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3.
BMC Infect Dis ; 22(1): 402, 2022 Apr 25.
Article in English | MEDLINE | ID: covidwho-1808343

ABSTRACT

The scientific response to the COVID-19 pandemic has produced an abundance of publications, including peer-reviewed articles and preprints, across a wide array of disciplines, from microbiology to medicine and social sciences. Genomics and precision health (GPH) technologies have had a particularly prominent role in medical and public health investigations and response; however, these domains are not simply defined and it is difficult to search for relevant information using traditional strategies. To quantify and track the ongoing contributions of GPH to the COVID-19 response, the Office of Genomics and Precision Public Health at the Centers for Disease Control and Prevention created the COVID-19 Genomics and Precision Health database (COVID-19 GPH), an open access knowledge management system and publications database that is continuously updated through machine learning and manual curation. As of February 11, 2022, COVID-GPH contained 31,597 articles, mostly on pathogen and human genomics (72%). The database also includes articles describing applications of machine learning and artificial intelligence to the investigation and control of COVID-19 (28%). COVID-GPH represents about 10% (22983/221241) of the literature on COVID-19 on PubMed. This unique knowledge management database makes it easier to explore, describe, and track how the pandemic response is accelerating the applications of genomics and precision health technologies. COVID-19 GPH can be freely accessed via https://phgkb.cdc.gov/PHGKB/coVInfoStartPage.action .


Subject(s)
COVID-19 , Artificial Intelligence , COVID-19/epidemiology , Genomics , Humans , Pandemics , Precision Medicine , SARS-CoV-2/genetics
5.
Int J Mol Sci ; 23(7)2022 Mar 22.
Article in English | MEDLINE | ID: covidwho-1785725

ABSTRACT

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.


Subject(s)
Bioprinting , Neoplasms , Bioprinting/methods , Humans , Hydrogels , Precision Medicine , Printing, Three-Dimensional , Tissue Engineering/methods , Tissue Scaffolds , Tumor Microenvironment
7.
Curr Opin Neurol ; 35(2): 143-144, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1758974

Subject(s)
Precision Medicine , Humans
8.
Crit Care ; 25(1): 404, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1745432

ABSTRACT

Identifying new effective treatments for the acute respiratory distress syndrome (ARDS), including COVID-19 ARDS, remains a challenge. The field of ARDS investigation is moving increasingly toward innovative approaches such as the personalization of therapy to biological and clinical sub-phenotypes. Additionally, there is growing recognition of the importance of the global context to identify effective ARDS treatments. This review highlights emerging opportunities and continued challenges for personalizing therapy for ARDS, from identifying treatable traits to innovative clinical trial design and recognition of patient-level factors as the field of critical care investigation moves forward into the twenty-first century.


Subject(s)
Precision Medicine , Respiratory Distress Syndrome/therapy , COVID-19/complications , Clinical Trials as Topic , Humans , Respiratory Distress Syndrome/virology
9.
Front Immunol ; 13: 794006, 2022.
Article in English | MEDLINE | ID: covidwho-1742215

ABSTRACT

To rapidly prognosticate and generate hypotheses on pathogenesis, leukocyte multi-cellularity was evaluated in SARS-CoV-2 infected patients treated in India or the United States (152 individuals, 384 temporal observations). Within hospital (<90-day) death or discharge were retrospectively predicted based on the admission complete blood cell counts (CBC). Two methods were applied: (i) a "reductionist" one, which analyzes each cell type separately, and (ii) a "non-reductionist" method, which estimates multi-cellularity. The second approach uses a proprietary software package that detects distinct data patterns generated by complex and hypothetical indicators and reveals each data pattern's immunological content and associated outcome(s). In the Indian population, the analysis of isolated cell types did not separate survivors from non-survivors. In contrast, multi-cellular data patterns differentiated six groups of patients, including, in two groups, 95.5% of all survivors. Some data structures revealed one data point-wide line of observations, which informed at a personalized level and identified 97.8% of all non-survivors. Discovery was also fostered: some non-survivors were characterized by low monocyte/lymphocyte ratio levels. When both populations were analyzed with the non-reductionist method, they displayed results that suggested survivors and non-survivors differed immunologically as early as hospitalization day 1.


Subject(s)
Blood Cell Count/methods , COVID-19/immunology , SARS-CoV-2/physiology , Adult , COVID-19/diagnosis , COVID-19/mortality , Diagnostic Tests, Routine , Female , Humans , India , Male , Middle Aged , Precision Medicine , Retrospective Studies , Software , Survival Analysis , United States
10.
Science ; 373(6561): 1304-1306, 2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1741512
11.
Biomolecules ; 12(3)2022 03 07.
Article in English | MEDLINE | ID: covidwho-1731936

ABSTRACT

A prodigious increment of scientific evidence in both preclinical and clinical studies is narrowing a major gap in knowledge regarding sex-specific biological responses observed in numerous branches of clinical practices. Some paradigmatic examples include neurodegenerative and mental disorders, immune-related disorders such as pathogenic infections and autoimmune diseases, oncologic conditions, and cardiovascular morbidities. The male-to-female proportion in a population is expressed as sex ratio and varies eminently with respect to the pathophysiology, natural history, incidence, prevalence, and mortality rates. The factors that determine this scenario incorporate both sex-associated biological differences and gender-dependent sociocultural issues. A broad narrative review focused on the current knowledge about the role of hormone regulation in gender medicine and gender peculiarities across key clinical areas is provided. Sex differences in immune response, cardiovascular diseases, neurological disorders, cancer, and COVID-19 are some of the hints reported. Moreover, gender implications in occupational health and health policy are offered to support the need for more personalized clinical medicine and public health approaches to achieve an ameliorated quality of life of patients and better outcomes in population health.


Subject(s)
COVID-19 , Quality of Life , COVID-19/epidemiology , Female , Hormones , Humans , Male , Precision Medicine , Sex Characteristics
12.
Int J Oncol ; 60(3)2022 03.
Article in English | MEDLINE | ID: covidwho-1726130

ABSTRACT

Biobanks constitute an integral part of precision medicine. They provide a repository of biospecimens that may be used to elucidate the pathophysiology, support diagnoses, and guide the treatment of diseases. The pilot biobank of rare malignant neoplasms has been established in the context of the Hellenic Network of Precision Medicine on Cancer and aims to enhance future clinical and/or research studies in Greece by collecting, processing, and storing rare malignant neoplasm samples with associated data. The biobank currently comprises 553 samples; 384 samples of hematopoietic and lymphoid tissue malignancies, 72 samples of pediatric brain tumors and 97 samples of malignant skin neoplasms. In this article, sample collections and their individual significance in clinical research are described in detail along with computational methods developed specifically for this project. A concise review of the Greek biobanking landscape is also delineated, in addition to recommended technologies, methodologies and protocols that were integrated during the creation of the biobank. This project is expected to re­enforce current clinical and research studies, introduce advances in clinical and genetic research and potentially aid in future targeted drug discovery. It is our belief that the future of medical research is entwined with accessible, effective, and ethical biobanking and that our project will facilitate research planning in the '­omic' era by contributing high­quality samples along with their associated data.


Subject(s)
Biological Specimen Banks/trends , Neoplasms/pathology , Precision Medicine/trends , Cell Line, Tumor , Greece , Humans , Precision Medicine/methods
13.
Molecules ; 27(3)2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1686901

ABSTRACT

The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system is best known for its role in genomic editing. It has also demonstrated great potential in nucleic acid biosensing. However, the specificity limitation in CRISPR/Cas has created a hurdle for its advancement. More recently, nucleic acid aptamers known for their high affinity and specificity properties for their targets have been integrated into CRISPR/Cas systems. This review article gives a brief overview of the aptamer and CRISPR/Cas technology and provides an updated summary and discussion on how the two distinctive nucleic acid technologies are being integrated into modern diagnostic and therapeutic applications.


Subject(s)
Aptamers, Nucleotide/therapeutic use , Biosensing Techniques/methods , CRISPR-Cas Systems , Gene Editing , Precision Medicine , Humans
14.
PLoS One ; 17(2): e0263750, 2022.
Article in English | MEDLINE | ID: covidwho-1674021

ABSTRACT

PURPOSE: To identify meanings of and challenges to enacting equitable diversification of genomics research, and specifically precision medicine research (PMR), teams. METHODS: We conducted in-depth interviews with 102 individuals involved in three U.S.-based precision medicine research consortia and conducted over 400 observation hours of their working group meetings, consortium-wide meetings, and conference presentations. We also reviewed published reports on genomic workforce diversity (WFD), particularly those relevant to the PMR community. RESULTS: Our study finds that many PMR teams encounter challenges as they strive to achieve equitable diversification on scientific teams. Interviewees articulated that underrepresented team members were often hired to increase the study's capacity to recruit diverse research participants, but are limited to on-the-ground staff positions with little influence over study design. We find existing hierarchies and power structures in the academic research ecosystem compound challenges for equitable diversification. CONCLUSION: Our results suggest that meaningful diversification of PMR teams will only be possible when team equity is prioritized as a core value in academic research communities.


Subject(s)
Biomedical Research/ethics , Cultural Diversity , Laboratory Personnel/ethics , Precision Medicine/ethics , Adolescent , Adult , Aged , Female , Genomics/ethics , Health Workforce/ethics , Humans , Laboratory Personnel/organization & administration , Male , Middle Aged , Patient Care Team/ethics , Patient Care Team/organization & administration , United States , Young Adult
15.
OMICS ; 26(2): 101-105, 2022 02.
Article in English | MEDLINE | ID: covidwho-1672119

ABSTRACT

Digital transformation is currently impacting not only health care but also education curricula for medicine and life sciences. The COVID-19 pandemic has accelerated the deployment of digital technologies such as the Internet of Things and artificial intelligence in diverse fields of biomedicine. Genomics and related fields of inquiry such as pharmacogenomics and personalized medicine have been making important progress over the past decades. However, the genomics knowledge of health care professionals and other stakeholders in society is not commensurate with the current state of progress in these scientific fields. The rise of digital health offers unprecedented opportunities both for health care professionals and the general public to expand their genomics literacy and education. This expert review offers an analysis of the bottlenecks that affect and issues that need to be addressed to catalyze genomics and personalized medicine education in the digital era. In addition, we summarize and critically discuss the various educational and awareness opportunities that presently exist to catalyze the delivery of genomics knowledge in ways closely attuned to the emerging field of digital health.


Subject(s)
COVID-19 , Precision Medicine , Artificial Intelligence , Genomics , Humans , Pandemics , SARS-CoV-2
16.
ACS Synth Biol ; 11(2): 528-537, 2022 02 18.
Article in English | MEDLINE | ID: covidwho-1655460

ABSTRACT

Over the past decades, there have been numerous outbreaks, including parasitic, fungal, bacterial, and viral infections, worldwide. The rate at which infectious diseases are emerging is disproportionate to the rate of development for new strategies that could combat them. Therefore, there is an increasing demand to develop novel, specific, sensitive, and effective methods for infectious disease diagnosis and treatment. Designed synthetic systems and devices are becoming powerful tools to treat human diseases. The advancement in synthetic biology offers efficient, accurate, and cost-effective platforms for detecting and preventing infectious diseases. Herein we focus on the latest state of living theranostics and its implications.


Subject(s)
Communicable Disease Control/methods , Synthetic Biology , Bacterial Physiological Phenomena , Bacteriophages/genetics , COVID-19/therapy , COVID-19/virology , Humans , Pandemics , Precision Medicine , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity
17.
OMICS ; 26(1): 35-50, 2022 01.
Article in English | MEDLINE | ID: covidwho-1635804

ABSTRACT

Pharmacogenomics is universally relevant for worldwide modern therapeutics and yet needs further development in resource-limited countries. While there is an abundance of genetic association studies in controlled medical settings, there is a paucity of studies with a naturalistic design in real-life clinical practice in patients with comorbidities and under multiple drug treatment regimens. African patients are often burdened with communicable and noncommunicable comorbidities, yet the application of pharmacogenomics in African clinical settings remains limited. Using warfarin as a model, this study aims at minimizing gaps in precision/personalized medicine research in African clinical practice. We present, therefore, pharmacogenomic profiles of a cohort of 503 black Africans (n = 252) and Mixed Ancestry (n = 251) patients from Southern Africa, on warfarin and co-prescribed drugs in a naturalized noncontrolled environment. Seventy-three (n = 73) single nucleotide polymorphisms (SNPs) in 29 pharmacogenes were characterized using a combination of allelic discrimination, Sanger sequencing, restriction fragment length polymorphism, and Sequenom Mass Array. The common comorbidities were hypertension (43-46%), heart failure (39-45%), diabetes mellitus (18%), arrhythmia (25%), and HIV infection (15%). Accordingly, the most common co-prescribed drugs were antihypertensives, antiarrhythmic drugs, antidiabetics, and antiretroviral therapy. We observed marked variation in major pharmacogenes both at interethnic levels and within African subpopulations. The Mixed Ancestry group presented a profile of genetic variants reflecting their European, Asian, and African admixture. Precision medicine requires that African populations begin to capture their own pharmacogenetic SNPs as they cannot always infer with absolute certainty from Asian and European populations. In the current historical moment of the COVID-19 pandemic, we also underscore that the spectrum of drugs interacting with warfarin will likely increase, given the systemic and cardiovascular effects of COVID-19, and the anticipated influx of COVID-19 medicines in the near future. This observational clinical pharmacogenomics study of warfarin, together with past precision medicine research, collectively, lends strong support for incorporation of pharmacogenetic profiling in clinical settings in African patients for effective and safe administration of therapeutics.


Subject(s)
COVID-19 , HIV Infections , Anticoagulants/therapeutic use , Humans , Pandemics , Pharmacogenetics , Polymorphism, Single Nucleotide/genetics , Precision Medicine , SARS-CoV-2 , Warfarin/therapeutic use
18.
Int J Mol Sci ; 23(2)2022 Jan 06.
Article in English | MEDLINE | ID: covidwho-1631344

ABSTRACT

Since the first evidence that stem cells can provide pro-resolving effects via paracrine secretion of soluble factors, growing interest has been addressed to define the most ideal cell source for clinical translation. Leftover or clinical waste samples of human amniotic fluid obtained following prenatal screening, clinical intervention, or during scheduled caesarean section (C-section) delivery at term have been recently considered an appealing source of mesenchymal progenitors with peculiar regenerative capacity. Human amniotic fluid stem cells (hAFSC) have been demonstrated to support tissue recovery in several preclinical models of disease by exerting paracrine proliferative, anti-inflammatory and regenerative influence. Small extracellular vesicles (EVs) concentrated from the hAFSC secretome (the total soluble trophic factors secreted in the cell-conditioned medium, hAFSC-CM) recapitulate most of the beneficial cell effects. Independent studies in preclinical models of either adult disorders or severe diseases in newborns have suggested a regenerative role of hAFSC-EVs. EVs can be eventually concentrated from amniotic fluid (hAF) to offer useful prenatal information, as recently suggested. In this review, we focus on the most significant aspects of EVs obtained from either hAFSC and hAF and consider the current challenges for their clinical translation, including isolation, characterization and quantification methods.


Subject(s)
Amniotic Fluid , Extracellular Vesicles , Precision Medicine , Stem Cells , Humans
19.
Clin Infect Dis ; 74(1): 149-151, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1621568
20.
Clin Infect Dis ; 74(1): 144-148, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1621566

ABSTRACT

We are learning that the host response to severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) infection is complex and highly dynamic. Effective initial host defense in the lung is associated with mild symptoms and disease resolution. Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction. The immune response in these patients is highly variable and can include moderate to severe systemic inflammation and/or marked systemic immune suppression. There is unlikely to be a "one size fits all" approach to immunomodulation in patients with coronavirus disease 2019 (COVID-19). We believe that a personalized, immunophenotype-driven approach to immunomodulation that may include anticytokine therapy in carefully selected patients and immunostimulatory therapies in others is the shortest path to success in the study and treatment of patients with critical illness due to COVID-19.


Subject(s)
COVID-19 , Immunomodulation , Precision Medicine , COVID-19/immunology , COVID-19/therapy , Cytokines , Humans , Immunity , Lung , SARS-CoV-2
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