Publications by authors named "Thiago Leal"

Alzheimer's disease (AD) is characterized by progressive cognitive decline, severe brain atrophy and neuroinflammation. We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 2a clinical trial that tested the safety and efficacy of laromestrocel, a bone-marrow-derived, allogeneic mesenchymal stem-cell therapy, in slowing AD clinical progression, atrophy and neuroinflammation. Participants across ten centers in the United States were randomly assigned 1:1:1:1 to four infusion groups: group 1 (placebo; four monthly infusions, n = 12); group 2 (25 million cells, one infusion followed by three monthly infusions of placebo, n = 13); group 3 (25 million cells; four monthly doses, n = 13); and group 4 (100 million cells; four monthly doses, n = 11).

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Background: Age and sex are known risk factors for Parkinson's Disease (PD), but it remains controversial if there are sex differences in the diagnosis latency. The objective of this study was to examine these sex differences in Latin America.

Methods: The Latin American Research Consortium on the Genetics of PD (LARGE-PD) includes PD patients from countries across Latin America who were diagnosed using the UK Brain Bank criteria.

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The Research Program () seeks to accelerate biomedical research and address the underrepresentation of minorities by recruiting over one million ethnically diverse participants across the United States. A key question is how self-identification with discrete, predefined race and ethnicity categories compares to genetic diversity at continental and subcontinental levels. To contextualize the genetic diversity in , we analyzed ~2 million common variants from 230,016 unrelated whole genomes using classical population genetics methods, alongside reference panels such as the 1000 Genomes Project, Human Genome Diversity Project, and Simons Genome Diversity Project.

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Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD.

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  • Researchers have advanced understanding of Parkinson's disease genetics through genome-wide association studies (GWAS) but have found that many genetic factors still contribute to its heritability, potentially due to interactions between variants (epistasis).
  • A new screening method, VARI3, was developed to investigate these interactions using data from numerous cohorts, successfully identifying notable variant interactions in genes like SNCA, MAPT, and WNT3.
  • The study demonstrated that these epistatic signals were present across different ethnic backgrounds, including European and Native American ancestries, and linked to important biological functions related to Parkinson's disease risk.
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  • Latin Americans are often overlooked in genetic studies, which can widen gaps in personalized medicine due to the challenges of accessing genetic data and consent processes.
  • The Genetics of Latin American Diversity (GLAD) Project compiles genetic information from over 53,000 individuals across various regions to explore diverse ancestry and gene flow in the Americas.
  • GLAD includes a tool called GLAD-match to align external genetic samples with its database while protecting individual privacy, thus supporting more inclusive genomic research and enhancing personalized medicine for Latin Americans.
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Autism Spectrum Disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as , , and .

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  • Genome-wide association studies have identified genetic risk factors but often rely on imputation panels that mainly represent European ancestry, affecting quality in underrepresented groups like Latin Americans.
  • This study examines how altering the composition of imputation reference panels impacts imputation quality in four different Latin American cohorts, specifically analyzing chromosomes 7 and X.
  • Results show that increasing the number of Latin Americans in the reference leads to better imputation quality, while excluding them, as well as adjustments in European and African representation, affects quality differently across populations and chromosomes.
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  • * Researchers studied 800 BL patients and 3,845 controls across four East African countries to see if genetic traits that protect against malaria also protect against BL, focusing on specific gene variants.
  • * Findings showed that the sickle cell gene variant (HBB-rs334(T)) was linked to lower risks of both malaria infection and BL, suggesting a possible connection between malaria and the development of Burkitt lymphoma.
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  • - The study analyzes genome-wide data from around 19,000 individuals of European ancestry, revealing that these populations are stratified and admixed at the subcontinental level, which can impact genetic research results.
  • - A new reference panel was created to include ancestral diversity that previous projects overlooked, emphasizing the complexity of ancestry in European and European American groups.
  • - Adjustments for both overall and specific ancestry revealed that some associations, like those between a variant in the LCT gene and certain health traits, were false positives, highlighting the importance of considering ancestry in genetic epidemiology.
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Background: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear.

Objective: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort.

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Parkinson's disease (PD) is an age-related neurological disorder known for the observational differences in its risk, progression, and severity between men and women. While estrogen has been considered to be a protective factor in the development of PD, there is little known about the role that fluctuations in hormones and immune responses from sex-specific health experiences have in the disease's development and severity. We sought to identify women-specific health experiences associated with PD severity, after adjusting for known PD factors, by developing and distributing a women-specific questionnaire across the United States and creating multivariable models for PD severity.

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Article Synopsis
  • * A virtual 3-day hackathon brought together 49 early-career scientists from 12 countries, focusing on building tools and pipelines specifically for PD research, with each team working on one of nine distinct projects.
  • * The hackathon not only generated resources to enhance research but also provided training and networking opportunities, ultimately fostering creative problem-solving and collaboration essential for emerging researchers in data science.
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Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals.

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  • The QT interval is a key measure in electrocardiograms that indicates the timing of heart muscle contractions and recoveries; abnormalities can lead to serious heart conditions.
  • A study involving over 250,000 individuals identified many genetic loci linked to various heart rhythm measures, revealing important genetic factors associated with QT, JT, and QRS intervals.
  • The findings suggest that certain gene variations could inform new treatments for arrhythmias and highlight genetic pathways involved in heart function and energy metabolism.
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Background: The COVID-19 pandemic has had an impact on mortality from several diseases worldwide, especially cardiovascular diseases (CVD). Brazil is a continent-sized country with significant differences in the health care structure between its federative units.

Objective: Analyze in-hospital mortality from CVDs in the Brazilian public health system during the first year of the COVID-19 pandemic (2020).

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Genetic and omics analyses frequently require independent observations, which is not guaranteed in real datasets. When relatedness cannot be accounted for, solutions involve removing related individuals (or observations) and, consequently, a reduction of available data. We developed a network-based relatedness-pruning method that minimizes dataset reduction while removing unwanted relationships in a dataset.

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Since the onset of the coronavirus disease 2019 (COVID-19) pandemic in Brazil, several government policies have been taken. Herein, we aimed to assess the impact of the COVID-19 pandemic on hospital admissions and in-hospital lethality for cardiovascular diseases (CVD) in Brazil in 2020. An ecological and time-series study on hospitalizations and deaths from CVD in Brazil was conducted from January 2018 to December 2020.

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PDE4B (phosphodiesterase-4B) has an important role in cancer and in pharmacology of some disorders, such as inflammatory diseases. Remarkably in Native Americans, PDE4B variants are associated with acute lymphoblastic leukemia (ALL) relapse, as this gene modulates sensitivity of glucocorticoids used in ALL chemotherapy. PDE4B allele rs6683977.

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Background: Meningitis is listed as one of the diseases requiring compulsory notification in Brazil. It can affect all age groups and also has no seasonality. Cases can be recorded in all months of the year and in all states of Brazil.

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Introduction: Tuberculosis is one of the ten leading causes of death and the leading infectious cause worldwide. The disease represents a challenge to health systems around the world. In 2018, it is estimated that 10 million people were affected by tuberculosis, and approximately 1.

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In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the allele in the gene is the most well-characterized allele responsible for the lactase persistence phenotype, the > (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products.

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