The top differentially altered pathways revealed by Gene Ontology (GO) clustering when comparing ... more The top differentially altered pathways revealed by Gene Ontology (GO) clustering when comparing Black and NLW HNSCC patients.
p330d/CENP-F is a recently described nuclear autoantigen that was detected in PHA-stimulated but ... more p330d/CENP-F is a recently described nuclear autoantigen that was detected in PHA-stimulated but not in resting peripheral lymphocytes. This protein accumulates in the nucleus during S-phase and reaches maximum levels during the G2 and M phases of the cell cycles. We compared the expression of p330d/CENP-F and proliferating cell nuclear antigen (PCNA) during the induction of terminal myeloid differentiation of HL-60 tumour cells. HL-60 cells were induced to differentiate with retinoic acid (RA), dimethyl sulfoxide (DMSO), and 3-nitrobenzothiazolo [3,2-]quinolinium (NBQ), and collected at different intervals. Control and treated cells were analyzed by two-parameter flow cytometry using propidium iodide and antibodies to p330d/CENP-F and PCNA. The percentage of p330d/CENP-F and PCNA positive cells was found to be proportional to the percentage of proliferating cells. After two cell cycles (65 h), the percentage of p330d/CENP-F and PCNA positive cells was reduced proportionately to the number of cells that had differentiated. Reduction in the expression of both antigens was completed after 120 h when 80% to 85% of the cells were arrested in G1 and displayed the mature phenotype. The expression of p330d/CENP-F and PCNA was also assessed in the growth inhibition of HT-29 cells induced by various concentrations of camptothecin (CPT), etoposide (VP-16), and aphidicolin (APH). There was a dose-dependent displacement of cells to late S-phase by CPT while VP-16 induced cells to accumulate in G2+M, and as expected these effects caused a strong increase in the cellular levels of both antigens. The arrest of cells in G1 by APH led to a significant decrease in their expression. The dramatic reduction in p330d/CENP-F levels during differentiation, and the correlation of its expression with the cell cycle effects of the cytotoxic drugs are consistent with the behaviour expected for a proliferation marker.
International Journal of Environmental Research and Public Health
The National Research Mentoring Network (NRMN) Strategic Empowerment Tailored for Health Equity I... more The National Research Mentoring Network (NRMN) Strategic Empowerment Tailored for Health Equity Investigators (SETH) study evaluates the value of adding Developmental Network to Coaching in the career advancement of diverse Early-Stage Investigators (ESIs). Focused NIH-formatted Mock Reviewing Sessions (MRS) prior to the submission of grants can significantly enhance the scientific merits of an ESI’s grant application. We evaluated the most prevalent design, analysis-related factors, and the likelihood of grant submissions and awards associated with going through MRS, using descriptive statistics, Chi-square, and logistic regression methods. A total of 62 out of 234 applications went through the MRS. There were 69.4% that pursued R grants, 22.6% career development (K) awards, and 8.0% other grant mechanisms. Comparing applications that underwent MRS versus those that did not (N = 172), 67.7% vs. 38.4% were submitted for funding (i.e., unadjusted difference of 29.3%; OR = 4.8, 95% CI...
International Journal of Environmental Research and Public Health
Background: Enhancement of diversity within the U.S. research workforce is a recognized need and ... more Background: Enhancement of diversity within the U.S. research workforce is a recognized need and priority at a national level. Existing comprehensive programs, such as the National Research Mentoring Network (NRMN) and Research Centers in Minority Institutions (RCMI), have the dual focus of building institutional research capacity and promoting investigator self-efficacy through mentoring and training. Methods: A qualitative comparative analysis was used to identify the combination of factors that explain the success and failure to submit a grant proposal by investigators underrepresented in biomedical research from the RCMI and non-RCMI institutions. The records of 211 participants enrolled in the NRMN Strategic Empowerment Tailored for Health Equity Investigators (NRMN-SETH) program were reviewed, and data for 79 early-stage, underrepresented faculty investigators from RCMI (n = 23) and non-RCMI (n = 56) institutions were included. Results: Institutional membership (RCMI vs. non-R...
Introduction: We previously identified by a genome-wide approach, differentially methylated genes... more Introduction: We previously identified by a genome-wide approach, differentially methylated genes in head and neck squamous cell carcinoma (HNSCC), including genes uniquely methylated in each HNSCC anatomic subsite. To define their potential prognostic value the validation of uniquely methylated genes in a cohort of HNSCC patients, according to the anatomic subsite, is warranted. Thus, here we present validation data of three potential DNA methylation biomarkers in a cohort comprising primary tumors of 54 HNSCC patients. Methods: Tumor DNA was extracted from HNSCC patients, stratified by the primary tumor anatomic subsite, which included 21 laryngeal cancers, 21 oral cavity cancer, and 12 pharyngeal cancers. The DNA methylation status of three candidate biomarkers, CDH1 for laryngeal cancer, PITX2 for oral cavity cancer, and SFRP1 for pharyngeal cancer were assessed. DNA methylation analysis was performed using qMSP MethyLight assay and quantitative methylation value for each gene w...
International Journal of Environmental Research and Public Health, 2021
Introduction: Adding developmental networks (DN) to grant-writing coaching can significantly enha... more Introduction: Adding developmental networks (DN) to grant-writing coaching can significantly enhance ESIs’ research careers. Herein, we present study design, ESIs’ characteristics and encountered challenges/lessons learned and their resolutions when deploying/implementing (a) NCR algorithm(s), (b) recruitment/retention and (c) implementing DN intervention. Methods: Nested Cluster Randomization (NCR) design governs this study implementation. The sample size is 220 ESIs intending to submit an NIH K, R, U, and/or Minority Supplement application(s). Primary outcome: intensity/sustainability of grant submission(s)/funding(s), measured by time to/between application(s). Outcome(s) analyses modes: summaries, Kaplan Meir and Cox proportional hazard models as a function of randomization groups and other predictors of outcomes. Results: In the present study, we recruited two cohorts of ESIs (N = 85): 39% African Americans, 18% Latinx, 18% Whites, 20% Asians and 6% Hawaiian/Pacific Islander/ot...
Several genomic epidemiology tools have been developed to track the public and population health ... more Several genomic epidemiology tools have been developed to track the public and population health impact of SARS-CoV-2 community spread worldwide. A SARS-CoV-2 Variant of Concern (VOC) B.1.1.7, known as 501Y.V1, which shows increased transmissibility, has rapidly become the dominant VOC in the United States (US). Our objective was to develop an evidenced-based genomic surveillance algorithm that combines RT-PCR and sequencing technologies to identify VOCs. Deidentified data were obtained from 508,969 patients tested for COVID-19 with the TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) in four CLIA certified clinical laboratories in Puerto Rico (n=86,639) and in three CLIA certified clinical laboratories in the US (n=422,330). TaqPath data revealed a frequency of S Gene Target Failure (SGTF) >47% for the last week of March 2021, in both Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in ...
International Journal of Environmental Research and Public Health, 2018
Junior investigators often have limited access to networks of scientific experts and resources th... more Junior investigators often have limited access to networks of scientific experts and resources that facilitate competitive grant submissions. Since environments in which scientists are trained are critically important for long-term success, we built and tested a virtual environment for early-stage investigators (ESIs) working on grant proposals. The aim of this study was to evaluate the virtual community’s influence on grant submission patterns among participants from underrepresented groups. As part of a grant writing coaching model, junior investigators were recruited into a professional development program designed to develop competitive grantsmanship skills. Designed by the Research Resources and Outreach Core (RROC) of the National Research Mentoring Network (NRMN), the Health Equity Learning Collaboratory (EQ-Collaboratory) provided a virtual community for social support, accountability, constructive feedback, and access to peer networks to help investigators overcome barriers...
Research projects in translational science are increasingly complex and require interdisciplinary... more Research projects in translational science are increasingly complex and require interdisciplinary collaborations. In the context of training translational researchers, this suggests that multiple mentors may be needed in different content areas. This study explored mentoring structure as it relates to perceived mentoring effectiveness and other characteristics of master's-level trainees in clinical-translational research training programs. A cross-sectional online survey of recent graduates of clinical research master's program was conducted. Of 73 surveys distributed, 56.2% (n = 41) complete responses were analyzed. Trainees were overwhelmingly positive about participation in their master's programs and the impact it had on their professional development. Overall the majority (≥75%) of trainees perceived they had effective mentoring in terms of developing skills needed for conducting clinical-translational research. Fewer trainees perceived effective mentoring in career...
Drugs which elicit cell differentiation might have an important role in the treatment of leukemia... more Drugs which elicit cell differentiation might have an important role in the treatment of leukemias and other neoplasias. Various chemotherapeutic agents promote leukemic cell differentiation. The HL-60 cell line is a useful model to study in vitro myeloid differentiation. Sublethal concentrations of 3-nitrobenzothiazolo[3,2-a]quinolinium (NBQ), an antitopoisomerase II drug, were given to HL-60 cells from one to five days to evaluate its capacity to induce differentiation. NBQinduced HL-60 cells reduced nitroblue tetrazolium (NBT), increased MY-4 receptors, increased phagocytic activity and displayed the granulocytic morphology. Flow cytometric DNA analysis of NBQ-induced cells revealed an arrest in the G1 phase a reduction in the relative percentage of cells in S and G2 + M phases. Our results suggest that NBQ induces an S-phase specific differentiation of HL-60 cells comparable to that previously described with dimethyl sulfoxide and retinoic acid. NBQ and its analogs, as differentiation inducers, may have potential utility as a novel therapeutic modality for leukemias.
Objective: Genetic variations at codon 72 of p53 gene results in altered activities for p53 and a... more Objective: Genetic variations at codon 72 of p53 gene results in altered activities for p53 and are suggested as a potential cancer risk. However, epidemiologic findings have been inconsistent. The p53 gene has a polymorphic site at exon 4 codon 72, which, in an occurrence of a base substitution, can produce Proline or Arginine (Arg72Pro). This polymorphism is differentially dispersed among different ethnic populations. The objective of this study is to evaluate the association between p53 polymorphism and head and neck squamous cell carcinoma (HNSCC) in the Puerto Rican population. Methods: Genotyping of the p53 polymorphism at exon 4 codon 72 was performed using PCR-based restriction fragment polymorphism (PCR-RFLP) in a study with 72 HNSCC patients. Correlations between clinicopathological parameters and p53 polymorphism were analyzed by Fisher's exact test and chi-square when suitable. Survival analysis of HNSCC patients, with each type of p53 genotype, was performed using M...
The top differentially altered pathways revealed by Gene Ontology (GO) clustering when comparing ... more The top differentially altered pathways revealed by Gene Ontology (GO) clustering when comparing Black and NLW HNSCC patients.
p330d/CENP-F is a recently described nuclear autoantigen that was detected in PHA-stimulated but ... more p330d/CENP-F is a recently described nuclear autoantigen that was detected in PHA-stimulated but not in resting peripheral lymphocytes. This protein accumulates in the nucleus during S-phase and reaches maximum levels during the G2 and M phases of the cell cycles. We compared the expression of p330d/CENP-F and proliferating cell nuclear antigen (PCNA) during the induction of terminal myeloid differentiation of HL-60 tumour cells. HL-60 cells were induced to differentiate with retinoic acid (RA), dimethyl sulfoxide (DMSO), and 3-nitrobenzothiazolo [3,2-]quinolinium (NBQ), and collected at different intervals. Control and treated cells were analyzed by two-parameter flow cytometry using propidium iodide and antibodies to p330d/CENP-F and PCNA. The percentage of p330d/CENP-F and PCNA positive cells was found to be proportional to the percentage of proliferating cells. After two cell cycles (65 h), the percentage of p330d/CENP-F and PCNA positive cells was reduced proportionately to the number of cells that had differentiated. Reduction in the expression of both antigens was completed after 120 h when 80% to 85% of the cells were arrested in G1 and displayed the mature phenotype. The expression of p330d/CENP-F and PCNA was also assessed in the growth inhibition of HT-29 cells induced by various concentrations of camptothecin (CPT), etoposide (VP-16), and aphidicolin (APH). There was a dose-dependent displacement of cells to late S-phase by CPT while VP-16 induced cells to accumulate in G2+M, and as expected these effects caused a strong increase in the cellular levels of both antigens. The arrest of cells in G1 by APH led to a significant decrease in their expression. The dramatic reduction in p330d/CENP-F levels during differentiation, and the correlation of its expression with the cell cycle effects of the cytotoxic drugs are consistent with the behaviour expected for a proliferation marker.
International Journal of Environmental Research and Public Health
The National Research Mentoring Network (NRMN) Strategic Empowerment Tailored for Health Equity I... more The National Research Mentoring Network (NRMN) Strategic Empowerment Tailored for Health Equity Investigators (SETH) study evaluates the value of adding Developmental Network to Coaching in the career advancement of diverse Early-Stage Investigators (ESIs). Focused NIH-formatted Mock Reviewing Sessions (MRS) prior to the submission of grants can significantly enhance the scientific merits of an ESI’s grant application. We evaluated the most prevalent design, analysis-related factors, and the likelihood of grant submissions and awards associated with going through MRS, using descriptive statistics, Chi-square, and logistic regression methods. A total of 62 out of 234 applications went through the MRS. There were 69.4% that pursued R grants, 22.6% career development (K) awards, and 8.0% other grant mechanisms. Comparing applications that underwent MRS versus those that did not (N = 172), 67.7% vs. 38.4% were submitted for funding (i.e., unadjusted difference of 29.3%; OR = 4.8, 95% CI...
International Journal of Environmental Research and Public Health
Background: Enhancement of diversity within the U.S. research workforce is a recognized need and ... more Background: Enhancement of diversity within the U.S. research workforce is a recognized need and priority at a national level. Existing comprehensive programs, such as the National Research Mentoring Network (NRMN) and Research Centers in Minority Institutions (RCMI), have the dual focus of building institutional research capacity and promoting investigator self-efficacy through mentoring and training. Methods: A qualitative comparative analysis was used to identify the combination of factors that explain the success and failure to submit a grant proposal by investigators underrepresented in biomedical research from the RCMI and non-RCMI institutions. The records of 211 participants enrolled in the NRMN Strategic Empowerment Tailored for Health Equity Investigators (NRMN-SETH) program were reviewed, and data for 79 early-stage, underrepresented faculty investigators from RCMI (n = 23) and non-RCMI (n = 56) institutions were included. Results: Institutional membership (RCMI vs. non-R...
Introduction: We previously identified by a genome-wide approach, differentially methylated genes... more Introduction: We previously identified by a genome-wide approach, differentially methylated genes in head and neck squamous cell carcinoma (HNSCC), including genes uniquely methylated in each HNSCC anatomic subsite. To define their potential prognostic value the validation of uniquely methylated genes in a cohort of HNSCC patients, according to the anatomic subsite, is warranted. Thus, here we present validation data of three potential DNA methylation biomarkers in a cohort comprising primary tumors of 54 HNSCC patients. Methods: Tumor DNA was extracted from HNSCC patients, stratified by the primary tumor anatomic subsite, which included 21 laryngeal cancers, 21 oral cavity cancer, and 12 pharyngeal cancers. The DNA methylation status of three candidate biomarkers, CDH1 for laryngeal cancer, PITX2 for oral cavity cancer, and SFRP1 for pharyngeal cancer were assessed. DNA methylation analysis was performed using qMSP MethyLight assay and quantitative methylation value for each gene w...
International Journal of Environmental Research and Public Health, 2021
Introduction: Adding developmental networks (DN) to grant-writing coaching can significantly enha... more Introduction: Adding developmental networks (DN) to grant-writing coaching can significantly enhance ESIs’ research careers. Herein, we present study design, ESIs’ characteristics and encountered challenges/lessons learned and their resolutions when deploying/implementing (a) NCR algorithm(s), (b) recruitment/retention and (c) implementing DN intervention. Methods: Nested Cluster Randomization (NCR) design governs this study implementation. The sample size is 220 ESIs intending to submit an NIH K, R, U, and/or Minority Supplement application(s). Primary outcome: intensity/sustainability of grant submission(s)/funding(s), measured by time to/between application(s). Outcome(s) analyses modes: summaries, Kaplan Meir and Cox proportional hazard models as a function of randomization groups and other predictors of outcomes. Results: In the present study, we recruited two cohorts of ESIs (N = 85): 39% African Americans, 18% Latinx, 18% Whites, 20% Asians and 6% Hawaiian/Pacific Islander/ot...
Several genomic epidemiology tools have been developed to track the public and population health ... more Several genomic epidemiology tools have been developed to track the public and population health impact of SARS-CoV-2 community spread worldwide. A SARS-CoV-2 Variant of Concern (VOC) B.1.1.7, known as 501Y.V1, which shows increased transmissibility, has rapidly become the dominant VOC in the United States (US). Our objective was to develop an evidenced-based genomic surveillance algorithm that combines RT-PCR and sequencing technologies to identify VOCs. Deidentified data were obtained from 508,969 patients tested for COVID-19 with the TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) in four CLIA certified clinical laboratories in Puerto Rico (n=86,639) and in three CLIA certified clinical laboratories in the US (n=422,330). TaqPath data revealed a frequency of S Gene Target Failure (SGTF) >47% for the last week of March 2021, in both Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in ...
International Journal of Environmental Research and Public Health, 2018
Junior investigators often have limited access to networks of scientific experts and resources th... more Junior investigators often have limited access to networks of scientific experts and resources that facilitate competitive grant submissions. Since environments in which scientists are trained are critically important for long-term success, we built and tested a virtual environment for early-stage investigators (ESIs) working on grant proposals. The aim of this study was to evaluate the virtual community’s influence on grant submission patterns among participants from underrepresented groups. As part of a grant writing coaching model, junior investigators were recruited into a professional development program designed to develop competitive grantsmanship skills. Designed by the Research Resources and Outreach Core (RROC) of the National Research Mentoring Network (NRMN), the Health Equity Learning Collaboratory (EQ-Collaboratory) provided a virtual community for social support, accountability, constructive feedback, and access to peer networks to help investigators overcome barriers...
Research projects in translational science are increasingly complex and require interdisciplinary... more Research projects in translational science are increasingly complex and require interdisciplinary collaborations. In the context of training translational researchers, this suggests that multiple mentors may be needed in different content areas. This study explored mentoring structure as it relates to perceived mentoring effectiveness and other characteristics of master's-level trainees in clinical-translational research training programs. A cross-sectional online survey of recent graduates of clinical research master's program was conducted. Of 73 surveys distributed, 56.2% (n = 41) complete responses were analyzed. Trainees were overwhelmingly positive about participation in their master's programs and the impact it had on their professional development. Overall the majority (≥75%) of trainees perceived they had effective mentoring in terms of developing skills needed for conducting clinical-translational research. Fewer trainees perceived effective mentoring in career...
Drugs which elicit cell differentiation might have an important role in the treatment of leukemia... more Drugs which elicit cell differentiation might have an important role in the treatment of leukemias and other neoplasias. Various chemotherapeutic agents promote leukemic cell differentiation. The HL-60 cell line is a useful model to study in vitro myeloid differentiation. Sublethal concentrations of 3-nitrobenzothiazolo[3,2-a]quinolinium (NBQ), an antitopoisomerase II drug, were given to HL-60 cells from one to five days to evaluate its capacity to induce differentiation. NBQinduced HL-60 cells reduced nitroblue tetrazolium (NBT), increased MY-4 receptors, increased phagocytic activity and displayed the granulocytic morphology. Flow cytometric DNA analysis of NBQ-induced cells revealed an arrest in the G1 phase a reduction in the relative percentage of cells in S and G2 + M phases. Our results suggest that NBQ induces an S-phase specific differentiation of HL-60 cells comparable to that previously described with dimethyl sulfoxide and retinoic acid. NBQ and its analogs, as differentiation inducers, may have potential utility as a novel therapeutic modality for leukemias.
Objective: Genetic variations at codon 72 of p53 gene results in altered activities for p53 and a... more Objective: Genetic variations at codon 72 of p53 gene results in altered activities for p53 and are suggested as a potential cancer risk. However, epidemiologic findings have been inconsistent. The p53 gene has a polymorphic site at exon 4 codon 72, which, in an occurrence of a base substitution, can produce Proline or Arginine (Arg72Pro). This polymorphism is differentially dispersed among different ethnic populations. The objective of this study is to evaluate the association between p53 polymorphism and head and neck squamous cell carcinoma (HNSCC) in the Puerto Rican population. Methods: Genotyping of the p53 polymorphism at exon 4 codon 72 was performed using PCR-based restriction fragment polymorphism (PCR-RFLP) in a study with 72 HNSCC patients. Correlations between clinicopathological parameters and p53 polymorphism were analyzed by Fisher's exact test and chi-square when suitable. Survival analysis of HNSCC patients, with each type of p53 genotype, was performed using M...
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Papers by Adriana Báez