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1.
Am J Pathol ; 191(8): 1442-1453, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34033750

RESUMO

Interstitial fibrosis and tubular atrophy (IFTA) on a renal biopsy are strong indicators of disease chronicity and prognosis. Techniques that are typically used for IFTA grading remain manual, leading to variability among pathologists. Accurate IFTA estimation using computational techniques can reduce this variability and provide quantitative assessment. Using trichrome-stained whole-slide images (WSIs) processed from human renal biopsies, we developed a deep-learning framework that captured finer pathologic structures at high resolution and overall context at the WSI level to predict IFTA grade. WSIs (n = 67) were obtained from The Ohio State University Wexner Medical Center. Five nephropathologists independently reviewed them and provided fibrosis scores that were converted to IFTA grades: ≤10% (none or minimal), 11% to 25% (mild), 26% to 50% (moderate), and >50% (severe). The model was developed by associating the WSIs with the IFTA grade determined by majority voting (reference estimate). Model performance was evaluated on WSIs (n = 28) obtained from the Kidney Precision Medicine Project. There was good agreement on the IFTA grading between the pathologists and the reference estimate (κ = 0.622 ± 0.071). The accuracy of the deep-learning model was 71.8% ± 5.3% on The Ohio State University Wexner Medical Center and 65.0% ± 4.2% on Kidney Precision Medicine Project data sets. Our approach to analyzing microscopic- and WSI-level changes in renal biopsies attempts to mimic the pathologist and provides a regional and contextual estimation of IFTA. Such methods can assist clinicopathologic diagnosis.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Nefropatias/diagnóstico , Nefropatias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Feminino , Fibrose , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
medRxiv ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39040167

RESUMO

The proliferation of medical podcasts has generated an extensive repository of audio content, rich in specialized terminology, diverse medical topics, and expert dialogues. Here we introduce a computational framework designed to enhance large language models (LLMs) by leveraging the informational content of publicly accessible medical podcast data. This dataset, comprising over 4, 300 hours of audio content, was transcribed to generate over 39 million text tokens. Our model, MedPodGPT, integrates the varied di-alogue found in medical podcasts to improve understanding of natural language nuances, cultural contexts, and medical knowledge. Evaluated across multiple benchmarks, MedPodGPT demonstrated an average improvement of 2.31% over standard open-source benchmarks and showcased an improvement of 2.58% in its zero-shot multilingual transfer ability, effectively generalizing to different linguistic contexts. By harnessing the untapped potential of podcast content, MedPodGPT advances natural language processing, offering enhanced capabilities for various applications in medical research and education.

3.
Sci Adv ; 10(11): eadh9547, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489372

RESUMO

Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor (CKLF) is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN. Using the MYCN-driven high-risk neuroblastoma as a model system, we demonstrated that as early as the premalignant stage, tumor cells secrete CKLF to attract CCR4-expressing CD4+ cells, inducing immunosuppression and tumor aggression. Genetic depletion of CD4+ T regulatory cells abolishes the immunorestrictive and protumorigenic effects of CKLF. Our work supports that disrupting CKLF-mediated cross-talk between tumor and CD4+ suppressor cells represents a promising immunotherapeutic approach to battling MYCN-driven tumors.


Assuntos
Quimiocinas , Proteínas com Domínio MARVEL , Proteína Proto-Oncogênica N-Myc , Neuroblastoma , Humanos , Linhagem Celular Tumoral , Quimiocinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas com Domínio MARVEL/metabolismo , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Neuroblastoma/terapia , Microambiente Tumoral
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