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1.
Cell Rep Med ; 5(4): 101506, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38593808

RESUMO

Prostate cancer (PCa) is a common malignancy in males. The pathology review of PCa is crucial for clinical decision-making, but traditional pathology review is labor intensive and subjective to some extent. Digital pathology and whole-slide imaging enable the application of artificial intelligence (AI) in pathology. This review highlights the success of AI in detecting and grading PCa, predicting patient outcomes, and identifying molecular subtypes. We propose that AI-based methods could collaborate with pathologists to reduce workload and assist clinicians in formulating treatment recommendations. We also introduce the general process and challenges in developing AI pathology models for PCa. Importantly, we summarize publicly available datasets and open-source codes to facilitate the utilization of existing data and the comparison of the performance of different models to improve future studies.


Assuntos
Inteligência Artificial , Neoplasias da Próstata , Masculino , Humanos , Tomada de Decisão Clínica
2.
Comput Biol Med ; 174: 108399, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615461

RESUMO

Glaucoma is one of the leading cause of blindness worldwide. Individuals affected by glaucoma, including patients and their family members, frequently encounter a deficit in dependable support beyond the confines of clinical environments. Seeking advice via the internet can be a difficult task due to the vast amount of disorganized and unstructured material available on these sites, nevertheless. This research explores how Large Language Models (LLMs) can be leveraged to better serve medical research and benefit glaucoma patients. We introduce Xiaoqing, a Natural Language Processing (NLP) model specifically tailored for the glaucoma field, detailing its development and deployment. To evaluate its effectiveness, we conducted two forms of experiments: comparative and experiential. In the comparative analysis, we presented 22 glaucoma-related questions in simplified Chinese to three medical NLP models (Xiaoqing LLMs, HuaTuo, Ivy GPT) and two general models (ChatGPT-3.5 and ChatGPT-4), covering a range of topics from basic glaucoma knowledge to treatment, surgery, research, management standards, and patient lifestyle. Responses were assessed for informativeness and readability. The experiential experiment involved glaucoma patients and non-patients interacting with Xiaoqing, collecting and analyzing their questions and feedback on the same criteria. The findings demonstrated that Xiaoqing notably outperformed the other models in terms of informativeness and readability, suggesting that Xiaoqing is a significant advancement in the management and treatment of glaucoma in China. We also provide a Web-based version of Xiaoqing, allowing readers to directly experience its functionality. The Web-based Xiaoqing is available at https://qa.glaucoma-assistant.com//qa.

3.
Front Nutr ; 11: 1364274, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549753

RESUMO

Soluble solid content (SSC), firmness, and color (L*, a*, and b*) are important physicochemical indices for assessing the quality and maturity of kiwifruits. Therefore, this research aimed to realize the nondestructive detection and visualization map for the physicochemical indices of kiwifruits at different maturity stages by hyperspectral imaging coupled with the chemometrics. To further improve the detection accuracy and working efficiency of the models, competitive adaptive reweighted sampling (CARS) and successive projection algorithm were employed to choose feature wavelengths for predicting the physicochemical indices of kiwifruits. Multiple linear regression (MLR) was designed to develop simplified detection models based on feature wavelengths for determining the physicochemical indices of kiwifruits. The results showed that 32, 18, 26, 29, and 32 feature wavelengths were extracted from 256 full wavelengths to predict the SSC, firmness, L*, a*, and b*, respectively, with the CARS algorithm. Not only was the working efficiency of the CARS-MLR model improved, but the prediction accuracy of the CARS-MLR model for determining the physicochemical indices was also at its relative best. The residual predictive deviations of the CARS-MLR model for determining the SSC, firmness, L*, a*, and b* were 3.09, 2.90, 2.32, 2.74, and 2.91, respectively, which were all above 2.3. Compared with the model based on the full spectra, the CARS-MLR model could be used to predict the physicochemical indices of kiwifruits. Finally, the visualization map for the physicochemical indices of kiwifruits at different maturity stages was generated by calculating the spectral response of each pixel on the kiwifruit samples with the CARS-MLR model. This made the detection for the physicochemical indices of kiwifruits more intuitive. This study demonstrates that hyperspectral imaging coupled with the chemometrics is promising for the nondestructive detection and visualization map for the physicochemical indices of kiwifruits, and also provides a novel theoretical basis for the nondestructive detection of kiwifruit quality.

4.
Cell Death Dis ; 15(3): 183, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429301

RESUMO

Metastatic BRAFV600E colorectal cancer (CRC) carries an extremely poor prognosis and is in urgent need of effective new treatments. While the BRAFV600E inhibitor encorafenib in combination with the EGFR inhibitor cetuximab (Enc+Cet) was recently approved for this indication, overall survival is only increased by 3.6 months and objective responses are observed in only 20% of patients. We have found that a limitation of Enc+Cet treatment is the failure to efficiently induce apoptosis in BRAFV600E CRCs, despite inducing expression of the pro-apoptotic protein BIM and repressing expression of the pro-survival protein MCL-1. Here, we show that BRAFV600E CRCs express high basal levels of the pro-survival proteins MCL-1 and BCL-XL, and that combining encorafenib with a BCL-XL inhibitor significantly enhances apoptosis in BRAFV600E CRC cell lines. This effect was partially dependent on the induction of BIM, as BIM deletion markedly attenuated BRAF plus BCL-XL inhibitor-induced apoptosis. As thrombocytopenia is an established on-target toxicity of BCL-XL inhibition, we also examined the effect of combining encorafenib with the BCL-XL -targeting PROTAC DT2216, and the novel BCL-2/BCL-XL inhibitor dendrimer conjugate AZD0466. Combining encorafenib with DT2216 significantly increased apoptosis induction in vitro, while combining encorafenib with AZD0466 was well tolerated in mice and further reduced growth of BRAFV600E CRC xenografts compared to either agent alone. Collectively, these findings demonstrate that combined BRAF and BCL-XL inhibition significantly enhances apoptosis in pre-clinical models of BRAFV600E CRC and is a combination regimen worthy of clinical investigation to improve outcomes for these patients.


Assuntos
Antineoplásicos , Apoptose , Carbamatos , Neoplasias Colorretais , Inibidores de Proteínas Quinases , Proteína bcl-X , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteína bcl-X/antagonistas & inibidores , Proteína bcl-X/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Apoptose/efeitos dos fármacos
5.
Indian Heart J ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38342141

RESUMO

BACKGROUND: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. RESULTS: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50-0.80). CONCLUSION: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.

6.
Heliyon ; 10(3): e24860, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38318073

RESUMO

The importance of N6-methyladenine (m6A) in mRNA metabolism, physiology, pathology and other life processes is well recognized. However, the exact role of m6A regulators in primary Sjögren's syndrome (PSS) remains unclear. In this study, we used bioinformatics and machine learning random forest approach to screen eight key m6A regulators from the Gene Expression Omnibus GSE7451, GSE40611 and GSE84844 datasets. An accurate nomogram model for predicting PSS risk was established based on these regulators. And using consensus clustering, patients diagnosed with PSS were classified into two different m6A patterns. We found that patients in group B had higher m6A scores compared to those in group A: furthermore, both groups were closely related to immunity and possibly to other diseases. These results emphasise the important role of m6A regulators in the pathogenesis of PSS. Our study of m6A patterns may inform future immunotherapy strategies for PSS.

7.
BMC Cancer ; 24(1): 264, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402382

RESUMO

AIM: Patients with advanced gastrointestinal stromal tumors (GISTs) exhibiting an imatinib plasma trough concentration (IM Cmin) under 1100 ng/ml may show a reduced drug response rate, leading to the suggestion of monitoring for IM Cmin. Consequently, the objective of this research was to create a customized IM Cmin classification model for patients with advanced GISTs from China. METHODS: Initial data and laboratory indicators from patients with advanced GISTs were gathered, and the above information was segmented into a training set, validation set, and testing set in a 6:2:2 ratio. Key variables associated with IM Cmin were identified to construct the classification model using the least absolute shrinkage and selection operator (LASSO) regression and forward stepwise binary logistic regression. Within the training and validation sets, nine ML classification models were constructed via the resampling method and underwent comparison through the Brier scores, the areas under the receiver-operating characteristic curve (AUROC), the decision curve, and the precision-recall (AUPR) curve to determine the most suitable model for this dataset. Two methods of internal validation were used to assess the most suitable model's classification performance: tenfold cross-validation and random split-sample validation (test set), and the value of the test set AUROC was used to evaluate the model's classification performance. RESULTS: Six key variables (gender, daily IM dose, metastatic site, red blood cell count, platelet count, and percentage of neutrophils) were ultimately selected to construct the classification model. In the validation set, it is found by comparison that the Extreme Gradient Boosting (XGBoost) model has the largest AUROC, the lowest Brier score, the largest area under the decision curve, and the largest AUPR value. Furthermore, as evaluated via internal verification, it also performed well in the test set (AUROC = 0.725). CONCLUSION: For patients with advanced GISTs who receive IM, initial data and laboratory indicators could be used to accurately estimate whether the IM Cmin is below 1100 ng/ml. The XGBoost model may stand a chance to assist clinicians in directing the administration of IM.


Assuntos
Tumores do Estroma Gastrointestinal , Humanos , Área Sob a Curva , China , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/sangue , Aprendizado de Máquina , Masculino , Feminino
8.
STAR Protoc ; 5(1): 102835, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38224493

RESUMO

Creating in vitro culture platforms for monkey embryos is crucial for understanding the initial 4 weeks of early primate embryogenesis. Here, we present a protocol to culture cynomolgus monkey embryos in vitro for 25 days post-fertilization and to delineate the key developmental events of gastrulation and early organogenesis. We describe steps for culturing with a 3D system, immunofluorescence analysis, single-cell RNA sequencing, and bioinformatic analysis. For complete details on the use and execution of this protocol, please refer to Gong et al. (2023).1.


Assuntos
Organogênese , Análise da Expressão Gênica de Célula Única , Animais , Macaca fascicularis , Organogênese/genética , Desenvolvimento Embrionário/genética , Biologia Computacional
9.
Artigo em Inglês | MEDLINE | ID: mdl-38194391

RESUMO

Infantile spasms (IS) is a neurological disorder causing mental and/or developmental retardation in many infants. Hypsarrhythmia is a typical symptom in the electroencephalography (EEG) signals with IS. Long-term EEG/video monitoring is most frequently employed in clinical practice for IS diagnosis, from which manual screening of hypsarrhythmia is time consuming and lack of sufficient reliability. This study aims to identify potential biomarkers for automatic IS diagnosis by quantitative analysis of the EEG signals. A large cohort of 101 IS patients and 155 healthy controls (HC) were involved. Typical hypsarrhythmia and non-hypsarrhythmia EEG signals were annotated, and normal EEG were randomly picked from the HC. Root mean square (RMS), teager energy (TE), mean frequency, sample entropy (SamEn), multi-channel SamEn, multi-scale SamEn, and nonlinear correlation coefficient were computed in each sub-band of the three EEG signals, and then compared using either a one-way ANOVA or a Kruskal-Wallis test (based on their distribution) and the receiver operating characteristic (ROC) curves. The effects of infant age on these features were also investigated. For most of the employed features, significant ( ) differences were observed between hypsarrhythmia EEG and non-hypsarrhythmia EEG or HC, which seem to increase with increased infant age. RMS and TE produce the best classification in the delta and theta bands, while entropy features yields the best performance in the gamma band. Our study suggests RMS and TE (delta and theta bands) and entropy features (gamma band) to be promising biomarkers for automatic detection of hypsarrhythmia in long-term EEG monitoring. The findings of our study indicate the feasibility of automated IS diagnosis using artificial intelligence.


Assuntos
Espasmos Infantis , Lactente , Humanos , Espasmos Infantis/diagnóstico , Estudos de Coortes , Reprodutibilidade dos Testes , Inteligência Artificial , Eletroencefalografia , Biomarcadores
10.
Arthritis Res Ther ; 26(1): 35, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263277

RESUMO

OBJECTIVE: Whether rheumatoid arthritis patients have an increased risk of cervical cancer remains controversial, and further research is needed on this clinical question. This study aims to investigate the association between rheumatoid arthritis and the susceptibility to cervical cancer by employing Mendelian randomization methodology, utilizing the extensive dataset from human genome-wide association data analysis. METHODS: The publicly accessible MR base database was utilized to obtain the complete genome, relevant research findings, and summarized data pertaining to rheumatoid arthritis and cervical cancer. Genetic tool variables, specifically single-nucleotide polymorphisms closely linked to rheumatoid arthritis, were chosen for analysis. Four methods, namely inverse variance weighted analysis, weighted median analysis, weighted mode, and MR-Egger regression, were employed. Statistical analysis was conducted to explore the potential association between rheumatoid arthritis and susceptibility to cervical cancer. RESULTS: The results of the inverse variance weighted analysis (OR = 1.096, 95% CI: 1.018-1.180, P = 0.015) indicate a significant causal relationship between rheumatoid arthritis and an increased risk of cervical cancer. Furthermore, the absence of horizontal pleiotropic effects (MR-Egger intercept = 0.00025, P = 0.574) and heterogeneity (QEgger = 2.239, I2Egger = 0.225, PEgger = 0.268, QIVW = 2.734, I2IVW = 0.220, PIVW = 0.999) suggests that the observed association is not influenced by confounding factors. Sensitivity analysis and other statistical methods also support the conclusion that genetic pleiotropy does not introduce bias to the findings. CONCLUSION: There is a causal relationship between rheumatoid arthritis and the occurrence of cervical cancer. People with rheumatoid arthritis is one of the high-risk groups for early screening of cervical cancer. The IL-18 may play a significant role in elevating the risk of cervical cancer among rheumatoid arthritis patients.


Assuntos
Artrite Reumatoide , Neoplasias do Colo do Útero , Humanos , Feminino , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Bases de Dados Factuais
11.
Gastrointest Endosc ; 99(3): 358-370.e11, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37852331

RESUMO

BACKGROUND AND AIMS: Increased reports on endoscopic resection (ER) of esophageal giant subepithelial lesions (g-SELs) have emerged in recent years. The aim of this study was to evaluate the efficacy, technical difficulty, and safety through our single-center experience. METHODS: Seventy-five patients with g-SELs undergoing endoscopic resection were included in the training set. Clinicopathologic features, procedure-related characteristics, postprocedural outcomes, and follow-up data were analyzed. A predictive nomogram model for procedural difficulty was proposed based on the multivariable logistic regression analysis. Internal and external validations were conducted to verify the model performance. RESULTS: The overall en bloc resection rate was 93.3%. Intraoperative and postoperative adverse events occurred in 7 (9.3%) and 13 (17.3%) patients, respectively. No recurrence or metastasis was observed. Thirty-two (42.7%) patients underwent a difficult procedure. Age (adjusted odds ratio [aOR], .915; P = .004), maximal tumor diameter ≥8 cm (aOR, 9.896; P = .009), irregular shape (aOR, 4.081; P = .053), extraluminal growth pattern (aOR, 5.419; P = .011), and submucosal tunneling endoscopic resection (aOR, .109; P = .042) were found to be statistically or clinically significant factors for predicting endoscopic resection difficulty, based on which a nomogram model was developed. Internal and external validations of the nomogram via receiver-operating characteristic curves and calibration curves achieved favorable results. CONCLUSIONS: Endoscopic resection serves as a promising therapeutic option for esophageal g-SELs. A younger patient age, large tumor size, irregular shape, and extraluminal growth may indicate increased endoscopic resection difficulty, whereas a submucosal tunneling endoscopic resection procedure tends to be of lower difficulty. Our nomogram model performs well for predicting endoscopic resection difficulty for esophageal g-SELs.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Endoscopia , Ressecção Endoscópica de Mucosa/métodos , Resultado do Tratamento , Estudos Retrospectivos
12.
Med Phys ; 51(1): 167-178, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37909833

RESUMO

BACKGROUND: Accurate 3D semantic segmentation models are essential for many clinical applications. To train a model for 3D segmentation, voxel-level annotation is necessary, which is expensive to obtain due to laborious work and privacy protection. To accurately annotate 3D medical data, such as MRI, a common practice is to annotate the volumetric data in a slice-by-slice contouring way along principal axes. PURPOSE: In order to reduce the annotation effort in slices, weakly supervised learning with a bounding box (Bbox) was proposed to leverage the discriminating information via a tightness prior assumption. Nevertheless, this method requests accurate and tight Bboxes, which will significantly drop the performance when tightness is not held, that is when a relaxed Bbox is applied. Therefore, there is a need to train a stable model based on relaxed Bbox annotation. METHODS: This paper presents a mixed-supervised training strategy to reduce the annotation effort for 3D segmentation tasks. In the proposed approach, a fully annotated contour is only required for a single slice of the volume. In contrast, the rest of the slices with targets are annotated with relaxed Bboxes. This mixed-supervised method adopts fully supervised learning, relaxed Bbox prior, and contrastive learning during the training, which ensures the network exploits the discriminative information of the training volumes properly. The proposed method was evaluated on two public 3D medical imaging datasets (MRI prostate dataset and Vestibular Schwannoma [VS] dataset). RESULTS: The proposed method obtained a high segmentation Dice score of 85.3% on an MRI prostate dataset and 83.3% on a VS dataset with relaxed Bbox annotation, which are close to a fully supervised model. Moreover, with the same relaxed Bbox annotations, the proposed method outperforms the state-of-the-art methods. More importantly, the model performance is stable when the accuracy of Bbox annotation varies. CONCLUSIONS: The presented study proposes a method based on a mixed-supervised learning method in 3D medical imaging. The benefit will be stable segmentation of the target in 3D images with low accurate annotation requirement, which leads to easier model training on large-scale datasets.


Assuntos
Imageamento Tridimensional , Neuroma Acústico , Masculino , Humanos , Pelve , Próstata , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina Supervisionado
13.
Med Image Anal ; 92: 103044, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38043455

RESUMO

Multi-sequence MRIs can be necessary for reliable diagnosis in clinical practice due to the complimentary information within sequences. However, redundant information exists across sequences, which interferes with mining efficient representations by learning-based models. To handle various clinical scenarios, we propose a sequence-to-sequence generation framework (Seq2Seq) for imaging-differentiation representation learning. In this study, not only do we propose arbitrary 3D/4D sequence generation within one model to generate any specified target sequence, but also we are able to rank the importance of each sequence based on a new metric estimating the difficulty of a sequence being generated. Furthermore, we also exploit the generation inability of the model to extract regions that contain unique information for each sequence. We conduct extensive experiments using three datasets including a toy dataset of 20,000 simulated subjects, a brain MRI dataset of 1251 subjects, and a breast MRI dataset of 2101 subjects, to demonstrate that (1) top-ranking sequences can be used to replace complete sequences with non-inferior performance; (2) combining MRI with our imaging-differentiation map leads to better performance in clinical tasks such as glioblastoma MGMT promoter methylation status prediction and breast cancer pathological complete response status prediction. Our code is available at https://github.com/fiy2W/mri_seq2seq.


Assuntos
Glioblastoma , Imageamento por Ressonância Magnética , Humanos , Mama
14.
Biosci Trends ; 17(6): 427-444, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37981319

RESUMO

Hepatocellular carcinoma (HCC) is associated with a highly heterogeneous immune environment that produces an immune response to various locoregional treatments (LRTs), which in turn affects the effectiveness of immunotherapy. Although LRTs still dominate HCC therapies, 50-60% of patients will ultimately be treated with systemic therapies and might receive those treatments for the rest of their life. TACE, SIRT, and thermal ablation can dramatically increase the immunosuppressive state of HCC, a condition that can be addressed by combination with immunotherapy to restore the activity of lymphocytes and the secretion of cellular immune factors. Immune treatment with locoregional and systemic treatments has dramatically changed the management of HCC. In this review, we examine the research on the changes in the immune microenvironment after locoregional or systemic treatment. We also summarize the regulation of various immune cells and immune factors in the tumor microenvironment and discuss the different infiltration degrees of immune cells and factors on the prognosis of HCC to better compare the efficacy between different treatment methods from the perspective of the tumor microenvironment. This information can be used to help develop treatment options for the upcoming new era of HCC treatment in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Imunoterapia/métodos , Imunidade , Fatores Imunológicos , Microambiente Tumoral
15.
Cancer Discov ; 14(2): 362-379, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-37877779

RESUMO

Mutations in the tumor suppressor TP53 cause cancer and impart poor chemotherapeutic responses, reportedly through loss-of-function, dominant-negative effects and gain-of-function (GOF) activities. The relative contributions of these attributes is unknown. We found that removal of 12 different TP53 mutants with reported GOFs by CRISPR/Cas9 did not impact proliferation and response to chemotherapeutics of 15 human cancer cell lines and colon cancer-derived organoids in culture. Moreover, removal of mutant TP53/TRP53 did not impair growth or metastasis of human cancers in immune-deficient mice or growth of murine cancers in immune-competent mice. DepMap mining revealed that removal of 158 different TP53 mutants had no impact on the growth of 391 human cancer cell lines. In contrast, CRISPR-mediated restoration of wild-type TP53 extinguished the growth of human cancer cells in vitro. These findings demonstrate that LOF but not GOF effects of mutant TP53/TRP53 are critical to sustain expansion of many tumor types. SIGNIFICANCE: This study provides evidence that removal of mutant TP53, thereby deleting its reported GOF activities, does not impact the survival, proliferation, metastasis, or chemotherapy responses of cancer cells. Thus, approaches that abrogate expression of mutant TP53 or target its reported GOF activities are unlikely to exert therapeutic impact in cancer. See related commentary by Lane, p. 211 . This article is featured in Selected Articles from This Issue, p. 201.


Assuntos
Neoplasias do Colo , Proteína Supressora de Tumor p53 , Humanos , Camundongos , Animais , Linhagem Celular Tumoral , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Mutação , Neoplasias do Colo/genética , Proliferação de Células
16.
IEEE J Biomed Health Inform ; 28(3): 1161-1172, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37878422

RESUMO

We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzhen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform.

17.
Neurochem Res ; 49(1): 184-198, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37702890

RESUMO

The inflammatory process mediated by nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain comprising 3 (NLRP3) inflammasome plays a predominant role in the neurological dysfunction following traumatic brain injury (TBI). SB332235, a highly selective antagonist of chemokine receptor 2 (CXCR2), has been demonstrated to exhibit anti-inflammatory properties and improve neurological outcomes in the central nervous system. We aimed to determine the neuroprotective effects of SB332235 in the acute phase after TBI in mice and to elucidate its underlying mechanisms. Male C57BL/6J animals were exposed to a controlled cortical impact, then received 4 doses of SB332235, with the first dose administered at 30 min after TBI, followed by additional doses at 6, 24, and 30 h. Neurological defects were assessed by the modified neurological severity score, while the motor function was evaluated using the beam balance and open field tests. Cognitive performance was evaluated using the novel object recognition test. Brain tissues were collected for pathological, Western blot, and immunohistochemical analyses. The results showed that SB332235 significantly ameliorated TBI-induced deficits, including motor and cognitive impairments. SB332235 administration suppressed expression of both CXCL1 and CXCR2 in TBI. Moreover, SB332235 substantially mitigated the augmented expression levels and activation of the NLRP3 inflammasome within the peri-contusional cortex induced by TBI. This was accompanied by the blocking of subsequent production of pro-inflammatory cytokines. Additionally, SB332235 hindered microglial activity induced by TBI. These findings confirmed the neuroprotective effects of SB332235 against TBI, and the involved mechanisms were in part due to the suppression of NLRP3 inflammasome activity. This study suggests that SB332235 may act as an anti-inflammatory agent to improve functional outcomes in brain injury when applied clinically.


Assuntos
Lesões Encefálicas Traumáticas , Fármacos Neuroprotetores , Masculino , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Camundongos Endogâmicos C57BL , Lesões Encefálicas Traumáticas/patologia
18.
IEEE J Biomed Health Inform ; 28(3): 1472-1483, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38090824

RESUMO

Stroke is a leading cause of disability and fatality in the world, with ischemic stroke being the most common type. Digital Subtraction Angiography images, the gold standard in the operation process, can accurately show the contours and blood flow of cerebral vessels. The segmentation of cerebral vessels in DSA images can effectively help physicians assess the lesions. However, due to the disturbances in imaging parameters and changes in imaging scale, accurate cerebral vessel segmentation in DSA images is still a challenging task. In this paper, we propose a novel Edge Regularization Network (ERNet) to segment cerebral vessels in DSA images. Specifically, ERNet employs the erosion and dilation processes on the original binary vessel annotation to generate pseudo-ground truths of False Negative and False Positive, which serve as constraints to refine the coarse predictions based on their mapping relationship with the original vessels. In addition, we exploit a Hybrid Fusion Module based on convolution and transformers to extract local features and build long-range dependencies. Moreover, to support and advance the open research in the field of ischemic stroke, we introduce FPDSA, the first pixel-level semantic segmentation dataset for cerebral vessels. Extensive experiments on FPDSA illustrate the leading performance of our ERNet.

19.
Waste Manag ; 174: 251-262, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38070444

RESUMO

China's tiered strategy to enhance county-level waste incineration for energy aligns with the sustainable development goals (SDGs), emphasizing the need for comprehensive assessments of waste-to-energy (WtE) plant suitability. Traditional assessment methodologies face challenges, particularly in suggesting innovative site alternatives, adapting to new data sets, and their dependence on strict assumptions. This study introduced enhancements in three pivotal dimensions. Methodologically, it leverages data-driven machine learning (ML) approaches to capture the complex relationships essential for site selection, reducing dependency on strict assumptions. In terms of predictive performance, the integration of oversampling with stacked ensemble models enhances the diversity and generalizability of ML models. The area under curve (AUC) scores from four ML models, enhanced by the oversampled dataset, demonstrated significant improvements compared to the original dataset. The stacking model excelled, achieving a score of 92%. It also led in overall Precision and Recall, reaching 85.2% and 85.08% respectively. Nevertheless, a noticeable discrepancy existed in Precision and Recall for positive classes. The stacking model topped Precision scores at 83.1%, followed by eXtreme Gradient Boosting (XGBoost) (82.61%). In terms of Recall, XGBoost recorded the lowest at 85.07%, while the other three classifiers all marked 88.06%. From an industry applicability standpoint, the stacking model provides innovative location alternatives and demonstrates adaptability in Hunan province, offering a reusable tool for WtE location. In conclusion, this study not only enhances the methodological aspects of WtE site selection but also provides practical and adaptable solutions, contributing positively to sustainable waste management practices.


Assuntos
Incineração , Gerenciamento de Resíduos , Aprendizado de Máquina , Fenômenos Físicos , Indústrias
20.
Gastrointest Endosc ; 99(1): 91-99.e9, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37536635

RESUMO

BACKGROUND AND AIMS: The efficacy and safety of colonoscopy performed by artificial intelligence (AI)-assisted novices remain unknown. The aim of this study was to compare the lesion detection capability of novices, AI-assisted novices, and experts. METHODS: This multicenter, randomized, noninferiority tandem study was conducted across 3 hospitals in China from May 1, 2022, to November 11, 2022. Eligible patients were randomized into 1 of 3 groups: the CN group (control novice group, withdrawal performed by a novice independently), the AN group (AI-assisted novice group, withdrawal performed by a novice with AI assistance), or the CE group (control expert group, withdrawal performed by an expert independently). Participants underwent a repeat colonoscopy conducted by an AI-assisted expert to evaluate the lesion miss rate and ensure lesion detection. The primary outcome was the adenoma miss rate (AMR). RESULTS: A total of 685 eligible patients were analyzed: 229 in the CN group, 227 in the AN group, and 229 in the CE group. Both AMR and polyp miss rate were lower in the AN group than in the CN group (18.82% vs 43.69% [P < .001] and 21.23% vs 35.38% [P < .001], respectively). The noninferiority margin was met between the AN and CE groups of both AMR and polyp miss rate (18.82% vs 26.97% [P = .202] and 21.23% vs 24.10% [P < .249]). CONCLUSIONS: AI-assisted colonoscopy lowered the AMR of novices, making them noninferior to experts. The withdrawal technique of new endoscopists can be enhanced by AI-assisted colonoscopy. (Clinical trial registration number: NCT05323279.).


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Pólipos , Humanos , Inteligência Artificial , Estudos Prospectivos , Colonoscopia/métodos , Projetos de Pesquisa , Adenoma/diagnóstico , Adenoma/patologia , Pólipos do Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico
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