CBR - Contribuições em Revistas Científicas / Contribution to Journals
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- Transcranial Magnetic Stimulation–Electroencephalography (TMS-EEG) in neurosurgery: unexplored path towards personalized brain surgeryPublication . Oliveira, Martim; Ribeiro, Sofia; Baig Mirza, Asfand; Vastani, Amisha; Díaz-Baamonde, Alba; Tanaka, Masumi; Elhag, Ali; Marchi, Francesco; Ghimire, Prajwal; Fayez, Feras; Patel, Sabina; Gullan, Richard; Bhangoo, Ranjeev; Ashkan, Keyoumars; Vergani, Francesco; Mirallave-Pescador, Ana; Lavrador, José PedroBackground: Transcranial Magnetic Stimulation–Electroencephalography (TMS-EEG) is a non-operative technique that allows for magnetic cortical stimulation (TMS) and analysis of the electrical currents generated in the brain (EEG). Despite the regular utilization of both techniques independently, little is known about the potential impact of their combination in neurosurgical practice. Methods: This scoping review, conducted following PRISMA guidelines, focused on TMS-EEG in epilepsy, neuro-oncology, and general neurosurgery. A literature search in Embase and Ovid MEDLINE returned 3596 records, which were screened based on predefined inclusion and exclusion criteria. After full-text review, three studies met the inclusion criteria. Two independent investigators conducted study selection and data extraction, with mediators resolving disagreements. The NHLBI tool was used to assess risk of bias in the included studies. Results: A total of 3596 articles were screened following the above-mentioned criteria: two articles and one abstract met the inclusion criteria. TMS-EEG is mentioned as a promising tool to evaluate tumor–brain interaction, improve preoperative speech mapping, and for lateralization epileptic focus in patients undergoing epilepsy surgery. Lack of detailed patient and outcome information preclude further considerations about TMS-EEG use beyond the potential applications of this technique. Conclusions: TMS-EEG research in neurosurgery is required to establish the role of this non-invasive brain stimulation-recording technique. Tumor–brain interaction, preoperative mapping, and seizure lateralization are in the front row for its future applications.
- Leveraging microphysiological systems to expedite understanding of host-parasite interactionsPublication . Zorrinho-Almeida, Maria; de-Carvalho, Jorge; Bernabeu, Maria; Pereira, Sara SilvaMicrophysiological systems (MPS) replicate the dynamic interactions between cells, tissues, and fluids. They have emerged as transformative tools for biology and have been increasingly applied to host–parasite interactions. Offering a better representation of cellular behavior compared with traditional in vitro models, MPS can facilitate the study of parasite tropism, immune evasion, and life cycle transitions across diverse parasitic diseases. Applications span multiple host tissues and pathogens, leveraging advanced bioengineering and microfabrication techniques to address long-standing knowledge gaps. Here, we review recent advances in MPS applied to parasitic diseases and identify persisting challenges and opportunities for investment. By refining these systems and integrating host multicellular models and parasites, MPS hold vast potential to revolutionize parasitology, enhancing our ability to combat parasitic diseases through deeper mechanistic understanding and targeted interventions.
- Diagnosis and management of acromegaly: a consensus statement of the pituitary study group of the portuguese society of endocrinology, diabetes and metabolismPublication . Cardoso, Luís Miguel; Marques, Pedro; Pereira, Maria Teresa; Agapito, Ana; Almeida, Rui; Amaral, Sara; Cattoni, Maria Begona; Bugalho, Maria João; Cortez, Luísa; Duarte, Diana Borges; Duarte, João Sequeira; Fonseca, Fernando; Gomes, Leonor; Manique, Inês; Marques, Olinda; Martins, Teresa; Oliveira, Maria João; Paiva, Isabel; Pereira, Josué; Santos, Ana Paula; Silva, Vânia Benido; Torres, Isabel; Amaral, Cláudia; Carvalho, DavideAcromegaly is characterised by hypersecretion of growth hormone and presents diagnostic and therapeutic challenges that require consensus and guidelines for effective management. The Pituitary Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism used a modified Delphi methodology to develop consensus recommendations for the diagnosis and management of acromegaly. A multidisciplinary panel of experts in acromegaly collaborated through this process to establish consensus-based statements. The authors did not receive any corporate funding or remuneration. The methodology employed to achieve these consensus recommendations included a literature review of specific topics, development of consensus statements, survey and interactive discussions, and a subsequent comprehensive analysis of the results to converge on key consensus statements for diagnosis, treatment, and monitoring strategies. By synthesising the available evidence and integrating expert opinion, this consensus document offers valuable insights for healthcare professionals, facilitating timely diagnosis, personalised treatment strategies developed by multidisciplinary teams, and enhanced patient care.
- Travel-associated international spread of Oropouche virus beyond the AmazonPublication . Iani, Felipe Campos de Melo; Pereira, Felicidade Mota; Oliveira, Elaine Cristina de; Rodrigues, Janete Taynã Nascimento; Machado, Mariza Hoffmann; Fonseca, Vagner; Adelino, Talita Emile Ribeiro; Guimarães, Natalia Rocha; Tomé, Luiz Marcelo Ribeiro; Gómez, Marcela Kelly Astete; Nardy, Vanessa Brandão; Ribeiro, Adriana Aparecida; Rosewell, Alexander; Ferreira, Álvaro Gil A.; Mello, Arabela Leal e Silva de; Fernandes, Brenda Machado Moura; Albuquerque, Carlos Frederico Campelo de; Pereira, Dejanira dos Santos; Pimentel, Eline Carvalho; Lima, Fábio Guilherme Mesquita; Silva, Fernanda Viana Moreira; Pereira, Glauco de Carvalho; Tegally, Houriiyah; Almeida, Júlia Deffune Profeta Cidin; Moreno, Keldenn Melo Farias; Vasconcelos, Klaucia Rodrigues; Santos, Leandro Cavalcante; Silva, Lívia Cristina Machado; Frutuoso, Livia C. V.; Lamounier, Ludmila Oliveira; Costa, Mariana Araújo; Oliveira, Marília Santini de; Anjos, Marlei Pickler Dediasi dos; Ciccozzi, Massimo; Lima, Maurício Teixeira; Pereira, Maira Alves; Rocha, Marília Lima Cruz; Silva, Paulo Eduardo de Souza da; Rabinowitz, Peter M.; Almeida, Priscila Souza de; Lessells, Richard; Gazzinelli, Ricardo T.; Cunha, Rivaldo Venancio da; Gonçalves, Sabrina; Santos, Sara Cândida Ferreira dos; Belettini, Senele Ana de Alcântara; Pedroso, Silvia Helena Sousa Pietra; Araújo, Sofia Isabel Rótulo; Silva, Stephanni Figueiredo da; Croda, Julio; Maciel, Ethel; Voorhis, Wes Van; Martin, Darren P.; Holmes, Edward C.; Oliveira, Tulio de; Lourenço, José; Alcantara, Luiz Carlos Junior; Giovanetti, MartaOropouche virus (OROV), first detected in Trinidad and Tobago in 1955, was historically confined to the Brazilian Amazon Basin. However, since late 2022, an increasing number of OROV cases have been reported across various regions of Brazil as well as in urban centers in Bolivia, Ecuador, Guyana, Colombia, Cuba, Panama, and Peru. In collaboration with Central Public Health Laboratories across Brazil, we integrated epidemiological metadata with genomic analyses from recent cases, generating 133 whole-genome sequences covering the virus’s three genomic segments (L, M, and S). These include the first genomes from regions outside the Amazon and from the first recorded fatal cases. Phylogenetic analyses show that the 2024 OROV genomes form a monophyletic group with sequences from the Amazon Basin sampled since 2022, revealing a rapid north-to-south viral movement into historically non-endemic areas. We identified 21 reassortment events, though it remains unclear whether these genomic changes have facilitated viral adaptation to local ecological conditions or contributed to phenotypic traits of public health significance. Our findings demonstrate how OROV has evolved through reassortment and spread rapidly across multiple states in Brazil, leading to the largest outbreak ever recorded outside the Amazon and the first confirmed fatalities. Additionally, by analysing travel-related cases, we provide the first insights into the international spread of OROV beyond Brazil, further highlighting the role of human mobility in its dissemination. The virus’s recent rapid geographic expansion and the emergence of severe cases emphasize the urgent need for enhanced surveillance across the Americas. In the absence of significant human population changes over the past two years, factors such as viral adaptation, deforestation, and climate shifts—either individually or in combination— may have facilitated the spread of OROV beyond the Amazon Basin through both local and travel-associated transmission.
- m6A landscape is more pervasive when Trypanosoma brucei exits the cell cyclePublication . Serra, Lúcia; Pereira, Sara Silva; Viegas, Idálio J.; Machado, Henrique; López-Escobar, Lara; Figueiredo, Luisa M.N6-methyladenosine (m6A) is an mRNA modification with important roles in gene expression. In African trypanosomes, this post-transcriptional modification is detected in hundreds of transcripts, and it affects the stability of the variant surface glycoprotein (VSG) transcript in the proliferating blood stream form. However, how the m6A landscape varies across the life cycle remains poorly defined. Using full-length, non-fragmented RNA, we immunoprecipitated and sequenced m6A-modified transcripts across three life cycle stages of Trypanosoma brucei – slender (proliferative), stumpy (quiescent), and procyclic forms (proliferative). We found that 1037 transcripts are methylated in at least one of these three life cycle stages. While 21% of methylated transcripts are common in the three stages of the life cycle, globally, each stage has a distinct methylome. Interestingly, 47% of methylated transcripts are detected in the quiescent stumpy form only, suggesting a critical role for m6A when parasites exit the cell cycle and prepare for transmission by the tsetse fly. In this stage, we found that a significant proportion of methylated transcripts encodes for proteins involved in RNA metabolism, which is consistent with their reduced transcription and translation. Moreover, we found that not all major surface proteins are regulated by m6A, as procyclins are not methylated, and that, within the VSG repertoire, not all VSG transcripts are demethylated upon parasite differentiation to procyclic form. This study reveals that the m6A regulatory landscape is specific to each life cycle stage, becoming more pervasive as T. brucei exits the cell cycle.
- Deciphering respiratory viral infections by harnessing organ-on-chip technology to explore the gut-lung axisPublication . Koceva, Hristina; Amiratashani, Mona; Akbarimoghaddam, Parastoo; Hoffmann, Bianca; Zhurgenbayeva, Gaukhar; Gresnigt, Mark S.; Marcelino, Vanessa Rossetto; Eggeling, Christian; Figge, Marc Thilo; Amorim, Maria-João; Mosig, Alexander S.The lung microbiome has recently gained attention for potentially affecting respiratory viral infections, including influenza A virus, respiratory syncytial virus (RSV) and SARS-CoV-2. We will discuss the complexities of the lung microenvironment in the context of viral infections and the use of organ-on-chip (OoC) models in replicating the respiratory tract milieu to aid in understanding the role of temporary microbial colonization. Leveraging the innovative capabilities of OoC, particularly through integrating gut and lung models, opens new avenues to understand the mechanisms linking inter-organ crosstalk and respiratory infections. We will discuss technical aspects of OoC lung models, ranging from the selection of cell substrates for extracellular matrix mimicry, mechanical strain, breathing mechanisms and air–liquid interface to the integration of immune cells and use of microscopy tools for algorithm-based image analysis and systems biology to study viral infection in vitro. OoC offers exciting new options to study viral infections across host species and to investigate human cellular physiology at a personalized level. This review bridges the gap between complex biological phenomena and the technical prowess of OoC models, providing a comprehensive roadmap for researchers in the field.
- Artificial intelligence-powered microscopy: transforming the landscape of parasitologyPublication . Niz, Mariana De; Pereira, Sara Silva; Kirchenbuechler, David; Lemgruber, Leandro; Arvanitis, ConstadinaMicroscopy and image analysis play a vital role in parasitology research; they are critical for identifying parasitic organisms and elucidating their complex life cycles. Despite major advancements in imaging and analysis, several challenges remain. These include the integration of interdisciplinary data; information derived from various model organisms; and data acquired from clinical research. In our view, artificial intelligence—with the latest advances in machine and deep learning—holds enormous potential to address many of these challenges. This review addresses how artificial intelligence, machine learning and deep learning have been used in the field of parasitology—mainly focused on Apicomplexan, Diplomonad, and Kinetoplastid groups. We explore how gaps in our understanding could be filled by AI in future parasitology research and diagnosis in the field. Moreover, it addresses challenges and limitations currently faced in implementing and expanding the use of artificial intelligence across biomedical fields. The necessary increased collaboration between biologists and computational scientists will facilitate understanding, development, and implementation of the latest advances for both scientific discovery and clinical impact. Current and future AI tools hold the potential to revolutionise parasitology and expand One Health principles.
- Common mechanistic pathways in rare congenital syndromes with primary microcephalyPublication . Jorge, Xavier; Milagre, Inês; Ferreira, Anita; Calado, Sofia; Oliveira, Raquel; Carvalhal, SaraPrimary microcephaly is an often-seen phenotype in several rare congenital syndromes. It is characterised by a smaller brain size at birth compared to the norm. The causes of this malformation are not fully understood, but genetic testing suggests a connection with defective genes involved in mitotic regulation and proteins related to DNA repair and replication pathways. Cohesinopathies represent a group of rare syndromes, where several subtypes exhibit spontaneous railroad chromosomes and primary microcephaly. This includes Roberts Syndrome, Warsaw Breakage Syndrome and a recently characterised syndrome caused by mutations in the BUB1 gene. Currently, we are examining fibroblast cells from patients with these syndromes to identify common mechanistic pathways. In this context, we have identified a new promising candidate: Topoisomerase II alpha, a protein responsible for resolving of the DNA catenation both in the DNA replication and mitosis. Defective localisation of Topoisomerase II alpha may contribute to the observed mitotic defects in these cells. We are currently exploring the impact of these defects on brain development using reprogramming techniques to assess proper neuronal differentiation.
- Bioengineered 3D microvessels and complementary animal models reveal mechanisms of Trypanosoma congolense sequestrationPublication . Porqueddu, Teresa; Zorrinho-Almeida, Maria; Niz, Mariana De; Casas-Sánchez, Aitor; Introini, Viola; Sender, Silvia Sanz; Carrasqueira, Diana; Figueiredo, Luísa M.; Bernabeu, Maria; Pereira, Sara SilvaIn the mammalian host, Trypanosoma congolense cytoadheres, or sequesters, to the vascular endothelium. Although sequestration influences clinical outcome, disease severity and organ pathology, its determinants and mediators remain unknown. Challenges such as the variability of animal models, the only-recently developed tools to genetically manipulate the parasite, and the lack of physiologically-relevant in vitro models have hindered progress. Here, we engineered brain and cardiac 3D bovine endothelial microvessel models that mimic the bovine brain microvasculature and the bovine aorta, respectively. By perfusing these models with two T. congolense strains, we investigated the roles of flow for parasite sequestration and tropism for different endothelial beds. We discovered that sequestration is dependent on cyclic adenosine monophosphate (cAMP) signalling, closely linked to parasite proliferation, but not associated with parasite transmission to the tsetse fly vector. Finally, by comparing the expression profiles of sequestered and non-sequestered parasites collected from a rodent model, we showed gene expression changes in sequestered parasites, including of surface variant antigens. This work presents a physiologically-relevant platform to study trypanosome interactions with the vasculature and provides a deeper understanding of the molecular and biophysical mechanisms underlying T. congolense sequestration.
- myAURA: a personalized health library for epilepsy management via knowledge graph sparsification and visualizationPublication . Correia, Rion Brattig; Rozum, Jordan C.; Cross, Leonard; Felag, Jack; Gallant, Michael; Guo, Ziqi; Herr II, Bruce W.; Min, Aehong; Sanchez-Valle, Jon; Rocha, Deborah Stungis; Valencia, Alfonso; Wang, Xuan; Börner, Katy; Miller, Wendy; Rocha, Luis M.Objectives: Report the development of the patient-centered myAURA application and suite of methods designed to aid epilepsy patients, caregivers, and clinicians in making decisions about self-management and care. Materials and Methods: myAURA rests on an unprecedented collection of epilepsy-relevant heterogeneous data resources, such as biomedical databases, social media, and electronic health records (EHRs). We use a patient-centered biomedical dictionary to link the collected data in a multilayer knowledge graph (KG) computed with a generalizable, open-source methodology. Results: Our approach is based on a novel network sparsification method that uses the metric backbone of weighted graphs to discover important edges for inference, recommendation, and visualization. We demonstrate by studying drug-drug interaction from EHRs, extracting epilepsy-focused digital cohorts from social media, and generating a multilayer KG visualization. We also present our patient-centered design and pilot-testing of myAURA, including its user interface. Discussion: The ability to search and explore myAURA’s heterogeneous data sources in a single, sparsified, multilayer KG is highly useful for a range of epilepsy studies and stakeholder support. Conclusion: Our stakeholder-driven, scalable approach to integrating traditional and nontraditional data sources enables both clinical discovery and data-powered patient self-management in epilepsy and can be generalized to other chronic conditions.