RESUMO
Early detection with accurate classification of solid pulmonary nodules is critical in reducing lung cancer morbidity and mortality. Computed tomography (CT) remains the most widely used imaging examination for pulmonary nodule evaluation; however, other imaging modalities, such as PET/CT and MRI, are increasingly used for nodule characterization. Current advances in solid nodule imaging are largely due to developments in machine learning, including automated nodule segmentation and computer-aided detection. This review explores current multi-modality solid pulmonary nodule detection and characterization with discussion of radiomics and risk prediction models.
Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imageamento por Ressonância Magnética , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Detecção Precoce de Câncer/métodosRESUMO
A 21-year-old woman self-ingested an 18-gauge needle that perforated the distal esophagus into the left inferior ventricular myocardium, with migration into the septum. Radiography, computed tomography, and echocardiography imaging characterized the needle's location. Following an initial endoscopy and pericardial tamponade drainage, complete needle removal occurred via median sternotomy and cardiopulmonary bypass. (Level of Difficulty: Intermediate.).
Assuntos
Coristoma/etiologia , Mucosa Olfatória/citologia , Paralisia/cirurgia , Transplante de Células-Tronco/efeitos adversos , Adulto , Vértebras Cervicais/lesões , Coristoma/complicações , Coristoma/radioterapia , Coristoma/cirurgia , Dor Crônica/etiologia , Dor Crônica/cirurgia , Fratura-Luxação/complicações , Humanos , Masculino , Paralisia/etiologia , Complicações Pós-Operatórias/radioterapia , Complicações Pós-Operatórias/cirurgia , Traumatismos da Medula Espinal/complicações , Fraturas da Coluna Vertebral/complicações , Transplante AutólogoRESUMO
We previously showed that APOBEC-mediated mutations in HIV CD8 T-cell epitopes generally reduce recognition by CD8 T cells. Here, we examined this effect in the context of histocompatibility-linked leukocyte antigen (HLA) alleles differentially associated with disease progression rates. For HLA-B57-restricted epitopes, APOBEC mutations generally diminished CD8 T cell recognition. Conversely, recognition of HLA-B35-restricted epitopes was consistently enhanced. For epitopes that can be presented by either HLA-A2 or A3, the same APOBEC mutation had differential effects on CD8 T cell recognition, depending on the individual's HLA genotype. The pattern of HLA dependence provides additional evidence that APOBEC action is channeled toward cytotoxic CD8 T-cell escape.
Assuntos
Citidina Desaminase/metabolismo , Epitopos/imunologia , Regulação Enzimológica da Expressão Gênica/imunologia , Antígenos HLA/imunologia , Desaminase APOBEC-1 , Linfócitos T CD8-Positivos , Citidina Desaminase/genética , Antígenos HLA/genética , Antígenos HLA/metabolismo , Humanos , MutaçãoRESUMO
BACKGROUND: Online content is a primary source of healthcare information for internet-using adults and a rich resource for health researchers. This paper explores the methodological and ethical issues of engaging in health research using social media. METHODS: A metamethod was performed on systematically selected studies that used social media as a data source for exploring public awareness and beliefs about Human Papillomaviruses (HPV) and HPV vaccination. Seven electronic databases were searched using a variety of search terms identified for each of three concepts: social media, HPV vaccine, and research method. Abstracts were assessed for eligibility of inclusion; six studies met the eligibility criteria and were subjected to content analysis. A 10-item coding scheme was developed to assess the clarity, congruence and transparency of research design, epistemological and methodological underpinnings and ethical considerations. RESULTS: The designs of the six selected studies were sound, although most studies could have been more transparent about how they built in rigor to ensure the trustworthiness and credibility of findings. Statistical analysis that intended to measure trends and patterns did so without the benefit of randomized sampling and other design elements for ensuring generalizability or reproducibility of findings beyond the specified virtual community. Most researchers did not sufficiently engage virtual users in the research process or consider the risk of privacy incursion. Most studies did not seek ethical approval from an institutional research board or permission from host websites or web service providers. CONCLUSIONS: The metamethod exposed missed opportunities for using the dialogical character of social media as well as a lack of attention to the unique ethical issues inherent in operating in a virtual community where social boundaries and issues of public and private are ambiguous. This suggests the need for more self-conscious and ethical research practices when using social media as a data source. Given the relative newness of virtual communities, researchers and ethics review boards must work together to develop expertise in evaluating the design of studies undertaken with virtual communities. We recommend that the principles of concern for welfare, respect for person, and justice to be applied in research using social media.
Assuntos
Pesquisa Biomédica/ética , Vacinas contra Papillomavirus/uso terapêutico , Projetos de Pesquisa , Mídias Sociais/ética , HumanosRESUMO
Due to constitutive expression in cells targeted by human immunodeficiency virus (HIV), and immediate mode of viral restriction upon HIV entry into the host cell, APOBEC3G (A3G) and APOBEC3F (A3F) have been considered primarily as agents of innate immunity. Recent bioinformatic and mouse model studies hint at the possibility that mutation of the HIV genome by these enzymes may also affect adaptive immunity but whether this occurs in HIV-infected individuals has not been examined. We evaluated whether APOBEC-mediated mutations within common HIV CD8+ T cell epitopes can potentially enhance or diminish activation of HIV-specific CD8+ T cells from infected individuals. We compared ex vivo activation of CD8+ T lymphocytes from HIV-infected individuals by wild type HIV peptide epitopes and synthetic variants bearing simulated A3G/F-induced mutations by measuring interferon-γ (IFN-γ) production. We found that A3G/F-induced mutations consistently diminished HIV-specific CD8+ T cell responses against the common epitopes we tested. If this reflects a significant trend in vivo, then adaptation by HIV to enrich sequences that are favored for mutation by A3G/F (A3G/F hotspots) in portions of its genome that encode immunogenic CD8+ T cell epitopes would favor CTL escape. Indeed, we found the most frequently mutated A3G motif (CCC) is enriched up to 6-fold within viral genomic sequences encoding immunodominant CD8+ T cell epitopes in Gag, Pol and Nef. Within each gene, A3G/F hotspots are more abundant in sequences encoding epitopes that are commonly recognized due to their HLA restriction. Thus, in our system, mutations of the HIV genome, mimicking A3G/F activity, appeared to abrogate or severely reduce CTL recognition. We suggest that the physiological significance of this potential effect in facilitating CTL escape is echoed in the adaptation of the HIV genome to enrich A3G/F hotspots in sequences encoding CTL epitopes that are more immunogenic at the population level.
Assuntos
Linfócitos T CD8-Positivos/virologia , Citidina Desaminase/genética , Citosina Desaminase/genética , Genoma Viral , HIV-1/genética , Desaminase APOBEC-3G , Biologia Computacional , DNA/genética , Epitopos/genética , Variação Genética , Antígenos HLA/genética , Humanos , Imunidade Inata , Interferon gama/metabolismo , Mutação , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genéticaRESUMO
The enzyme APOBEC3G (A3G) mutates the human immunodeficiency virus (HIV) genome by converting deoxycytidine (dC) to deoxyuridine (dU) on minus strand viral DNA during reverse transcription. A3G restricts viral propagation by degrading or incapacitating the coding ability of the HIV genome. Thus, this enzyme has been perceived as an innate immune barrier to viral replication whilst adaptive immunity responses escalate to effective levels. The discovery of A3G less than a decade ago led to the promise of new anti-viral therapies based on manipulation of its cellular expression and/or activity. The rationale for therapeutic approaches has been solidified by demonstration of the effectiveness of A3G in diminishing viral replication in cell culture systems of HIV infection, reports of its mutational footprint in virions from patients, and recognition of its unusually robust enzymatic potential in biochemical studies in vitro. Despite its effectiveness in various experimental systems, numerous recent studies have shown that the ability of A3G to combat HIV in the physiological setting is severely limited. In fact, it has become apparent that its mutational activity may actually enhance viral fitness by accelerating HIV evolution towards the evasion of both anti-viral drugs and the immune system. This body of work suggests that the role of A3G in HIV infection is more complex than heretofore appreciated and supports the hypothesis that HIV has evolved to exploit the action of this host factor. Here we present an overview of recent data that bring to light historical overestimation of A3G's standing as a strictly anti-viral agent. We discuss the limitations of experimental systems used to assess its activities as well as caveats in data interpretation.