37 research outputs found
Role of nuclear bodies in apoptosis signalling
AbstractPromyelocytic leukemia nuclear bodies (PML NBs) are dynamic macromolecular multiprotein complexes that recruit and release a plethora of proteins. A considerable number of PML NB components play vital roles in apoptosis, senescence regulation and tumour suppression. The molecular basis by which PML NBs control these cellular responses is still just beginning to be understood. In addition to PML itself, numerous further tumour suppressors including transcriptional regulator p53, acetyl transferase CBP (CREB binding protein) and protein kinase HIPK2 (homeodomain interacting protein kinase 2) are recruited to PML NBs in response to genotoxic stress or oncogenic transformation and drive the senescence and apoptosis response by regulating p53 activity. Moreover, in response to death-receptor activation, PML NBs may act as nuclear depots that release apoptotic factors, such as the FLASH (FLICE-associated huge) protein, to amplify the death signal. PML NBs are also associated with other nuclear domains including Cajal bodies and nucleoli and share apoptotic regulators with these domains, implying crosstalk between NBs in apoptosis regulation. In conclusion, PML NBs appear to regulate cell death decisions through different, pathway-specific molecular mechanisms
Evaluating Deep Learning-based Melanoma Classification using Immunohistochemistry and Routine Histology: A Three Center Study
Pathologists routinely use immunohistochemical (IHC)-stained tissue slides
against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to
improve their accuracy in diagnosing melanomas. The use of diagnostic Deep
Learning (DL)-based support systems for automated examination of tissue
morphology and cellular composition has been well studied in standard
H&E-stained tissue slides. In contrast, there are few studies that analyze IHC
slides using DL. Therefore, we investigated the separate and joint performance
of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA
classifier achieved an area under receiver operating characteristics curve
(AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the
H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined
classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD
datasets. DL MelanA-based assistance systems show the same performance as the
benchmark H&E classification and may be improved by multi stain classification
to assist pathologists in their clinical routine
Dermatologist-like explainable AI enhances trust and confidence in diagnosing melanoma
Although artificial intelligence (AI) systems have been shown to improve the
accuracy of initial melanoma diagnosis, the lack of transparency in how these
systems identify melanoma poses severe obstacles to user acceptance.
Explainable artificial intelligence (XAI) methods can help to increase
transparency, but most XAI methods are unable to produce precisely located
domain-specific explanations, making the explanations difficult to interpret.
Moreover, the impact of XAI methods on dermatologists has not yet been
evaluated. Extending on two existing classifiers, we developed an XAI system
that produces text and region based explanations that are easily interpretable
by dermatologists alongside its differential diagnoses of melanomas and nevi.
To evaluate this system, we conducted a three-part reader study to assess its
impact on clinicians' diagnostic accuracy, confidence, and trust in the
XAI-support. We showed that our XAI's explanations were highly aligned with
clinicians' explanations and that both the clinicians' trust in the support
system and their confidence in their diagnoses were significantly increased
when using our XAI compared to using a conventional AI system. The clinicians'
diagnostic accuracy was numerically, albeit not significantly, increased. This
work demonstrates that clinicians are willing to adopt such an XAI system,
motivating their future use in the clinic
Evaluating deep learning-based melanoma classification using immunohistochemistry and routine histology: A three center study.
Pathologists routinely use immunohistochemical (IHC)-stained tissue slides against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to improve their accuracy in diagnosing melanomas. The use of diagnostic Deep Learning (DL)-based support systems for automated examination of tissue morphology and cellular composition has been well studied in standard H&E-stained tissue slides. In contrast, there are few studies that analyze IHC slides using DL. Therefore, we investigated the separate and joint performance of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA classifier achieved an area under receiver operating characteristics curve (AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD datasets. DL MelanA-based assistance systems show the same performance as the benchmark H&E classification and may be improved by multi stain classification to assist pathologists in their clinical routine
Additional results derived by using different fusion approaches: Dist-opt means weighted by the distance to the individual models optimal thresholds; dist-05 means weighted by the distance to the default threshold of 0.5; avg denotes the fusion by conducting a simple average of all scores; perf means weighted based on the individual models validation performance in a way that better performing models contribute more to the fused result.
Additional results derived by using different fusion approaches: Dist-opt means weighted by the distance to the individual models optimal thresholds; dist-05 means weighted by the distance to the default threshold of 0.5; avg denotes the fusion by conducting a simple average of all scores; perf means weighted based on the individual models validation performance in a way that better performing models contribute more to the fused result.</p
ROC plots by data modality with corresponding AUROC values.
A: Results from Dresden B: Results from Erlangen C: Results from Naples. Red: MelanA-based performance taking all magnifications into account Purple: H&E-based performance Black: combined model using H&E as well as MelanA by aggregating the individual scores. (TIF)</p
S2 Dataset -
Pathologists routinely use immunohistochemical (IHC)-stained tissue slides against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to improve their accuracy in diagnosing melanomas. The use of diagnostic Deep Learning (DL)-based support systems for automated examination of tissue morphology and cellular composition has been well studied in standard H&E-stained tissue slides. In contrast, there are few studies that analyze IHC slides using DL. Therefore, we investigated the separate and joint performance of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA classifier achieved an area under receiver operating characteristics curve (AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD datasets. DL MelanA-based assistance systems show the same performance as the benchmark H&E classification and may be improved by multi stain classification to assist pathologists in their clinical routine.</div
Schematic diagram of the different models.
The red box shows the pipeline for MelanA-stained WSIs and the purple box the pipeline for H&E-stained WSIs. We tessellated MelanA-stained WSIs corresponding to different magnifications and trained individual models on each tile size. The class probabilities for each tile were predicted and aggregated into a slide score by averaging all tile scores. For the H&E-based model we proceeded in the same way.</p
Description of the population in our datasets.
For continuous features we report median, range, and number of NAs, for categorical features we report the total number of observations per group. Here the training population as well as all three test populations are described. Melanoma in situ describes the early stage of a malignant melanoma that has not yet broken through the basement membrane. However, features at the cellular level do not differ between melanoma in situ and malignant melanoma.</p
S5 Dataset -
Pathologists routinely use immunohistochemical (IHC)-stained tissue slides against MelanA in addition to hematoxylin and eosin (H&E)-stained slides to improve their accuracy in diagnosing melanomas. The use of diagnostic Deep Learning (DL)-based support systems for automated examination of tissue morphology and cellular composition has been well studied in standard H&E-stained tissue slides. In contrast, there are few studies that analyze IHC slides using DL. Therefore, we investigated the separate and joint performance of ResNets trained on MelanA and corresponding H&E-stained slides. The MelanA classifier achieved an area under receiver operating characteristics curve (AUROC) of 0.82 and 0.74 on out of distribution (OOD)-datasets, similar to the H&E-based benchmark classification of 0.81 and 0.75, respectively. A combined classifier using MelanA and H&E achieved AUROCs of 0.85 and 0.81 on the OOD datasets. DL MelanA-based assistance systems show the same performance as the benchmark H&E classification and may be improved by multi stain classification to assist pathologists in their clinical routine.</div