1,491 results on '"João Gonçalves"'
Search Results
2. Improving Computer-Aided Medical Diagnosis Using Generative Adversarial Networks for Carotid Artery Ultrasound Image Data Augmentation and Classification
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Ricardo Fitas and João Gonçalves
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cnn ,gan ,medical images ,carotid artery ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
Cardiovascular diseases are a leading cause of death globally, making early detection of atherosclerosis critical for prevention. Carotid artery ultrasound imaging is a common diagnostic tool; however, the limited availability of labelled medical images hinders the training of deep learning models. This study examines generative adversarial networks (GANs) for data augmentation and classification of carotid artery Doppler images to improve computer-aided medical diagnosis. Four convolutional neural networks (CNNs) – AlexNet, VGGNet, GoogleNet, and CifarNet – are evaluated for their classification performance on original and extended datasets. AlexNet outperforms the other models, achieving a classification accuracy of 94.18% on the extended dataset. The GAN implementation for data augmentation and overfitting reduction demonstrates the potential of generative models in enhancing the performance of deep learning models in medical image analysis, particularly in the "common artery carotid" class. This research contributes to understanding GANs as a valuable tool for data augmentation and classification in the context of carotid artery ultrasound images.
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- 2024
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3. Editorial: Molecular mechanisms of cilia related diseases
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Sara Carvalhal, Bruno Carmona, Anne-Marie Tassin, and João Gonçalves
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cilium ,ciliopathies ,molecular mechanisms of disease ,rare genetic diseases ,organelle ,cytoskeleton ,signalling ,Biology (General) ,QH301-705.5 - Published
- 2024
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4. Exploring mixed lepton-quark interactions in non-resonant leptoquark production at the LHC
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João Gonçalves, António P. Morais, António Onofre, and Roman Pasechnik
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Specific BSM Phenomenology ,Theories of Flavour ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract Searches for new physics (NP) at particle colliders typically involve multivariate analysis of kinematic distributions of final state particles produced in a decay of a hypothetical NP resonance. Since the pair-production cross-sections mediated by such resonances are strongly suppressed by the NP scale, this analysis becomes less relevant for NP searches for masses of the BSM resonance above 1 TeV. On the other hand, t-channel processes are less sensitive to the mass of the virtual mediator and therefore larger phase-space can be potentially probed as well as the couplings between the NP particles and the Standard Model fields. The fact that transitions between different generations of quarks and leptons may exist, the potential of the search presented in this article can be used, as a reference guide, to enlarge significantly the scope of searches performed at the LHC to flavour off-diagonal channels, in a theoretically consistent approach. In this work, we study non-resonant production of scalar leptoquarks which have been proposed in the literature to provide a potential avenue for radiative generation of neutrino masses, accommodating as well the existing flavour physics data. Final states involving just two muons at the LHC (μ + μ − ), are used as a well-motivated case study.
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- 2023
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5. Infectious Foci, Comorbidities and Its Influence on the Outcomes of Septic Critically Ill Patients
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Ana Maria Oliveira, André Oliveira, Raquel Vidal, and João Gonçalves-Pereira
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infection foci ,bacteremia ,hospital-acquired infections ,septic shock ,ICU ,SAPS II ,Biology (General) ,QH301-705.5 - Abstract
Sepsis is among the most frequent diagnoses on admission to the intensive care unit (ICU). A systemic inflammatory response, activated by uncontrolled infection, fosters hypoperfusion and multiorgan failure and often leads to septic shock and mortality. These infections arise from a specific anatomic source, and how the infection foci influence the outcomes is unknown. All patients admitted to the ICU of Hospital de Vila Franca de Xira, between 1 January 2017 and 31 June 2023, were screened for sepsis and categorized according to their infection foci. During the study period, 1296 patients (32.2%) had sepsis on admission. Their mean age was 67.5 ± 15.3 and 58.1% were male; 73.0% had community-acquired infections. The lung was the main focus of infection. Septic shock was present in 37.9% of the patients and was associated with hospital mortality. Severe imbalances were noted in its incidence, and there was lower mortality in lung infections. The hospital-acquired infections had a slightly higher mortality but, after adjustment, this difference was non-significant. Patients with secondary bacteremia had a worse prognosis (one-year adjusted hazard ratio of 1.36, 95% confidence interval 1.06–1.74, p = 0.015), especially those with an isolated non-fermenting Gram-negative infection. Lung, skin, and skin structure infections and peritonitis had a worse prognosis, whilst urinary, biliary tract, and other intra-abdominal infections had a better one-year outcome.
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- 2024
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6. Sickle Cell Anemia Screening in Newborns and Analysis of Haplotypes in Patients from Santiago Island, Cape Verde
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Ariana Freire, Laura Charola-Ramos, Elisa González-Guerra, João Gonçalves, Vanusa Rocha, Vera Afreixo, Enrique Martínez-Carretero, and José M. Raya
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Sickle cell anemia (SCA) results from a mutation in the β-globin gene, leading to the production of mutant hemoglobin, known as hemoglobin S (HbS). Despite being a genetic disorder, the phenotype of SCA can be influenced by the level of fetal hemoglobin (HbF), which is associated with beta S-globin haplotypes. In this study, we conducted newborn screening (NBS) using samples collected from umbilical cord blood in two hospitals on Santiago Island, Cape Verde. In newborns, HbS was detected using high-performance liquid chromatography (HPLC) on dried blood spot, with confirmation through polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). In addition, we assessed the hematological and clinical characteristics of a second population group consisting of patients diagnosed with SCA. Haplotype determination was performed on both newborns with HbS and patients with SCA. Beta S-globin haplotypes were determined using PCR-RFLP. Hematological values were analyzed using standard methods. Out of 346 newborns, 21 (6%) were carriers of the sickle cell trait (HbAS) while none were identified as homozygous for sickle cell disease (HbSS). Among both groups of individuals, four haplotypes were identified: Senegal, Arabi-Indian, Bantu, and Benin. The Senegal haplotype was the most prevalent, possibly reflecting the ethnic origin of the mutations observed. Hematological values did not differ significantly among haplotypes. However, higher levels of HbF were associated with better hematological values. These findings suggest a positive impact of elevated HbF levels on reducing the severity of SCA. Finally, we demonstrated how the combination of technics, HPLC and molecular analysis, provided a consistent and reproducible results that can be used for NBS for SCA.
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- 2024
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7. Machine Learning-Based Model Helps to Decide which Patients May Benefit from Pancreatoduodenectomy
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Emanuel Vigia, Luís Ramalhete, Edite Filipe, Luís Bicho, Ana Nobre, Paulo Mira, Maria Macedo, Catarina Aguiar, Sofia Corado, Beatriz Chumbinho, Jorge Balaia, Pedro Custódio, João Gonçalves, and Hugo P. Marques
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pancreatic cancer ,machine learning ,survival ,decision support ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Pancreatic ductal adenocarcinoma is an invasive tumor with similar incidence and mortality rates. Pancreaticoduodenectomy has morbidity and mortality rates of up to 60% and 5%, respectively. The purpose of our study was to assess preoperative features contributing to unfavorable 1-year survival prognosis. Study Design: Retrospective, single-center study evaluating the impact of preoperative features on short-term survival outcomes in head PDAC patients. Forty-four prior features of 172 patients were tested using different supervised machine learning models. Patient records were randomly divided into training and validation sets (80–20%, respectively), and model performance was assessed by area under curve (AUC) and classification accuracy (CA). Additionally, 33 patients were included as an independent revalidation or holdout dataset group. Results: Eleven relevant features were identified: age, sex, Ca-19-9, jaundice, ERCP with biliary stent, neutrophils, lymphocytes, lymphocyte/neutrophil ratio, neoadjuvant treatment, imaging tumor size, and ASA. Tree regression (tree model) and logistic regression (LR) performed better than the other tested models. The tree model had an AUC = 0.92 and CA = 0.85. LR had an AUC = 0.74 and CA = 0.78, allowing the development of a nomogram based on absolute feature significance. The best performance model was the tree model which allows us to have a decision tree to help clinical decisions. Discussion and conclusions: Based only on preoperative data, it was possible to predict 1-year survival (91.5% vs. 78.1% alive and 70.9% vs. 76.6% deceased for the tree model and LR, respectively). These results contribute to informed decision-making in the selection of which patients with PDAC can benefit from pancreatoduodenectomy. A machine learning algorithm was developed for the recognition of unfavorable 1-year survival prognosis in patients with pancreatic ductal adenocarcinoma. This will contribute to the identification of patients who would benefit from pancreatoduodenectomy. In our cohort, the tree regression model had an AUC = 0.92 and CA = 0.85, whereas the logistic regression had an AUC = 0.74 and CA = 0.78. To further inform decision-making, a decision tree based on tree regression was developed.
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- 2023
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8. Intra-observer reproducibility and inter-observer agreement of Fels skeletal age assessments among male tennis players 8–16 years
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Paulo Sousa-e-Silva, Manuel J. Coelho-e-Silva, Jorge M. Celis-Moreno, Daniela C. Costa, Diogo V. Martinho, Luís P. Ribeiro, Tomas Oliveira, João Gonçalves-Santos, Oscar M. Tavares, Joaquim M. Castanheira, Telmo Pereira, Jorge Conde, Ricardo R. Cayolla, Pedro Duarte-Mendes, Gillian K. Myburgh, Sean P. Cumming, and Robert M. Malina
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Youth sports ,Biological maturation ,Bone age ,Skeletal maturation ,Maturity status ,Pediatrics ,RJ1-570 - Abstract
Abstract Background Skeletal age (SA) is an estimate of biological maturity status that is commonly used in sport-related medical examinations. This study considered intra-observer reproducibility and inter-observer agreement of SA assessments among male tennis players. Methods SA was assessed with the Fels method in 97 male tennis players with chronological ages (CA) spanning 8.7–16.8 years. Radiographs were evaluated by two independent trained observers. Based on the difference between SA and CA, players were classified as late, average or early maturing; if a player was skeletally mature, he was noted as such as an SA is not assigned. Results The magnitude of intra-individual differences between repeated SA assessments were d = 0.008 year (observer A) and d = 0.001 year (observer B); the respective coefficients of variation were 1.11% and 1.75%. Inter-observer mean differences were negligible (t = 1.252, p = 0.210) and the intra-class correlation coefficient was nearly perfect (ICC = 0.995). Concordance of classifications of players by maturity status between observers was 90%. Conclusion Fels SA assessments were highly reproducible and showed an acceptable level of inter-observer agreement between trained examiners. Classifications of players by skeletal maturity status based on assessments of the two observers were highly concordant, though not 100%. The results highlight the importance of experienced observers in skeletal maturity assessments.
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- 2023
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9. Deep learning searches for vector-like leptons at the LHC and electron/muon colliders
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António P. Morais, António Onofre, Felipe F. Freitas, João Gonçalves, Roman Pasechnik, and Rui Santos
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Astrophysics ,QB460-466 ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract The discovery potential of both singlet and doublet vector-like leptons (VLLs) at the Large Hadron Collider (LHC) as well as at the not-so-far future muon and electron machines is explored. The focus is on a single production channel for LHC direct searches while double production signatures are proposed for the leptonic colliders. A Deep Learning algorithm to determine the discovery (or exclusion) statistical significance at the LHC is employed. While doublet VLLs can be probed up to masses of 1 TeV, their singlet counterparts have very low cross sections and can hardly be tested beyond a few hundreds of GeV at the LHC. This motivates a physics-case analysis in the context of leptonic colliders where one obtains larger cross sections in VLL double production channels, allowing to probe higher mass regimes otherwise inaccessible even to the LHC high-luminosity upgrade.
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- 2023
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10. Critically ill patient mortality by age: long-term follow-up (CIMbA-LT)
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João Gonçalves-Pereira, André Oliveira, Tatiana Vieira, Ana Rita Rodrigues, Maria João Pinto, Sara Pipa, Ana Martinho, Sofia Ribeiro, and José-Artur Paiva
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Follow-up ,Long term ,Age ,Survival ,Mortality ,SAPS-II ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background The past years have witnessed dramatic changes in the population admitted to the intensive care unit (ICU). Older and sicker patients are now commonly treated in this setting due to the newly available sophisticated life support. However, the short- and long-term benefit of this strategy is scarcely studied. Methods The Critically Ill patients’ mortality by age: Long-Term follow-up (CIMbA-LT) was a multicentric, nationwide, retrospective, observational study addressing short- and long-term prognosis of patients admitted to Portuguese multipurpose ICUs, during 4 years, according to their age and disease severity. Patients were followed for two years after ICU admission. The standardized hospital mortality ratio (SMR) was calculated according to the Simplified Acute Physiology Score (SAPS) II and the follow-up risk, for patients discharged alive from the hospital, according to official demographic national data for age and gender. Survival curves were plotted according to age group. Results We included 37.118 patients, including 15.8% over 80 years old. The mean SAPS II score was 42.8 ± 19.4. The ICU all-cause mortality was 16.1% and 76% of all patients survive until hospital discharge. The SAPS II score overestimated hospital mortality [SMR at hospital discharge 0.7; 95% confidence interval (CI) 0.63–0.76] but accurately predicted one-year all-cause mortality [1-year SMR 1.01; (95% CI 0.98–1.08)]. Survival curves showed a peak in mortality, during the first 30 days, followed by a much slower survival decline thereafter. Older patients had higher short- and long-term mortality and their hospital SMR was also slightly higher (0.76 vs. 0.69). Patients discharged alive from the hospital had a 1-year relative mortality risk of 6.3; [95% CI 5.8–6.7]. This increased risk was higher for younger patients [21.1; (95% CI 15.1–39.6) vs. 2.4; (95% CI 2.2–2.7) for older patients]. Conclusions Critically ill patients’ mortality peaked in the first 30 days after ICU admission. Older critically ill patients had higher all-cause mortality, including a higher hospital SMR. A long-term increased relative mortality risk was noted in patients discharged alive from the hospital, but this was more noticeable in younger patients.
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- 2023
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11. Epidemiology and Burden of Ventilator-Associated Pneumonia among Adult Intensive Care Unit Patients: A Portuguese, Multicenter, Retrospective Study (eVAP-PT Study)
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Paulo Mergulhão, João Gonçalves Pereira, Antero Vale Fernandes, Andriy Krystopchuk, João Miguel Ribeiro, Daniel Miranda, Heloísa Castro, Carla Eira, Juvenal Morais, Cristina Lameirão, Sara Gomes, Dina Leal, Joana Duarte, Leonor Pássaro, Filipe Froes, and Ignacio Martin-Loeches
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hospital stay ,invasive mechanical ventilation ,nosocomial infections ,sepsis ,VAP (ventilator-associated pneumonia) ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Ventilator-associated pneumonia (VAP) is a prevailing nosocomial infection in critically ill patients requiring invasive mechanical ventilation (iMV). The impact of VAP is profound, adversely affecting patient outcomes and placing a significant burden on healthcare resources. This study assessed for the first time the contemporary VAP epidemiology in Portugal and its burden on the healthcare system and clinical outcomes. Additionally, resource consumption (duration of iMV, intensive care unit (ICU), hospital length of stay (LOS)) and empirical antimicrobial therapy were also evaluated. This multicenter, retrospective study included patients admitted to the hospital between July 2016 and December 2017 in a participating ICU, who underwent iMV for at least 48 h. Patients with a VAP diagnosis were segregated for further analysis (n = 197). Control patients, ventilated for >48 h but without a VAP diagnosis, were also included in a 1:1 ratio. Cumulative VAP incidence was computed. All-cause mortality was assessed at 28, 90, and 365 days after ICU admission. Cumulative VAP incidence was 9.2% (95% CI 8.0–10.5). The all-cause mortality rate in VAP patients was 24.9%, 34.0%, and 40.6%, respectively, and these values were similar to those observed in patients without VAP diagnosis. Further, patients with VAP had significantly longer ICU (27.5 vs. 11.0 days, p < 0.001) and hospital LOS (61 vs. 35.9 days, p < 0.001), more time under iMV (20.7 vs. 8.0 days, p < 0.001) and were more often subjected to tracheostomy (36.5 vs. 14.2%; p < 0.001). Patients with VAP who received inappropriate empirical antimicrobials had higher 28-day mortality, 34.3% vs. 19.5% (odds ratio 2.16, 95% CI 1.10–4.23), although the same was not independently associated with 1-year all-cause mortality (p = 0.107). This study described the VAP impact and burden on the Portuguese healthcare system, with approximately 9% of patients undergoing iMV for >48 h developing VAP, leading to increased resource consumption (longer ICU and hospital LOS). An unexpectedly high incidence of inappropriate, empirical antimicrobial therapy was also noted, being positively associated with a higher mortality risk of these patients. Knowledge of the Portuguese epidemiology characterization of VAP and its multidimensional impact is essential for efficient treatment and optimized long-term health outcomes of these patients.
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- 2024
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12. Useful Exergy as an Intermediate Input in a Two-Sector Model of the United States Economy
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João Gonçalves, João Santos, Matthew Heun, Paul E. Brockway, and Tiago Domingos
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multisector economy ,useful exergy ,national accounts ,economic growth ,Technology - Abstract
Conventional economic growth models treat production/consumption as abstractions linked only by money flows, disregarding their connection to the physical world. Nevertheless, the existing literature suggests that energy flows can influence production and links useful exergy prices with economic growth. Useful exergy is energy measured at the stage where it produces an end-use (and is a measurement of energy quality). Not all approaches in the literature use this metric and they often consider energy as a primary input (despite it being an intermediate input). We explore the relationship between energy flows and economic growth for the US through a framework where useful exergy, the output of an “extended energy sector” (where all effects of increasing primary-to-final-to-useful exergy efficiency are located), is an intermediate input for a “non-energy sector”. Together, they encompass the entire economy. We conclude that the share of investment in the extended energy sector grew with the overall economic growth throughout 1960–2020, while the labour share decreased. The non-energy sector contributed the largest share of consumption, exports, imports and labour. In recent years, the energy sector has overtaken it in terms of investment. Our two-sector model has important implications for current climate policy, namely regarding the Integrated Assessment Models on which it is based.
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- 2024
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13. Balancing Act: Tubulin Glutamylation and Microtubule Dynamics in Toxoplasma gondii
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Inês L. S. Delgado, João Gonçalves, Rita Fernandes, Sara Zúquete, Afonso P. Basto, Alexandre Leitão, Helena Soares, and Sofia Nolasco
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Toxoplasma gondii ,tubulin glutamylation ,tubulin post-translational modifications ,apical complex ,microtubules ,Biology (General) ,QH301-705.5 - Abstract
The success of the intracellular parasite Toxoplasma gondii in invading host cells relies on the apical complex, a specialized microtubule cytoskeleton structure associated with secretory organelles. The T. gondii genome encodes three isoforms of both α- and β-tubulin, which undergo specific post-translational modifications (PTMs), altering the biochemical and biophysical proprieties of microtubules and modulating their interaction with associated proteins. Tubulin PTMs represent a powerful and evolutionarily conserved mechanism for generating tubulin diversity, forming a biochemical ‘tubulin code’ interpretable by microtubule-interacting factors. T. gondii exhibits various tubulin PTMs, including α-tubulin acetylation, α-tubulin detyrosination, Δ5α-tubulin, Δ2α-tubulin, α- and β-tubulin polyglutamylation, and α- and β-tubulin methylation. Tubulin glutamylation emerges as a key player in microtubule remodeling in Toxoplasma, regulating stability, dynamics, interaction with motor proteins, and severing enzymes. The balance of tubulin glutamylation is maintained through the coordinated action of polyglutamylases and deglutamylating enzymes. This work reviews and discusses current knowledge on T. gondii tubulin glutamylation. Through in silico identification of protein orthologs, we update the recognition of putative proteins related to glutamylation, contributing to a deeper understanding of its role in T. gondii biology.
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- 2024
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14. Antiviral Action against SARS-CoV-2 of a Synthetic Peptide Based on a Novel Defensin Present in the Transcriptome of the Fire Salamander (Salamandra salamandra)
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Ana Luisa A. N. Barros, Vladimir C. Silva, Atvaldo F. Ribeiro-Junior, Miguel G. Cardoso, Samuel R. Costa, Carolina B. Moraes, Cecília G. Barbosa, Alex P. Coleone, Rafael P. Simões, Wanessa F. Cabral, Raul M. Falcão, Andreanne G. Vasconcelos, Jefferson A. Rocha, Daniel D. R. Arcanjo, Augusto Batagin-Neto, Tatiana Karla S. Borges, João Gonçalves, Guilherme D. Brand, Lucio H. G. Freitas-Junior, Peter Eaton, Mariela Marani, Massuo J. Kato, Alexandra Plácido, and José Roberto S. A. Leite
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amphibians ,transcriptomics ,antimicrobial peptides ,bioinformatics ,antiviral action ,SARS-CoV-2 infection ,Pharmacy and materia medica ,RS1-441 - Abstract
The potential emergence of zoonotic diseases has raised significant concerns, particularly in light of the recent pandemic, emphasizing the urgent need for scientific preparedness. The bioprospection and characterization of new molecules are strategically relevant to the research and development of innovative drugs for viral and bacterial treatment and disease management. Amphibian species possess a diverse array of compounds, including antimicrobial peptides. This study identified the first bioactive peptide from Salamandra salamandra in a transcriptome analysis. The synthetic peptide sequence, which belongs to the defensin family, was characterized through MALDI TOF/TOF mass spectrometry. Molecular docking assays hypothesized the interaction between the identified peptide and the active binding site of the spike WT RBD/hACE2 complex. Although additional studies are required, the preliminary evaluation of the antiviral potential of synthetic SS-I was conducted through an in vitro cell-based SARS-CoV-2 infection assay. Additionally, the cytotoxic and hemolytic effects of the synthesized peptide were assessed. These preliminary findings highlighted the potential of SS-I as a chemical scaffold for drug development against COVID-19, hindering viral infection. The peptide demonstrated hemolytic activity while not exhibiting cytotoxicity at the antiviral concentration.
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- 2024
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15. Co-occurrences and species distribution models show the structuring role of dominant species in the Vez watershed, in Portugal
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Cristiana Alves, Bruno Marcos, João Gonçalves, Peter Verburg, Loïc Pellissier, and Angela Lomba
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Plant communities ,Co-occurrence Community Importance Index ,Biotic variables ,Community structure ,Interspecific relationships ,Species importance ranking ,Ecology ,QH540-549.5 - Abstract
Knowing the structural role of species within communities is important for their conservation and management in the context of recent/ongoing biodiversity loss. In a community, dominant species can influence the distribution and composition of subordinate species. Despite existing research, an approach is lacking to help understand the important role of dominant species in the community, without requiring more detailed data. In this study, we describe an approach to rank the relative importance of plant species within a community based on their abundance and co-occurrence patterns. The Co-occurrence Community Importance Index (CoCII) – a newly proposed index translating the degree of influence that each dominant species has on all its co-occurring subordinate species – was calculated and analysed. We used both abiotic and biotic variables within a species distribution models framework, with data collected in the Vez watershed in the North of Portugal. Our analysis included 114 plants – 26 dominant and 88 subordinate species. Spearman correlations were used to analyse potential interspecific relationships between co-occurring dominant and subordinate species. Using the CoCII, we ranked the relative importance of each dominant species within the plant community. Our results support the role of plant-plant interaction patterns regarding our study area's most highly inter-correlated species. Our approach to ranking species' importance can be directly translated into conservation schemes for managing and maintaining the structure of plant communities. Moreover, it can provide insights into the relative importance of dominant species in a plant community from commonly available datasets including presence-absence, presence-only, or percentage cover data, which allows for the relatively cost-efficient in-field collection and monitoring infield. Furthermore, this approach could allow us to advance the field of community ecology by providing essential information on the species that assure the stability of natural or semi-natural habitats of conservation concern.
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- 2023
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16. Diverse monogenic subforms of human spermatogenic failure
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Liina Nagirnaja, Alexandra M. Lopes, Wu-Lin Charng, Brian Miller, Rytis Stakaitis, Ieva Golubickaite, Alexandra Stendahl, Tianpengcheng Luan, Corinna Friedrich, Eisa Mahyari, Eloise Fadial, Laura Kasak, Katinka Vigh-Conrad, Manon S. Oud, Miguel J. Xavier, Samuel R. Cheers, Emma R. James, Jingtao Guo, Timothy G. Jenkins, Antoni Riera-Escamilla, Alberto Barros, Filipa Carvalho, Susana Fernandes, João Gonçalves, Christina A. Gurnett, Niels Jørgensen, Davor Jezek, Emily S. Jungheim, Sabine Kliesch, Robert I. McLachlan, Kenan R. Omurtag, Adrian Pilatz, Jay I. Sandlow, James Smith, Michael L. Eisenberg, James M. Hotaling, Keith A. Jarvi, Margus Punab, Ewa Rajpert-De Meyts, Douglas T. Carrell, Csilla Krausz, Maris Laan, Moira K. O’Bryan, Peter N. Schlegel, Frank Tüttelmann, Joris A. Veltman, Kristian Almstrup, Kenneth I. Aston, and Donald F. Conrad
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Science - Abstract
The GEMINI consortium sequenced 1,000 cases of idiopathic male infertility and identified a plausible Mendelian cause in 20% of cases. The infertility genes can be grouped by expression pattern, facilitating their interpretation and follow-up.
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- 2022
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17. Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility
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Miriam Cerván-Martín, Frank Tüttelmann, Alexandra M. Lopes, Lara Bossini-Castillo, Rocío Rivera-Egea, Nicolás Garrido, Saturnino Lujan, Gema Romeu, Samuel Santos-Ribeiro, José A. Castilla, M. Carmen Gonzalvo, Ana Clavero, Vicente Maldonado, F. Javier Vicente, Sara González-Muñoz, Andrea Guzmán-Jiménez, Miguel Burgos, Rafael Jiménez, Alberto Pacheco, Cristina González, Susana Gómez, David Amorós, Jesus Aguilar, Fernando Quintana, Carlos Calhaz-Jorge, Ana Aguiar, Joaquim Nunes, Sandra Sousa, Isabel Pereira, Maria Graça Pinto, Sónia Correia, Josvany Sánchez-Curbelo, Olga López-Rodrigo, Javier Martín, Iris Pereira-Caetano, Patricia I. Marques, Filipa Carvalho, Alberto Barros, Jörg Gromoll, Lluís Bassas, Susana Seixas, João Gonçalves, Sara Larriba, Sabine Kliesch, Rogelio J. Palomino-Morales, and F. David Carmona
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Biology (General) ,QH301-705.5 - Abstract
A GWAS in a large case-control cohort of European ancestry identifies two genomic regions, the MHC class II gene HLA-DRB1 and an upstream locus of VRK1, that are associated with the most severe phenotype of spermatogenic failure.
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- 2022
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18. Phenomenology at the large hadron collider with deep learning: the case of vector-like quarks decaying to light jets
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Felipe F. Freitas, João Gonçalves, António P. Morais, and Roman Pasechnik
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Astrophysics ,QB460-466 ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract In this work, we continue our exploration of TeV-scale vector-like fermion signatures inspired by a Grand Unification scenario based on the trinification gauge group. A particular focus is given to pair-production topologies of vector-like quarks (VLQs) at the LHC, in a multi-jet plus a charged lepton and a missing energy signature. We employ Deep Learning methods and techniques based in evolutive algorithms that optimize hyper-parameters in the neural network construction, whose objective is to maximise the Asimov estimate for distinct VLQ masses. In this article, we consider the implications of an innovative approach by simultaneously combining detector images (also known as jet images) and tabular data containing kinematic information from the final states. With this technique we are able to exclude VLQs, that are specific for the considered model, up to a mass of 800 GeV in both the high-luminosity the Run-III phases of the LHC programme.
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- 2022
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19. Clinical nutrition issues in 2022: What is missing to trust supplemental parenteral nutrition (SPN) in ICU patients?
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Mette M. Berger, Rosa Burgos, Michael P. Casaer, Edoardo De Robertis, Juan Carlos Lopez Delgado, Vincent Fraipont, João Gonçalves-Pereira, Claude Pichard, and Christian Stoppe
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Clinical nutrition ,Critically ill ,Intensive care unit ,Nutrition care ,Supplemental parenteral nutrition ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract A multidisciplinary group of international physicians involved in the medical nutrition therapy (MNT) of adult critically ill patients met to discuss the value, role, and open questions regarding supplemental parenteral nutrition (SPN) along with oral or enteral nutrition (EN), particularly in the intensive care unit (ICU) setting. This manuscript summarizes the discussions and results to highlight the importance of SPN as part of a comprehensive approach to MNT in critically ill adults and for researchers to generate new evidence based on well-powered randomized controlled trials (RCTs). The experts agreed on several key points: SPN has shown clinical benefits, resulting in this strategy being included in American and European guidelines. Nevertheless, its use is heterogeneous across European countries, due to the persistence of uncertainties, such as the optimal timing and the risk of overfeeding in absence of indirect calorimetry (IC), which results in divergent opinions and barriers to SPN implementation. Education is also insufficient. The experts agreed on actions needed to increase evidence quality on SPN use in specific patients at a given time point during acute critical illness or recovery.
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- 2022
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20. Mainstreaming remotely sensed ecosystem functioning in ecological niche models
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Adrián Regos, João Gonçalves, Salvador Arenas‐Castro, Domingo Alcaraz‐Segura, Antoine Guisan, and João P. Honrado
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Energy and water balance ,habitat dynamics ,habitat suitability modelling ,heat dynamics ,land surface temperature ,model‐assisted monitoring ,Technology ,Ecology ,QH540-549.5 - Abstract
Abstract Biodiversity is declining globally at unprecedented rates. Ecological niche models (ENMs) are one of the most widely used toolsets to appraise global change impacts on biodiversity. Here, we identify a variety of advantages of incorporating remotely sensed ecosystem functioning attributes (EFAs) into ENMs. The development of ENMs that explicitly incorporate ecosystem functioning will allow a more holistic and integrative perspective of the habitat dynamics. The synergies between the increasingly available open‐access satellite images and cloud‐based platforms for planetary‐scale geospatial analysis offer an unprecedented opportunity to incorporate ecosystem processes and disturbances (such as fires, insect outbreaks or droughts) that have been so far largely neglected in ecological niche characterization and modelling. The most paradigmatic example of EFAs is the application of time series of spectral vegetation indices related to primary productivity and carbon cycle. EFAs related to surface energy balance and water cycles derived from remote sensing products such as land surface temperature or soil moisture enable a fine‐scale characterization of the species' niche—eventually improving the predictive performance of ENMs. All these advantages confirm that a new generation of ENMs based on such EFAs would offer great perspectives to increase our ability to monitor habitat suitability trends and population dynamics. However, despite the technical advances and increasing effort of remote sensing community to develop integrative EFAs, ENMs have yet to make full profit of the most recent developments by integrating them in ENMs. A coordinated agenda for remote sensing experts and ecological modellers will be essential over the coming years to bridge the gap between remote sensing and ecology disciplines and to take full (and timely) advantage of the fast‐growing body of Earth observation data and remote sensing technologies—with special emphasis on the development and testing of new variables related to key processes driving ecosystem functioning.
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- 2022
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21. Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease
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André Lopes Simão, Carolina Santos Palma, Laura Izquierdo-Sanchez, Antonella Putignano, Angela Carvalho-Gomes, Andreas Posch, Paola Zanaga, Irina Girleanu, Mariana Moura Henrique, Carlos Araújo, Delphine Degre, Thierry Gustot, Iván Sahuco, Elia Spagnolo, Sofia Carvalhana, Miguel Moura, Diogo AE. Fernandes, Jesus M. Banales, Manuel Romero-Gomez, Anca Trifan, Francesco Paolo Russo, Rudolf Stauber, Marina Berenguer, Christophe Moreno, João Gonçalves, Helena Cortez-Pinto, and Rui E. Castro
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Chronic liver disease ,Cirrhosis ,COVID-19 vaccine ,Humoral immunity ,SARS-CoV-2 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into ‘low’ or ‘high’ responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted ‘low’ humoral response, whereas viral hepatitis and antiviral therapy predicted ‘high’ humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a ‘lower’ humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a ‘higher’ humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.
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- 2023
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22. Computer-Aided Visual Inspection of Glass-Coated Tableware Ceramics for Multi-Class Defect Detection
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Rafaela Carvalho, Ana C. Morgado, João Gonçalves, Anil Kumar, Alberto Gil e Sá Rolo, Rui Carreira, and Filipe Soares
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defect inspection ,quality control ,ceramics ,machine learning ,multi-class ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Quality control procedures in the manufacturing of tableware ceramics require a demanding, monotonous, subjective, and faulty human manual inspection. This paper presents two machine learning strategies and the results of a semi-automated visual inspection of ceramics tableware applied to a private dataset acquired during the VAICeramics project. In one method, an anomaly detection step was integrated to pre-select possible defective patches before passing through an object detector and defects classifier. In the alternative one, all patches are directly provided to the object detector and then go through the classification phase. Contrary to expectations, the inclusion of the anomaly detector demonstrated a slight reduction in the performance of the pipeline, which may result from error propagation. Regarding the proposed methodology for defect detection, it exhibits average performance in monochromatic images with more than 600 real defects in total, efficiently identifying the most common defect classes in highly reflective surfaces. However, when applied to newly acquired images, the pipeline encounters challenges revealing a lack of generalization ability and experiencing limitations in detecting specific defect classes, due to their appearance and limited available samples used for training. Only two defect types presented high classification performance, namely Dots and Cracked defects.
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- 2023
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23. Polyphenol Composition by HPLC-DAD-(ESI-)MS/MS and Bioactivities of Extracts from Grape Agri-Food Wastes
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Jonata M. Ueda, Karoline Ribeiro Griebler, Tiane C. Finimundy, Daniele B. Rodrigues, Lavínia Veríssimo, Tânia C. S. P. Pires, João Gonçalves, Isabel P. Fernandes, Eliana Pereira, Lillian Barros, Sandrina A. Heleno, and Ricardo C. Calhelha
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grape marc ,by-products ,phenolic compounds ,antioxidant ,antimicrobial ,Organic chemistry ,QD241-441 - Abstract
Background: Grape agri-food wastes, such as skin, seeds, and other discarded by-products, contain phytochemical compounds that offer potential health benefits. Methods: This study aimed to investigate the polyphenol composition and bioactivities of different extracts obtained from grape marc and seeds, with the goal of exploring their potential for application as natural food additives. Results: Regardless of the extraction method used (dynamic maceration, ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE)), all extracts exhibited relatively high concentrations of phenolic compounds. The chemical characterization of the extracts revealed the presence of specific compounds and chemical groups associated with each extraction methodology. Moreover, the extracts displayed satisfactory antioxidant activities, especially in inhibiting lipoperoxidation as assessed by the TBARS assay. Additionally, the extracts demonstrated effective inhibition against different strains of bacteria and fungi known as food contaminants. Taken together, these findings indicate that those extracts have the potential to be tested as natural antioxidants and preservatives with sustainable origins in food and beverage systems. Among the extraction methods evaluated, traditional maceration and UAE provided extracts with the highest antioxidant and antimicrobial activities. Conclusions: Our results suggest the opportunity to explore grape marc and seeds discarded by the winery industry in Portugal as natural sources of bioactive compounds, which could be employed as functional food ingredients or technological additives. The valorization of grape biowastes offers a promising strategy to reduce waste and harness their potential health benefits.
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- 2023
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24. Valor prognóstico da hiperlactatemia em pacientes admitidos com infecção em unidades de terapia intensiva: estudo multicêntrico
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Catarina Mendes Silva, João Pedro Baptista, Paulo Mergulhão, Filipe Froes, João Gonçalves-Pereira, José Manuel Pereira, Claudia Camila Dias, and José Artur Paiva
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Hiperlactatemia ,Infecções ,Lactato ,Mortalidade hospitalar ,Prognóstico ,Unidades de terapia intensiva ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
RESUMO Objetivo: Avaliar a influência das características dos pacientes na hiperlactatemia em uma população admitida com infecção em unidades de terapia intensiva, bem como a influência da gravidade da hiperlactatemia na mortalidade hospitalar. Metódos: Foi realizada uma análise post hoc da hiperlactatemia no INFAUCI, um estudo nacional prospectivo, observacional e multicêntrico, que incluiu 14 unidades de terapia intensiva portuguesas. Foram selecionados pacientes admitidos com infecção em unidades de terapia intensiva com dosagem de lactato nas primeiras 12 horas de admissão. A sepse foi identificada de acordo com a definição Sepsis-2 aceita no momento da coleta de dados. A gravidade da hiperlactatemia foi classificada como leve (2 - 3,9mmol/L), moderada (4,0 - 9,9mmol/L) ou grave (> 10mmol/L). Resultados: De 1.640 pacientes admitidos com infecção, a hiperlactatemia ocorreu em 934 (57%) e foi classificada como leve, moderada e grave em 57,0%, 34,4% e 8,7% dos pacientes, respectivamente. A presença de hiperlactatemia e um maior grau de hiperlactatemia se associaram a um maior Simplified Acute Physiology Score II, a maior Índice de Comorbidade de Charlson e à presença de choque séptico. Em relação à curva Receiver Operating Characteristic do lactato para mortalidade hospitalar, foi encontrada área sob a curva de 0,64 (IC95% 0,61 - 0,72), que aumentou para 0,71 (IC95% 0,68 - 0,74) quando se combinou o Sequential Organ Failure Assessment. A mortalidade intra-hospitalar com outras covariáveis ajustadas pelo Simplified Acute Physiology Score II se associou à hiperlactatemia moderada e grave, com razão de chances de 1,95 (IC95% 1,4 - 2,7; p < 0,001) e 4,54 (IC95% 2,4 - 8,5; p < 0,001), respectivamente. Conclusão: Os níveis de lactato sanguíneo correlacionam-se independentemente com a mortalidade intra-hospitalar para graus moderados e graves de hiperlactatemia.
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- 2022
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25. Influência de variáveis macroeconômicas no preço das ações do setor financeiro da b3
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Vinícius Naves Andrade, João Gonçalves Silva Muntaser, and Thiago Alberto dos Reis Prado
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macroeconomics variables ,financial market ,stock exchange ,b3 ,financial sector ,Economic history and conditions ,HC10-1085 ,Economics as a science ,HB71-74 - Abstract
This study aimed to analyze the influence of macroeconomic variables on the behavior of stock prices of companies in the financial sector on the Brazilian stock exchange. The model of linear regression with panel data was applied in order to verify the relationship between the independent variables and the dependent variable. From the regression model coefficients, it is suggested that there is a negative relationship between the independent variable Special System for Settle-ment and Custody (Sistema Especial de Liquidação e de Custódia [Selic]) interest rate and the dependent variable, which suggests that an increase in the basic in-terest rate will imply a reduction in stock prices of the financial sector. The study also suggests that there is a positive relationship between the independent variable gross domestic product (GDP) and the dependent variable, assuming that, when there is an increase in the country’s wealth production, there is also an increase in the price of shares in the financial sector of B3.
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- 2022
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26. Collider signatures of vector-like fermions from a flavor symmetric model
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Cesar Bonilla, A. E. Cárcamo Hernández, João Gonçalves, Felipe F. Freitas, António P. Morais, and R. Pasechnik
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Beyond Standard Model ,vector-like quarks ,Hadron-Hadron scattering (experiments) ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract We propose a model with two Higgs doublets and several SU(2) scalar singlets with a global non-Abelian flavor symmetry Q 6 × Z 2 $$ {\mathcal{Q}}_6\times {\mathcal{Z}}_2 $$ . This discrete group accounts for the observed pattern of fermion masses and mixing angles after spontaneous symmetry breaking. In this scenario only the third generation of fermions get their masses as in the Standard Model (SM). The masses of the remaining fermions are generated through a seesaw-like mechanism. To that end, the matter content of the model is enlarged by introducing electrically charged vector-like fermions (VLFs), right handed Majorana neutrinos and several SM scalar singlets. Here we study the processes involving VLFs that are within the reach of the Large Hadron Collider (LHC). We perform collider studies for vector-like leptons (VLLs) and vector-like quarks (VLQs), focusing on double production channels for both cases, while for VLLs single production topologies are also included. Utilizing genetic algorithms for neural network optimization, we determine the statistical significance for a hypothetical discovery at future LHC runs. In particular, we show that we can not safely exclude VLLs for masses greater than 200 GeV. For VLQ’s in our model, we show that we can probe their masses up to 3.8 TeV, if we take only into account the high-luminosity phase of the LHC. Considering Run-III luminosities, we can also exclude VLQs for masses up to 3.4 TeV. We also show how the model with predicted VLL masses accommodates the muon anomalous magnetic moment.
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- 2022
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27. Unveiling LoRa’s Oceanic Reach: Assessing the Coverage of the Azores LoRaWAN Network from an Island
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João Pinelo, André Dionísio Rocha, Miguel Arvana, João Gonçalves, Nuno Cota, and Pedro Silva
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maritime communications ,LoRa ,LoRaWAN ,low power wide area network (LP-WAN) ,Internet of Things (IoT) ,Chemical technology ,TP1-1185 - Abstract
In maritime settings, effective communication between vessels and land infrastructure is crucial, but existing technologies often prove impractical for energy-sensitive IoT applications, like deploying sensors at sea. In this study, we explore the viability of a low-power, cost-effective wireless communication solution for maritime sensing data. Specifically, we conduct an experimental assessment of the Azorean Long Range Wide Area Network (LoRaWAN) coverage. Our tests involve positioning the gateway at the island’s highest point and installing end nodes on medium-sized fishing vessels. Through measurements of received signal strength indicator (RSSI), signal-to-noise ratio (SNR), and lines of sight (LOS), we showcase the potential of LoRaWAN transmissions to achieve communication distances exceeding 130 km in a LOS-free scenario over the ocean. These findings highlight the promising capabilities of LoRaWAN for reliable and long-range maritime communication of sensing data.
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- 2023
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28. Chemical and Bioactive Screening of Green Polyphenol-Rich Extracts from Chestnut By-Products: An Approach to Guide the Sustainable Production of High-Added Value Ingredients
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Daniele Bobrowski Rodrigues, Lavínia Veríssimo, Tiane Finimundy, Joana Rodrigues, Izamara Oliveira, João Gonçalves, Isabel P. Fernandes, Lillian Barros, Sandrina A. Heleno, and Ricardo C. Calhelha
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C. sativa ,biowaste ,LC-MS ,natural preservatives ,phenolic compounds ,green extraction methods ,Chemical technology ,TP1-1185 - Abstract
Opportunities for the valorisation of agro-industrial residues of the chestnut (Castanea sativa Mill.) production chain have been fostered with the production of multifunctional polyphenol-rich extracts with the potential to be introduced as natural additives or active components in several products. Nonetheless, it is crucial to explore the feasibility of different extracts from the various by-products for these applications through the exhaustive study of their composition and bioactivities without losing sight of the sustainable character of the process. This work aimed at the screening of the phenolic compound composition and bioactivities of different green extracts of chestnut burs, shells and leaves, as the first step to establish their potential application as natural ingredients, primarily as food preservatives. To this end, maceration (MAC) as a conventional extraction method besides ultrasound and microwave-assisted extractions (UAE and MAE) was employed to obtain the extracts from chestnut by-products using water (W) and hydroethanolic solution (HE) as solvents. Phenolic compounds were analysed by HPLC-DAD-(ESI-)MS/MS; the antioxidant capacity was assessed by colourimetric assays, and the antimicrobial activity was evaluated against several strains of food-borne bacteria and fungi. The leaf extracts obtained by MAC-HE and UAE-HE presented the highest concentration of phenolic compounds (70.92 ± 2.72 and 53.97 ± 2.41 mg.g−1 extract dw, respectively), whereas, for burs and shells, the highest recovery of total phenolic compounds was achieved by using UAE-HE and UAE-W (36.87 ± 1.09 and 23.03 ± 0.26 mg.g−1 extract dw, respectively). Bis-HHDP-glucose isomers, chestanin and gallic acid were among the most abundant compounds. Bur extracts (MAC-HE and UAE-HE) generally presented the highest antioxidant capacity as measured by TBARS, while the best results in DPPH and reducing power assays were found for shell extracts (MAE-W and MAC-HE). Promising antibacterial activity was noticed for the aqueous extracts of burs, leaves and hydroethanolic extracts of shells, with emphasis on the MAE-W extract of burs that showed bactericidal activity against E. cloacae, P. aeruginosa and S. aureus (MBC 5 mg.mL−1). Overall, it can be concluded that chestnut by-products, including burs, shells and leaves, are sources of polyphenolic compounds with significant antioxidant and antimicrobial activities. The choice of extraction method and solvent greatly influenced the composition and bioactivity of the extracts. These findings highlight the potential of chestnut by-products for the development of natural additives, particularly for food preservation, while also emphasizing the importance of sustainable utilization of agricultural waste materials. Further research is warranted to optimize extraction techniques and explore additional applications for these valuable bioactive compounds.
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- 2023
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29. Long-term clinical outcomes after upgrade to resynchronization therapy: A propensity score–matched analysis
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Mariana Brandão, MD, MSc, João Gonçalves Almeida, MD, MSc, Paulo Fonseca, MD, MSc, Joel Monteiro, MD, MSc, Elisabeth Santos, MSc, Filipa Rosas, MSc, José Nogueira Ribeiro, MSc, Marco Oliveira, MD, MSc, Helena Gonçalves, MD, MSc, João Primo, MD, MSc, and Ricardo Fontes-Carvalho, MD, PhD
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Cardiac resynchronization therapy ,Upgrade ,Heart failure ,Pacemaker ,Implantable cardioverter-defibrillator ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Upgrade to cardiac resynchronization therapy (CRT) is common in Europe, despite little and conflicting evidence. Objective: To compare long-term clinical outcomes in a cohort of patients receiving de novo or upgrade to CRT. Methods: Single-center retrospective study of 295 consecutive patients submitted to CRT implantation between 2007 and 2018. Upgraded and de novo patients complying with a dedicated follow-up protocol were compared in terms of clinical (NYHA class improvement without major adverse cardiac events [MACE] in the first year of follow-up) and echocardiographic (left ventricle end-systolic volume reduction of >15% during the first year) response. Results: No differences in the rate of clinical (59.3% vs 62.6%, P = .765) or echocardiographic response (72.2% vs 71.9%, P = .970) between groups were observed. Device-related complications were also comparable between groups (8.9% vs 8.4%, P = .892). Occurrence of MACE and all-cause mortality were analyzed over a median follow-up of 3 (interquartile range 1–6) years: MACE occurred less frequently in the de novo group (hazard ratio [HR]: 0.55, 95% confidence interval [CI]: 0.34–0.90, P = .018), but all-cause mortality was similar among groups (HR: 0.87, 95% CI: 0.46–1.64, P = .684). Propensity score–matching analysis was performed to adjust for possible confounder variables. In the propensity-matched samples, all-cause mortality (HR: 1.26, 95% CI: 0.56–2.77, P = .557) and MACE (HR: 0.84, 95% CI: 0.46–1.54, P = .574) were comparable between upgrade and de novo patients. Conclusion: Survival after upgrade to resynchronization therapy was comparable to de novo implants. Additionally, clinical and echocardiographic response to CRT in upgraded patients were similar to de novo patients.
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- 2021
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30. Impella support for cardiogenic shock and high-risk percutaneous coronary intervention: A single-center experience
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Mariana Brandão, Daniel Caeiro, Gustavo Pires-Morais, João Gonçalves Almeida, Pedro Gonçalves Teixeira, Marisa Passos Silva, Marta Ponte, Adelaide Dias, Marco Oliveira, Alberto Rodrigues, and Pedro Braga
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Suporte circulatório mecânico ,Impella® ,Choque cardiogénico ,Intervenção coronária percutânea ,Doença coronária ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Introduction and Objectives: The use of mechanical circulatory support is increasing in cases of cardiogenic shock (CS) and high-risk percutaneous coronary intervention (HR-PCI). The Impella® is a percutaneous ventricular assist device that unloads the left ventricle by ejecting blood to the ascending aorta. We report our center's experience with the use of the Impella® device in these two clinical settings. Methods: We performed a single-center retrospective study including all consecutive patients implanted with the Impella® between 2007 and 2019 for CS treatment or prophylactic support of HR-PCI. Data on clinical and safety endpoints were collected and analyzed. Results: Twenty-two patients were included: 12 were treated for CS and 10 underwent an HR-PCI procedure. In the CS-treated population, the main cause of CS was acute myocardial infarction (five patients); hemolysis was the most frequent device-related complication (63.7%). In-hospital, cumulative 30-day and one-year mortality were 58.3%, 66.6% and 83.3%, respectively. In the HR-PCI group, all patients had multivessel disease (mean baseline SYNTAX I score: 44.1±13.7). In-hospital, 30-day and one-year mortality were 10.0%, 10.0% and 20.0%, respectively. There were no device- or procedure-related deaths in either group. Conclusion: The short- and long-term results of Impella®-supported HR-PCI were comparable to those in the literature. In the CS group, in-hospital and short-term outcomes were poor, with high mortality and non-negligible complication rates. Resumo: Introdução e objetivos: O uso de suporte mecânico no choque cardiogénico (CS) e intervenção coronária percutânea de alto risco (HR-PCI) tem aumentado. O Impella® é um sistema de suporte ventricular percutâneo que ejeta sangue do ventrículo esquerdo para a aorta ascendente. Reportamos a experiência do nosso centro com o Impella® nestes dois cenários clínicos. Métodos: Estudo retrospetivo unicêntrico incluindo todos os doentes consecutivos submetidos a implantação de Impella® entre 2007 e 2019, para tratamento de CS ou suporte profilático para HR-PCI. Dados sobre endpoints clínicos e de segurança foram analisados. Resultados: Foram incluídos 22 doentes: 12 tratados por CS e 10 submetidos a HR-PCI. Na população de CS, a principal causa de choque foi o enfarte agudo do miocárdio (5 doentes); a hemólise foi a complicação relacionada com o dispositivo mais frequente (63,7%); a mortalidade intra-hospitalar, a 30 dias e um ano, foi, respetivamente, 58,3%, 66,6% e 83,3%. No grupo da HR-PCI, todos os doentes apresentavam doença multivaso (SYNTAX I score médio: 44,1±13,7); a mortalidade intra-hospitalar, a 30 dias e um ano, foi, respetivamente, 10,0%, 10,0% e 20,0%. Não houve mortes relacionadas com o dispositivo ou procedimento em ambos os grupos. Conclusão: Os resultados em curto e longo prazo da HR-PCI protegida por Impella® foram comparáveis aos da literatura disponível. No grupo de CS, os resultados intra-hospitalares e em curto prazo foram desanimadores, com elevada mortalidade e taxas de complicações apreciáveis.
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- 2021
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31. Contribution of TEX15 genetic variants to the risk of developing severe non-obstructive oligozoospermia
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Andrea Guzmán-Jiménez, Sara González-Muñoz, Miriam Cerván-Martín, Rocío Rivera-Egea, Nicolás Garrido, Saturnino Luján, Samuel Santos-Ribeiro, José A. Castilla, M. Carmen Gonzalvo, Ana Clavero, F. Javier Vicente, Vicente Maldonado, Javier Villegas-Salmerón, Miguel Burgos, Rafael Jiménez, Maria Graça Pinto, Isabel Pereira, Joaquim Nunes, Josvany Sánchez-Curbelo, Olga López-Rodrigo, Iris Pereira-Caetano, Patricia Isabel Marques, Filipa Carvalho, Alberto Barros, Lluís Bassas, Susana Seixas, João Gonçalves, Alexandra M. Lopes, Sara Larriba, Rogelio J. Palomino-Morales, F. David Carmona, Lara Bossini-Castillo, IVIRMA Group, and Lisbon Clinical Group
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oligozoospermia ,spermatogenesis ,TEX15 ,polymorphisms ,association study ,Biology (General) ,QH301-705.5 - Abstract
Background: Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this idiopathic form of male infertility represents a complex condition. In this study, we aimed to evaluate whether common genetic variation in TEX15, which encodes a key player in spermatogenesis, is involved in the susceptibility to idiopathic SPGF.Materials and Methods: We designed a genetic association study comprising a total of 727 SPGF cases (including 527 NOA and 200 SO) and 1,058 unaffected men from the Iberian Peninsula. Following a tagging strategy, three tag single-nucleotide polymorphisms (SNPs) of TEX15 (rs1362912, rs323342, and rs323346) were selected for genotyping using TaqMan probes. Case-control association tests were then performed by logistic regression models. In silico analyses were also carried out to shed light into the putative functional implications of the studied variants.Results: A significant increase in TEX15-rs1362912 minor allele frequency (MAF) was observed in the group of SO patients (MAF = 0.0842) compared to either the control cohort (MAF = 0.0468, OR = 1.90, p = 7.47E-03) or the NOA group (MAF = 0.0472, OR = 1.83, p = 1.23E-02). The genotype distribution of the SO population was also different from those of both control (p = 1.14E-02) and NOA groups (p = 4.33–02). The analysis of functional annotations of the human genome suggested that the effect of the SO-associated TEX15 variants is likely exerted by alteration of the binding affinity of crucial transcription factors for spermatogenesis.Conclusion: Our results suggest that common variation in TEX15 is involved in the genetic predisposition to SO, thus supporting the notion of idiopathic SPGF as a complex trait.
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- 2022
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32. A quantitative Gidas-Ni-Nirenberg-type result for the $p$-Laplacian via integral identities
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Dipierro, Serena, da Silva, João Gonçalves, Poggesi, Giorgio, and Valdinoci, Enrico
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Mathematics - Analysis of PDEs - Abstract
We prove a quantitative version of a Gidas-Ni-Nirenberg-type symmetry result involving the $p$-Laplacian. Quantitative stability is achieved here via integral identities based on the proof of rigidity established by J. Serra in 2013, which extended to general dimension and the $p$-Laplacian operator an argument proposed by P. L. Lions in dimension $2$ for the classical Laplacian. Stability results for the classical Gidas-Ni-Nirenberg symmetry theorem (involving the classical Laplacian) via the method of moving planes were established by Rosset in 1994 and by Ciraolo, Cozzi, Perugini, Pollastro in 2024. To the authors' knowledge, the present paper provides the first quantitative Gidas-Ni-Nirenberg-type result involving the $p$-Laplacian for $p \neq 2$. Even for the classical Laplacian (i.e., for $p=2$), this is the first time that integral identities are used to achieve stability for a Gidas-Ni-Nirenberg-type result. In passing, we obtain a quantitative estimate for the measure of the singular set and an explicit uniform gradient bound.
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- 2024
33. An autonomous mobile manipulator to build outdoor structures consisting of heterogeneous brick patterns
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Meysam Basiri, João Gonçalves, José Rosa, Alberto Vale, and Pedro Lima
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Autonomous mobile manipulator ,Unmanned ground vehicle ,Brick-shaped object detection ,MBZIRC competition ,Outdoor object perception and manipulation ,Industrial automation and construction ,Science ,Technology - Abstract
Abstract This paper describes the implementation of an autonomous mobile manipulator to build outdoor structures consisting of heterogeneous brick patterns, finding applications in different industrial automation, manufacturing and civil construction scenarios. This system was developed for the Mohamed Bin Zayed International Robotics Challenge (MBZIRC) 2020, to demonstrate the novel real-world application of constructing structures using teams of robots, showcasing once again the role of major scientific competitions in advancing the state of the art towards exploring solutions to open problems. The paper presents in detail the hardware and software architectures of the developed mobile manipulator, integrating different research results and developments into a functional complex robot system, while proposing methods to detect, approach and manipulate differently sized/colored bricks to build a wall of predefined pattern given to the robot just before the building task starts. Article Highlights Full system description of an autonomous mobile manipulator for construction tasks tested in a realistic setting Algorithms for detection, localization, picking and placement of heterogeneous building blocks to form large structures Versatile service robot capable of smooth adaptation to other functions developed through scientific robot competitions
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- 2021
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34. LUZP1: A new player in the actin-microtubule cross-talk
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João Gonçalves
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LUZP1 ,Actin ,Microtubules ,Centrosome ,Cilium ,Cytology ,QH573-671 - Abstract
LUZP1 (leucine zipper protein 1) was first described as being important for embryonic development. Luzp1 null mice present defective neural tube closure and cardiovascular problems, which cause perinatal death. Since then, LUZP1 has also been implicated in the etiology of diseases like the 1p36 and the Townes-Brocks syndromes, and the molecular mechanisms involving this protein started being uncovered. Proteomics studies placed LUZP1 in the interactomes of the centrosome-cilium interface, centriolar satellites, and midbody. Concordantly, LUZP1 is an actin and microtubule-associated protein, which localizes to the centrosome, the basal body of primary cilia, the midbody, actin filaments and cellular junctions. LUZP1, like its interactor EPLIN, is an actin-stabilizing protein and a negative regulator of primary cilia formation. Moreover, through the regulation of actin, LUZP1 has been implicated in the regulation of cell cycle progression, cell migration and epithelial cell apical constriction. This review discusses the latest findings concerning LUZP1 molecular functions and implications in disease development.
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- 2022
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35. Multiple Lines of Ecological Evidence Support Ancient Contact Between the African Wild Dog and the Dhole
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Rita Gomes Rocha, João Gonçalves, Pedro Tarroso, Pedro Monterroso, and Raquel Godinho
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fossil evidence ,interglacial periods ,Levant region ,hypervolume analysis ,species distribution models ,wolf-like canids ,Evolution ,QH359-425 ,Ecology ,QH540-549.5 - Abstract
Genomic tools have greatly enhanced our ability to uncover ancient interspecific gene flow, including cases involving allopatric lineages and/or lineages that have gone extinct. Recently, a genomic analysis revealed the unexpected gene flow between the African wild dog (Lycaon pictus) and the dhole (Cuon alpinus). The two species have currently highly disjunct and patchy distributions in Africa and Asia, respectively, which are remnants of a much wider past distribution. Yet, no reported evidence of their past contact has ever been documented. By hindcasting the past potential distribution of both species during the Last Glacial Maximum and the Last Interglacial, validating paleoclimatic reconstructions with fossil evidence, quantifying the intersection of their bioclimatic niches, and assessing interspecific compatibility, we investigate the location and favorable conditions for such contact and its ecological validity. We were able to identify the Levant region in Eastern Mediterranean during the Last Interglacial as the most suitable spatio-ecological context for the co-occurrence of the two canids, and to provide evidence of a highly significant overlap of the African wild dog niche with the wider niche of the dhole. These results, combined with ecologic traits, including key compatibility features such as cooperative breeding and hunting, provide consistent support for the potential co-occurrence of both canids. We suggest that the ranges of these canids came into contact multiple times during periods resembling the Last Interglacial, eventually facilitating gene flow between the African wild dog and the dhole in their post-divergence history. Our results are highly supportive of the key role of the Levant region in providing connectivity between African and Eurasian faunas and provide further impetus to combine different tools and approaches in advancing the understanding of species evolutionary histories.
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- 2022
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36. Incidence of Antibiotic Treatment Failure in Patients with Nursing Home-Acquired Pneumonia and Community Acquired Pneumonia
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Mariana Lopes, Gonçalo Alves Silva, Rui Filipe Nogueira, Daniela Marado, João Gonçalves, Carlos Athayde, Dilva Silva, Ana Figueiredo, Jorge Fortuna, and Armando Carvalho
- Subjects
nursing home-acquired pneumonia ,community-acquired pneumonia ,antimicrobial drug resistance ,epidemiology ,treatment failure ,Other systems of medicine ,RZ201-999 - Abstract
Purpose: Nursing home-acquired pneumonia (NHAP) patients are at higher risk of multi-drug resistant infection (MDR) than those with community-acquired pneumonia (CAP). Recent evidence suggests a single risk factor for MDR does not accurately predict the need for broad-spectrum antibiotics. The goal of this study was to compare the rate antibiotic failure between NHAP and CAP patients. Methods: Demographic characteristics, co-morbidities, clinical and laboratory variables, antibiotic therapy, and mortality data were collected retrospectively for all patients with pneumonia admitted to an Internal Medicine Service between April 2017 and April 2018. Results: In total, 313 of 556 patients had CAP and 243 had NHAP. NHAP patients were older, and were more likely to be dependent, to have recent antibiotic use, and to experience treatment failure (odds ratio (OR) 1.583; 95% CI 1.102–2.276; p = 0.013). In multivariate analysis, patient’s origin did not predict treatment failure (OR 1.083; 95% CI 0.726–1.616; p = 0.696). Discussion: Higher rates of antibiotic failure and mortality in NHAP patients were explained by the presence of other risk factors such as comorbidities, more severe presentation, and age. Admission from a nursing home is not a sufficient condition to start broader-spectrum antibiotics.
- Published
- 2021
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37. Phenomenology of vector-like leptons with Deep Learning at the Large Hadron Collider
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Felipe F. Freitas, João Gonçalves, António P. Morais, and Roman Pasechnik
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Beyond Standard Model ,Quark Masses and SM Parameters ,GUT ,Gauge Symmetry ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract In this paper, a model inspired by Grand Unification principles featuring three generations of vector-like fermions, new Higgs doublets and a rich neutrino sector at the low scale is presented. Using the state-of-the-art Deep Learning techniques we perform the first phenomenological analysis of this model focusing on the study of new charged vector-like leptons (VLLs) and their possible signatures at CERN’s Large Hadron Collider (LHC). In our numerical analysis we consider signal events for vector-boson fusion and VLL pair production topologies, both involving a final state containing a pair of charged leptons of different flavor and two sterile neutrinos that provide a missing energy. We also consider the case of VLL single production where, in addition to a pair of sterile neutrinos, the final state contains only one charged lepton. We propose a novel method to identify missing transverse energy vectors by comparing the detector response with Monte-Carlo simulated data. All calculated observables are provided as data sets for Deep Learning analysis, where a neural network is constructed, based on results obtained via an evolutive algorithm, whose objective is to maximise either the accuracy metric or the Asimov significance for different masses of the VLL. Taking into account the effect of the three analysed topologies, we have found that the combined significance for the observation of new VLLs at the high-luminosity LHC can range from 5.7σ, for a mass of 1.25 TeV, all the way up to 28σ if the VLL mass is 200 GeV. We have also shown that by the end of the LHC Run-III a 200 GeV VLL can be excluded with a confidence of 8.8 standard deviations. The results obtained show that our model can be probed well before the end of the LHC operations and, in particular, providing important phenomenological information to constrain the energy scale at which new gauge symmetries emergent from the considered Grand Unification picture can be manifest.
- Published
- 2021
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38. A escultura no cinema de Pedro Costa
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João Gonçalves
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escultura ,cinema ,corpo ,objecto ,recomposição ,Visual arts ,N1-9211 ,Motion pictures ,PN1993-1999 - Abstract
Admirado pela linguagem inovadora com que constrói retratos de pessoas a viver em situações limite, Pedro Costa é uma figura consensual no panorama do cinema contemporâneo de autor. Entre 1997 e 2006, produziu aquele que é, por muitos considerado, o seu corpo de trabalho mais relevante: um conjunto de três filmes, conhecido por “Trilogia das Fontainhas”, do qual fazem parte Ossos (1997), No Quarto da Vanda (2000) e Juventude em Marcha (2006). Exemplos que nos permitem identificar alguns dos aspectos mais singulares da sua obra. Produzidos à volta de uma ligação entre Cabo Verde e Portugal, os três filmes exploram uma série de oposições, entre um bairro de uma periferia pobre e o centro de uma capital europeia com sinais de riqueza; entre distância e proximidade, comunidade e não comunidade, deslocação e localização, lugar e contexto. Numa escala mais pequena, a substituição da ilha pelo bairro, a relação do corpo com a parede a surgir em espaços de dimensões reduzidas, simultaneamente interiores e exteriores. Espaços fechados e abertos, privados e públicos, pessoais e políticos. Com este estudo propõe-se que o antagonismo presente nestes trabalhos [...].
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- 2020
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39. Late Quaternary range shifts of marcescent oaks unveil the dynamics of a major biogeographic transition in southern Europe
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Carlos Vila-Viçosa, João Gonçalves, João Honrado, Ângela Lomba, Rubim S. Almeida, Francisco Maria Vázquez, and Cristina Garcia
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Medicine ,Science - Abstract
Abstract Marcescent forests are ecotones distributed across southern Europe that host increased levels of biodiversity but their persistence is threatened by global change. Here we study the range dynamics of these forests in the Iberian Peninsula (IP) during the Late Quaternary, a period of profound climate and anthropic changes. We modeled and compared the distribution of eight oak taxa for the present and two paleoclimatic environments, the Last Glacial Maximum (LGM, ~ 21 kya) and the Mid-Holocene (MH, ~ 6 kya). Presence records were combined with bioclimatic and topographic data in an ensemble modelling framework to obtain spatial projections for present and past conditions across taxa. Substantial distribution shifts were projected between the three studied periods, that were explained by precipitation, winter cold and terrain ruggedness. Results were congruent with paleoclimatic records of the IP and showed that range shifts of these contact zones concurred with range dynamics of both Submediterranean and Temperate oaks. Notably, the distribution ranges of hybrid oaks and marcescent forests matched throughout the late Quaternary. This study contributes to unveil the complex Late-Quaternary biogeography of the ecotone belt occupied by marcescent forests and, more broadly, of Mediterranean oaks. Improved knowledge of species’ responses to climate dynamics will allow us to anticipate and manage future range shifts driven by climate change.
- Published
- 2020
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40. Skeletal age assessed by TW2 using 20-bone, carpal and RUS score systems: Intra-observer and inter-observer agreement among male pubertal soccer players.
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Paulo Sousa-E-Silva, Manuel J Coelho-E-Silva, Andre Seabra, Daniela C Costa, Diogo V Martinho, João P Duarte, Tomás Oliveira, João Gonçalves-Santos, Inês Rodrigues, Luis P Ribeiro, António J Figueiredo, Jan M Konarski, Sean P Cumming, and Robert M Malina
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Medicine ,Science - Abstract
The purpose of this study was to determine intra- and inter-observer agreement for the three skeletal ages derived from the TW2 method among male pubertal soccer players. The sample included 142 participants aged 11.0-15.3 years. Films of the left hand-wrist were evaluated twice by each of two observers. Twenty bones were rated and three scoring systems used to determine SA adopting the TW2 version: 20-bone, CARPAL and RUS. Overall agreement rates were 95.1% and 93.8% for, respectively, Observer A and Observer B. Although, agreement rates between observers differed for 13 bones (5 carpals, metacarpal-I, metacarpal-III, metacarpal-V, proximal phalanges-I, III and V, distal phalanx-III), intra-class correlationa were as follows: 0.990 (20-bone), 0.969 (CARPAL), and 0.988 (RUS). For the three SA protocols, BIAS was negligible: 0.02 years (20-bone), 0.04 years (CARPAL), and 0.03 years (RUS). Observer-associated error was not significant for 20-bone SA (TEM = 0.25 years, %CV = 1.86) neither RUS SA (TEM = 0.31 years, %CV = 2.22). Although the mean difference for CARPAL SAs between observers (observer A: 12.48±1.18 years; observer B: 12.29±1.24 years; t = 4.662, p
- Published
- 2022
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41. Ki-67 and CK-19 are predictors of locoregional recurrence in papillary thyroid carcinoma
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Aline de Oliveira Ribeiro Viana, João Gonçalves Filho, Ana Lúcia Noronha Francisco, Clóvis Antônio Lopes Pinto, and Luiz Paulo Kowalski
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Otorhinolaryngology ,RF1-547 - Published
- 2020
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42. Scaling left ventricular mass in adolescent female soccer players
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Diogo V. Martinho, João Valente-dos-Santos, Manuel J. Coelho-e-Silva, Arturo O. Gutiérrez, João P. Duarte, Pedro Lourenço-Farinha, Leonardo G. O. Luz, João Gonçalves-Santos, Dalmo R. L. Machado, Neiva Leite, Jorge Conde, Joaquim M. Castanheira, Sean P. Cumming, Lauren B. Sherar, and Robert M. Malina
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Youth sport ,Female athletes ,Growth ,Cardiac function ,Skeletal age ,Scaling ,Pediatrics ,RJ1-570 - Abstract
Abstract Background The aim of the study was to examine the contribution of chronological age (CA), skeletal maturation, training experience and concurrent body size descriptors, to inter-individual variance in left ventricular mass (LVM) among female adolescent soccer players. Methods The sample included 228 female soccer players 11.8–17.1 years. Training experience defined as years of participation in competitive soccer (range 2–9 years), was obtained by interview. Stature, body mass and skinfolds (triceps, medial calf) were measured. Fat mass was estimated; Fat-free mass was derived. LVM was assessed by echocardiography. Skeletal maturity status was as the difference of skeletal age (SA, Fels method) minus CA. Results Fat-free mass was the most prominent single predictor of LVM (R2 = 36.6%). It was associated with an allometric coefficient close to linearity (k = 0.924, 95%CI: 0.737 to 1.112). A significant multiplicative allometric model including body mass, fat-free mass, CA, training experience and skeletal maturity status was also obtained (R = 0.684; R2 = 46.2%). Conclusion Stature has limitations as a valid size descriptor of LVM. Body mass, fat-free mass, training experience, CA, body mass and skeletal maturity status were relevant factors contributing to inter-individual variability in LVM.
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- 2020
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43. The Identity Constitution of the Craft Beer Consumer in the City of Fortaleza (Brazil)
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João Gonçalves Menezes, Minelle E. Silva, and José Sarto Freire Castelo
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consumer culture ,identity profiles ,craft beer ,Business ,HF5001-6182 - Abstract
With the transformation of the market into a provider of relevant symbolic resources, individuals like to demonstrate consumer goods that reflect their values and shared lifestyles. Thus, the aim of this study is to define identity profiles of craft beer enthusiasts based on their consumption practices. Using exploratory qualitative research, 55 consumers were interviewed and observations were made in the city of Fortaleza, Ceará, Brazil. The results present five consumer identity profiles in the culture of the craft beer consumer: Beginner, Adventurer, Beer Evangelist, Expert, and Beer Snob. The research enriches the studies inherent in consumer culture by presenting identity profiles based on consumption habits, and what is more, the research also makes a contribution by presenting the segmentation methodology in which the suggested identities can serve as a mechanism for industry organizations in the search for relationship strategies with the target audience.
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- 2020
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44. β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity
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João Gonçalves Pereira, Joana Fernandes, Ana Rita Duarte, and Susana Mendes Fernandes
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β-lactam ,pharmacokinetics ,pharmacodynamics ,critical care ,dosing ,organ failure ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time β-lactam antibiotic dose adjustments according to the patient’s condition are critical. The continuous infusion of β-lactams and the therapeutic monitoring of their concentration have both been proposed to improve their efficacy, but strong data to support their use are still lacking. The knowledge of the pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further increase the dosing conundrum. Recent data have emerged linking overexposure to β-lactams to central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition, it is well recognized that β-lactam exposure facilitates resistance selection and that correct dosing can help to overcome it. In this review, we discuss recent data regarding real-time β-lactam antibiotic dose adjustment, options in special populations, and the impacts on mitochondria and the microbiome.
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- 2022
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45. Epidemiological, Clinical, and Genomic Profile in Head and Neck Cancer Patients and Their Families
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Thiago Celestino Chulam, Fernanda Bernardi Bertonha, Rolando André Rios Villacis, João Gonçalves Filho, Luiz Paulo Kowalski, and Silvia Regina Rogatto
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head and neck cancer ,familial cancer ,cancer predisposition ,risk factors ,copy number alterations ,Biology (General) ,QH301-705.5 - Abstract
Inherited cancer predisposition genes are described as risk factors in head and neck cancer (HNC) families. To explore the clinical and epidemiological data and their association with a family history of cancer, we recruited 74 patients and 164 relatives affected by cancer. The germline copy number alterations were evaluated in 18 patients using array comparative genomic hybridization. Two or more first-degree relatives with HNC, tobacco-associated tumor sites (lung, esophagus, and pancreas), or other related tumors (breast, colon, kidney, bladder, cervix, stomach carcinomas, and melanoma) were reported in 74 families. Ten index patients had no exposure to any known risk factors. Family members presented tumors of 19 topographies (30 head and neck, 26 breast, 21 colon). In first-degree relatives, siblings were frequently affected by cancer (n = 58, 13 had HNC). Breast cancer (n = 21), HNC (n = 19), and uterine carcinoma (n = 15) were commonly found in first-degree relatives and HNC in second-degree relatives (n = 11). Nineteen germline genomic imbalances were detected in 13 patients; three presented gains of WRD genes. The number of HNC patients, the degree of kinship, and the tumor types detected in each relative support the role of heredity in these families. Germline alterations may potentially contribute to cancer development.
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- 2022
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46. Edge-Compatible Deep Learning Models for Detection of Pest Outbreaks in Viticulture
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João Gonçalves, Eduardo Silva, Pedro Faria, Telmo Nogueira, Ana Ferreira, Cristina Carlos, and Luís Rosado
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viticulture ,pests monitoring ,insect detection ,object detection ,deep learning ,machine-learning ,Agriculture - Abstract
The direct effect of global warming on viticulture is already apparent, with unexpected pests and diseases as one of the most concerning consequences. Deploying sticky traps on grape plantations to attract key insects has been the backbone of conventional pest management programs. However, they are time-consuming processes for winegrowers, conducted through visual inspection via the manual identification and counting of key insects. Additionally, winegrowers usually lack taxonomy expertise for accurate species identification. This paper explores the usage of deep learning on the edge to identify and quantify pest counts automatically. Different mobile devices were used to acquire a dataset of yellow sticky and delta traps, consisting of 168 images with 8966 key insects manually annotated by experienced taxonomy specialists. Five different deep learning models suitable to run locally on mobile devices were selected, trained, and benchmarked to detect five different insect species. Model-centric, data-centric, and deployment-centric strategies were explored to improve and fine-tune the considered models, where they were tested on low-end and high-end mobile devices. The SSD ResNet50 model proved to be the most suitable architecture for deployment on edge devices, with accuracies per class ranging from 82% to 99%, the F1 score ranging from 58% to 84%, and inference speeds per trap image of 19.4 s and 62.7 s for high-end and low-end smartphones, respectively. These results demonstrate the potential of the approach proposed to be integrated into a mobile-based solution for vineyard pest monitoring by providing automated detection and the counting of key vector insects to winegrowers and taxonomy specialists.
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- 2022
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47. HIV Vif protein in docetaxel treatment of breast cancer cells
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Pedro Cipriano, Susana Bandarra, João Gonçalves, Ana Clara Ribeiro, and Isabel Barahona
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Medicine - Abstract
AbstractIntroduction Breast cancer is one of the most frequently diagnosed cancers in the world and is also the leading cause of death in women diagnosed with this disease. Recently, APOBEC3 proteins have been identified as potent mutagenic agents of genomic DNA associated with the onset, progression and treatment resistance of various types of cancer. On the other hand, Vif1 from HIV-1 and Vif2 from HIV-2 are proteins encoded by HIV-1 and HIV-2, respectively, that during viral infection plays a crucial role in the inhibition/degradation of APOBEC3. In this work it was tested the hypothesis that both Vif1 and Vif2 mediated APOBEC3 inhibition will increase the cytotoxicity of docetaxel in a triple-negative breast cancer cell line.Materials and methods Breast cancer HCC1806 cell line was used as well as two new derived cell lines, with vif1 and vif2 genes integrated and expressing vif in fusion with Zs Green fluorescent protein, mentioned hereinafter simply as VIF-1 and VIF-2 cells. Cell viability assays were performed by MTT reduction after 24 h and 48 h exposure of cells (HCC1806, VIF-1 and VIF-2) to different concentrations of docetaxel.Results Our results in the presence of docetaxel for 24 h have shown that cell viability decreases in all cell lines around 30% or 40%. Moreover, there is no significant differences in cell viability of parental cell line HCC1806 and any of the modified lines (VIF-1 and VIF-2) at any of the docetaxel concentrations tested (p-value > .05 – independent sample t-test). Additionally, after 48 h exposure to docetaxel, cell survival also decreases significantly to values between 38 and 43% (Figure 1), but again we could not see significant differences in cell viability among HCC1806, VIF-1 and VIF-2 cells treated to any tested concentration of docetaxel. Discussion and conclusions: The hypothesis that Vif will enhance triple negative breast cancer cells sensitivity to treatments with docetaxel was not verified. The lack of effect of Vif in cells sensitivity in the presence of docetaxel may be explained by the fact that cell target of docetaxel is Microtubules and Vif proteins do not interfere with Microtubules. Probably, the presence of Vif will only alter sensibility of breast cancer cells when using drugs that affect the DNA, the known target of APOBEC3. Therefore, treatment with drugs independent of DNA seems to be also independent of APOBEC3 levels in cells.[Figure: see text]
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- 2021
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48. Effect of Vif in doxorubicin treated breast cancer cells
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Susana Bandarra, Pedro Cipriano, João Gonçalves, Ana Clara Ribeiro, and Isabel Barahona
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Medicine - Abstract
AbstractIntroduction Several studies linked DNA cytosine deaminase APOBEC3 to mutational process driving carcinogenesis [1]. However, APOBEC3 expression varies in breast cancer cells [2] and their role in breast cancer treatment remains elusive. The HIV-1 and HIV-2 Vif proteins are APOBEC3 specific inhibitors that recruit the host E3 ubiquitin ligase complex, inducing APOBEC3 ubiquitination and degradation in proteasomes [1]. In this work, our aim is to inhibit APOBEC3 using Vif and determine the sensibility of breast cancer cells to a non-hormonal treatment with doxorubicin.Materials and methods Triple negative breast cancer cell line HCC1806 was transduced with lentiviruses containing Vif-1 and Vif-2 genes in fusion with ZsGreen reporter gene producing two different cell lines named as VIF1 and VIF2 cells. Before cells treatment with doxorubicin, the expression of the fluorescent marker and Vif was confirmed by Fluorescent Activated Cell Sorting (FACS-AriaIII) and PCR, respectively. Characterisation of doxorubicin dose-and time-responsive cell viability was performed using MTT assay.Results High-titers of Vif-delivering lentiviruses were produced and used to transduce efficiently the HCC1806 cells. More than 99% of sorting population expressed ZsGreen indicating that Vif-1 and Vif-2 genes were integrated in genomic DNA and expressed in VIF1 and VIF2 cell lines. After treatment with doxorubicin for 24 h, all cell lines showed significant decrease of viability when compared with untreated cells, proportional to the concentration of doxorubicin (Figure 1). Comparison between cell viability of HCC1806 (parental) and VIF1 shows no difference in contrast with the behaviour of VIF2 cells that after doxorubicin treatment showed a significant increase in viability. Discussion and conclusions: The increased viability of doxorubicin treated VIF2 cells correspond to the development of cells resistance to doxorubicin. This resistance of VIF2 cells is probably related to the APOBEC3 inhibition by Vif 2 protein. Our results raise concerns about general use of doxorubicin as breast cancer treatment, especially when APOBEC3 expression is low.[Figure: see text]
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- 2021
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49. Intensive cardiovascular care units after half a century: Insights from the Portuguese experience
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Pedro Gonçalves-Teixeira, Ana Raquel Barbosa, Marisa Silva, João Gonçalves Almeida, Marta Ponte, Adelaide Dias, Ricardo Fontes-Carvalho, Pedro Braga, and Daniel Caeiro
- Subjects
Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2020
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50. Ensino do gênero grafite: uma experiência com adolescentes em privação de liberdade
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Flávia Karolina Lima-Duarte, Rossana Viana Gaia, João Gonçalves Torres-Filho, and Diogo Rodrigo do Nascimento
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gênero textual ,unidade de internação masculina ,ensino de língua portuguesa ,Education (General) ,L7-991 - Abstract
Este artigo, resultado de uma pesquisa de iniciação científica, tem por objetivo analisar a reflexão crítica de socioeducandos de uma Unidade de Internação Masculina a partir do ensino do gênero grafite. A base teórica selecionada se apropria de reflexões sobre práticas educativas em ambientes de encarceramento, bem como sobre a relevância histórico-social do gênero grafite. A metodologia incluiu seleção dos participantes, oficinas de desenho e de pintura, leitura de imagens estáticas e fílmicas, produção de desenhos e entrevistas. Os resultados demonstram que, inicialmente, os participantes tiveram dificuldade em compreender a função social do grafite e a importância desse gênero como instrumento de reivindicação de direitos; contudo, no decorrer do processo, a partir das estratégias metodológicas utilizadas, os socioeducandos começaram a perceber que, por meio desse gênero, eles podem denunciar os problemas existentes em suas comunidades e reivindicar seus direitos. Como conclusão, indica-se a necessidade de desenvolver mais pesquisas que contribuam com a reflexão crítica de adolescentes em ambiente de privação de liberdade.
- Published
- 2019
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