Artigos e Materiais de Revistas Científicas - FM/MDR

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.


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  • article 0 Citação(ões) na Scopus
    Saúde cardiovascular e habitação: um diálogo importante travado nos assentamentos precários de São Paulo
    ABSTRACT The reduction of infectious diseases and longer life favored the greater prevalence of chronic diseases such as cancer, diabetes, cardiovascular and respiratory diseases. In general, the geographical scale of studies on socioeconomic conditions and health problems is the municipality. In this geographical scale there is no clear separation between the types of settlement. Intraurban studies by type of settlement can contribute to a more faithful portrait on inequalities in living conditions. In this study, data from residents of the municipality of São Paulo were analyzed who were admitted and those who died, by diseases of the circulatory system from 2010 to 2016 for deaths and from 2011 to 2016, for hospitalizations. Each hospitalization and death was attributed to the settlement of housing according to type: non-regular settlement, precarious or regular. The following calculations were made: proportion of hospital admissions by the Unified Health System (SUS) by groups of causes, standardized rates by gender and age group, hospitalization/inhabitant according to sex, age group and type of settlement and standardized rates by gender and age standardized mortality rates due to circulatory diseases. The results found an even more wicked situation in precarious settlements for all age groups, both sexes. The difference in cardiovascular health between the three types of settlements, evaluated through the proportions of hospital hospitalizations and mortality rates, show that almost 1,700,000 people in São Paulo are in a major disadvantage compared to the group formed by 85% of the population. In terms of hospitalizations, rates are higher in non-regular settlement. In this sense, it can be speculated that there is greater access to health service for residents of non-regular settlement in relation to those of precarious settlements. This access is reverted to lower mortality when the rates of both groups are compared. If we consider only two groups (regular and non-regular settlements), the situation of greater disadvantage in precarious settlements is diluted, becoming invisible. Such results can provide health surveillance to define specific programs for these settlements, as well as territory management, in general, to provide better housing conditions.
  • article 0 Citação(ões) na Scopus
    Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk
    (2024) UENAL, Pelin; LU, Ye; BUENO-DE-MESQUITA, Bas; EIJCK, Casper H. J. van; TALAR-WOJNAROWSKA, Renata; SZENTESI, Andrea; GAZOULI, Maria; KREIVENAITE, Edita; TAVANO, Francesca; MALECKA-WOJCIESKO, Ewa; EROSS, Balint; OLIVERIUS, Martin; BUNDUC, Stefania; AOKI, Mateus Nobrega; VODICKOVA, Ludmila; BOGGI, Ugo; GIACCHERINI, Matteo; KONDRACKIENE, Jurate; CHAMMAS, Roger; PALMIERI, Orazio; THEODOROPOULOS, George E.; BIJLSMA, Maarten F.; BASSO, Daniela; MOHELNIKOVA-DUCHONOVA, Beatrice; SOUCEK, Pavel; IZBICKI, Jakob R.; KIUDELIS, Vytautas; VANELLA, Giuseppe; ARCIDIACONO, Paolo Giorgio; WLODARCZYK, Barbara; HACKERT, Thilo; SCHOETTKER, Ben; UZUNOGLU, Faik G.; BAMBI, Franco; GOETZ, Mara; HLAVAC, Viktor; BRENNER, Hermann; PERRI, Francesco; CARRARA, Silvia; LANDI, Stefano; HEGYI, Peter; DIJK, Frederike; MAIELLO, Evaristo; CAPRETTI, Giovanni; TESTONI, Sabrina Gloria Giulia; PETRONE, Maria Chiara; STOCKER, Hannah; ERMINI, Stefano; ARCHIBUGI, Livia; GENTILUOMO, Manuel; CAVESTRO, Giulia Martina; PEZZILLI, Raffaele; FRANCO, Gregorio Di; MILANETTO, Anna Caterina; SPERTI, Cosimo; NEOPTOLEMOS, John P.; MORELLI, Luca; VOKACOVA, Klara; PASQUALI, Claudio; LAWLOR, Rita T.; BAZZOCCHI, Francesca; KUPCINSKAS, Juozas; CAPURSO, Gabriele; CAMPA, Daniele; CANZIAN, Federico
    Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 x 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 x 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 x 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 x 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.
  • article 0 Citação(ões) na Scopus
    Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease
    (2024) SILVA-BATISTA, Carla; LIRA, Jumes; COELHO, Daniel Boari; LIMA-PARDINI, Andrea Cristina de; NUCCI, Mariana Penteado; MATTOS, Eugenia Casella Tavares; MAGALHAES, Fernando Henrique; BARBOSA, Egberto Reis; TEIXEIRA, Luis Augusto; AMARO JUNIOR, Edson; UGRINOWITSCH, Carlos; HORAK, Fay B.
    Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2 = 0.32, p = 0.0006) and APA amplitude (R2 = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.
  • article 0 Citação(ões) na Scopus
    Maxillary sinus volumetric changes in jet aircraft pilots: A multislice computed tomography pilot study
    (2023) SILVA, Yeda da; MUNHOZ, Luciana; PARGA FILHO, Jose Rodrigues; DAMASCENO, Andreza Gomes; ROSA, Cesar Felipe Franca da; ZUKOVSKI, Eduardo Bilaqui; TENG, Erik Zhu; CASTRO, Claudio Campi de
    Purpose: This study evaluated maxillary sinus volume changes in military jet aircraft pilot candidates before and after the training program, in comparison with a control group, considering the effects of pressurization, altitude, and total flight hours, through multislice computed tomography.Materials and Methods: Fifteen fighter pilots were evaluated before initiating the training program and after the final approval. The control group consisted of 41 young adults who had not flown during their military career. The volumes of each maxillary sinus were measured individually before and at the end of the training program.Results: When comparing the initial and final volumes in the pilots, a statistically significant increase was observed both in the left and right maxillary sinuses. When evaluating the average total volume of the maxillary sinuses (i.e., the average volume of the right and left maxillary sinuses together), a significant increase in the volume of the maxillary sinuses was observed in the pilot group when compared to the control group.Conclusion: The maxillary sinus volumes in aircraft pilot candidates increased after the 8-month training program. This may be explained by changes in the gravitational force, the expansion of gas, and positive pressure from oxygen masks. This unprecedented investigation among pilots might lead to other investigations considering paranasal sinus alterations in this singular population. (Imaging Sci Dent 20220173)
  • article 0 Citação(ões) na Scopus
    A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma
    (2023) GIACCHERINI, Matteo; GORI, Leonardo; GENTILUOMO, Manuel; FARINELLA, Riccardo; CERVENA, Klara; SKIECEVICIENE, Jurgita; DIJK, Frederike; CAPURSO, Gabriele; VEZAKIS, Antonis; ARCHIBUGI, Livia; CHAMMAS, Roger; HUSSEIN, Tamas; TAVANO, Francesca; HEGYI, Peter; LOVECEK, Martin; IZBICKI, Jakob R.; BRENNER, Hermann; MOHELNIKOVA-DUCHONOVA, Beatrice; DELL'ANNA, Giuseppe; KUPCINSKAS, Juozas; ERMINI, Stefano; AOKI, Mateus Nobrega; NEOPTOLEMOS, John P.; GAZOULI, Maria; PASQUALI, Claudio; PEZZILLI, Raffaele; TALAR-WOJNAROWSKA, Renata; OLIVERIUS, Martin; AL-SAEEDI, Mohammed; LUCCHESI, Maurizio; FURBETTA, Niccolo; CARRARA, Silvia; EIJCK, Casper H. J. van; MALECKAS, Almantas; MILANETTO, Anna Caterina; LAWLOR, Rita T.; SCHOETTKER, Ben; BOGGI, Ugo; MORELLI, Luca; GINOCCHI, Laura; PISANI, Ruggero Ponz de Leon; SPERTI, Cosimo; ZERBI, Alessandro; ARCIDIACONO, Paolo Giorgio; UZUNOGLU, Faik G.; BUNDUC, Stefania; HOLLECZEK, Bernd; GIOFFREDA, Domenica; MALECKA-WOJCIESKO, Ewa; KIUDELIS, Mindaugas; SZENTESI, Andrea; LAARHOVEN, Hanneke W. M. van; SOUCEK, Pavel; GOETZ, Mara; EROSS, Balint; CAVESTRO, Giulia Martina; BASSO, Daniela; PERRI, Francesco; LANDI, Stefano; CANZIAN, Federico; CAMPA, Daniele
    Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 x 10(-9)), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 x 10(-6)). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting re-analysis of genome-wide association studies (GWASs) in light of functional data. [GRAPHICS] .
  • article 0 Citação(ões) na Scopus
    Patentometric analysis as a subsid to the management of technological innovation: a case study in radiopharmaceuticals for cancer
    (2023) CHAVES, Henrique Koch; SILVA, Julia Maria Brandao da; SILVEIRA, Carla Cristina de Freitas da; MARQUES, Fabio Luiz Navarro; MAGALHAES, Jorge Lima de
    Objective: Prospect the evolution of patent applications onIdentify, extract, process data, organize and make available technological information in the form of graphical interfaces described in oncology patents containing the radioisotopes gallium-68 (Ga-68), copper-64 (Cu-64) and zirconium-89 ((89)Z) in order to understand the development of science and technology in the area. Method: The ORBIT Intelligence (R) platform from the company QUESTEL (R) was used to identify, extract, process the data, organize and make available the technological information in the form of graphical interfaces, analysis of the filed patents in force in the last 20 years in the main patent offices in the world. Result: For gallium-68, copper-64 and zirconium-89, respectively, 36, 18 and 10 families of patents containing the search terms described in the methodology were identified. In both cases, China stands out in the number of filed patent applications, depositing 61% of the total analyzed. It was also observed that many of the analyzed documents were deposited by universities, reinforcing the concept of company-university partnership. The results obtained point out that the area of this study continues to grow and the understanding of the information present in the patent documents makes it possible to reflect on spaces to intensify the development of innovations in the oncology area. Conclusions: The results obtained demonstrate the relevance of information for the management of a country's technological development, which can serve as an efficient method to analyze, compare and monitor research and development activities in cancer and also support the planning processes organizations, as well as supporting public and private health policies.
  • article 0 Citação(ões) na Scopus
    Assessment of bioactive peptides derived from laminin-111 as prospective breast cancer-targeting agents
    (2024) MENDONCA, Fernanda Ferreira; SOBRAL, Danielle Vieira; DURANTE, Ana Claudia Ranucci; MIRANDA, Ana Claudia Camargo; MEJIA, Jorge; FARIA, Daniele de Paula; MARQUES, Fabio Luiz Navarro; BARBOZA, Marycel Figols de; FUSCALDI, Leonardo Lima; MALAVOLTA, Luciana
    Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the alpha 1, beta 1, and gamma 1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 (131I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [131I]I-YIKVAV and [131I]I-YIGSR. Conversely, [131I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from - 2.12 to - 1.10. Serum protein binding assay for [131I]I-YIKVAV and [131I]I-YIGSR reached approximately equal to 48% and approximately equal to 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized alpha 1 and beta 1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.
  • article 1 Citação(ões) na Scopus
    Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: an extracted individual patient data and trial-level meta-analysis
    (2024) CUNHA, Mateus Trinconi; GOUVEIA, Mariana Carvalho; LAZAR NETO, Felippe; TESTA, Laura; HOFF, Paulo Marcelo; AZAMBUJA, Evandro de; BONADIO, Renata Colombo
    Background: Neoadjuvant immunotherapy (nIO) has emerged as a treatment option for stage II-III triple-negative breast cancer (TNBC). While randomised clinical trials (RCTs) demonstrated pathological complete response rate benefit to nIO added to chemotherapy, additional data on long-term outcomes is warranted. We performed this analysis to evaluate long-term efficacy outcomes of nIO in TNBC.Methods: We searched databases for RCTs evaluating nIO in early-stage TNBC. A meta-analysis of extracted individual patient data (EIPD) was performed to evaluate EFS and OS, with data from reported Kaplan-Meier plots. Additionally, we conducted a trial-level meta-analysis using fixed and random effects models.Results: The literature search resulted in four included RCTs with available EFS or OS (KEYNOTE-522, IMpassion031, I-SPY2 and GeparNuevo). EIPD showed that the addition of nIO to chemotherapy provides statistically significant benefits in EFS (HR 0.62, 0.50-0.76; p < 0.001) and OS (HR 0.62, 0.46-0.82, p < 0.001). Number needed to treat to avoid one EFS or OS event in 4 years was 9 and 14, respectively. Trial-level meta-analysis yielded similar results (EFS: HR 0.64, 0.51-0.79; OS: 0.57, 0.37-0.89).Conclusions: Results show that nIO combined with chemotherapy can provide significant EFS and OS benefits, supporting its use as standard treatment for early-stage TNBC.
  • article 0 Citação(ões) na Scopus
    Evaluation of Non-Invasive Methods for (R)-[11C]PK11195 PET Image Quantification in Multiple Sclerosis
    (2024) MANTOVANI, Dimitri B. A.; PITOMBEIRA, Milena S.; SCHUCK, Phelipi N.; ARAUJO, Adriel S. de; BUCHPIGUEL, Carlos Alberto; FARIA, Daniele de Paula; SILVA, Ana Maria M. da
    This study aims to evaluate non-invasive PET quantification methods for (R)-[C-11]PK11195 uptake measurement in multiple sclerosis (MS) patients and healthy controls (HC) in comparison with arterial input function (AIF) using dynamic (R)-[C-11]PK11195 PET and magnetic resonance images. The total volume of distribution (VT) and distribution volume ratio (DVR) were measured in the gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, cerebellum, and brainstem using AIF, the image-derived input function (IDIF) from the carotid arteries, and pseudo-reference regions from supervised clustering analysis (SVCA). Uptake differences between MS and HC groups were tested using statistical tests adjusted for age and sex, and correlations between the results from the different quantification methods were also analyzed. Significant DVR differences were observed in the gray matter, white matter, putamen, pallidum, thalamus, and brainstem of MS patients when compared to the HC group. Also, strong correlations were found in DVR values between non-invasive methods and AIF (0.928 for IDIF and 0.975 for SVCA, p < 0.0001). On the other hand, (R)-[C-11]PK11195 uptake could not be differentiated between MS patients and HC using VT values, and a weak correlation (0.356, p < 0.0001) was found between VTAIF and VTIDIF. Our study shows that the best alternative for AIF is using SVCA for reference region modeling, in addition to a cautious and appropriate methodology.
  • article 0 Citação(ões) na Scopus
    Impact of baseline and interim quantitative PET parameters on outcomes of classical Hodgkin Lymphoma
    (2024) SANTOS, Fernanda Maria; MARIN, Jose Flavio Gomes; LIMA, Marcos Santos; SILVA-JUNIOR, Wellington Fernandes; ALVES, Lucas Bassolli O.; MOREIRA, Frederico R.; VELASQUES, Rodrigo Dolphini; ATANAZIO, Marcelo Junqueira; MAIA, Ana Carolina Arrais; BUCHPIGUEL, Carlos A.; BUCCHERI, Valeria; ROCHA, Vanderson
    Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (Delta SUVmax, Delta TMTV and Delta TLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among Delta SUVmax, Delta TMTV and Delta TLG, only a Delta SUVmax >= 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (Delta SUVmax >= 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the Delta SUV(max )to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification.
  • article 0 Citação(ões) na Scopus
    Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic
    (2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, Geraldo
    Introduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
  • article 1 Citação(ões) na Scopus
    Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma
    Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals. Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology. Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics. Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.
  • article 7 Citação(ões) na Scopus
    Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo
    The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a ""kill-switch""mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in vivo in comparison to free aptamers. Finally, we confirm the efficacy of the ""kill-switch""mechanism in vivo in murine and porcine models.
  • article 0 Citação(ões) na Scopus
    A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex
    (2023) JANDREY, Elisa Helena Farias; BARNABE, Gabriela Filoso; MALDAUN, Marcos; ASPRINO, Paula Fontes; SANTOS, Natalia Cristina dos; INOUE, Lilian Tiemi; ROZANSKI, Andrei; GALANTE, Pedro Alexandre Favoretto; MARIE, Suely Kazue Nagahashi; OBA-SHINJO, Sueli Mieko; SANTOS, Tiago Goss dos; CHAMMAS, Roger; LANCELLOTTI, Carmen Lucia Penteado; FURNARI, Frank B.; CAMARGO, Anamaria Aranha; COSTA, Erico Tosoni
    Background. Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.Methods We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility.Results. ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces gamma-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-beta and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs.Conclusions. Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.
  • article 44 Citação(ões) na Scopus
    Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1-Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042
    (2021) MANS, Aaron S.; HERBST, Roy S.; JR, Gilberto de Castro; HUI, Rina; PELED, Nir; KIM, Dong-Wan; NOVELLO, Silvia; SATOUCHI, Miyako; WU, Yi-Long; GARON, Edward B.; RECK, Martin; ROBINSON, Andrew G.; SAMKARI, Ayman; PIPERDI, Bilal; EBIANA, Victoria; LIN, Jianxin; MOK, Tony S. K.
    Introduction: We retrospectively evaluated outcomes in patients with programmed death-ligand 1 (PD-L1)-positive non-small-cell lung cancer (NSCLC) to determine whether baseline (i.e., at study enrollment) brain metastases were associated with the efficacy of pembrolizumab versus chemotherapy.Methods: We pooled data for patients with previously treated or untreated PD-L1-positive (tumor proportion score [TPS], >= 1%) advanced or metastatic NSCLC in KEYNOTE-001 (NCT01295827), KEYNOTE-010 (NCT01905657), KEYNOTE 024 (NCT02142738), and KEYNOTE-042 (NCT02220894). Patients received pembrolizumab (2 mg/kg, 10 mg/kg, or 200 mg every 3 wk or 10 mg/kg every 2 wk); chemotherapy was a comparator in all studies except KEYNOTE-001. All studies included patients with previously treated, stable brain metastases.Results: A total of 3170 patients were included, 293 (9.2%) with and 2877 (90.8%) without baseline brain metastases; median (range) follow-up at data cutoff was 12.9 (0.1-43.7) months. Pembrolizumab improved overall survival versus chemotherapy in patients with or without baseline brain metastases: benefit was seen in patients with PD-L1 TPS >= 50% (0.67 [95% confidence intervals (CI): 0.44-1.02] and 0.66 [95% CI: 0.58-0.76], respectively) and PD-L1 TPS >= 1% (0.83 [95% CI: 0.62-1.10] and 0.78 [95% CI: 0.710.85], respectively). Progression-free survival was improved, objective response rates were higher, and duration of response was longer with pembrolizumab versus chemotherapy regardless of brain metastasis status. The incidence of treatment-related adverse events with pembrolizumab versus chemotherapy was 66.3% versus 84.4% in patients with brain metastases and 67.2% versus 88.3% in those without.Conclusions: Pembrolizumab monotherapy improved outcomes and was associated with fewer adverse events than chemotherapy in patients with treatment naive and previously treated PD-L1-positive advanced/metastatic NSCLC regardless of the presence of baseline treated, stable brain metastases.(c) 2021 The Authors.
  • article 2 Citação(ões) na Scopus
    Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression
    (2023) TOBIAS, Gabriel C.; GOMES, Joao L. P.; FERNANDES, Larissa G.; VOLTARELLI, Vanessa A.; ALMEIDA, Ney R. de; JANNIG, Paulo R.; SOUZA, Rodrigo W. Alves de; NEGRAO, Carlos E.; OLIVEIRA, Edilamar M.; CHAMMAS, Roger; ALVES, Christiano R. R.; BRUM, Patricia C.
    Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26). Exercise training also slowed tumor growth in melanoma B16F10, colon tumor 26 (CT26), and Lewis lung carcinoma (LLC) tumor-bearing mice, with minor effects in mammary carcinoma 4T1, MDA-MB-231, and MMTV-PyMT mice. In silico analyses using transcriptome profiles derived from these models revealed that platelet factor 4 (Pf4) is one of the main upregulated genes associated with splenomegaly during cancer progression. To understand whether exercise training would modulate the expression of these genes in the tumor and spleen, we investigated particularly the CT26 model, which displayed splenomegaly and had a clear response to the exercise training effects. RT-qPCR analysis confirmed that trained CT26 tumor-bearing mice had decreased Pf4 mRNA levels in both the tumor and spleen when compared to untrained CT26 tumor-bearing mice. Furthermore, exercise training specifically decreased Pf4 mRNA levels in the CT26 tumor cells. Aspirin treatment did not change tumor growth, splenomegaly, and tumor Pf4 mRNA levels, confirming that exercise decreased non-platelet Pf4 mRNA levels. Finally, tumor Pf4 mRNA levels are deregulated in The Cancer Genome Atlas Program (TCGA) samples and predict survival in multiple cancer types. This highlights the potential therapeutic value of exercise as a complementary approach to cancer treatment and underscores the importance of understanding the exercise-induced transcriptional changes in the spleen for the development of novel cancer therapies.
  • article 0 Citação(ões) na Scopus
    (2023) DARCE, George Felipe Bezerra; MAKDISSI, Fabio Ferrari; ANDO, Sabrina de Mello; FONSECA, Gilton Marques; KRUGER, Jaime Arthur Pirola; COELHO, Fabricio Ferreira; ROCHA, Manoel de Souza; HERMAN, Paulo
    BACKGROUND: Hepatosplenic schistosomiasis is an endemic disease prevalent in tropical countries and is associated with a high incidence of portal vein thrombosis. Inflammatory changes caused by both parasitic infection and portal thrombosis can lead to the development of chronic liver disease with potential carcinogenesis. AIMS: To assess the incidence of portal vein thrombosis and hepatocellular carcinoma in patients with schistosomiasis during long-term follow-up. METHODS: A retrospective study was conducted involving patients with schistosomiasis followed up at our institution between 1990 and 2021. RESULTS: A total of 126 patients with schistosomiasis were evaluated in the study. The mean follow-up time was 16 years (range 5-31). Of the total, 73 (57.9%) patients presented portal vein thrombosis during follow-up. Six (8.1%) of them were diagnosed with hepatocellular carcinoma, all with portal vein thrombosis diagnosed more than ten years before. CONCLUSIONS: The incidence of hepatocellular carcinoma in patients with schistosomiasis and chronic portal vein thrombosis highlights the importance of a systematic long-term follow-up in this group of patients.
  • article
    Oral squamous cell carcinoma cancer stem cells have different drug sensitive to pharmacological NFκB and histone deacetylation inhibition
    (2023) SILVA, Luan Cesar; LEITE, Amanda Almeida; BORGATO, Gabriell Bonifacio; WAGNER, Vivian Petersen; MARTINS, Manoela Domingues; LOUREIRO, Felippe Jose Almeida; LOPES, Marcio Ajudarte; SANTOS-SILVA, Alan Roger; SPERANDIO, Marcelo; JUNIOR, Gilberto de Castro; KOWALSKI, Luiz Paulo; SQUARIZE, Cristiane H.; CASTILHO, Rogerio Moraes; VARGAS, Pablo Agustin
    Despite many progresses in the development of new systemic therapies for oral squamous cell carcinoma (OSCC), the five-year survival rate of OSCC is low. The traditional chemotherapies approach (cisplatin - CDDP) shows some limitations like drug toxicity, limited efficacy, and drug resistance. Promising studies suggested OSCC cancer stem cells (CSC) presented resistance to CDDP. We have previously studied many targets, and we extensively showed the efficacy of the NF kappa B signaling and the role of histones acetylation, on different malignant tumors, including adenoid cystic carcinoma and mucoepidermoid carcinoma, but until then the effects of the NFkB inhibitor and histone deacetylase (HDAC) inhibitor on the biology of OSCC were not evaluated. Here we assessed the pharmacological inhibitor of NF kappa B emetine and HDAC inhibitor SAHA on the behavior of CSC derived from OSCC. Our data suggested that CDDP administration resulted in reduced viability of bulk OSCC cells and increased CSC. A single and isolated shot of emetine and SAHA were able to disrupt CSC by inhibiting the NF kappa B pathway and increasing the histone acetylation levels, respectively. Further, the combined administration of emetine and SAHA presented the same CSC disruption as seen in emetine alone.
  • article 0 Citação(ões) na Scopus
    Betapapillomavirus natural history and co-detection with alphapapillomavirus in cervical samples of adult women
    (2023) MALAGON, Talia; RIBEIRO, Aline Lopes; NUNES, Emily Montosa; GHEIT, Tarik; EL-ZEIN, Mariam; VILLA, Luisa L.; FRANCO, Eduardo L.; SICHERO, Laura
    Human papillomaviruses (HPV) of the genus Betapapillomavirus can infect both cutaneous and mucosal sites, but research on their natural history at mucosal sites remains scarce. We examined the risk factors and co-detection patterns of HPVs of the Betapapillomavirus and Alphapapillomavirus genera in cervical samples of the Ludwig-McGill cohort study. We assessed a subset of 505 women from the Ludwig-McGill cohort study from Sao Paulo, Brazil. Cervical samples over the first year of follow-up were tested for DNA of over 40 alphapapillomavirus types and 43 betapapillomavirus types using a type-specific multiplex genotyping polymerase chain reaction assay. We assessed the risk factors for prevalent and incident betapapillomavirus type detection, and whether types were detected more frequently together than expected assuming independence using permutation tests, logistic regression, and Cox regression. We observed significant within-genus clustering but not cross-genus clustering. Multiple betapapillomavirus types were co-detected in the same sample 2.24 (95% confidence interval [CI]: 1.65-3.29) times more frequently than expected. Conversely, co-detections of alphapapillomavirus and betapapillomavirus types in the same sample occurred only 0.64 (95% CI: 0.51-0.83) times as often as expected under independence. In prospective analyses, positivity to one HPV genus was associated with a nonsignificant lower incidence of detection of types in the other genus. Lifetime number of sex partners and new sex partner acquisition were associated with lower risks of prevalent and incident betapapillomavirus detection. Betapapillomaviruses are commonly found in the cervicovaginal tract. Results suggest potentially different mechanisms of transmission for betapapillomavirus genital infections other than vaginal sex.
  • article 2 Citação(ões) na Scopus
    28-day prognostic value of coronary artery calcification burden in critically ill patients with COVID-19
    (2023) FARIAS, Lucas de Padua Gomes de; ASSUNCAO-JR, Antonildes Nascimento; ARAUJO-FILHO, Jose de Arimateia Batista; FONSECA, Eduardo Kaiser Ururahy Nunes; STRABELLI, Daniel Giunchetti; SAWAMURA, Marcio Valente Yamada; CERRI, Giovanni Guido; FERREIRA, Juliana Carvalho; NOMURA, Cesar Higa