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"Feldman, Michael"
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Handbook of emotions
This text provides a comprehensive analysis of what is currently known about emotion in human behaviour. It demonstrates the vitality and strength of the field and illuminates promising directions for future research with new and revised chapters.
Book
A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue
Over 26 million people worldwide suffer from heart failure annually. When the cause of heart failure cannot be identified, endomyocardial biopsy (EMB) represents the gold-standard for the evaluation of disease. However, manual EMB interpretation has high inter-rater variability. Deep convolutional neural networks (CNNs) have been successfully applied to detect cancer, diabetic retinopathy, and dermatologic lesions from images. In this study, we develop a CNN classifier to detect clinical heart failure from H&E stained whole-slide images from a total of 209 patients, 104 patients were used for training and the remaining 105 patients for independent testing. The CNN was able to identify patients with heart failure or severe pathology with a 99% sensitivity and 94% specificity on the test set, outperforming conventional feature-engineering approaches. Importantly, the CNN outperformed two expert pathologists by nearly 20%. Our results suggest that deep learning analytics of EMB can be used to predict cardiac outcome.
Journal Article
The art of music
\"The Art of music is a handsomely illustrated and rich interdisciplinary look at the mutual influence between music and the visual arts across cultures and eras. The book sheds new light on more familiar artists at the intersection of the visual and the musical, such as Wassily Kandinsky and Arnold Schoenberg, and presents new scholarship on less well-known examples in the arts of Asia, Africa, the Americas, and Europe, from antique pottery to contemporary video and sound art. Essays consider key works and themes such as synesthesia and other formal and theoretical crossovers, motifs of musicians, and performative and ritual functions of music, musical instruments, and art. With more than 250 color images illustrating works of art in diverse traditions, The Art of music offers enriching reading for scholars and general audiences alike\"-- Provided by publisher.
Book
Inferring super-resolution tissue architecture by integrating spatial transcriptomics with histology
Spatial transcriptomics (ST) has demonstrated enormous potential for generating intricate molecular maps of cells within tissues. Here we present iStar, a method based on hierarchical image feature extraction that integrates ST data and high-resolution histology images to predict spatial gene expression with super-resolution. Our method enhances gene expression resolution to near-single-cell levels in ST and enables gene expression prediction in tissue sections where only histology images are available.
iStar predicts gene expression with near-single-cell resolution from histology images.
Journal Article
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
In this study, involving melanoma patients and a mouse model for melanoma, an optimal anti-tumour response was induced by using a combination of radiation with anti-CTLA4 and anti-PD-L1 antibody therapies, each attacking the tumour from a different angle.
Three-way treatment of melanoma
This study, involving melanoma patients and a mouse model for melanoma, demonstrates that an optimal anti-tumour response involves a combination of the three tested treatment modalities: high-dose radiation, together with two different types of immune checkpoint inhibitors (anti-CTLA4 and anti PD-L1), each attacking the tumour from a different angle.
Immune checkpoint inhibitors
1
result in impressive clinical responses
2
,
3
,
4
,
5
, but optimal results will require combination with each other
6
and other therapies. This raises fundamental questions about mechanisms of non-redundancy and resistance. Here we report major tumour regressions in a subset of patients with metastatic melanoma treated with an anti-CTLA4 antibody (anti-CTLA4) and radiation, and reproduced this effect in mouse models. Although combined treatment improved responses in irradiated and unirradiated tumours, resistance was common. Unbiased analyses of mice revealed that resistance was due to upregulation of PD-L1 on melanoma cells and associated with T-cell exhaustion. Accordingly, optimal response in melanoma and other cancer types requires radiation, anti-CTLA4 and anti-PD-L1/PD-1. Anti-CTLA4 predominantly inhibits T-regulatory cells (T
reg
cells), thereby increasing the CD8 T-cell to T
reg
(CD8/T
reg
) ratio. Radiation enhances the diversity of the T-cell receptor (TCR) repertoire of intratumoral T cells. Together, anti-CTLA4 promotes expansion of T cells, while radiation shapes the TCR repertoire of the expanded peripheral clones. Addition of PD-L1 blockade reverses T-cell exhaustion to mitigate depression in the CD8/T
reg
ratio and further encourages oligoclonal T-cell expansion. Similarly to results from mice, patients on our clinical trial with melanoma showing high PD-L1 did not respond to radiation plus anti-CTLA4, demonstrated persistent T-cell exhaustion, and rapidly progressed. Thus, PD-L1 on melanoma cells allows tumours to escape anti-CTLA4-based therapy, and the combination of radiation, anti-CTLA4 and anti-PD-L1 promotes response and immunity through distinct mechanisms.
Journal Article
Epithelial cell size dysregulation in human lung adenocarcinoma
Human cells tightly control their dimensions, but in some cancers, normal cell size control is lost. In this study we measure cell volumes of epithelial cells from human lung adenocarcinoma progression in situ. By leveraging artificial intelligence (AI), we reconstruct tumor cell shapes in three dimensions (3D) and find airway type 2 cells display up to 10-fold increases in volume. Surprisingly, cell size increase is not caused by altered ploidy, and up to 80% of near-euploid tumor cells show abnormal sizes. Size dysregulation is not explained by cell swelling or senescence because cells maintain cytoplasmic density and proper organelle size scaling, but is correlated with changes in tissue organization and loss of a novel network of processes that appear to connect alveolar type 2 cells. To validate size dysregulation in near-euploid cells, we sorted cells from tumor single-cell suspensions on the basis of size. Our study provides data of unprecedented detail for cell volume dysregulation in a human cancer. Broadly, loss of size control may be a common feature of lung adenocarcinomas in humans and mice that is relevant to disease and identification of these cells provides a useful model for investigating cell size control and consequences of cell size dysregulation.
Journal Article
Co-Occurring Gland Angularity in Localized Subgraphs: Predicting Biochemical Recurrence in Intermediate-Risk Prostate Cancer Patients
Quantitative histomorphometry (QH) refers to the application of advanced computational image analysis to reproducibly describe disease appearance on digitized histopathology images. QH thus could serve as an important complementary tool for pathologists in interrogating and interpreting cancer morphology and malignancy. In the US, annually, over 60,000 prostate cancer patients undergo radical prostatectomy treatment. Around 10,000 of these men experience biochemical recurrence within 5 years of surgery, a marker for local or distant disease recurrence. The ability to predict the risk of biochemical recurrence soon after surgery could allow for adjuvant therapies to be prescribed as necessary to improve long term treatment outcomes. The underlying hypothesis with our approach, co-occurring gland angularity (CGA), is that in benign or less aggressive prostate cancer, gland orientations within local neighborhoods are similar to each other but are more chaotically arranged in aggressive disease. By modeling the extent of the disorder, we can differentiate surgically removed prostate tissue sections from (a) benign and malignant regions and (b) more and less aggressive prostate cancer. For a cohort of 40 intermediate-risk (mostly Gleason sum 7) surgically cured prostate cancer patients where half suffered biochemical recurrence, the CGA features were able to predict biochemical recurrence with 73% accuracy. Additionally, for 80 regions of interest chosen from the 40 studies, corresponding to both normal and cancerous cases, the CGA features yielded a 99% accuracy. CGAs were shown to be statistically signicantly ([Formula: see text]) better at predicting BCR compared to state-of-the-art QH methods and postoperative prostate cancer nomograms.
Journal Article
Hilbert Transform Applications in Mechanical Vibration
Hilbert Transform Applications in Mechanical Vibration addresses recent advances in theory and applications of the Hilbert transform to vibration engineering, enabling laboratory dynamic tests to be performed more rapidly and accurately. The author integrates important pioneering developments in signal processing and mathematical models with typical properties of mechanical dynamic constructions such as resonance, nonlinear stiffness and damping. A comprehensive account of the main applications is provided, covering dynamic testing and the extraction of the modal parameters of nonlinear vibration systems, including the initial elastic and damping force characteristics. This unique merger of technical properties and digital signal processing allows the instant solution of a variety of engineering problems and the in-depth exploration of the physics of vibration by analysis, identification and simulation.
This book will appeal to both professionals and students working in mechanical, aerospace, and civil engineering, as well as naval architecture, biomechanics, robotics, and mechatronics.
Hilbert Transform Applications in Mechanical Vibration employs modern applications of the Hilbert transform time domain methods including:
* The Hilbert Vibration Decomposition method for adaptive separation of a multi-component non-stationary vibration signal into simple quasi-harmonic components; this method is characterized by high frequency resolution, which provides a comprehensive account of the case of amplitude and frequency modulated vibration analysis.
* The FREEVIB and FORCEVIB main applications, covering dynamic testing and extraction of the modal parameters of nonlinear vibration systems including the initial elastic and damping force characteristics under free and forced vibration regimes. Identification methods contribute to efficient and accurate testing of vibration systems, avoiding effort-consuming measurement and analysis.
* Precise identification of nonlinear and asymmetric systems considering high frequency harmonics on the base of the congruent envelope and congruent frequency.
* Accompanied by a website at www.wiley.com/go/feldman, housing MATLAB®/ SIMULINK codes.
eBook
Deep-learning approaches for Gleason grading of prostate biopsies
Gleason grades are assigned by pathologists based on prostate cancer morphology to describe the loss of tissue structure and order1 and are strongly correlated with disease aggressiveness and patient outcome.2 Gleason scoring categorises tumour tissue into patterns from 1 (low risk) to 5 (high risk). Pathologists use a much lower threshold, in some cases making a cancerous diagnosis on the basis of 1% or less of the tissue appearing malignant.8 A challenge for deep-learning approaches is that they tend to be black box and not easily interpreted, contrasting with handcrafted approaches in which the model's decisions can be tied to explainable morphological descriptors. Both the approaches of Ström and colleagues and Bulten and colleagues are to be commended for attempting to tackle the issue of the lack of transparency of neural network strategies, an attribute that will probably be needed for these automated decision support tools to achieve widespread acceptance and regulatory approval.
Journal Article