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Twenty years after the September 11th, 2001 terrorist attacks, the association between exposures present at the World Trade Center (WTC) site and the risk of several specific types of cancer has been reported among rescue and recovery workers. The authors' objective was to conduct an updated review of these data. Most studies have found elevated rates of both prostate and thyroid cancers compared with rates in the general population, and some have reported statistically significant differences for the rates of all cancers as well. Studies including a larger combined cohort of WTC-exposed rescue and recovery workers from 3 main cohorts have since replicated findings for these cancers, with additional years of follow-up. Among this combined cohort, although a lower-than-expected standardized incidence ratio for all cancers was observed, WTC exposure was also related to an increased risk of cutaneous melanoma and tonsil cancer. Importantly, another study found that WTC-exposed rescue and recovery workers who are enrolled in the federally funded medical monitoring and treatment program experienced improved survival post-cancer diagnosis compared with New York state patients with cancer. On the basis of these combined cohort studies, the full effect of WTC exposure on cancer risk is becoming clearer. Consequently, the authors believe that surveillance of those with WTC exposure should be continued, and in-depth analysis of epidemiologic, molecular, and clinical aspects of specific cancers in these workers should be pursued.
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Melanoma , Exposición Profesional , Ataques Terroristas del 11 de Septiembre , Neoplasias Cutáneas , Estudios de Cohortes , Humanos , Masculino , Exposición Profesional/efectos adversos , Trabajo de RescateRESUMEN
Plasmacytoid dendritic cells (pDCs) are a unique sentinel cell type that can detect pathogen-derived nucleic acids and respond with rapid and massive production of type I interferon. This review summarizes our current understanding of pDC biology, including transcriptional regulation, heterogeneity, role in antiviral immune responses, and involvement in immune pathology, particularly in autoimmune diseases, immunodeficiency, and cancer. We also highlight the remaining gaps in our knowledge and important questions for the field, such as the molecular basis of unique interferon-producing capacity of pDCs. A better understanding of cell type-specific positive and negative control of pDC function should pave the way for translational applications focused on this immune cell type.
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Enfermedades Autoinmunes/inmunología , Diferenciación Celular , Células Dendríticas/fisiología , Neoplasias/inmunología , Virosis/inmunología , Animales , Regulación de la Expresión Génica , Humanos , Inmunidad Celular , Interferón Tipo I/metabolismoRESUMEN
A health workforce capable of implementing genomic medicine requires effective genomics education. Genomics education interventions developed for health professions over the last two decades, and their impact, are variably described in the literature. To inform an evaluation framework for genomics education, we undertook an exploratory scoping review of published needs assessments for, and/or evaluations of, genomics education interventions for health professionals from 2000 to 2023. We retrieved and screened 4,659 records across the two searches with 363 being selected for full-text review and consideration by an interdisciplinary working group. 104 articles were selected for inclusion in the review-60 needs assessments, 52 genomics education evaluations, and eight describing both. Included articles spanned all years and described education interventions in over 30 countries. Target audiences included medical specialists, nurses/midwives, and/or allied health professionals. Evaluation questions, outcomes, and measures were extracted, categorized, and tabulated to iteratively compare measures across stages of genomics education evaluation: planning (pre-implementation), development and delivery (implementation), and impact (immediate, intermediate, or long-term outcomes). They are presented here along with descriptions of study designs. We document the wide variability in evaluation approaches and terminology used to define measures and note that few articles considered downstream (long-term) outcomes of genomics education interventions. Alongside the evaluation framework for genomics education, results from this scoping review form part of a toolkit to help educators to undertake rigorous genomics evaluation that is fit for purpose and can contribute to the growing evidence base of the contribution of genomics education in implementation strategies for genomic medicine.
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Genómica , Evaluación de Necesidades , Genómica/educación , Humanos , Personal de Salud/educaciónRESUMEN
Is there a formula for a competitive NIH grant application? The Serenity Prayer may provide one: "Grant me the serenity to accept the things I cannot change, the ability to change the things I can, and the wisdom to know the difference." But how to tell the difference? In this Perspective, we provide an inclusive roadmap-elements of NIH funding. Collectively, we have over 30 y of peer review experience as NIH Scientific Review Officers in addition to over 30 y of program experience as NIH Program Officers. This article distills our NIH experience. We use Euclid's 13-book landmark, The Elements, as our template to humbly share what we learned. We have three specific aims: inform, guide, and motivate prospective applicants. We also address ways that support diversity and inclusion among applicants and young investigators in biomedical research. The elements we describe come from a wide range of sources. Some themes will be general. Some will be specific. All will be candid. The ultimate goal is a competitive application, serenity, and hopefully both.
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Investigación Biomédica , Humanos , Estados Unidos , Investigadores , Revisión por Pares , Motivación , National Institutes of Health (U.S.)RESUMEN
Engineered gene drives create potential for both widespread benefits and irreversible harms to ecosystems. CRISPR-based systems of allelic conversion have rapidly accelerated gene drive research across diverse taxa, putting field trials and their necessary risk assessments on the horizon. Dynamic process-based models provide flexible quantitative platforms to predict gene drive outcomes in the context of system-specific ecological and evolutionary features. Here, we synthesize gene drive dynamic modeling studies to highlight research trends, knowledge gaps, and emergent principles, organized around their genetic, demographic, spatial, environmental, and implementation features. We identify the phenomena that most significantly influence model predictions, discuss limitations of biological complexity and uncertainty, and provide insights to promote responsible development and model-assisted risk assessment of gene drives.
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Tecnología de Genética Dirigida , Ecosistema , Evolución Biológica , Medición de RiesgoRESUMEN
The field of quantum computing (QC) is expanding, with efforts being made to apply it to areas previously covered by classical algorithms and methods. Bioinformatics is one such domain that is developing in terms of QC. This article offers a broad mapping review of methods and algorithms of QC in bioinformatics, marking the first of its kind. It presents an overview of the domain and aids researchers in identifying further research directions in the early stages of this field of knowledge. The work presented here shows the current state-of-the-art solutions, focuses on general future directions, and highlights the limitations of current methods. The gathered data includes a comprehensive list of identified methods along with descriptions, classifications, and elaborations of their advantages and disadvantages. Results are presented not just in a descriptive table but also in an aggregated and visual format.
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Algoritmos , Biología Computacional , Teoría Cuántica , Biología Computacional/métodos , HumanosRESUMEN
The process of drug development is expensive and time-consuming. In contrast, drug repurposing can be introduced to clinical practice more quickly and at a reduced cost. Over the last decade, there has been a significant expansion of large biobanks that link genomic data to electronic health record data, public availability of various databases containing biological and clinical information and rapid development of novel methodologies and algorithms in integrating different sources of data. This review aims to provide a thorough summary of different strategies that utilize genomic data to seek drug-repositioning opportunities. We searched MEDLINE and EMBASE databases to identify eligible studies up until 1 May 2023, with a total of 102 studies finally included after two-step parallel screening. We summarized commonly used strategies for drug repurposing, including Mendelian randomization, multi-omic-based and network-based studies and illustrated each strategy with examples, as well as the data sources implemented. By leveraging existing knowledge and infrastructure to expedite the drug discovery process and reduce costs, drug repurposing potentially identifies new therapeutic uses for approved drugs in a more efficient and targeted manner. However, technical challenges when integrating different types of data and biased or incomplete understanding of drug interactions are important hindrances that cannot be disregarded in the pursuit of identifying novel therapeutic applications. This review offers an overview of drug repurposing methodologies, providing valuable insights and guiding future directions for advancing drug repurposing studies.
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Reposicionamiento de Medicamentos , Genómica , Humanos , Algoritmos , Desarrollo de Medicamentos , Descubrimiento de Drogas/métodos , Reposicionamiento de Medicamentos/métodosRESUMEN
Atherosclerosis is an arterial disease process characterized by the focal subendothelial accumulation of apolipoprotein-B-containing lipoproteins, immune and vascular wall cells, and extracellular matrix. The lipoproteins acquire features of damage-associated molecular patterns and trigger first an innate immune response, dominated by monocyte-macrophages, and then an adaptive immune response. These inflammatory responses often become chronic and non-resolving and can lead to arterial damage and thrombosis-induced organ infarction. The innate immune response is regulated at various stages, from hematopoiesis to monocyte changes and macrophage activation. The adaptive immune response is regulated primarily by mechanisms that affect the balance between regulatory and effector T cells. Mechanisms related to cellular cholesterol, phenotypic plasticity, metabolism, and aging play key roles in affecting these responses. Herein, we review select topics that shed light on these processes and suggest new treatment strategies.
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Aterosclerosis/inmunología , Macrófagos/inmunología , Monocitos/inmunología , Linfocitos T/inmunología , Inmunidad Adaptativa/inmunología , Animales , Humanos , Inmunidad Innata/inmunología , Lipoproteínas/inmunología , Modelos InmunológicosRESUMEN
Tools have been developed to facilitate communication and support information exchange between people diagnosed with cancer and their physicians. Patient-reported outcome measures, question prompt lists, patient-held records, tape recordings of consultations, decision aids, and survivorship care plans have all been promoted as potential tools, and there is extensive literature exploring their impact on patient outcomes. Eleven systematic reviews of studies evaluating tools to facilitate patient-physician communication were reviewed and summarized in this overview of systematic reviews. Across the systematic reviews, 87 publications reported on 84 primary studies involving 15,381 participants. Routine use of patient-reported outcome measures and feedback of results to clinicians can improve pain management, physician-patient communication, and symptom detection and control; increase utilization of supportive care; and increase patient involvement in care. Question prompt lists can increase the number of questions asked by patients without increasing consultation length and may encourage them to reflect and plan questions before the consultation. There is limited benefit in audio recording consultations or using patient-held records during consultations. Physicians should be supported by adequately resourced health services to respond effectively to the range of clinical and broader patient needs identified through the routine use of tools to facilitate communication.
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Comunicación , Neoplasias , Relaciones Médico-Paciente , Derivación y Consulta , Humanos , Neoplasias/diagnóstico , Neoplasias/psicología , Neoplasias/terapia , Participación del Paciente , Medición de Resultados Informados por el PacienteRESUMEN
Disparities continue to pose major challenges in various aspects of science. One such aspect is editorial board composition, which has been shown to exhibit racial and geographical disparities. However, the literature on this subject lacks longitudinal studies quantifying the degree to which the racial composition of editors reflects that of scientists. Other aspects that may exhibit racial disparities include the time spent between the submission and acceptance of a manuscript and the number of citations a paper receives relative to textually similar papers, but these have not been studied to date. To fill this gap, we compile a dataset of 1,000,000 papers published between 2001 and 2020 by six publishers, while identifying the handling editor of each paper. Using this dataset, we show that most countries in Asia, Africa, and South America (where the majority of the population is ethnically non-White) have fewer editors than would be expected based on their share of authorship. Focusing on US-based scientists reveals Black as the most underrepresented race. In terms of acceptance delay, we find, again, that papers from Asia, Africa, and South America spend more time compared to other papers published in the same journal and the same year. Regression analysis of US-based papers reveals that Black authors suffer from the greatest delay. Finally, by analyzing citation rates of US-based papers, we find that Black and Hispanic scientists receive significantly fewer citations compared to White ones doing similar research. Taken together, these findings highlight significant challenges facing non-White scientists.
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Autoria , Publicaciones , Humanos , Asia , Población Negra , Hispánicos o LatinosRESUMEN
SUMMARYThis narrative review and meta-analysis summarizes a broad evidence base on the benefits-and also the practicalities, disbenefits, harms and personal, sociocultural and environmental impacts-of masks and masking. Our synthesis of evidence from over 100 published reviews and selected primary studies, including re-analyzing contested meta-analyses of key clinical trials, produced seven key findings. First, there is strong and consistent evidence for airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Second, masks are, if correctly and consistently worn, effective in reducing transmission of respiratory diseases and show a dose-response effect. Third, respirators are significantly more effective than medical or cloth masks. Fourth, mask mandates are, overall, effective in reducing community transmission of respiratory pathogens. Fifth, masks are important sociocultural symbols; non-adherence to masking is sometimes linked to political and ideological beliefs and to widely circulated mis- or disinformation. Sixth, while there is much evidence that masks are not generally harmful to the general population, masking may be relatively contraindicated in individuals with certain medical conditions, who may require exemption. Furthermore, certain groups (notably D/deaf people) are disadvantaged when others are masked. Finally, there are risks to the environment from single-use masks and respirators. We propose an agenda for future research, including improved characterization of the situations in which masking should be recommended or mandated; attention to comfort and acceptability; generalized and disability-focused communication support in settings where masks are worn; and development and testing of novel materials and designs for improved filtration, breathability, and environmental impact.
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COVID-19 , Máscaras , Infecciones del Sistema Respiratorio , SARS-CoV-2 , Humanos , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/transmisión , COVID-19/prevención & control , COVID-19/transmisión , Dispositivos de Protección Respiratoria/normasRESUMEN
In recent years, environmental epidemiology and toxicology have seen a growing interest in the environmental factors that contribute to the increased prevalence of neurodevelopmental disorders, with the purpose of establishing appropriate prevention strategies. A literature review was performed, and 192 articles covering the topic of endocrine disruptors and neurodevelopmental disorders were found, focusing on polychlorinated biphenyls, polybrominated diphenyl ethers, bisphenol A, and pesticides. This study contributes to analyzing their effect on the molecular mechanism in maternal and infant thyroid function, essential for infant neurodevelopment, and whose alteration has been associated with various neurodevelopmental disorders. The results provide scientific evidence of the association that exists between the environmental neurotoxins and various neurodevelopmental disorders. In addition, other possible molecular mechanisms by which pesticides and endocrine disruptors may be associated with neurodevelopmental disorders are being discussed.
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Disruptores Endocrinos , Trastornos del Neurodesarrollo , Plaguicidas , Disruptores Endocrinos/efectos adversos , Disruptores Endocrinos/toxicidad , Humanos , Trastornos del Neurodesarrollo/inducido químicamente , Trastornos del Neurodesarrollo/epidemiología , Plaguicidas/toxicidad , Plaguicidas/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/efectos adversos , Fenoles/efectos adversos , Fenoles/toxicidad , Femenino , Compuestos de Bencidrilo/efectos adversos , Compuestos de Bencidrilo/toxicidad , Animales , Éteres Difenilos Halogenados/toxicidad , Bifenilos Policlorados/toxicidad , Bifenilos Policlorados/efectos adversos , EmbarazoRESUMEN
This systematic review and meta-analysis aimed to determine the association between the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and dementia onset as well as cognitive function in patients with diabetes mellitus. We comprehensively searched the MEDLINE, Embase, and CENTRAL databases to select relevant studies published up to August 2023. The use of SGLT-2 inhibitors significantly lowers dementia risk compared to SGLT-2i non-users (Hazard ratio: 0.68, 95 % CI: 0.50-0.92). Furthermore, our findings indicated a positive effect of SGLT-2 inhibitor use on cognitive function score improvement, as demonstrated by the standardized mean difference of 0.88 (95 % CI: 0.32-1.44), particularly among populations with mild cognitive impairment or dementia. This systematic review and meta-analysis indicate a potential role of SGLT-2 inhibitors in reducing the risk of dementia in patients with diabetes mellitus. These findings underscore the need for well-controlled large clinical trials and future research in this field.
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Cognición , Demencia , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Demencia/epidemiología , Cognición/efectos de los fármacos , Cognición/fisiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/epidemiología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiologíaRESUMEN
Worldwide, over 150 million adolescent and adult women use oral contraceptives (OC). An association between OC-use and the emergence of symptoms of mental disorders has been suggested. This systematic review and meta-analysis provide an overview of published research regarding symptoms of mental disorders in association with OC-use, factoring the influence of OC types, age of first-use, duration of OC-intake, and previous diagnoses of mental disorders. A systematic literature search was conducted between June-July 2022. 22 studies were included. While most found no significant OC-use effects on mental symptoms, some hinted at OCs as a potential risk. The existing evidence regarding the potential link between progestin-only OC-use and an elevated risk of mental symptoms in comparison to combined OC-use remains inconclusive. However, due to emerging indications suggesting that the formulation of OC might play a role in mental health outcomes, this topic warrants further investigation. Moreover, indications of an increased risk for depressive symptoms in adolescent OC-users should be noted. Hence, while general population effects seem unlikely, they cannot be completely disregarded. The decision on OC-use should depend on the patient's medical history and should be re-evaluated regularly.
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Anticonceptivos Orales , Trastornos Mentales , Adulto , Adolescente , Humanos , Femenino , Anticonceptivos Orales/efectos adversos , AnticoncepciónRESUMEN
The use of population descriptors such as race, ethnicity, and ancestry in science, medicine, and public health has a long, complicated, and at times dark history, particularly for genetics, given the field's perceived importance for understanding between-group differences. The historical and potential harms that come with irresponsible use of these categories suggests a clear need for definitive guidance about when and how they can be used appropriately. However, while many prior authors have provided such guidance, no established consensus exists, and the extant literature has not been examined for implied consensus and sources of disagreement. Here, we present the results of a scoping review of published normative recommendations regarding the use of population categories, particularly in genetics research. Following PRISMA guidelines, we extracted recommendations from n = 121 articles matching inclusion criteria. Articles were published consistently throughout the time period examined and in a broad range of journals, demonstrating an ongoing and interdisciplinary perceived need for guidance. Examined recommendations fall under one of eight themes identified during analysis. Seven are characterized by broad agreement across articles; one, "appropriate definitions of population categories and contexts for use," revealed substantial fundamental disagreement among articles. Additionally, while many articles focus on the inappropriate use of race, none fundamentally problematize ancestry. This work can be a resource to researchers looking for normative guidance on the use of population descriptors and can orient authors of future guidelines to this complex field, thereby contributing to the development of more effective future guidelines for genetics research.
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Etnicidad , Problema de Conducta , Humanos , Pueblo Asiatico , Consenso , Etnicidad/genética , InvestigadoresRESUMEN
DNA methylation is a fundamental epigenetic modification involved in various biological processes and diseases. Analysis of DNA methylation data at a genome-wide and high-throughput level can provide insights into diseases influenced by epigenetics, such as cancer. Recent technological advances have led to the development of high-throughput approaches, such as genome-scale profiling, that allow for computational analysis of epigenetics. Deep learning (DL) methods are essential in facilitating computational studies in epigenetics for DNA methylation analysis. In this systematic review, we assessed the various applications of DL applied to DNA methylation data or multi-omics data to discover cancer biomarkers, perform classification, imputation and survival analysis. The review first introduces state-of-the-art DL architectures and highlights their usefulness in addressing challenges related to cancer epigenetics. Finally, the review discusses potential limitations and future research directions in this field.
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Aprendizaje Profundo , Neoplasias , Humanos , Metilación de ADN , Epigénesis Genética , Genoma , Neoplasias/genéticaRESUMEN
The three-dimensional structure of RNA molecules plays a critical role in a wide range of cellular processes encompassing functions from riboswitches to epigenetic regulation. These RNA structures are incredibly dynamic and can indeed be described aptly as an ensemble of structures that shifts in distribution depending on different cellular conditions. Thus, the computational prediction of RNA structure poses a unique challenge, even as computational protein folding has seen great advances. In this review, we focus on a variety of machine learning-based methods that have been developed to predict RNA molecules' secondary structure, as well as more complex tertiary structures. We survey commonly used modeling strategies, and how many are inspired by or incorporate thermodynamic principles. We discuss the shortcomings that various design decisions entail and propose future directions that could build off these methods to yield more robust, accurate RNA structure predictions.
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Epigénesis Genética , ARN , ARN/metabolismo , Aprendizaje Automático , Estructura Secundaria de Proteína , Biología Computacional/métodosRESUMEN
PURPOSE: Evaluation of genetic mutations in cancers is important because distinct mutational profiles help determine individualized drug therapy. However, molecular analyses are not routinely performed in all cancers because they are expensive, time-consuming and not universally available. Artificial intelligence (AI) has shown the potential to determine a wide range of genetic mutations on histologic image analysis. Here, we assessed the status of mutation prediction AI models on histologic images by a systematic review. METHODS: A literature search using the MEDLINE, Embase and Cochrane databases was conducted in August 2021. The articles were shortlisted by titles and abstracts. After a full-text review, publication trends, study characteristic analysis and comparison of performance metrics were performed. RESULTS: Twenty-four studies were found mostly from developed countries, and their number is increasing. The major targets were gastrointestinal, genitourinary, gynecological, lung and head and neck cancers. Most studies used the Cancer Genome Atlas, with a few using an in-house dataset. The area under the curve of some of the cancer driver gene mutations in particular organs was satisfactory, such as 0.92 of BRAF in thyroid cancers and 0.79 of EGFR in lung cancers, whereas the average of all gene mutations was 0.64, which is still suboptimal. CONCLUSION: AI has the potential to predict gene mutations on histologic images with appropriate caution. Further validation with larger datasets is still required before AI models can be used in clinical practice to predict gene mutations.
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Inteligencia Artificial , Neoplasias de la Tiroides , Humanos , Benchmarking , Bases de Datos Factuales , MutaciónRESUMEN
As we enter a new era of mRNA-based therapeutics, evidence on genetic or environmental factors that might predispose to unknown off-target side effects, gains in importance. Among these factors, exercise appears likely to have influenced otherwise cryptic cases of early-onset postvaccination myocarditis. And the existence of a distinct late-onset myocarditis is now being recognized. Here, three case-history reports suggest crypticity (the author's own case), unless provoked by a preexisting cardiac morbidity (one case), or by immune checkpoint blockade to enhance anticancer autoimmunity (several cases). These reports are supported by noninvasive fluorodeoxyglucose-based cardiac scan comparisons of multiple vaccinated and unvaccinated subjects. In pre-pandemic decades, applications for funds by the leading innovator in mRNA-based therapeutics seldom gained peer-review approval. Thus, at the start of the pandemic, the meager data on such side effects could justify only emergency approval. We must do better.
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COVID-19 , Miocarditis , Vacunación , Miocarditis/etiología , Humanos , Masculino , COVID-19/prevención & control , COVID-19/inmunología , Vacunación/efectos adversos , Femenino , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Persona de Mediana Edad , SARS-CoV-2/inmunología , AdultoRESUMEN
Multiple Sclerosis (MS) is one of the immune-mediated demyelinating disorders. Multiple components, including the environment and genetics, are possible factors in the pathogenesis of MS. Also, it can be said that infections are a key component of the host's response to MS development. Finally, we evaluated the relationship between different pathogens and MS disease in this umbrella research. We systematically collected and analysed multiple meta-analyses focused on one particular topic. We utilised the Scopus, PubMed, and Web of Science databases starting with inception until 30 May 2023. The methodological quality of the analysed meta-analysis has been determined based on Assessing the Methodological Quality of Systematic Reviews 2 and Grade, and graph construction and statistical analysis were conducted using Comprehensive Meta-Analysis. The Confidence Interval of effect size was 95% in meta-analyses, and p < 0.05 indicated a statistically meaningful relationship. The included studies evaluated the association between MS and 12 viruses containing SARS-CoV-2, Epstein-Barr virus (EBV), Hepatitis B virus, varicella-zoster virus (VZV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, HSV-1, HSV-2, Cytomegalovirus, Human Papillomavirus, and influenza. SARS-CoV-2, with a 3.74 odds ratio, has a significantly more potent negative effect on MS among viral infections. After that, EBV, HHV-6, HSV-2, and VZV, respectively, with 3.33, 2.81, 1.76, and 1.72 odds ratios, had a significantly negative relationship with MS (p < 0.05). Although the theoretical evidence mostly indicates that EBV has the greatest effect on MS, recent epidemiological studies have challenged this conclusion and put forward possibilities that SARS-CoV-2 is the culprit. Hence, it was necessary to investigate the effects of SARS-CoV-2 and EBV on MS.