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Nature ; 613(7943): 355-364, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36599988


DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2-5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

Células , Metilação de DNA , Epigênese Genética , Epigenoma , Humanos , Linhagem Celular , Células/classificação , Células/metabolismo , Cromatina/genética , Cromatina/metabolismo , Ilhas de CpG/genética , DNA/genética , DNA/metabolismo , Desenvolvimento Embrionário , Elementos Facilitadores Genéticos , Especificidade de Órgãos , Proteínas do Grupo Polycomb/metabolismo , Sequenciamento Completo do Genoma
Nature ; 611(7934): 24-27, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36323815
Nefrología (Madrid) ; 42(6): 645-655, nov.-dic. 2022. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-212593


Aunque el fósforo es un elemento indispensable para la vida, en la naturaleza no se encuentra en estado nativo sino combinado en forma de fosfatos inorgánicos (PO43−), con niveles plasmáticos estrechamente regulados que se asocian a efectos deletéreos y mortalidad cuando estos se encuentran fuera de la normalidad. El interés creciente sobre el acúmulo de PO43− en la fisiopatología humana se originó en el papel que se le atribuyó en la patogenia del hiperparatiroidismo secundario a la enfermedad renal crónica. En este artículo revisamos los mecanismos por los cuales se justificaba dicho efecto y conmemoramos la importante contribución de un grupo español liderado por el Dr. M. Rodríguez, ahora hace justo 25 años, cuando demostraron por primera vez el efecto directo del PO43− sobre la regulación de la síntesis y secreción de hormona paratiroidea (manteniendo la integridad estructural de las glándulas paratiroides en su nuevo modelo experimental. Además de demostrar la importancia del ácido araquidónico (AA) y la vía de la fosfolipasa A2-AA como mediadora de respuestas en la glándula paratiroidea, estos hallazgos fueron predecesores de la reciente descripción del importante papel del PO43− sobre la actividad del receptor-sensor de calcio y alimentaron asimismo diversas líneas de investigación sobre la importancia de la sobrecarga de PO43−, no solo en la fisiopatología del hiperparatiroidismo secundario sino también en su papel patogénico sistémico. (AU)

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO43−), with tightly regulated plasma levels that are associated with deleterious effects and mortality when these are out of bounds. The growing interest in the accumulation of PO43− in human pathophysiology originated in its attributed role in the pathogenesis of secondary hyperparathyroidism in chronic kidney disease. In this article, we review the mechanisms by which this effect was justified and we commemorate the important contribution of a Spanish group led by Dr. M. Rodríguez, just 25 years ago, when they first demonstrated the direct effect of PO43− on the regulation of the synthesis and secretion of parathyroid hormone by maintaining the structural integrity of the parathyroid glands in their original experimental model. In addition to demonstrating the importance of arachidonic acid (AA) and the phospholipase A2-AA pathway as a mediator of parathyroid gland response, these findings were predecessors of the recent description of the important role of PO43− on the activity of the calcium sensor-receptor, and also fueled various lines of research on the importance of PO43− overload not only for the pathophysiology of secondary hyperparathyroidism but also of its systemic pathogenic role. (AU)

Humanos , Fósforo , Células , Hormônio Paratireóideo , Fosfatos , Distúrbio Mineral e Ósseo na Doença Renal Crônica , Glândulas Paratireoides
J Vis Exp ; (186)2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-36121285


Stimulated Raman scattering (SRS) microscopy is a label-free chemical imaging technology. Live-cell imaging with SRS has been demonstrated for many biological and biomedical applications. However, long-term time-lapse SRS imaging of live cells has not been widely adopted. SRS microscopy often uses a high numerical aperture (NA) water-immersion objective and a high NA oil-immersion condenser to achieve high-resolution imaging. In this case, the gap between the objective and the condenser is only a few millimeters. Therefore, most commercial stage-top environmental chambers cannot be used for SRS imaging because of their large thickness with a rigid glass cover. This paper describes the design and fabrication of a flexible chamber that can be used for time-lapse live-cell imaging with transmitted SRS signal detection on an upright microscope frame. The flexibility of the chamber is achieved by using a soft material - a thin natural rubber film. The new enclosure and chamber design can be easily added to an existing SRS imaging setup. The testing and preliminary results demonstrate that the flexible chamber system enables stable, long-term, time-lapse SRS imaging of live cells, which can be used for various bioimaging applications in the future.

Células/citologia , Microscopia Óptica não Linear/métodos , Análise Espectral Raman/métodos , Imagem com Lapso de Tempo/métodos , Animais , Células/ultraestrutura , Humanos , Microscopia Óptica não Linear/instrumentação , Análise Espectral Raman/normas , Imagem com Lapso de Tempo/instrumentação , Imagem com Lapso de Tempo/normas , Água
Bioinformatics ; 38(Supplement_2): ii148-ii154, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36124797


MOTIVATION: A wide variety of experimental methods are available to characterize different properties of single cells in a complex biosample. However, because these measurement techniques are typically destructive, researchers are often presented with complementary measurements from disjoint subsets of cells, providing a fragmented view of the cell's biological processes. This creates a need for computational tools capable of integrating disjoint multi-omics data. Because different measurements typically do not share any features, the problem requires the integration to be done in unsupervised fashion. Recently, several methods have been proposed that project the cell measurements into a common latent space and attempt to align the corresponding low-dimensional manifolds. RESULTS: In this study, we present an approach, Synmatch, which produces a direct matching of the cells between modalities by exploiting information about neighborhood structure in each modality. Synmatch relies on the intuition that cells which are close in one measurement space should be close in the other as well. This allows us to formulate the matching problem as a constrained supermodular optimization problem over neighborhood structures that can be solved efficiently. We show that our approach successfully matches cells in small real multi-omics datasets and performs favorably when compared with recently published state-of-the-art methods. Further, we demonstrate that Synmatch is capable of scaling to large datasets of thousands of cells. AVAILABILITY AND IMPLEMENTATION: The Synmatch code and data used in this manuscript are available at

Arch. latinoam. nutr ; 72(3): 205-217, sept. 2022. ilus, tab, graf
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1399287


Las catequinas del té verde (Camellia sinensis) (CTV) presentan efectos benéficos para la salud asociados a su potencial antioxidante. Por otra parte, el estrés oxidante es una de las vías de inducción de daño genotóxico. De ahí que, en la presente revisión se realizó un análisis de los efectos antigenotóxicos y genotóxicos de las CTV, haciendo énfasis en las vías implicadas en estos procesos y sus efectos en la salud. Se realizó una revisión de artículos indexados en las bases de datos de PubMed® y Science Direct® (2021) con las palabras clave "green tea" y "green tea catechins". Se delimitaron los estudios utilizando los operadores booleanos "AND", "OR" y "NOT" ("antigenotoxic", "genotoxic", "antioxidant" y "prooxidant"). En su mayoría se consideraron las publicaciones del 2016 al 2021. Se observó que los efectos benéficos en la salud de las CTV están relacionados con: a) su actividad antioxidante mediante la captura, inhibición y prevención de la formación de las especies reactivas de oxígeno; b) la regulación del sistema antioxidante endógeno; c) la activación de los mecanismos de reparación al contribuir en la eliminación del aducto 8-hidroxi-2'-desoxiguanosina; d) la inducción de apoptosis en células con daño al ADN; y e) la inhibición de la inflamación relacionada con su actividad antiapoptótica. Si bien, en algunos de los estudios se reportaron efectos genotóxicos, estos a su vez contribuyeron en la eliminación de células con daño genético, por lo que, no se puede considerar del todo a la actividad genotóxica de las CTV como perjudiciales para la salud(AU)

The green tea catechins (Camellia sinensis) (CTV) have beneficial effects for health associated with their antioxidant potential. Moreover, oxidative stress is one of the pathways for inducing genotoxic damage. Hence, in this review, an analysis of the antigenotoxic and genotoxic effects of CTV was carried out, emphasizing the pathways involved in these processes and their effects on health. A review of articles indexed in the PubMed® and ScienceDirect® (2021) databases with the keywords "green tea" and "green tea catechins" was carried out. Studies were delimited using the Boolean operators "AND", "OR" and "NOT" ("antigenotoxic", "genotoxic", "antioxidant" and "prooxidant"). For the most part, publications from 2016 to 2021 were considered. It was observed that the beneficial health effects of CTVs are related to: a) their antioxidant activity through the capture, inhibition and prevention of the formation of reactive oxygen species; b) the regulation of the endogenous antioxidant system; c) the activation of the repair mechanisms by contributing to the elimination of the 8-hydroxy-2'-deoxyguanosine adduct; d) the induction of apoptosis in cells with DNA damage; and e) the inhibition of inflammation related to its antiapoptotic activity. Although some of the studies reported genotoxic effects, these in turn contributed to the elimination of cells with genetic damage. Therefore, the genotoxic activity of CTV cannot be considered as harmful to health

Chá , Catequina/análise , Estresse Oxidativo , Publicações , Células , PubMed , Antioxidantes
Contrast Media Mol Imaging ; 2022: 7355233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935314


This exploration is to solve the efficiency and accuracy of cell recognition in biological experiments. Neural network technology is applied to the research of cell image recognition. The cell image recognition problem is solved by constructing an image recognition algorithm. First, with an in-depth understanding of computer functions, as a basic intelligent algorithm, the artificial neural network (ANN) is widely used to solve the problem of image recognition. Recently, the backpropagation neural network (BPNN) algorithm has developed into a powerful pattern recognition tool and has been widely used in image edge detection. Then, the structural model of BPNN is introduced in detail. Given the complexity of cell image recognition, an algorithm based on the ANN and BPNN is used to solve this problem. The BPNN algorithm has multiple advantages, such as simple structure, easy hardware implementation, and good learning effect. Next, an image recognition algorithm based on the BPNN is designed and the image recognition process is optimized in combination with edge computing technology to improve the efficiency of algorithm recognition. The experimental results show that compared with the traditional image pattern recognition algorithm, the recognition accuracy of the designed algorithm for cell images is higher than 93.12%, so it has more advantages for processing the cell image algorithm. The results show that the BPNN edge computing can improve the scientific accuracy of cell recognition results, suggesting that edge computing based on the BPNN has a significant practical value for the research and application of cell recognition.

Algoritmos , Células , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes
Proc Natl Acad Sci U S A ; 119(35): e2200741119, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36001689


The next robotics frontier will be led by biohybrids. Capable biohybrid robots require microfluidics to sustain, improve, and scale the architectural complexity of their core ingredient: biological tissues. Advances in microfluidics have already revolutionized disease modeling and drug development, and are positioned to impact regenerative medicine but have yet to apply to biohybrids. Fusing microfluidics with living materials will improve tissue perfusion and maturation, and enable precise patterning of sensing, processing, and control elements. This perspective suggests future developments in advanced biohybrids.

Materiais Biomiméticos , Células , Microfluídica , Robótica
Proc Natl Acad Sci U S A ; 119(28): e2201250119, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35867744


Phase separation has emerged as an essential concept for the spatial organization inside biological cells. However, despite the clear relevance to virtually all physiological functions, we understand surprisingly little about what phases form in a system of many interacting components, like in cells. Here we introduce a numerical method based on physical relaxation dynamics to study the coexisting phases in such systems. We use our approach to optimize interactions between components, similar to how evolution might have optimized the interactions of proteins. These evolved interactions robustly lead to a defined number of phases, despite substantial uncertainties in the initial composition, while random or designed interactions perform much worse. Moreover, the optimized interactions are robust to perturbations, and they allow fast adaption to new target phase counts. We thus show that genetically encoded interactions of proteins provide versatile control of phase behavior. The phases forming in our system are also a concrete example of a robust emergent property that does not rely on fine-tuning the parameters of individual constituents.

Condensados Biomoleculares , Células , Fenômenos Físicos , Modelos Teóricos , Proteínas
Science ; 376(6594): eabl4896, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35549404


Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

Atlas como Assunto , Células , Especificidade de Órgãos , Splicing de RNA , Análise de Célula Única , Transcriptoma , Linfócitos B/metabolismo , Células/metabolismo , Humanos , Especificidade de Órgãos/genética , Linfócitos T/metabolismo
Proc Natl Acad Sci U S A ; 119(22): e2201644119, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35605126


Spatial resolution in MRI is ultimately limited by the signal detection sensitivity of NMR, since resolution equal to ρiso in all three dimensions requires the detection of NMR signals from a volume ρiso3. With inductively detected NMR at room temperature, it has therefore proven difficult to achieve isotropic resolution better than ρiso = 3.0 µm, even with radio-frequency microcoils, optimized samples, high magnetic fields, optimized pulse sequence methods, and data acquisition times around 60 h. Here we show that spatial resolution can be improved and data acquisition times can be reduced substantially by performing MRI measurements at 5 K and using dynamic nuclear polarization (DNP) to enhance sensitivity. We describe the experimental apparatus and methods, and we report images of test samples with ρiso = 2.6 µm and ρiso = 1.7 µm, with signal-to-noise ratios greater than 15, acquired in 31.5 and 81.6 h, respectively. Image resolutions are verified by quantitative comparisons with simulations. These results establish a promising direction for high-resolution MRI of small samples. With further improvements in the experimental apparatus and in paramagnetic dopants for DNP, DNP-enhanced low-temperature MRI with ρiso < 1.0 µm is likely to become feasible, potentially enabling informative studies of structures within typical eukaryotic cells, cell clusters, and tissue samples.

Temperatura Baixa , Imageamento por Ressonância Magnética , Células , Eucariotos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Razão Sinal-Ruído
Curr Opin Chem Biol ; 68: 102151, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35483127


Electrogenetics, the combination of electronics and genetics, is an emerging field of mammalian synthetic biology in which electrostimulation is used to remotely program user-designed genetic elements within designer cells to generate desired outputs. Here, we describe recent advances in electro-induced therapeutic gene expression and therapeutic protein secretion in engineered mammalian cells. We also review available tools and strategies to engineer electro-sensitive therapeutic designer cells that are able to sense electrical pulses and produce appropriate clinically relevant outputs in response. We highlight current limitations facing mammalian electrogenetics and suggest potential future directions for research.

Engenharia Celular , Células , Estimulação Elétrica , Genética , Mamíferos , Biologia Sintética , Animais , Engenharia Celular/métodos , Fenômenos Fisiológicos Celulares/genética , Células/metabolismo , Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica , Eletrônica , Regulação da Expressão Gênica , Mamíferos/genética , Biossíntese de Proteínas , Biologia Sintética/métodos , Telemetria
Nanoscale ; 14(11): 4334-4347, 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35253828


The brush model was introduced to interpret AFM indentation data collected on biological cells in a more consistent way compared just to the traditional Hertz model. It takes into account the presence of non-Hertzian deformation of the pericellular brush-like layer surrounding cells (a mix of glycocalyx molecules and microvilli/microridges). The model allows finding the effective Young's modulus of the cell body in a less depth-dependent manner. In addition, it allows finding the force due to the pericellular brush layer. Compared to simple mechanical models used to interpret the indentation experiments, the brush model has additional complexity. It raises the concern about the possible unambiguity of separation of mechanical properties of the cell body and pericellular layer. Here we present the analysis of the robustness of the brush model and demonstrate a weak dependence of the obtained results on the uncertainties within the model and experimental data. We critically analyzed the use of the brush model on a variety of AFM force curves collected on rather distinct cell types: human cervical epithelial cells, rat neurons, and zebrafish melanocytes. We conclude that the brush model is robust; the errors in the definition of the effective Young's modulus due to possible uncertainties of the model and experimental data are within 4%, which is less than the error, for example, due to a typical uncertainty in the spring constant of the AFM cantilever. We also discuss the errors of parameterization of the force due to the pericellular brush layer.

Células , Microscopia de Força Atômica , Modelos Biológicos , Animais , Módulo de Elasticidade , Glicocálix , Humanos , Ratos , Reprodutibilidade dos Testes , Peixe-Zebra
Rev. cir. traumatol. buco-maxilo-fac ; 22(1): 49-55, jan.-mar. 2022. ilus, tab
Artigo em Português | LILACS, BBO - Odontologia | ID: biblio-1392234


Introdução: As limitações das terapias atuais para doenças degenerativas da articulação temporomandibular (ATM) levaram ao aumento do interesse em estratégias regenerativas. A engenharia de tecidos (ET), combinando células-tronco, arcabouços e fatores de crescimento, pode fornecer uma substituição biológica funcional e permanente das estruturas da ATM, além de prevenir o avanço de doenças degenerativas. Objetivo: Este artigo descreve as perspectivas atuais da ET das estruturas da ATM em modelos animais. Metodologia: As abordagens da ET foram categorizadas de acordo com as estruturas primárias da ATM: 1) o disco articular, 2) o côndilo mandibular e 3) a fossa glenóide e eminência articular. Resultados: As áreas com a maior quantidade de estudos são o côndilo mandibular e disco articular, em estudos que abordam o uso de arcabouços tridimensionais, de origem sintética e/ou natural, podendo ou não estar associados a células tronco (diferenciadas ou não) e a fatores de crescimento. Conclusão: A ET da ATM ainda é uma área relativamente nova, em desenvolvimento e em constante avanço. Os avanços tecnológicos desenvolvidos nessa área têm o potencial de auxiliar no desenvolvimento de terapias mais eficientes e menos invasivos... (AU)

Introducción: Las limitaciones de las terapias actuales para las enfermedades degenerativas de la articulación temporomandibular (ATM) han llevado a un mayor interés en las estrategias regenerativas. La ingeniería de tejidos, que combina células, andamios y factores de crecimiento, puede proporcionar un reemplazo biológico funcional y permanente de las estructuras de la ATM, además de prevenir el avance de enfermedades degenerativas. Objetivo: Este artículo describe las perspectivas actuales de la ingeniería de tecidos de las estructuras de la ATM en modelos animales. Metodología: Los enfoques de ingeniería de tejidos se clasificaron según las estructuras primarias de la ATM: 1) el disco articular, 2) el cóndilo mandibular y 3) la fosa glenoidea y la eminencia articular. Resultados: Las áreas con mayor número de estudios son el cóndilo mandibular y el disco articular, en estudios que abordan el uso de estructuras tridimensionales, de origen sintético y/o natural, que pueden o no estar asociadas a células (diferenciadas o no) y con factores de crecimiento. Conclusión: La ingeniería de tejidos de la ATM es todavía un área relativamente nueva, en desarrollo y en constante avance. Los avances tecnológicos desarrollados en esta área tienen el potencial de ayudar en el desarrollo de terapias más eficientes y menos invasivas... (AU)

Introduction: The limitations of current therapies for degenerative diseases of the temporomandibular joint (TMJ) have led to increased interest in regenerative strategies. Tissue engineering (TE), combining stem cells, scaffolds, and growth factors, can provide a functional and permanent biological replacement of TMJ structures, in addition to preventing the advancement of degenerative diseases. Aim: This article describes current TE perspectives of TMJ structures in animal models. Methods: TE approaches were categorized according to the primary TMJ structures: 1) the articular disc, 2) the mandibular condyle, and 3) the glenoid fossa and articular eminence. Results: The areas with the greatest number of studies are the mandibular condyle and articular disc, in studies that address the use of three-dimensional scaffolds, of synthetic and/ or natural origin, which may or may not be associated with stem cells (differentiated or not) and with growth factors. Conclusion: TE of the TMJ is still a relatively new, developing, and constantly advancing area. The technological advances developed in this area have the potential to assist in the development of more efficient and less invasive therapies... (AU)

Animais , Células-Tronco , Articulação Temporomandibular , Células , Modelos Animais , Engenharia Tecidual , Peptídeos e Proteínas de Sinalização Intercelular , Crescimento e Desenvolvimento , Produtos Biológicos , Desenvolvimento Tecnológico , Côndilo Mandibular
Rev. colomb. gastroenterol ; 37(1): 95-98, Jan.-Mar. 2022. graf
Artigo em Inglês, Espanhol | LILACS | ID: biblio-1376911


Abstract Lymphomatous polyposis (LP) is the endoscopic feature of primary gastrointestinal mantle cell lymphoma (MCL), a rare type of B-cell non-Hodgkin's lymphoma (NHL) and a typical but rare endoscopic pattern of gastrointestinal tract involvement (GIT) by nodal MCL. We present the case of a 62-year-old man with nodal MCL, with LP as a manifestation of GIT, and review the literature.

Resumen La poliposis linfomatosa (PL) es la característica endoscópica del linfoma de células del manto (LCM) gastrointestinal primario, un tipo infrecuente de linfoma no Hodgkin (LNH) de células B, así como un patrón endoscópico típico, pero infrecuente, del compromiso del tracto gastrointestinal (TGI) por LCM nodal. Presentamos el caso de un hombre de 62 años con LCM nodal, con PL como manifestación del compromiso gastrointestinal, y realizamos una revisión de la literatura.

Humanos , Masculino , Pessoa de Meia-Idade , Linfoma não Hodgkin , Células , Linfoma de Célula do Manto , Trato Gastrointestinal , Relatório de Pesquisa , Literatura
Sci Rep ; 12(1): 2924, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35190567


Classifying and analyzing human cells is a lengthy procedure, often involving a trained professional. In an attempt to expedite this process, an active area of research involves automating cell classification through use of deep learning-based techniques. In practice, a large amount of data is required to accurately train these deep learning models. However, due to the sparse human cell datasets currently available, the performance of these models is typically low. This study investigates the feasibility of using few-shot learning-based techniques to mitigate the data requirements for accurate training. The study is comprised of three parts: First, current state-of-the-art few-shot learning techniques are evaluated on human cell classification. The selected techniques are trained on a non-medical dataset and then tested on two out-of-domain, human cell datasets. The results indicate that, overall, the test accuracy of state-of-the-art techniques decreased by at least 30% when transitioning from a non-medical dataset to a medical dataset. Reptile and EPNet were the top performing techniques tested on the BCCD dataset and HEp-2 dataset respectively. Second, this study evaluates the potential benefits, if any, to varying the backbone architecture and training schemes in current state-of-the-art few-shot learning techniques when used in human cell classification. To this end, the best technique identified in the first part of this study, EPNet, is used for experimentation. In particular, the study used 6 different network backbones, 5 data augmentation methodologies, and 2 model training schemes. Even with these additions, the overall test accuracy of EPNet decreased from 88.66% on non-medical datasets to 44.13% at best on the medical datasets. Third, this study presents future directions for using few-shot learning in human cell classification. In general, few-shot learning in its current state performs poorly on human cell classification. The study proves that attempts to modify existing network architectures are not effective and concludes that future research effort should be focused on improving robustness towards out-of-domain testing using optimization-based or self-supervised few-shot learning techniques.

Células/classificação , Técnicas Citológicas/métodos , Conjuntos de Dados como Assunto , Aprendizado Profundo , Estudos de Viabilidade , Humanos
Clin. transl. oncol. (Print) ; 24(2): 331-341, febrero 2022. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-203438


IntroductionPenile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias.Materials and methodsA cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed.ResultsOur study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival.ConclusionPD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

Ciências da Saúde , Carcinoma de Células Escamosas , Microambiente Tumoral , Neoplasias Penianas , Células/imunologia , Sobrevivência , Infecções por Papillomavirus