March 2024, Brazil reported an unprecedented Oropouche fever outbreak, driven by the emergence of a reassortant lineage of the Oropouche virus (OROV) expanding beyond the Amazon Basin. To investigate the expansion dynamics of OROV, we implemented complementary phylogeographic and ecological niche modelling approaches that aimed to characterize the environmental factors associated with the range expansion and the risk of local circulation, respectively. Our analyses reveal a multiscale expansion process with both shortand long-distance dispersal events and diffusion velocities in line with air traffic-mediated jumps. We identify banana and cocoa cultivation, temperature, the predicted suitability of the primary vector Culicoides paraensis and human population density as key environmental factors associated with OROV range expansion in new areas. We further show that OROV circulated in areas of enhanced ecological suitability immediately preceding its explosive epidemic expansion in the Amazon. Our study provides valuable insights into the dispersal and ecological dynamics of OROV, highlighting the probable role of human mobility in the long-distance colonization of new areas and raising concern over high viral suitability along the Brazilian coast.
- The emerging role of chemokines and chemokine receptors in the biological and clinical behaviour of pituitary neuroendocrine tumours: an exploratory transcriptomic studyPublication . Silva, Ana Luísa; Barry, Sayka; Hipólito, Ana; Severino, Mariana de Griné; Joaquim, Rita; Hall, Charlotte; Oliveira, Tiago; López-Presa, Dolores; Borrecho, Gonçalo; Tortosa, Francisco; Nobre, Ema; Faria, Claudia C.; Korbonits, Márta; Marques, PedroThe chemokine network in the microenvironment of pituitary neuroendocrine tumours (PitNETs) may modulate tumour biology, aggressiveness, and treatment responses. We aimed to study the role of various chemokines and chemokine receptors in defining PitNET phenotype and clinical outcomes. We included 96 patients (51 females) with available snap-frozen PitNET tissue from surgery between 2014 and 2020. Chemokine and chemokine receptors were studied by RT-qPCR. Fold difference in mRNA expression was calculated using the ΔΔCt method; chemokine and receptor expression levels were normalised to the expression of the control gene TBP, and expressed relative to a reference sample. Ten chemokines and receptors were studied (CCL2, CCL3, CCL4, CXCL8, CX3CL1, CCR2, CCR4, CCR5, CXCR1, CXCR2), and their expression correlated with clinico-pathological and outcome data, as well as other available microenvironment-related data. We found strong positive correlations between all chemokines and chemokine receptors. Higher chemokine and receptor expression levels were seen in patients who had pituitary apoplexy (CCR2, CXCR1), hypopituitarism at diagnosis (CCL2, CCR4), Ki-67 >3% (CCL4, CXCR2), as well as in patients who required re-operation (CCL3, CXCL8, CXCR2), multimodal therapy (CCL2), and had active disease at last-follow-up (CCL2). There was a positive correlation between the number of pituitary surgeries and expression levels of CCL3, CXCL8, CX3CL1, CXCR1, and CXCR2. Compared to nonfunctioning-PitNETs, somatotropinomas had higher expression of CCL2, CCL4, and CCR2, and lower expression of CX3CL1 and CCR4. Expression of CDH1 (encoding E-cadherin) correlated negatively with CCL2, CCL4, CCR2, CCR4, and CXCR2, while the expression of ZEB1 (mesenchymal marker) positively correlated with CCL3, CCL4, and CX3CL1. PitNETs expressing higher levels of CCL4, CX3CL1, CCR4, CCR5, and CXCR1 had more and bigger vessels. Somatotropinomas treated pre-operatively with somatostatin analogues were associated with higher expression of CCL2, CCR4, CXCR1, and CXCR2, while nonfunctioning-PitNETs pre-surgically treated with dopamine agonists were associated with lower expression of CCL3, CCL4, CX3CL1, CCR5, CXCR1, and CXCR2. Our data suggests that chemokines and chemokine receptors may be involved in the modulation of different tumorigenic mechanisms in PitNETs, including tumour proliferation, epithelial-to-mesenchymal transition, and angiogenesis, and may be associated with more aggressive and difficult-to-treat disease.
- Evolutionary dynamics of epitopes of limited variability on the head of influenza H1 haemagglutininPublication . Lourenço, José; Zinad, Hany; Kempton, James; Gupta, SunetraIt is commonly assumed that naturally protective targets of immunity in influenza are highly variable. Theoretical work suggests, by contrast, that influenza evolution is primarily driven by naturally protective responses against epitopes of limited variability (ELV). At least one ELV has been identified on the head region of haemagglutinin of H1 influenza, opening up the possibility of producing a universal influenza vaccine. Here, for the first time, we provide a comprehensive catalogue of ELVs within the head region of H1 haemagglutinin and explain how they arise within its apparently high variable landscape. We show that the head region of H1 haemagglutinin can be decomposed into a number of discrete variable regions (VRs): ELVs tend to include a limited number of VRs compared to other epitopes either because of the smaller footprint of the associated antibody or because they are centred on VRs that are relatively isolated from others. Thus, the variability of an antibody binding site is determined by the number of variable residues included in its footprint rather than the intrinsic entropy of any particular region.
- Discovery and cultivation of prokaryotic taxa in the age of metagenomics and artificial intelligencePublication . Jiménez, Diego Javier; Marasco, Ramona; Schultz, Júnia; Rodríguez, Carlos Andrés Díaz; Nogales, Juan; Rodriguez-R, Luis Miguel; Overmann, Jörg; Rosado, Alexandre SoaresDespite advances in sequencing, microbial genomics, and cultivation techniques, the vast majority of prokaryotic species remain uncultured, which is a persistent bottleneck in microbiology and microbial ecology. This perspective outlines a conceptual framework to improve the transition from genomeresolved metagenomics to the targeted isolation of yet-uncultured prokaryotic taxa. The proposed framework integrates the induced reshaping of microbiomes, genome-based inferences of physiological and phenotypic traits, culture media design, and targeted culturomics, enabling hypothesis-driven cultivation. In addition, this manuscript addresses the critical limitations in the field, including the sequence-to-function gap, and emphasizes the synergistic potential of experimental microbiology, microbial ecology, metagenomics, and artificial intelligence (AI)-based predictions to enhance rational and actionable roadmaps for discovering and cultivating novel prokaryotic lineages.
- Land and climate suitability for West Nile virus in Atlantic archipelagos guided by historical data from EuropePublication . Geraldes, Martim A.; Giovanetti, Marta; Cunha, Mónica V.; Lourenço, JoséWest Nile (WNV) is a zoonotic mosquito-borne virus with an expanding geographical and epidemic activity worldwide. Computational studies have contributed to the understanding of factors driving WNV occurrence, particularly in North America and Europe. Archipelagos have largely been overlooked, despite the risk to unique local avian species and human populations. In this study, we apply an ecological niche approach, trained on WNV occurrence and (a)biotic factors from European countries to project ecological suitability for WNV occurrence across several Atlantic archipelagos. The approach gives weight to the temporal dimension, generating novel insights on seasonality both for Europe and the archipelagos. For European countries, modelling results align with previous findings on spatial hotspots and (a)biotic drivers of WNV occurrence, while further unravelling properties of at-risk human populations within dynamically suitable land areas. For Atlantic archipelagos, results constitute a novel and detailed perspective on local ecological suitability for WNV occurrence, providing a data-driven framework that identifies spatial hotspots, defines seasonal patterns and quantifies the local population at risk. The synthetic data generated in this study supports the development of targeted preparedness, surveillance and mitigation plans tailored to the unique ecological and seasonal dynamics of each region under study.