Neuroprotection by 4R-cembranoid against Gulf War Illness-related Chemicals is mediated by ERK, PI3K, and CaMKII pathways.

Gulf War Illness (GWI) has been consistently linked to exposure to pyridostigmine (PB), N,N-Diethyl-meta-toluamide (DEET), permethrin (PER), and traces of sarin. In this study, diisopropylfluorophosphate (DFP, sarin surrogate) and the GWI-related chemicals were found to reduce the number of functionally active neurons in rat hippocampal slices. These findings confirm a link between GWI neurotoxicants and N-Methyl-D-Aspartate (NMDA)-mediated excitotoxicity, which was successfully reversed by Edelfosine (a phospholipase Cβ (PLCβ3) inhibitor) and Flupirtine (a Kv7 channel agonist).

Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality.

Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases divided into poor and normal responders) were enrolled, along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control).

Indirect reference interval estimation using a convolutional neural network with application to cancer antigen 125.

Indirect methods for reference interval (RI) estimation, which use data acquired from routine pathology testing, have the potential to accelerate the establishment of RIs to account for variables such as gender and age to improve clinical assessments. However, they require more sophisticated methods of analysis due to the potential influence of pathological patients in raw clinical datasets. In this paper we develop a novel convolutional neural network (CNN) model trained on synthetic data to identify underlying healthy distributions within pathological admixtures.

Assessing the Impact of AI Education on Hispanic Healthcare Professionals' Perceptions and Knowledge.

This study investigates the awareness and perceptions of artificial intelligence (AI) among Hispanic healthcare-related professionals, focusing on integrating AI in healthcare. The study participants were recruited from an asynchronous course offered twice within a year at the University of Puerto Rico Medical Science Campus, titled "Artificial Intelligence and Machine Learning Applied to Health Disparities Research", which aimed to bridge the gaps in AI knowledge among participants. The participants were divided into Experimental ( = 32; data-illiterate) and Control ( = 18; data-literate) groups, and pre-test and post-test surveys were administered to assess knowledge and attitudes toward AI.

Plasma Proteins Associated with COVID-19 Severity in Puerto Rico.

Viral strains, age, and host factors are associated with variable immune responses against SARS-CoV-2 and disease severity. Puerto Ricans have a genetic mixture of races: European, African, and Native American. We hypothesized that unique host proteins/pathways are associated with COVID-19 disease severity in Puerto Rico.

Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs.

The development of novel antiplasmodial compounds with broad-spectrum activity against different stages of parasites is crucial to prevent malaria disease and parasite transmission. This study evaluated the antiplasmodial activity of seven novel hydrazone compounds (referred to as CB compounds: CB-27, CB-41, CB-50, CB-53, CB-58, CB-59, and CB-61) against multiple stages of parasites. All CB compounds inhibited blood stage proliferation of drug-resistant or sensitive strains of in the low micromolar to nanomolar range.

Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2.

SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus's macro- and microevolution.

Quantitative Proteomics Reveal That CB2R Agonist JWH-133 Downregulates NF-κB Activation, Oxidative Stress, and Lysosomal Exocytosis from HIV-Infected Macrophages.

HIV-associated neurocognitive disorders (HAND) affect 15-55% of HIV-positive patients and effective therapies are unavailable. HIV-infected monocyte-derived macrophages (MDM) invade the brain of these individuals, promoting neurotoxicity. We demonstrated an increased expression of cathepsin B (CATB), a lysosomal protease, in monocytes and post-mortem brain tissues of women with HAND.

Antimalarial Drug Combination Predictions Using the Machine Learning Synergy Predictor (MLSyPred©) tool.

Purpose: Antimalarial drug resistance is a global public health problem that leads to treatment failure. Synergistic drug combinations can improve treatment outcomes and delay the development of drug resistance. Here, we describe the implementation of a freely available computational tool, Machine Learning Synergy Predictor (MLSyPred©), to predict potential synergy in antimalarial drug combinations.

Discovery of Ancestry-specific Variants Associated with Clopidogrel Response among Caribbean Hispanics.

Background: High on-treatment platelet reactivity (HTPR) with clopidogrel is predictive of ischemic events in adults with coronary artery disease. Despite strong data suggesting HTPR varies with ethnicity, including clinical and genetic variables, no genome-wide association study (GWAS) of clopidogrel response has been performed among Caribbean Hispanics. This study aimed to identify genetic predictors of HTPR in a cohort of Caribbean Hispanic cardiovascular patients from Puerto Rico.

Unsupervised machine learning method for indirect estimation of reference intervals for chronic kidney disease in the Puerto Rican population.

Reference intervals (RIs) for clinical laboratory values are extremely important for diagnostics and treatment of patients. However, the determination of these ranges is costly and time-consuming. As a result, often different unverified RIs are used in practice for the same analyte and the same range is used for all patients despite evidence that the values are gender, age, and ethnicity dependent.

Non-Random Enrichment of Single-Nucleotide Polymorphisms Associated with Clopidogrel Resistance within Risk Loci Linked to the Severity of Underlying Cardiovascular Diseases: The Role of Admixture.

Cardiovascular disease (CVD) is one of the leading causes of death in Puerto Rico, where clopidogrel is commonly prescribed to prevent ischemic events. Genetic contributors to both a poor clopidogrel response and the severity of CVD have been identified mainly in Europeans. However, the non-random enrichment of single-nucleotide polymorphisms (SNPs) associated with clopidogrel resistance within risk loci linked to underlying CVDs, and the role of admixture, have yet to be tested.

BioLegato: a programmable, object-oriented graphic user interface.

Background: Biologists are faced with an ever-changing array of complex software tools with steep learning curves, often run on High Performance Computing platforms. To resolve the tradeoff between analytical sophistication and usability, we have designed BioLegato, a programmable graphical user interface (GUI) for running external programs.

Results: BioLegato can run any program or pipeline that can be launched as a command.

The 29-nucleotide deletion in SARS-CoV: truncated versions of ORF8 are under purifying selection.

Background: Accessory proteins have diverse roles in coronavirus pathobiology. One of them in SARS-CoV (the causative agent of the severe acute respiratory syndrome outbreak in 2002-2003) is encoded by the open reading frame 8 (ORF8). Among the most dramatic genomic changes observed in SARS-CoV isolated from patients during the peak of the pandemic in 2003 was the acquisition of a characteristic 29-nucleotide deletion in ORF8.

Evaluation of AIML + HDR-A Course to Enhance Data Science Workforce Capacity for Hispanic Biomedical Researchers.

Artificial intelligence (AI) and machine learning (ML) facilitate the creation of revolutionary medical techniques. Unfortunately, biases in current AI and ML approaches are perpetuating minority health inequity. One of the strategies to solve this problem is training a diverse workforce.

Summary of Year-One Effort of the RCMI Consortium to Enhance Research Capacity and Diversity with Data Science.

Despite being disproportionately impacted by health disparities, Black, Hispanic, Indigenous, and other underrepresented populations account for a significant minority of graduates in biomedical data science-related disciplines. Given their commitment to educating underrepresented students and trainees, minority serving institutions (MSIs) can play a significant role in enhancing diversity in the biomedical data science workforce. Little has been published about the reach, curricular breadth, and best practices for delivering these data science training programs.

Research Infrastructure Core Facilities at Research Centers in Minority Institutions: Part I-Research Resources Management, Operation, and Best Practices.

Funded by the National Institutes of Health (NIH), the Research Centers in Minority Institutions (RCMI) Program fosters the development and implementation of innovative research aimed at improving minority health and reducing or eliminating health disparities. Currently, there are 21 RCMI Specialized (U54) Centers that share the same framework, comprising four required core components, namely the Administrative, Research Infrastructure, Investigator Development, and Community Engagement Cores. The Research Infrastructure Core (RIC) is fundamentally important for biomedical and health disparities research as a critical function domain.

Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta.

Zika virus (ZIKV) compromises placental integrity, infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in ZIKV infection and inflammation.

Local Ancestry-Informed Candidate Pathway Analysis of Warfarin Stable Dose in Latino Populations.

Accuracy of warfarin dose prediction algorithms may be improved by including data from diverse populations in genetic studies of dose variability. Here, we surveyed single nucleotide polymorphisms in vitamin K-related genetic pathways for association with warfarin dose requirements in two admixed Latino populations in standard-principal component adjusted and contemporary-local ancestry adjusted regression models. A total of five variants from vitamin K-related genes/pathways were associated with warfarin dose in both cohorts (P < 0.

A MACHINE LEARNING-BASED APPROACH TO EPILEPTIC SEIZURE PREDICTION USING ELECTRO-ENCEPHALOGRAPHIC SIGNALS.

The brain is made up of billions of neurons, which control all actions performed by us. In epilepsy, the pattern order of brain signals is altered, causing epileptiform discharges in an individual's brain. Approximately 1% of the world population has epilepsy and, therefore, there is a need for studies that can help in the diagnosis and treatment of this disorder.

Reduced RBPMS Levels Promote Cell Proliferation and Decrease Cisplatin Sensitivity in Ovarian Cancer Cells.

Worldwide, the number of cancer-related deaths continues to increase due to the ability of cancer cells to become chemotherapy-resistant and metastasize. For women with ovarian cancer, a staggering 70% will become resistant to the front-line therapy, cisplatin. Although many mechanisms of cisplatin resistance have been proposed, the key mechanisms of such resistance remain elusive.

Inhibition of Cathepsin B and SAPC Secreted by HIV-Infected Macrophages Reverses Common and Unique Apoptosis Pathways.

Human immunodeficiency virus 1 (HIV-1) infects blood monocytes that cross the blood-brain barrier to the central nervous system, inducing neuronal damage. This is prompted by the secretion of viral and neurotoxic factors by HIV-infected macrophages, resulting in HIV-associated neurocognitive disorders. One of these neurotoxic factors is cathepsin B (CATB), a lysosomal cysteine protease that plays an important role in neurodegeneration.

A novel artificial intelligence-based approach for identification of deoxynucleotide aptamers.

The selection of a DNA aptamer through the Systematic Evolution of Ligands by EXponential enrichment (SELEX) method involves multiple binding steps, in which a target and a library of randomized DNA sequences are mixed for selection of a single, nucleotide-specific molecule. Usually, 10 to 20 steps are required for SELEX to be completed. Throughout this process it is necessary to discriminate between true DNA aptamers and unspecified DNA-binding sequences.

Zika virus infection of the placenta alters extracellular matrix proteome.

Zika virus (ZIKV) infection has been associated with fetal abnormalities by compromising placental integrity, but the mechanisms by which this occurs are unknown. Flavivirus can deregulate the host proteome, especially extracellular matrix (ECM) proteins. We hypothesize that a deregulation of specific ECM proteins by ZIKV, affects placental integrity.