CBR - Contribuições em Revistas Científicas / Contribution to Journals
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- CANA v1.0.0: efficient quantification of canalization in automata networksPublication . Marcus, Austin M.; Rozum, Jordan; Sizek, Herbert; Rocha, Luis M.SUMMARY: The biomolecular networks underpinning cell function exhibit canalization, or the buffering of fluctuations required to function in a noisy environment. We present a new major release of CANA, v1.0.0, an open-source Python package for understanding canalization in automata network models, discrete dynamical systems in which activation of biomolecular entities (e.g. transcription of genes) is modeled as the activity of coupled automata. One understudied putative mechanism for canalization is the functional equivalence of biomolecular regulators (e.g. among the transcription factors for a gene). We study this mechanism using the theory of symmetry in discrete functions. We present a new exact method, schematodes, for finding maximal symmetry groups among the inputs to discrete functions, and integrate it into CANA. The schematodes method substantially outperforms the inexact method of previous CANA versions both in speed and accuracy. We apply CANA v1.0.0 to study symmetry in 74 experimentally supported automata network models from the Cell Collective (CC) repository. The symmetry distribution is significantly different in the CC than in random automata with the same in-degree (connectivity) and bias (average output) (Kolmogorov-Smirnov test, P???.001). Its spread is much wider than in a null model (IQR 0.31 versus IQR 0.20 with equal medians), demonstrating that the CC is enriched in functions with extreme symmetry or asymmetry.
- Ecchordosis physaliphora: a rare and challenging clinical entity in a patient with acromegalyPublication . Marques, Pedro; Neto, Lia; Tortosa, Francisco; Sagarribay, Amets
- Outcomes of transcatheter aortic valve replacement in younger low-risk patients: a comprehensive meta-analysis of efficacy and safetyPublication . Almeida, António Rocha de; Lima, Maria Rita; Gomes, Daniel A.; Almeida, Manuel de Sousa; Fernandes, Renato; Oliveira, Eduardo Infante; Gonçalves, Pedro Araújo; Teles, Rui Campante; Patrício, LinoBackground and aims: Severe aortic stenosis (AS) was traditionally managed with surgical aortic valve replacement (SAVR). Transcatheter aortic valve implantation (TAVI) emerged as a less invasive alternative, initially for high-risk patients. This meta-analysis evaluates the outcomes of TAVI in younger, low-risk patients, in whom SAVR is currently the gold standard. Methods: Following PRISMA guidelines, we systematically searched randomized controlled trials (RCTs) comparing TAVI with SAVR in younger (mean age <75 years) low-risk patients (STS score <4%) with severe AS. The primary endpoint was a composite of death or disabling stroke. Secondary endpoints included all-cause mortality, disabling stroke, atrial fibrillation (AF), permanent pacemaker implantation (PPI), bleeding, functional class (NYHA), and quality-of-life (KCCQ score) improvements. Results: Four RCTs were included with 4,252 patients (2,125 TAVI and 2,127 SAVR). At a mean follow-up of 16 ± 5 months, TAVI showed a non-significant reduction in the composite of death or disabling stroke [2.8% vs. 5.1% risk ratio (RR) 0.98, 95% confidence interval (CI) (0.96–1.00), p = 0.11] and all-cause mortality [2.1% vs. 3.7%, RR 0.99, 95% CI (0.97–1.00), p = 0.15]. The incidence of disabling stroke was significantly lower in TAVI [0.9 vs. 2.1 RR 0.99, 95% CI (0.98–1.00), p < 0.01]. Hospital readmission [7.1% vs. 9.5% RR 0.97, 95% CI (0.96–0.99), p < 0.01] and bleeding rates [4.7% vs. 16%, RR 0.87, 95% CI (0.82–0.93), p < 0.01] were significantly lower in the TAVI group. Conversely, TAVI had a higher PPI rate [14% vs. 6%, RR 1.08, 95% CI (1.02–1.14), p < 0.01]. Faster symptomatic and quality-of-life improvements were sustained in the TAVI group. Conclusions: TAVI is a viable option for younger low-risk patients with severe AS, being non-inferior to SAVR in short-term outcomes. The benefits of TAVI include a lower risk of disabling stroke, hospital readmission, and bleeding, as well as quicker improvements in symptoms and quality of life. However, higher PPI rates require careful patient selection. The results support a tailored approach to TAVI in younger patients, with ongoing evaluation of long-term outcomes. Systematic Review Registration: https: www.crd.york.ac.uk/PROSPERO/view/CRD42024559473, PROSPERO (CRD42024559473).
- Quantifying edge relevance for epidemic spreading via the semi-metric topology of complex networksPublication . Soriano-Paños, David; Costa, Felipe Xavier; Rocha, Luis M.Sparsification aims at extracting a reduced core of associations that best preserves both the dynamics and topology of networks while reducing the computational cost of simulations. We show that the semi-metric topology of complex networks yields a natural and algebraically-principled sparsification that outperforms existing methods on those goals. Weighted graphs whose edges represent distances between nodes are \textit{semi-metric} when at least one edge breaks the triangle inequality (transitivity). We first confirm with new experiments that the \textit{metric backbone}—a unique subgraph of all edges that obey the triangle inequality and thus preserve all shortest paths—recovers Susceptible-Infected dynamics over the original non-sparsified graph. This recovery is improved when we remove only those edges that break the triangle inequality significantly, i.e., edges with large semi-metric distortion. Based on these results, we propose the new \textit{semi-metric distortion sparsification} method to progressively sparsify networks in decreasing order of semi-metric distortion. Our method recovers the macro- and micro-level dynamics of epidemic outbreaks better than other methods while also yielding sparser yet connected subgraphs that preserve all shortest paths. Overall, we show that semi-metric distortion overcomes the limitations of edge betweenness in ranking the dynamical relevance of edges not participating in any shortest path, as it quantifies the existence and strength of alternative transmission pathways.
- Establishing a dengue genomic monitoring in Cuba: uncovering virus dynamics to enhance local responsePublication . Pérez, Melissa; Álvarez, Mayling; Perez, Lissette; Benitez, Ana Julia; Serrano, Silvia; Adelino, Talita Emile Ribeiro; Fonseca, Vagner; Resik, Sonia; Kouri, Vivian; Gresh, Lionel; Franco, Leticia; Rico, Jairo Mendez; Lourenço, José; Alcantara, Luiz Carlos Junior; Guzman, Maria G.; Giovanetti, MartaBackground: A major dengue outbreak was reported by the Cuban Ministry of Health in 2022, highlighting the need for strong surveillance, with high pediatric cases showing warning signs. Using phylogenetic and epidemiologic approaches, we provide evidence toward a better understanding of dengue's recent transmission history. Methods: This study details the implementation of the genomic surveillance system for Dengue virus. Pre-screened DENV-3 positive samples (reverse transcription–polymerase chain reaction [RT-PCR] cycle threshold [Ct] <30) with epidemiologic metadata—including symptom onset, sample collection date, sex, age, residence, symptoms, and disease classification—underwent whole genome sequencing using Nanopore technology. Results: Genome sequences from 2022 to 2023 confirmed DENV-3 genotype III circulation in western, central, and eastern Cuba, covering 15 provinces and one special municipality. All cases were autochthonous, with 93% classified as dengue without warning signs and 7% as severe dengue. Long-term analysis identified a seasonal window of heightened suitability from May to November. Phylogenetic analyses revealed that DENV-3 genotype III has been introduced into Cuba multiple times, primarily from Asia and the Americas. These independent introduction events, likely driven by international travel and trade, underscore the importance of continued viral importation monitoring. The newly sequenced Cuban DENV-3 genotype III genomes were assigned to two distinct sub-lineages within genotype III: 3III_C, corresponding to the older American lineage I (2001-2014), and 3III_B.3, representing a novel introduction into Cuba associated with the more recent American lineage II (2022-2023). Evidence suggests that 3III_C, previously circulating in the country, may have been replaced by 3III_B.3 around 2020. Conclusions: This study outlines the development of a dengue genomic monitoring system in the country. The system will contribute to Cuba's public health response, facilitating timely interventions and potentially reducing the disease's impact on the local population.
- The seasonality and spatial landscape of the historical climate-based suitability of Aedes-borne viruses in four atlantic archipelagosPublication . Geraldes, Martim A.; Giovanetti, Marta; Cunha, Mónica V.; Lourenço, JoséWhile archipelagos have a demonstrated role in the stepping-stone process of the global dissemination of Aedes-borne viruses, they are often neglected in epidemiological and modelling studies. Over the past 20 years, some Atlantic archipelagos have witnessed a series of Aedes-borne viral outbreaks, prompting inquiries into the local historical suitability for transmission. In this study, the climate-based suitability for transmission of Aedes-borne viruses between 1980 and 2019 across Madeira, the Canaries, Cape Verde, and São Tomé e Príncipe archipelagos was estimated. For each island, we characterized the seasonality of climate-based suitability, mapped the spatial landscape of suitability, and quantified the historical effects of climate change. Results show that both island-level suitability and the historical impact of climate change decrease with distance from the equator, while significant seasonality patterns are observed only in subtropical climates. This study provides a unique historical perspective on the role of climate in shaping Aedes-borne virus transmission potential in Atlantic archipelagos. The findings herein described can inform local public health initiatives, including human-based prevention, targeted viral surveillance, and mosquito control programs.
- Focused digital cohort selection from social media using the metric backbone of biomedical knowledge graphsPublication . Guo, Ziqi; Felag, Jack; Rozum, Jordan C.; Correia, Rion Brattig; Wang, Xuan; Rocha, Luis M.Social media data allows researchers to construct large digital cohorts — groups of users who post health-related content — to study the interplay between human behavior and medical treatment. Identifying the users most relevant to a specific health problem is, however, a challenge in that social media sites vary in the generality of their discourse. While X (formerly Twitter), Instagram, and Facebook cater to wide ranging topics, Reddit subgroups and dedicated patient advocacy forums trade in much more specific, biomedically-relevant discourse. To filter relevant users on any social media, we have developed a general method and tested it on epilepsy discourse. We analyzed the text from posts by users who mention epilepsy drugs at least once in the general-purpose social media sites X and Instagram, the epilepsy-focused Reddit subgroup (r/Epilepsy), and the Epilepsy Foundation of America (EFA) forums. We used a curated medical terminology dictionary to generate a knowledge graph (KG) from each social media site, whereby nodes represent terms, and edge weights denote the strength of association between pairs of terms in the collected text. Our method is based on computing the metric backbone of each KG, which yields the (sparsified) subgraph of edges that participate in shortest paths. By comparing the subset of users who contribute to the backbone to the subset who do not, we show that epilepsy-focused social media users contribute to the KG backbone in much higher proportion than do general-purpose social media users. Furthermore, using human annotation of Instagram posts, we demonstrate that users who do not contribute to the backbone are much more likely to use dictionary terms in a manner inconsistent with their biomedical meaning and are rightly excluded from the cohort of interest. Our metric backbone approach, thus, has several benefits: it yields focused user cohorts who engage in discourse relevant to a targeted biomedical problem; unlike engagement-based approaches, it can retain low-engagement users who nonetheless contribute meaningful biomedical insights and filter out very vocal users who contribute no relevant content, it is parameter-free, algebraically principled, does not require classifiers or human-curation, and is simple to compute with the open-source code we provide.
- Comparative study of humoral and cellular immunity against SARS-CoV-2 induced by different COVID-19 vaccine types: insights into protection against wildtype, Delta and JN.1 omicron strainsPublication . Hasan, Zahra; Masood, Kiran Iqbal; Qaiser, Shama; Kanji, Akbar; Mwenda, Fridah; Alenquer, Marta; Iqbal, Junaid; Ferreira, Filipe; Wassan, Yaqub; Balouch, Sadaf; Yameen, Maliha; Hussain, Shahneel; Begum, Kehkashan; Feroz, Khalid; Muhammad, Sajid; Sadiqa, Ayesha; Akhtar, Mishgan; Habib, Atif; Ahmed, Syed Muhammad Areeb; Mian, Afsar Ali; Hussain, Rabia; Amorim, Maria Joao; Bhutta, Zulfiqar A.We investigated the effectiveness of different COVID-19 vaccinations administered in Pakistan by studying the effect of inactivated virus, mRNA and vector formulations. This study in 916 participants was conducted between October 2021 and July 2022. Subjects receiving inactivated (A), mRNA (B), one-dose vector (C), and two-dose vector (D) vaccines were sampled at baseline, 6, 12, and 24 weeks. Serum IgG antibodies to wildtype Spike and its receptor binding domain (RBD) were measured. Pseudovirus particle-based neutralizing assays against wildtype, Delta, and JN.1 variants were performed. T cell IFN-γ responses to SARS-CoV-2 antigens were measured. Participants were aged 37.05 ± 14.44 years and comprised 48.6 % females. Baseline Spike seropositivity rose from 90 % to 96 % by 24 weeks; and 40 % to 90 % against RBD. Group B participants had the highest anti-RBD levels which peaked by 6 weeks. IgG RBD in group A and C increased up until 24 weeks. Anti-RBD levels were reduced in those over 50 years. At baseline neutralizing titers were present at 38.5 % against wildtype and in 34.2 % against Delta variants. Titers doubled in vaccine groups A-C by 12 weeks, with highest titers in B and lowest in group C participants. At baseline, neutralizing titers against the JN.1 variant were absent but low titers were evident in 10 % of participants after 12 weeks. T cell reactivity to SARS-CoV-2 increased from 31 % at baseline to 50 % in group A and 73 % in group B participants by 6 weeks after vaccination. Presence of immunity against wildtype and Delta variants in one-third of participants at baseline could be due to sub-clinical infections. Increase in humoral and cellular immunity was greater after mRNA as compared with inactivated vaccinations. As COVID-19 morbidity in the population remained low, our data supports effectiveness of multiple vaccine formulations in protecting against severe COVID-19 in this high transmission population.
- Fast and flu-rious: how to prevent and treat emerging influenza A virusesPublication . Sesifredo, Isabel; Batalha, Íris Luz; Amorim, Maria João
- Predictors of therapeutic failure in GH and prolactin co-secreting pituitary adenomasPublication . Araujo-Castro, Marta; Biagetti, Betina; Menéndez, Edelmiro; Novoa-Testa, Iría; Cordido, Fernando; Berrocal, Víctor Rodríguez; Pascual-Corrales, Eider; Guerrero-Pérez, Fernando; Vicente, Almudena; García-Centeno, Rogelio; González, Laura; García, María Dolores Ollero; Echarri, Ana Irigaray; Rodríguez, María Dolores Moure; Novo-Rodríguez, Cristina; Calatayud, María; Villar-Taibo, Rocío; Bernabéu, Ignacio; Alvarez-Escola, Cristina; Jimenéz, Carmen Tenorio; Abellán-Galiana, Pablo; Venegas, Eva; González-Molero, Inmaculada; Iglesias, Pedro; Blanco, Concepción; Lara, Fernando Vidal Ostos de; Novoa, María Paz de Miguel; Torres, Elena López Mezquita; Hanzu, Felicia; Lamas, Cristina; Rodríguez, Silvia Aznar; Aulinas, Anna; Recio, José María; Aviles-Pérez, María Dolores; Núñez, Miguel Antonio Sampedro; Camara, Rosa; Fano, Miguel Paja; Fajardo, Carmen; Cardoso, Luís; Marques, Pedro; Martínez-Sáez, Elena; Ruz-Caracuel, Ignacio; Marazuela, Mónica; Puig-Domingo, ManelAim: To evaluate which factors are associated with a higher probability of failure to surgical and first-generation somatostatin receptor ligands (fgSRLs) treatment in patients with growth hormone and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). Methods: Acromegaly patients with GH&PRL-PAs included in the ACRO-SPAIN study were enrolled. GH&PRL-PAs were defined as tumors with serum PRL levels above the upper limit of normal and positive immunostaining for GH and PRL, or with PRL levels ≥100 ng/mL when immunostaining data were not available. Results: A total of 126 acromegaly patients with GH&PRL-PAs who underwent transsphenoidal pituitary surgery were included, and 42.1% (n = 53) were biochemically cured at the immediate postoperative evaluation. Knosp grade >2 (odds ratio (OR) 3.48, 95% CI 1.28–9.38), higher serum GH (OR 1.01, 95% CI 1.01–1.08) and IGF-1 (OR 1.60, 95% CI 1.05–2.45) levels were associated with a lower probability of surgical cure. Sixty-eight patients received first-line medical therapy as follows: fgSRLs in monotherapy (n = 22), fgSRL plus cabergoline (n = 37), cabergoline in monotherapy (n = 7) and pegvisomant in monotherapy (n = 2). Among the cases treated with fgSRL in monotherapy, 18.2% (n = 4/22) were resistant. We identified as predictors of fgSRL resistance (in monotherapy and combined with cabergoline) a Knosp grade >2 (OR 8.75, P = 0.003), high GH levels at acromegaly diagnosis (OR 1.02, P = 0.031) and higher postoperative GH levels (OR 1.05, P = 0.006), but no predictors of response to fgSRL in monotherapy were identified. Conclusion: The clinical predictors of surgical failure and of fgSRL resistance in patients with GH&PRL-PAs are similar to those described in acromegaly without PRL, co-secretion.