Publications by authors named "Valentina Talevi"

3 Publications

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Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.

Genome Med 2021 01 13;13(1). Epub 2021 Jan 13.

Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Background: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system.

Methods: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings.

Results: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.

Conclusions: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.
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http://dx.doi.org/10.1186/s13073-020-00823-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805430PMC
January 2021

Variation of Serum Lycopene in Response to 100% Watermelon Juice: An Exploratory Analysis of Genetic Variants in a Randomized Controlled Crossover Study.

Curr Dev Nutr 2020 Jul 17;4(7):nzaa102. Epub 2020 Jun 17.

Department of Human Nutrition, University of Alabama, Tuscaloosa, AL, USA.

Background: Watermelon, a rich source of lycopene, has garnered attention for cardioprotective effects including cholesterol reduction and promotion of redox balance. It is unknown whether 100% watermelon juice may represent a food-first approach to confer cardioprotective benefits of lycopene.

Objectives: This study examined influences of 100% watermelon juice on serum lycopene, lipids, and antioxidant capacity. Secondly, the study explored genetic influences on lycopene metabolism and bioavailability.

Methods: A placebo-controlled, randomized, double-blind, crossover trial with postmenopausal women ( = 16, mean ± SD age: 60 ± 4.1 y) assessed effects of 100% watermelon juice on mechanistic and clinical outcomes influencing vascular function. Participants maintained low-lycopene diets for a 1-wk run-in period and throughout the study. Morning and evening consumption of 100% watermelon juice provided a daily dose of 14.4 ± 0.34 mg lycopene. Study arms of 4 wk were separated by a 2-wk washout period. Saliva was collected for genetic analysis of single nucleotide polymorphisms, and fasting blood samples were taken pre- and post-study arms. Statistical analyses included mixed models, linear regression, and nonparametric tests.

Results: Serum lycopene exhibited a significant treatment effect ( = 0.002) along with notable interindividual responses; however, significant improvements in serum lipids or antioxidant capacity were not observed. Genetic variant rs6564851 in the β-carotene 15,15'-oxygenase-1 () gene was associated with changes in lycopene such that TT homozygotes exhibited a significantly greater increase (β ± SE: 13.4 ± 1.6,  = 1.4 × 10).

Conclusions: Watermelon juice supplementation did not result in improvements in serum lipids or antioxidant capacity; however, results support findings in which watermelon juice significantly, yet differentially, increased circulating lycopene. Genetics appears to explain some of the variability. Given that dose has been shown to overcome individual responsiveness to lycopene interventions, future investigations with varying doses of lycopene-rich foods would be strengthened by genotyping so as to establish personalized nutrition recommendations.This trial was registered at clinicaltrials.gov as NCT03626168.
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http://dx.doi.org/10.1093/cdn/nzaa102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363307PMC
July 2020

Identification of single nucleotide pleomorphisms associated with periodontal disease in head and neck cancer irradiation patients by exome sequencing.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 Jul 22;130(1):32-42.e4. Epub 2020 May 22.

Department of Oral Medicine, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA; College of Computing and Informatics, Department of Bioinformatics and Genomics, UNC-Charlotte, Charlotte, NC, USA. Electronic address:

Objective: Periodontal disease (PD) is a common oral complication in patients with head and neck cancer (HNC) undergoing radiation therapy (RT). Our objective was to identify candidate single nucleotide polymorphisms (SNPs) associated with PD in radiation-treated patients with HNC.

Study Design: DNA was extracted from the saliva of patients with HNC (n = 69) before RT. Clinical attachment loss (CAL) increment greater than 0.2 mm over 24 months after RT was used to define PD progression. After exome sequencing, SNPs associated with post-RT PD progression were identified by using logistic regression and homozygosity analyses. The web tools STRING, the Database for Annotation, Visualization and Integrated Discovery (DAVID), GeneCodis, and Ensembl Variant Effect Predictor were used for functional analysis.

Results: Of the 48 patients with HNC with post-RT PD progression, 24 had no tooth with 5 mm or greater pocket depth before RT, whereas of the 21 patients with HNC without progression, 11 had PD initially. A total of 330 SNPs (249 genes) with over-represented homozygous genotype (98.5% variant allele) were found to be associated with post-RT PD. Sixty of these corresponded to PD-related pathways, including previously identified genes. In patients with HNC with post-RT PD progression, SNPs were found in genes (n = 10) in contrast to those without progression (n = 7).

Conclusions: The SNPs of collagen genes were identified, potentially defining susceptibility to PD in patients with HNC, and this could be further investigated to characterize PD drug targets.
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http://dx.doi.org/10.1016/j.oooo.2020.02.013DOI Listing
July 2020