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1.
Mol Cell ; 82(2): 447-462.e6, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34856123

RESUMO

Quantitative subcellular metabolomic measurements can explain the roles of metabolites in cellular processes but are subject to multiple confounding factors. We developed stable isotope labeling of essential nutrients in cell culture-subcellular fractionation (SILEC-SF), which uses isotope-labeled internal standard controls that are present throughout fractionation and processing to quantify acyl-coenzyme A (acyl-CoA) thioesters in subcellular compartments by liquid chromatography-mass spectrometry. We tested SILEC-SF in a range of sample types and examined the compartmentalized responses to oxygen tension, cellular differentiation, and nutrient availability. Application of SILEC-SF to the challenging analysis of the nuclear compartment revealed a nuclear acyl-CoA profile distinct from that of the cytosol, with notable nuclear enrichment of propionyl-CoA. Using isotope tracing, we identified the branched chain amino acid isoleucine as a major metabolic source of nuclear propionyl-CoA and histone propionylation, thus revealing a new mechanism of crosstalk between metabolism and the epigenome.


Assuntos
Acil Coenzima A/metabolismo , Compartimento Celular , Núcleo Celular/metabolismo , Metabolismo Energético , Histonas/metabolismo , Metabolômica , Processamento de Proteína Pós-Traducional , Animais , Diferenciação Celular , Cromatografia Líquida , Citosol/metabolismo , Epigênese Genética , Células Hep G2 , Humanos , Isoleucina , Metaboloma , Camundongos , Mitocôndrias/metabolismo , Oxigênio/metabolismo , Espectrometria de Massas por Ionização por Electrospray
2.
Annu Rev Cell Dev Biol ; 30: 23-37, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25000992

RESUMO

The physicist Ernest Rutherford said, "If your experiment needs statistics, you ought to have done a better experiment." Although this aphorism remains true for much of today's research in cell biology, a basic understanding of statistics can be useful to cell biologists to help in monitoring the conduct of their experiments, in interpreting the results, in presenting them in publications, and when critically evaluating research by others. However, training in statistics is often focused on the sophisticated needs of clinical researchers, psychologists, and epidemiologists, whose conclusions depend wholly on statistics, rather than the practical needs of cell biologists, whose experiments often provide evidence that is not statistical in nature. This review describes some of the basic statistical principles that may be of use to experimental biologists, but it does not cover the sophisticated statistics needed for papers that contain evidence of no other kind.


Assuntos
Biologia Celular , Estatística como Assunto , Causalidade , Interpretação Estatística de Dados , Probabilidade , Reprodutibilidade dos Testes , Projetos de Pesquisa , Distribuições Estatísticas
3.
Annu Rev Cell Dev Biol ; 30: 535-60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25062362

RESUMO

Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous.


Assuntos
Cães/genética , Genoma , Animais , Tamanho Corporal/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/veterinária , Cruzamento , Mapeamento Cromossômico , Modelos Animais de Doenças , Doenças do Cão/genética , Cães/anatomia & histologia , Cães/classificação , Extremidades/anatomia & histologia , Estudo de Associação Genômica Ampla , Glicoproteínas/genética , Glicoproteínas/fisiologia , Proteína HMGA2/genética , Proteína HMGA2/fisiologia , Cabelo/anatomia & histologia , Cardiopatias/genética , Cardiopatias/veterinária , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/veterinária , Osteossarcoma/genética , Osteossarcoma/veterinária , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Seleção Genética , Pele/anatomia & histologia , Crânio/anatomia & histologia , Proteína Smad2/genética , Proteína Smad2/fisiologia , Especificidade da Espécie , Cauda/anatomia & histologia
4.
CA Cancer J Clin ; 70(1): 47-70, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31815293

RESUMO

Historical advances in the care of patients with non-Hodgkin lymphoma (NHL) have been restricted largely to patients with B-cell lymphoma. The peripheral T-cell lymphomas (PTCLs), which are rare and heterogeneous in nature, have yet to experience the same degree of improvement in outcome over the past 20 to 30 years. It is estimated that there are approximately 80,000 and 14,000 cases, respectively, of NHL and Hodgkin lymphoma per year in the United States. As a subgroup of NHL, the PTCLs account for 6% to 10% of all cases of NHL, making them exceedingly rare. In addition, the World Health Organization 2017 classification describes 29 distinct subtypes of PTCL. This intrinsic diversity, coupled with its rarity, has stymied progress in the disease. In addition, most subtypes carry an inferior prognosis compared with their B-cell counterparts, an outcome largely attributed to the fact that most treatment paradigms for patients with PTCL have been derived from B-cell neoplasms, a radically different disease. In fact, the first drug ever approved for patients with PTCL was approved only a decade ago. The plethora of recent drug approvals in PTCL, coupled with a deeper understanding of the molecular pathogenesis of the disease, has stimulated the field to pursue new avenues of research that are now largely predicated on the development of novel, targeted small molecules, which include a host of epigenetic modifiers and biologics. There is an expectation these advances may begin to favorably challenge the chemotherapy paradigms that have been used in the T-cell malignancies.


Assuntos
Antineoplásicos/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Estadiamento de Neoplasias , Humanos , Linfoma de Células T Periférico/patologia , Prognóstico
5.
Proc Natl Acad Sci U S A ; 121(25): e2313193121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38857390

RESUMO

Renewable Portfolio Standards (RPSs) are one of the most prevalent and impactful clean energy policies implemented by states in the United States. This paper investigates the regional spillover effect of RPS policies using a directed dyad panel dataset of renewable electricity generation in US states from 1991 to 2021. Regional spillover effect is measured in two ways: by considering the influence of an RPS enacted in neighboring states and in states in the same regional transmission organization or independent system operator region. We use dyadic fixed effects estimation and conclude that the neighboring state's RPS stringency score is a strong determinant of a state's total renewable electricity generation. For states without an RPS, the positive influence of an RPS in a neighboring state is larger when the non-RPS state has more abundant renewable energy resources than the neighboring RPS state. Our findings suggest that past RPS policy evaluation research using a confined within-state focus may have underestimated the holistic impact of an RPS, as the impacts of an RPS policy can extend beyond the enacting state's borders. Overall, this study contributes to an improved understanding of the holistic impact of state RPS policies.

6.
Proc Natl Acad Sci U S A ; 120(14): e2205773119, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36972443

RESUMO

Plant genetic resources (PGR), including collections held in national and international gene banks, provide access to a wide array of genetic diversity and are critical to genomics research, conservation efforts, and applied breeding. Yet, there is a general lack of awareness in the research community about the rules and treaties that govern the use of PGR, about access and benefit sharing obligations contained in international treaties and/or national laws, and about how best to comply with potentially applicable requirements. This article provides a brief history and overview of three key international agreements, namely the Convention on Biological Diversity, the Nagoya Protocol, and the International Treaty on Plant Genetic Resources for Food and Agriculture, which collectively address responsibilities and obligations related to the use of much of the world's PGR. By highlighting the coverage and key considerations of each agreement, the article provides a guide for those who use PGR in plant genetics research to better understand when and how international agreements apply, and-where the rules are unclear-to suggest best practices for compliance with existing agreements.


Assuntos
Melhoramento Vegetal , Plantas , Plantas/genética , Cooperação Internacional , Alimentos , Biodiversidade
7.
Annu Rev Genet ; 51: 45-62, 2017 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-28853922

RESUMO

The standard genetic code (SGC) is virtually universal among extant life forms. Although many deviations from the universal code exist, particularly in organelles and prokaryotes with small genomes, they are limited in scope and obviously secondary. The universality of the code likely results from the combination of a frozen accident, i.e., the deleterious effect of codon reassignment in the SGC, and the inhibitory effect of changes in the code on horizontal gene transfer. The structure of the SGC is nonrandom and ensures high robustness of the code to mutational and translational errors. However, this error minimization is most likely a by-product of the primordial code expansion driven by the diversification of the repertoire of protein amino acids, rather than a direct result of selection. Phylogenetic analysis of translation system components, in particular aminoacyl-tRNA synthetases, shows that, at a stage of evolution when the translation system had already attained high fidelity, the correspondence between amino acids and cognate codons was determined by recognition of amino acids by RNA molecules, i.e., proto-tRNAs. We propose an experimentally testable scenario for the evolution of the code that combines recognition of amino acids by unique sites on proto-tRNAs (distinct from the anticodons), expansion of the code via proto-tRNA duplication, and frozen accident.


Assuntos
Biota/genética , Evolução Molecular , Código Genético , Genoma , Modelos Genéticos , Biossíntese de Proteínas , Aminoácidos/genética , Aminoácidos/metabolismo , Aminoacil-tRNA Sintetases/genética , Aminoacil-tRNA Sintetases/metabolismo , Anticódon/química , Anticódon/metabolismo , Códon/química , Códon/metabolismo , Extinção Biológica , Transferência Genética Horizontal , Filogenia , RNA de Transferência/genética , RNA de Transferência/metabolismo
8.
J Proteome Res ; 23(8): 3052-3063, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38533909

RESUMO

Quantitation of proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is complex, with a multiplicity of options ranging from label-free techniques to chemically and metabolically labeling proteins. Increasingly, for clinically relevant analyses, stable isotope-labeled (SIL) internal standards (ISs) represent the "gold standard" for quantitation due to their similar physiochemical properties to the analyte, wide availability, and ability to multiplex to several peptides. However, the purchase of SIL-ISs is a resource-intensive step in terms of cost and time, particularly for screening putative biomarker panels of hundreds of proteins. We demonstrate an alternative strategy utilizing nonhuman sera as the IS for quantitation of multiple human proteins. We demonstrate the effectiveness of this strategy using two high abundance clinically relevant analytes, vitamin D binding protein [Gc globulin] (DBP) and albumin (ALB). We extend this to three putative risk markers for cardiovascular disease: plasma protease C1 inhibitor (SERPING1), annexin A1 (ANXA1), and protein kinase, DNA-activated catalytic subunit (PRKDC). The results show highly specific, reproducible, and linear measurement of the proteins of interest with comparable precision and accuracy to the gold standard SIL-IS technique. This approach may not be applicable to every protein, but for many proteins it can offer a cost-effective solution to LC-MS/MS protein quantitation.


Assuntos
Espectrometria de Massa com Cromatografia Líquida , Espectrometria de Massas em Tandem , Animais , Humanos , Biomarcadores/sangue , Análise Custo-Benefício , Marcação por Isótopo/métodos , Espectrometria de Massa com Cromatografia Líquida/métodos , Peptídeos/química , Peptídeos/sangue , Peptídeos/análise , Proteômica/métodos , Proteômica/economia , Padrões de Referência , Reprodutibilidade dos Testes , Albumina Sérica/análise , Albumina Sérica/química , Espectrometria de Massas em Tandem/métodos , Tripsina/química , Tripsina/metabolismo , Proteína de Ligação a Vitamina D/sangue , Proteína de Ligação a Vitamina D/química
9.
Stroke ; 55(8): 2103-2112, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39038099

RESUMO

BACKGROUND: Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays. METHODS: We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center. RESULTS: Between January 1, 2018, and December 31, 2021, a total of 6803 patients received EVT at 20 participating centers (median age, 73 years; 50% women; and 50% treated with intravenous thrombolysis). Patients transferred for EVT (n=3376) had lower rates of M2 occlusion (22% versus 27%) and higher rates of basilar occlusion (9% versus 5%) compared with those patients presenting directly at an EVT-capable center (n=3373). Door-to-needle times were shorter in patients receiving intravenous thrombolysis before transfer compared with those presenting directly to an EVT center (32 versus 36 minutes). Patients transferred for EVT had shorter door-to-arterial access times (37 versus 87 minutes) but longer last seen normal-to-arterial access times (322 versus 181 minutes) compared with those presenting directly to an EVT-capable center. No differences in arterial access-to-reperfusion times, successful reperfusion rates (85% versus 86%), or adverse periprocedural events were found between the 2 groups. Patients transferred to EVT centers had a similar likelihood for good functional outcome (modified Rankin Scale score, 0-2; 41% versus 43%; risk ratio, 0.95 [95% CI, 0.88-1.01]; adjusted risk ratio, 0.98 [95% CI, 0.91-1.05]) and a higher risk for all-cause mortality at 90 days (29% versus 25%; risk ratio, 1.15 [95% CI, 1.05-1.27]; adjusted risk ratio, 1.14 [95% CI, 1.03-1.28]) compared with patients presenting directly to an EVT center. CONCLUSIONS: Patients transferred for EVT experience significant delays from the time they were last seen normal to the initiation of EVT.


Assuntos
Procedimentos Endovasculares , AVC Isquêmico , Transferência de Pacientes , Sistema de Registros , Trombectomia , Tempo para o Tratamento , Humanos , Feminino , Masculino , Idoso , Procedimentos Endovasculares/métodos , Canadá/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Trombectomia/métodos , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica/métodos , Resultado do Tratamento
10.
Rep Prog Phys ; 87(8)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38821047

RESUMO

This is a review article about neutrino mass and mixing and flavour model building strategies based on modular symmetry. After a brief survey of neutrino mass and lepton mixing, and various Majorana seesaw mechanisms, we construct and parameterise the lepton mixing matrix and summarise the latest global fits, before discussing the flavour problem of the Standard Model. We then introduce some simple patterns of lepton mixing, introduce family (or flavour) symmetries, and show how they may be applied to direct, semi-direct and tri-direct CP models, where the simple patterns of lepton mixing, or corrected versions of them, may be enforced by the full family symmetry or a part of it, leading to mixing sum rules. We then turn to the main subject of this review, namely a pedagogical introduction to modular symmetry as a candidate for family symmetry, from the bottom-up point of view. After an informal introduction to modular symmetry, we introduce the modular group, and discuss its fixed points and residual symmetry, assuming supersymmetry throughout. We then introduce finite modular groups of levelNand modular forms with integer or rational modular weights, corresponding to simple geometric groups or their double or metaplectic covers, including the most general finite modular groups and vector-valued modular forms, with detailed results forN=2,3,4,5. The interplay between modular symmetry and generalized CP symmetry is discussed, deriving CP transformations on matter multiplets and modular forms, highlighting the CP fixed points and their implications. In general, compactification of extra dimensions generally leads to a number of moduli, and modular invariance with factorizable and non-factorizable multiple moduli based on symplectic modular invariance and automorphic forms is reviewed. Modular strategies for understanding fermion mass hierarchies are discussed, including the weighton mechanism, small deviations from fixed points, and texture zeroes. Then examples of modular models are discussed based on single modulusA4models, a minimalS4'model of leptons (and quarks), and a multiple moduli model based on threeS4groups capable of reproducing the Littlest Seesaw model. We then extend the discussion to include Grand Unified Theories based on modular (flipped)SU(5) andSO(10). Finally we briefly mention some issues related to top-down approaches based on string theory, including eclectic flavour symmetry and moduli stabilisation, before concluding.

11.
Am J Epidemiol ; 193(3): 548-560, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-37939113

RESUMO

In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501-510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Resultados Negativos , Saliva , Nasofaringe
12.
Cancer ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302215

RESUMO

Lung cancer is the leading cause of cancer death in the United States and across the world. The American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) was established in 2017 as a consortium of public, private, and voluntary organizations with a mission to lower the impact of lung cancer via prevention, early detection, and optimal therapy. The ACS NLCRT supports a comprehensive scope of work that covers the lung cancer continuum, from risk reduction, tobacco prevention and control, and early detection (screening and incidental lung nodule management) to guideline-based staging, biomarker testing, treatment, and survivorship and overarching issues such as stigma and nihilism, health equity, and tactical approaches such as state coalition efforts and policy initiatives. Applying a multidimensional and multisector approach, over 220 public, private, and government agency member organizations and 250 volunteer experts, patients, and caregiver advocate representatives collaborate to address challenges across the lung cancer continuum by catalyzing action to conceive, build, and strengthen innovative solutions. The wide-ranging membership allows the ACS NLCRT to harness the collective power and expertise of the entire lung cancer community by connecting leaders, communities, and systems to improve equity and access. These national, state, and local relationships provide partnerships for the dissemination of ACS NLCRT-developed tools and resources. This article describes the ACS NLCRT and introduces the series of accompanying and future articles that together make up the ACS NLCRT strategic plan, which provides a roadmap for future research, investment, and collaboration to reduce lung cancer mortality and lung cancer-related stigma and enhance survivorship.

13.
Cancer ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302235

RESUMO

More than a decade has passed since researchers in the Early Lung Cancer Action Project and the National Lung Screening Trial demonstrated the ability to save lives of high-risk individuals from lung cancer through regular screening by low dose computed tomography scan. The emergence of the most recent findings in the Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) further strengthens and expands on this evidence. These studies demonstrate the benefit of integrating lung cancer screening into clinical practice, yet lung cancer continues to lead cancer mortality rates in the United States. Fewer than 20% of screen eligible individuals are enrolled in lung cancer screening, leaving millions of qualified individuals without the standard of care and benefit they deserve. This article, part of the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) strategic plan, examines the impediments to successful adoption, dissemination, and implementation of lung cancer screening. Proposed solutions identified by the ACS NLCRT Implementation Strategies Task Group and work currently underway to address these challenges to improve uptake of lung cancer screening are discussed. PLAIN LANGUAGE SUMMARY: The evidence supporting the benefit of lung cancer screening in adults who previously or currently smoke has led to widespread endorsement and coverage by health plans. Lung cancer screening programs should be designed to promote high uptake rates of screening among eligible adults, and to deliver high-quality screening and follow-up care.

14.
Am J Transplant ; 24(2): 190-212, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37704059

RESUMO

The Organ Procurement and Transplantation Network conducts a robust death verification process when augmenting the United States transplant registry with external sources of data. Process enhancements added over 35,000 externally verified deaths across waitlist candidates and transplant recipients for all organs beginning in April 2022. Ninety-four percent of added posttransplant deaths occurred beyond 5 years posttransplant, and over 74% occurred beyond 10 years. Deceased donor solid organ recipients transplanted from January 1, 2010, through October 31, 2020, were analyzed from January and July 2022 Organ Procurement and Transplantation Network Standard Transplant Analysis and Research and the Scientific Registry of Transplant Recipients Standard Analysis Files to quantify the impact of including vs excluding unverified deaths (not releasable to researchers) on posttransplant patient survival estimates. Across all organs, 1- and 5-year posttransplant survival rates were not substantially impacted; meaningful differences were observed in 10-year survival among kidney recipients. These findings bear important implications for anyone who utilized transplant registry data to examine long-term outcomes prior to the updated verification process. Users of transplant surveillance data should interpret results of long-term outcomes cautiously, particularly differences across subpopulations, and the transplant community should identify ways to improve data quality and minimize the reporting burden on transplant institutions.


Assuntos
Obtenção de Tecidos e Órgãos , Humanos , Estados Unidos/epidemiologia , Sistema de Registros , Transplantados , Taxa de Sobrevida , Doadores de Tecidos
15.
Biochem Biophys Res Commun ; 690: 149311, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016246

RESUMO

Carbon dots (CDs) are an emerging class of fluorescent quantum dot nanomaterials that have attracted considerable scientific attention for biomedical or bioimaging applications due to their physicochemical and biochemical properties. With the emergence of massive novel synthetic CDs applying to biomedical fields of science, evaluating their biosafety before any biological application is essential. However, there is no universal protocol or routine procedures for toxicity detection and biosafety assessment of CDs in general biological environments. Herein, we provide an ideal and fast operating system to detect the biotoxicity of CDs, which has been preliminary practiced. Briefly, the obtained CDs will be evaluated by in vitro cytotoxicity assay using cell counting kit-8, lactate dehydrogenase assay kit, and flow cytometry. Meanwhile, the model creature zebrafish is employed to perform in vivo evaluation by measuring body length, hatching rate, heart rate, and morphological observation. Our operating procedure condenses previous scattered biosafety detection methods into a rapid standard evaluation protocol that can be applied to early biotoxicity screening of CDs. This protocol will accelerate CDs biological exploitation and guide future industrialized biosafety assessment in large-scale applications.


Assuntos
Nanoestruturas , Pontos Quânticos , Animais , Carbono/toxicidade , Carbono/química , Peixe-Zebra , Pontos Quânticos/toxicidade , Pontos Quânticos/química , Corantes Fluorescentes/química
16.
Mod Pathol ; 37(4): 100439, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38286221

RESUMO

This work puts forth and demonstrates the utility of a reporting framework for collecting and evaluating annotations of medical images used for training and testing artificial intelligence (AI) models in assisting detection and diagnosis. AI has unique reporting requirements, as shown by the AI extensions to the Consolidated Standards of Reporting Trials (CONSORT) and Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklists and the proposed AI extensions to the Standards for Reporting Diagnostic Accuracy (STARD) and Transparent Reporting of a Multivariable Prediction model for Individual Prognosis or Diagnosis (TRIPOD) checklists. AI for detection and/or diagnostic image analysis requires complete, reproducible, and transparent reporting of the annotations and metadata used in training and testing data sets. In an earlier work by other researchers, an annotation workflow and quality checklist for computational pathology annotations were proposed. In this manuscript, we operationalize this workflow into an evaluable quality checklist that applies to any reader-interpreted medical images, and we demonstrate its use for an annotation effort in digital pathology. We refer to this quality framework as the Collection and Evaluation of Annotations for Reproducible Reporting of Artificial Intelligence (CLEARR-AI).


Assuntos
Inteligência Artificial , Lista de Checagem , Humanos , Prognóstico , Processamento de Imagem Assistida por Computador , Projetos de Pesquisa
17.
Magn Reson Med ; 92(1): 69-81, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38308141

RESUMO

PURPOSE: The purpose of the study is to identify differences between axisymmetric diffusion kurtosis imaging (DKI) and standard DKI, their consequences for biophysical parameter estimates, and the protocol choice influence on parameter estimation. METHODS: Noise-free and noisy, synthetic diffusion MRI human brain data is simulated using standard DKI for a standard and the fast "199" acquisition protocol. First the noise-free "baseline" difference between both DKI models is estimated and the influence of fiber complexity is investigated. Noisy data is used to establish the signal-to-noise ratio at which the baseline difference exceeds noise variability. The influence of protocol choices and denoising is investigated. The five axisymmetric DKI tensor metrics (AxTM), the parallel and perpendicular diffusivity and kurtosis and mean of the kurtosis tensor are used to compare both DKI models. Additionally, the baseline difference is also estimated for the five parameters of the WMTI-Watson model. RESULTS: The parallel and perpendicular kurtosis and all of the WMTI-Watson parameters had large baseline differences. Using a Westin or FA mask reduced the number of voxels with large baseline difference, that is, by selecting voxels with less complex fibers. For the noisy data, precision was worsened by the fast "199" protocol but adaptive denoising can help counteract these effects. CONCLUSION: For the diffusivities and mean of the kurtosis tensor, axisymmetric DKI with a standard protocol delivers similar results as standard DKI. Fiber complexity is one main driver of the baseline differences. Using the "199" protocol worsens precision in noisy data but adaptive denoising mitigates these effects.


Assuntos
Encéfalo , Razão Sinal-Ruído , Humanos , Encéfalo/diagnóstico por imagem , Algoritmos , Imagem de Tensor de Difusão/métodos , Processamento de Imagem Assistida por Computador/métodos , Simulação por Computador , Reprodutibilidade dos Testes , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos
18.
Genet Med ; 26(8): 101145, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38836869

RESUMO

Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy causing progressive muscle loss and weakness. Although clinical features can manifest at any age, it is the most common form of muscular dystrophy with onset in adulthood. DM1 is an autosomal dominant condition, resulting from an unstable CTG expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. The age of onset and the severity of the phenotype are roughly correlated with the size of the CTG expansion. Multiple methodologies can be used to diagnose affected individuals with DM1, including polymerase chain reaction, Southern blot, and triplet repeat-primed polymerase chain reaction. Recently, triplet repeat interruptions have been described, which may affect clinical outcomes of a fully-variable allele in DMPK. This document supersedes the Technical Standards and Guidelines for Myotonic Dystrophy originally published in 2009 and reaffirmed in 2015. It is designed for genetic testing professionals who are already familiar with the disease and the methods of analysis.


Assuntos
Testes Genéticos , Genética Médica , Genômica , Distrofia Miotônica , Miotonina Proteína Quinase , Expansão das Repetições de Trinucleotídeos , Distrofia Miotônica/genética , Distrofia Miotônica/diagnóstico , Humanos , Miotonina Proteína Quinase/genética , Testes Genéticos/normas , Testes Genéticos/métodos , Genética Médica/normas , Genética Médica/métodos , Expansão das Repetições de Trinucleotídeos/genética , Genômica/métodos , Genômica/normas , Estados Unidos
19.
Mass Spectrom Rev ; 42(3): 1008-1031, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-34549449

RESUMO

Activity assays are indispensable for studying biochemical properties of enzymes. The purposes of measuring activity are wide ranging from a simple detection of the presence of an enzyme to kinetic experiments evaluating the substrate specificity, reaction mechanisms, and susceptibility to inhibitors. Common activity assay methods include spectroscopy, electrochemical sensors, or liquid chromatography coupled with various detection techniques. This review focuses on the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a growing and modern alternative, which offers high speed of analysis, sensitivity, versatility, possibility of automation, and cost-effectiveness. It may reveal reaction intermediates, side products or measure more enzymes at once. The addition of an internal standard or calculating the ratios of the substrate and product peak intensities and areas overcome the inherent inhomogeneous distribution of analyte and matrix in the sample spot, which otherwise results in a poor reproducibility. Examples of the application of MALDI-TOF MS for assaying hydrolases (including peptidases and ß-lactamases for antibiotic resistance tests) and other enzymes are provided. Concluding remarks summarize advantages and challenges coming from the present experience, and draw future perspectives such as a screening of large libraries of chemical compounds for their substrate or inhibitory properties towards enzymes.


Assuntos
Lasers , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Reprodutibilidade dos Testes , Cromatografia Líquida , Cinética
20.
Ann Surg Oncol ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112735

RESUMO

PURPOSE: This study was designed to assess the advantages of radical antegrade modular pancreatosplenectomy (RAMPS) over standard retrograde pancreatosplenectomy (SPRS) in terms of disease-free survival (DFS) by comparing clinical outcomes. METHODS: Clinical data from 154 patients who underwent distal pancreatectomy at Tianjin Medical University Cancer Institute and Hospital between January 2015 and August 2018 were collected. We compared the preoperative conditions, postoperative complications, and survival outcomes of patients who underwent two different surgical procedures. By creating a LASSO-Cox model, we determined the parameters affecting DFS and the risk ratios of the two surgical procedures on DFS. RESULTS: The R0 resection rate (85.23% vs. 68.18%, P = 0.003), negative posterior margin rate (96.59% vs. 75.76%, P < 0.001), and tumor bed recurrence rate (15.29% vs. 40.00%, P = 0.001) significantly differed between the RAMPS and SPRS groups. The 1-, 3-, and 5-year survival and DFS rates of the RAMPS group were significantly better than those of the SPRS group (P < 0.05). Disease-free survival analysis based on Kaplan-Meier curves revealed that RAMPS was superior to SPRS (P < 0.001). CONCLUSIONS: We recommend RAMPS as the preferred procedure for treating ductal adenocarcinoma of the pancreatic body and tail due to its enhanced lymph node repair capacity and visualization of posterior pancreatic sections, which can increase DFS in patients.

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