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  1. AU="Helder I. Nakaya"
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  1. Article ; Online: Why should obese youth be prioritized in COVID-19 vaccination programs? A nationwide retrospective study

    Michelle G. Discacciati / Sirlei Siani / Ana Campa / Helder I Nakaya

    The Lancet Regional Health. Americas, Vol 7, Iss , Pp 100167- (2022)

    2022  

    Abstract: Summary: Background: The dominant effect of age on COVID-19 mortality obscures the impact of other risk factors. Although the elderly is at a greater risk of severe disease and death due to COVID-19, the interaction of obesity and age was not carefully ... ...

    Abstract Summary: Background: The dominant effect of age on COVID-19 mortality obscures the impact of other risk factors. Although the elderly is at a greater risk of severe disease and death due to COVID-19, the interaction of obesity and age was not carefully assessed. This analysis is especially critical for prioritizing groups to receive COVID-19 vaccination. Methods: Starting with 1,120,767 unvaccinated individuals registered in a Brazilian surveillance system, we selected 313,898 hospitalized COVID-19 patients aged 20 to 89 who had a BMI ≥ 25 kg/m2 and cardiovascular diseases (CVD) or diabetes, as well as individuals with no risk factors associated with severe COVID-19. Patient data were stratified by age, obesity, BMI, and comorbidities, and subsequently, subjected to crude and adjusted odds ratio, hazard ratio, and Kaplan–Meier curves. Disease outcomes were invasive and non-invasive ventilatory support, intensive care unit (ICU) admission, and death. Findings: Obesity alone is a risk factor for in-hospital mortality and is more significant than cardiovascular disease and diabetes. Furthermore, obesity, cardiovascular disease, and diabetes increase the risk of severity and death by COVID-19 more significantly in young adults than in the elderly. When categorizing patients by obesity classes, the severity of obesity was found to be associated with a higher risk of admission to the ICU and death from COVID-19 than the non-obese young adults or elderly population. Interpretation: Our findings highlight the increased risk of severe COVID-19 on the Brazilian obese youth. As SARS-CoV-2 may become a recurrent seasonal infection, future vaccination campaigns against COVID-19 should prioritize obese young individuals. Fundings: This work was supported by the Brazilian National Council for Scientific and Technological Development (grant number 313662/2017-7 and 307356/2017-5; the São Paulo Research Foundation (grant numbers 2018/14933-2); and CAPES.
    Keywords Public aspects of medicine ; RA1-1270
    Subject code 610
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Editorial

    Helder I. Nakaya / Juilee Thakar / Vinicius Maracaja-Coutinho

    Frontiers in Genetics, Vol

    User-Friendly Tools Applied to Genetics or Systems Biology

    2020  Volume 11

    Keywords user-friendly tools ; systems biology ; omics analyses ; bioinformatics and computational biology ; computational tool and servers ; Genetics ; QH426-470
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: OUTBREAK

    Raúl Arias-Carrasco / Jeevan Giddaluru / Lucas E. Cardozo / Felipe Martins / Vinicius Maracaja-Coutinho / Helder I. Nakaya

    Biological Research, Vol 54, Iss 1, Pp 1-

    a user-friendly georeferencing online tool for disease surveillance

    2021  Volume 6

    Abstract: Abstract The current COVID-19 pandemic has already claimed more than 3.7 million victims and it will cause more deaths in the coming months. Tools that track the number and locations of cases are critical for surveillance and help in making policy ... ...

    Abstract Abstract The current COVID-19 pandemic has already claimed more than 3.7 million victims and it will cause more deaths in the coming months. Tools that track the number and locations of cases are critical for surveillance and help in making policy decisions for controlling the outbreak. However, the current surveillance web-based dashboards run on proprietary platforms, which are often expensive and require specific computational knowledge. We developed a user-friendly web tool, named OUTBREAK, that facilitates epidemic surveillance by showing in an animated graph the timeline and geolocations of cases of an outbreak. It permits even non-specialist users to input data most conveniently and track outbreaks in real-time. We applied our tool to visualize the SARS 2003, MERS, and COVID19 epidemics, and provided them as examples on the website. Through the zoom feature, it is also possible to visualize cases at city and even neighborhood levels. We made the tool freely available at https://outbreak.sysbio.tools/ . OUTBREAK has the potential to guide and help health authorities to intervene and minimize the effects of outbreaks.
    Keywords Outbreak ; Pandemic ; Epidemiology ; Surveillance ; Georeferencing ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Noninvasive prenatal paternity determination using microhaplotypes

    Jaqueline Yu Ting Wang / Martin R. Whittle / Renato David Puga / Anatoly Yambartsev / André Fujita / Helder I. Nakaya

    BMC Medical Genomics, Vol 13, Iss 1, Pp 1-

    a pilot study

    2020  Volume 8

    Abstract: Abstract Background The use of noninvasive techniques to determine paternity prenatally is increasing because it reduces the risks associated with invasive procedures. Current methods, based on SNPs, use the analysis of at least 148 markers, on average. ... ...

    Abstract Abstract Background The use of noninvasive techniques to determine paternity prenatally is increasing because it reduces the risks associated with invasive procedures. Current methods, based on SNPs, use the analysis of at least 148 markers, on average. Methods To reduce the number of regions, we used microhaplotypes, which are chromosomal segments smaller than 200 bp containing two or more SNPs. Our method employs massively parallel sequencing and analysis of microhaplotypes as genetic markers. We tested 20 microhaplotypes and ascertained that 19 obey Hardy–Weinberg equilibrium and are independent, and data from the 1000 Genomes Project were used for population frequency and simulations. Results We performed simulations of true and false paternity, using the 1000 Genomes Project data, to confirm if the microhaplotypes could be used as genetic markers. We observed that at least 13 microhaplotypes should be used to decrease the chances of false positives. Then, we applied the method in 31 trios, and it was able to correctly assign the fatherhood in cases where the alleged father was the real father, excluding the inconclusive results. We also cross evaluated the mother-plasma duos with the alleged fathers for false inclusions within our data, and we observed that the use of at least 15 microhaplotypes in real data also decreases the false inclusions. Conclusions In this work, we demonstrated that microhaplotypes can be used to determine prenatal paternity by using only 15 regions and with admixtures of DNA.
    Keywords Microhaplotype ; Noninvasive ; Probability of paternity ; Prenatal ; Single nucleotide polymorphism ; Internal medicine ; RC31-1245 ; Genetics ; QH426-470
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Imbalanced IL-1B and IL-18 Expression in Sézary Syndrome

    Kelly Cristina Gomes Manfrere / Marina Passos Torrealba / Frederico Moraes Ferreira / Emanuella Sarmento Alho de Sousa / Denis Miyashiro / Franciane Mouradian Emidio Teixeira / Ricardo Wesley Alberca Custódio / Helder I. Nakaya / Yasmin Alefe Leuzzi Ramos / Mirian Nacagami Sotto / Anders Woetmann / Niels Ødum / Alberto José da Silva Duarte / José Antonio Sanches / Maria Notomi Sato

    International Journal of Molecular Sciences, Vol 24, Iss 4674, p

    2023  Volume 4674

    Abstract: Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and ...

    Abstract Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3 , whereas the pathway analysis indicated a further downregulation of IL1B -associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.
    Keywords Sézary syndrome ; lymph nodes ; inflammasome ; IL-1B ; IL-18 ; erythroderma skin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania ( L. ) chagasi in Amazonian Brazil

    Vania Lucia R. da Matta / André N. Gonçalves / Cláudia Maria C. Gomes / Islam H. Chouman / Frederico M. Ferreira / Marliane B. Campos / Luciana V. Lima / Thiago Vasconcelos dos Santos / Patrícia Karla Ramos / Rodrigo R. Furtado / Marcia D. Laurenti / Carlos Eduardo P. Corbett / Helder I. Nakaya / Fernando T. Silveira

    Microorganisms, Vol 11, Iss 653, p

    2023  Volume 653

    Abstract: Individuals infected with Leishmania ( L. ) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical–immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant ... ...

    Abstract Individuals infected with Leishmania ( L. ) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical–immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical–immunological (symptomatic and asymptomatic) profiles of human L. ( L. ) chagasi -infection in the Brazilian Amazon.
    Keywords Leishmania ( L. ) chagasi ; human infection ; transcriptomic analysis ; symptomatic ; asymptomatic ; clinical-immunological profiles ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Automatic detection of the parasite Trypanosoma cruzi in blood smears using a machine learning approach applied to mobile phone images

    Mauro César Cafundó Morais / Diogo Silva / Matheus Marques Milagre / Maykon Tavares de Oliveira / Thaís Pereira / João Santana Silva / Luciano da F. Costa / Paola Minoprio / Roberto Marcondes Cesar Junior / Ricardo Gazzinelli / Marta de Lana / Helder I. Nakaya

    PeerJ, Vol 10, p e

    2022  Volume 13470

    Abstract: Chagas disease is a life-threatening illness caused by the parasite Trypanosoma cruzi. The diagnosis of the acute form of the disease is performed by trained microscopists who detect parasites in blood smear samples. Since this method requires a ... ...

    Abstract Chagas disease is a life-threatening illness caused by the parasite Trypanosoma cruzi. The diagnosis of the acute form of the disease is performed by trained microscopists who detect parasites in blood smear samples. Since this method requires a dedicated high-resolution camera system attached to the microscope, the diagnostic method is more expensive and often prohibitive for low-income settings. Here, we present a machine learning approach based on a random forest (RF) algorithm for the detection and counting of T. cruzi trypomastigotes in mobile phone images. We analyzed micrographs of blood smear samples that were acquired using a mobile device camera capable of capturing images in a resolution of 12 megapixels. We extracted a set of features that describe morphometric parameters (geometry and curvature), as well as color, and texture measurements of 1,314 parasites. The features were divided into train and test sets (4:1) and classified using the RF algorithm. The values of precision, sensitivity, and area under the receiver operating characteristic (ROC) curve of the proposed method were 87.6%, 90.5%, and 0.942, respectively. Automating image analysis acquired with a mobile device is a viable alternative for reducing costs and gaining efficiency in the use of the optical microscope.
    Keywords Trypanosoma cruzi ; Blood trypomastigote ; Parasitemia ; Machine learning ; SVM ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 600
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19

    Bruna GG Pinto / Antonio ER Oliveira / Youvika Singh / Leandro Jimenez / Andre NA Goncalves / Rodrigo LT Ogava / Rachel Creighton / Jean PS Peron / Helder I Nakaya

    Abstract: The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as ... ...

    Abstract The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. The angiotensin-converting enzyme 2 (ACE2) was identified as a crucial factor that facilitates SARS-CoV2 to bind and enter host cells. To date, no study has assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. We also found other genes, such as RAB1A, that can be important for SARS-CoV-2 infection in the lung. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. In fact, epigenetic marks found in ACE2 locus were compatible to with those promoted by KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.
    Keywords covid19
    Publisher medrxiv
    Document type Article ; Online
    DOI 10.1101/2020.03.21.20040261
    Database COVID19

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  9. Article ; Online: São Paulo School of Advanced Sciences on Vaccines

    Sara Sorgi / Vivian Bonezi / Mariana R. Dominguez / Alba Marina Gimenez / Irina Dobrescu / Silvia Boscardin / Helder I. Nakaya / Daniel Y. Bargieri / Irene S. Soares / Eduardo L. V. Silveira

    Journal of Venomous Animals and Toxins including Tropical Diseases, Vol

    an overview

    2020  Volume 26

    Abstract: Abstract Two years ago, we held an exciting event entitled the São Paulo School of Advanced Sciences on Vaccines (SPSASV). Sixty-eight Ph.D. students, postdoctoral fellows and independent researchers from 37 different countries met at the Mendes Plaza ... ...

    Abstract Abstract Two years ago, we held an exciting event entitled the São Paulo School of Advanced Sciences on Vaccines (SPSASV). Sixty-eight Ph.D. students, postdoctoral fellows and independent researchers from 37 different countries met at the Mendes Plaza Hotel located in the city of Santos, SP - Brazil to discuss the challenges and the new frontiers of vaccinology. The SPSASV provided a critical and comprehensive view of vaccine research from basics to the current state-of-the-art techniques performed worldwide. For 10 days, we discussed all the aspects of vaccine development in 36 lectures, 53 oral presentations and 2 poster sessions. At the end of the course, participants were further encouraged to present a model of a grant proposal related to vaccine development against individual pathogens. Among the targeted pathogens were viruses (Chikungunya, HIV, RSV, and Influenza), bacteria (Mycobacterium tuberculosis and Streptococcus pyogenes), parasites (Plasmodium falciparum or Plasmodium vivax), and the worm Strongyloides stercoralis. This report highlights some of the knowledge shared at the SPSASV.
    Keywords Vaccine history ; WHO priorities and challenges ; Immune responses ; Antigen search ; Delivery systems and strategies ; Arctic medicine. Tropical medicine ; RC955-962 ; Toxicology. Poisons ; RA1190-1270 ; Zoology ; QL1-991
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher SciELO
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients

    João L Silva-Filho / João CK Dos-Santos / Carla Judice / Dario Beraldi / Kannan Venugopal / Diogenes Lima / Helder I Nakaya / Erich V De Paula / Stefanie CP Lopes / Marcus VG Lacerda / Matthias Marti / Fabio TM Costa

    eLife, Vol

    2021  Volume 10

    Abstract: Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia, remains a matter of intense debate. Estimation of total P. vivax biomass based on ... ...

    Abstract Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia, remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study, we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses, and ex vivo assays. Patterns of clinical features, parasite burden, and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlow and Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlow patients clustered with healthy donors and Vivaxhigh patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation, and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhigh patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients’ signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia, and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral ...
    Keywords Plasmodium vivax ; malaria parasite ; total biomass ; tissue infection ; endothelial activation ; haematopoiesis ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 616 ; 572
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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