Tensor Decomposition of Largest Convolutional Eigenvalues Reveals Pathologic Predictive Power of RhoB in Rectal Cancer Biopsy.

RhoB protein belongs to the Rho GTPase family, which plays an important role in governing cell signaling and tissue morphology. Its expression is known to have implications in pathologic processes of diseases. In particular, the role of RhoB in rectal cancer is not well understood. Investigation in the regulation and communication of this protein, detected by immunohistochemical staining on the microscope, can help gain insightful information leading to optimal disease treatment options. Herein, deep learning-based image analysis and the decomposition of multiway arrays were used to study the predictive factor of RhoB in two cohorts of patients with rectal cancer having survival rates of <5 and >5 years. The results show distinctions between the tensor decomposition factors of the two cohorts.

Deep learning-based meta-classifier approach for COVID-19 classification using CT scan and chest X-ray images.

Literature survey shows that convolutional neural network (CNN)-based pretrained models have been largely used for CoronaVirus Disease 2019 (COVID-19) classification using chest X-ray (CXR) and computed tomography (CT) datasets. However, most of the methods have used a smaller number of data samples for both CT and CXR datasets for training, validation, and testing. As a result, the model might have shown good performance during testing, but this type of model will not be more effective on unseen COVID-19 data samples. Generalization is an important term to be considered while designing a classifier that can perform well on completely unseen datasets. Here, this work proposes a large-scale learning with stacked ensemble meta-classifier and deep learning-based feature fusion approach for COVID-19 classification. The features from the penultimate layer (global average pooling) of EfficientNet-based pretrained models were extracted and the dimensionality of the extracted features reduced using kernel principal component analysis (PCA). Next, a feature fusion approach was employed to merge the features of various extracted features. Finally, a stacked ensemble meta-classifier-based approach was used for classification. It is a two-stage approach. In the first stage, random forest and support vector machine (SVM) were applied for prediction, then aggregated and fed into the second stage. The second stage includes logistic regression classifier that classifies the data sample of CT and CXR into either COVID-19 or Non-COVID-19. The proposed model was tested using large CT and CXR datasets, which are publicly available. The performance of the proposed model was compared with various existing CNN-based pretrained models. The proposed model outperformed the existing methods and can be used as a tool for point-of-care diagnosis by healthcare professionals.

Cerebral dopamine neurotrophic factor-deficiency leads to degeneration of enteric neurons and altered brain dopamine neuronal function in mice.

Cerebral dopamine neurotrophic factor (CDNF) is neuroprotective for nigrostriatal dopamine neurons and restores dopaminergic function in animal models of Parkinson's disease (PD). To understand the role of CDNF in mammals, we generated CDNF knockout mice (Cdnf-/-), which are viable, fertile, and have a normal life-span. Surprisingly, an age-dependent loss of enteric neurons occurs selectively in the submucosal but not in the myenteric plexus. This neuronal loss is a consequence not of increased apoptosis but of neurodegeneration and autophagy. Quantitatively, the neurodegeneration and autophagy found in the submucosal plexus in duodenum, ileum and colon of the Cdnf-/- mouse are much greater than in those of Cdnf+/+ mice. The selective vulnerability of submucosal neurons to the absence of CDNF is reminiscent of the tendency of pathological abnormalities to occur in the submucosal plexus in biopsies of patients with PD. In contrast, the number of substantia nigra dopamine neurons and dopamine and its metabolite concentrations in the striatum are unaltered in Cdnf-/- mice; however, there is an age-dependent deficit in the function of the dopamine system in Cdnf-/- male mice analyzed. This is observed as D-amphetamine-induced hyperactivity, aberrant dopamine transporter function, and as increased D-amphetamine-induced dopamine release demonstrating that dopaminergic axon terminal function in the striatum of the Cdnf-/- mouse brain is altered. The deficiencies of Cdnf-/- mice, therefore, are reminiscent of those seen in early stages of Parkinson's disease.

Pattern recognition and probabilistic measures in alignment-free sequence analysis.

With the massive production of genomic and proteomic data, the number of available biological sequences in databases has reached a level that is not feasible anymore for exact alignments even when just a fraction of all sequences is used. To overcome this inevitable time complexity, ultrafast alignment-free methods are studied. Within the past two decades, a broad variety of nonalignment methods have been proposed including dissimilarity measures on classical representations of sequences like k-words or Markov models. Furthermore, articles were published that describe distance measures on alternative representations such as compression complexity, spectral time series or chaos game representation. However, alignments are still the standard method for real world applications in biological sequence analysis, and the time efficient alignment-free approaches are usually applied in cases when the accustomed algorithms turn out to fail or be too inconvenient.

Clustered nuclei splitting via curvature information and gray-scale distance transform.

Clusters or clumps of cells or nuclei are frequently observed in two dimensional images of thick tissue sections. Correct and accurate segmentation of overlapping cells and nuclei is important for many biological and biomedical applications. Many existing algorithms split clumps through the binarization of the input images; therefore, the intensity information of the original image is lost during this process. In this paper, we present a curvature information, gray scale distance transform, and shortest path splitting line-based algorithm which can make full use of the concavity and image intensity information to find out markers, each of which represents an individual object, and detect accurate splitting lines between objects using shortest path and junction adjustment. The proposed algorithm is tested on both synthetic and real nuclei images. Experiment results show that the performance of the proposed method is better than that of marker-controlled watershed method and ellipse fitting method.

Automated CT detection of intestinal abnormalities and ischemia for decision making in emergency medicine.

BACKGROUND: Evaluation of computed tomography (CT) for the diagnosis of intestinal wall abnormalities and ischemia is important for clinical decision making in patients with acute abdominal pain to which if surgery should be performed in the emergency department. Interpretation of such information on CT is usually based on visual assessment by medical professionals and still remains a challenge in a variety of settings of the medical emergency care. This paper reports a pilot study in the implementation of image processing methods for automated detection of intestinal wall abnormalities and bowel ischemia, which can be of a potential application for CT-based detection of the intestinal disease. METHODS: CT scans of 3 patients of ischemia, one benign and one control subjects were used in this study. Statistical and geometrical features of the CT scans were extracted for pattern classification using two distance measures and the k-nearest neighbor algorithm. The automated detection of intestinal abnormalities and ischemia was carried out using labeled data from the training process with various proportions of training and testing samples to validate the results. RESULTS: Detection rates of intestinal ischemia and abnormalities are promising in terms of sensitivity and specificity, where the sensitivity is higher than the specificity in all test cases. The overall classification accuracy between the diseased and control subjects can be as high as 100% when all CT scans were included for measuring the difference between a cohort of three patients of ischemia and a single control subject. CONCLUSION: The proposed approach can be utilized as a computer-aided tool for decision making in the emergency department, where the availability of expert knowledge of the radiologist and surgeon about this complex bowel disease is limited.

Exploring Extravasation in Cancer Patients.

Extravasation, the unintended leakage of intravenously administered substances, poses significant challenges in cancer treatment, particularly during chemotherapy and radiotherapy. This comprehensive review explores the pathophysiology, incidence, risk factors, clinical presentation, diagnosis, prevention strategies, management approaches, complications, and long-term effects of extravasation in cancer patients. It also outlines future directions and research opportunities, including identifying gaps in the current knowledge and proposing areas for further investigation in extravasation prevention and management. Emerging technologies and therapies with the potential to improve extravasation prevention and management in both chemotherapy and radiotherapy are highlighted. Such innovations include advanced vein visualization technologies, smart catheters, targeted drug delivery systems, novel topical treatments, and artificial intelligence-based image analysis. By addressing these aspects, this review not only provides healthcare professionals with insights to enhance patient safety and optimize clinical practice but also underscores the importance of ongoing research and innovation in improving outcomes for cancer patients experiencing extravasation events.

Diagnosis of pathological speech with streamlined features for long short-term memory learning.

BACKGROUND: Pathological speech diagnosis is crucial for identifying and treating various speech disorders. Accurate diagnosis aids in developing targeted intervention strategies, improving patients' communication abilities, and enhancing their overall quality of life. With the rising incidence of speech-related conditions globally, including oral health, the need for efficient and reliable diagnostic tools has become paramount, emphasizing the significance of advanced research in this field. METHODS: This paper introduces novel features for deep learning in the analysis of short voice signals. It proposes the incorporation of time-space and time-frequency features to accurately discern between two distinct groups: Individuals exhibiting normal vocal patterns and those manifesting pathological voice conditions. These advancements aim to enhance the precision and reliability of diagnostic procedures, paving the way for more targeted treatment approaches. RESULTS: Utilizing a publicly available voice database, this study carried out training and validation using long short-term memory (LSTM) networks learning on the combined features, along with a data balancing strategy. The proposed approach yielded promising performance metrics: 90% accuracy, 93% sensitivity, 87% specificity, 88% precision, an F1 score of 0.90, and an area under the receiver operating characteristic curve of 0.96. The results surpassed those obtained by the networks trained using wavelet-time scattering coefficients, as well as several algorithms trained with alternative feature types. CONCLUSIONS: The incorporation of time-frequency and time-space features extracted from short segments of voice signals for LSTM learning demonstrates significant promise as an AI tool for the diagnosis of speech pathology. The proposed approach has the potential to enhance the accuracy and allow for real-time pathological speech assessment, thereby facilitating more targeted and effective therapeutic interventions.

Exploring Nonlinear Dynamics In Brain Functionality Through Phase Portraits And Fuzzy Recurrence Plots.

Much of the complexity and diversity found in nature are driven by nonlinear phenomena, and this holds true for the brain. Nonlinear dynamics theory has been successfully utilized in explaining brain functions from a biophysics standpoint, and the field of statistical physics continues to make substantial progress in understanding brain connectivity and function. This study delves into complex brain functional connectivity using biophysical nonlinear dynamics approaches. We aim to uncover hidden information in high-dimensional and nonlinear neural signals, with the hope of providing a useful tool for analyzing information transitions in functionally complex networks. By utilizing phase portraits and fuzzy recurrence plots, we investigated the latent information in the functional connectivity of complex brain networks. Our numerical experiments, which include synthetic linear dynamics neural time series and a biophysically realistic neural mass model, showed that phase portraits and fuzzy recurrence plots are highly sensitive to changes in neural dynamics, and they can also be used to predict functional connectivity based on structural connectivity. Furthermore, the results showed that phase trajectories of neuronal activity encode low-dimensional dynamics, and the geometric properties of the limit-cycle attractor formed by the phase portraits can be used to explain the neurodynamics. Additionally, our results showed that the phase portrait and fuzzy recurrence plots can be used as functional connectivity descriptors, and both metrics were able to capture and explain nonlinear dynamics behavior during specific cognitive tasks. In conclusion, our findings suggest that phase portraits and fuzzy recurrence plots could be highly effective as functional connectivity descriptors, providing valuable insights into nonlinear dynamics in the brain.

Features and networks of the mandible on computed tomography.

The mandible or lower jaw is the largest and hardest bone in the human facial skeleton. Fractures of the mandible are reported to be a common facial trauma in emergency medicine and gaining insights into mandibular morphology in different facial types can be helpful for trauma treatment. Furthermore, features of the mandible play an important role in forensics and anthropology for identifying gender and individuals. Thus, discovering hidden information of the mandible can benefit interdisciplinary research. Here, for the first time, a method of artificial intelligence-based nonlinear dynamics and network analysis are used for discovering dissimilar and similar radiographic features of mandibles between male and female subjects. Using a public dataset of 10 computed tomography scans of mandibles, the results suggest a difference in the distribution of spatial autocorrelation between genders, uniqueness in network topologies among individuals and shared values in recurrence quantification.

Spatial chaos and complexity in the intracellular space of cancer and normal cells.

BACKGROUND: One of the most challenging problems in biological image analysis is the quantification of the dynamical mechanism and complexity of the intracellular space. This paper investigates potential spatial chaos and complex behavior of the intracellular space of typical cancer and normal cell images whose structural details are revealed by the combination of scanning electron microscopy and focused ion beam systems. Such numerical quantifications have important implications for computer modeling and simulation of diseases. METHODS: Cancer cell lines derived from a human head and neck squamous cell carcinoma (SCC-61) and normal mouse embryonic fibroblast (MEF) cells produced by focused ion beam scanning electron microscopes were used in this study. Spatial distributions of the organelles of cancer and normal cells can be analyzed at both short range and long range of the bounded dynamical system of the image space, depending on the orientations of the spatial cell. A procedure was designed for calculating the largest Lyapunov exponent, which is an indicator of the potential chaotic behavior in intracellular images. Furthermore, the sample entropy and regularity dimension were applied to measure the complexity of the intracellular images. RESULTS: Positive values of the largest Lyapunov exponents (LLEs) of the intracellular space of the SCC-61 were obtained in different spatial orientations for both long-range and short-range models, suggesting the chaotic behavior of the cell. The MEF has smaller positive values of LLEs in the long range than those of the SCC-61, and zero vales of the LLEs in the short range analysis, suggesting a non-chaotic behavior. The intracellular space of the SCC-61 is found to be more complex than that of the MEF. The degree of complexity measured in the spatial distribution of the intracellular space in the diagonal direction was found to be approximately twice larger than the complexity measured in the horizontal and vertical directions. CONCLUSION: Initial findings are promising for characterizing different types of cells and therefore useful for studying cancer cells in the spatial domain using state-of-the-art imaging technology. The measures of the chaotic behavior and complexity of the spatial cell will help computational biologists gain insights into identifying associations between the oscillation patterns and spatial parameters of cells, and appropriate model for simulating cancer cell signaling networks for cancer treatment and new drug discovery.

Development of a brain MRI-based hidden Markov model for dementia recognition.

BACKGROUND: Dementia is an age-related cognitive decline which is indicated by an early degeneration of cortical and sub-cortical structures. Characterizing those morphological changes can help to understand the disease development and contribute to disease early prediction and prevention. But modeling that can best capture brain structural variability and can be valid in both disease classification and interpretation is extremely challenging. The current study aimed to establish a computational approach for modeling the magnetic resonance imaging (MRI)-based structural complexity of the brain using the framework of hidden Markov models (HMMs) for dementia recognition. METHODS: Regularity dimension and semi-variogram were used to extract structural features of the brains, and vector quantization method was applied to convert extracted feature vectors to prototype vectors. The output VQ indices were then utilized to estimate parameters for HMMs. To validate its accuracy and robustness, experiments were carried out on individuals who were characterized as non-demented and mild Alzheimer's diseased. Four HMMs were constructed based on the cohort of non-demented young, middle-aged, elder and demented elder subjects separately. Classification was carried out using a data set including both non-demented and demented individuals with a wide age range. RESULTS: The proposed HMMs have succeeded in recognition of individual who has mild Alzheimer's disease and achieved a better classification accuracy compared to other related works using different classifiers. Results have shown the ability of the proposed modeling for recognition of early dementia. CONCLUSION: The findings from this research will allow individual classification to support the early diagnosis and prediction of dementia. By using the brain MRI-based HMMs developed in our proposed research, it will be more efficient, robust and can be easily used by clinicians as a computer-aid tool for validating imaging bio-markers for early prediction of dementia.

Classification of Caenorhabditis Elegans Locomotion Behaviors With Eigenfeature-Enhanced Long Short-Term Memory Networks.

The free-living nematode Caenorhabditis elegans is an ideal model for understanding behavior and networks of neurons. Experimental and quantitative analyses of neural circuits and behavior have led to system-level understanding of behavioral genetics and process of transformation from sensory integration in stimulus environments to behavioral outcomes. The ability to differentiate locomotion behavior between wild-type and mutant Caenorhabditis elegans strains allows precise inference on and gaining insights into genetic and environmental influences on behaviors. This paper presents an eigenfeature-enhanced deep-learning method for classifying the dynamics of locomotion behavior of wild-type and mutant Caenorhabditis elegans. Classification results obtained from public benchmark time-series data of eigenworms illustrate the superior performance of the new method over several existing classifiers. The proposed method has potential as a useful artificial-intelligence tool for automated identification of the nematode worm behavioral patterns aiming at elucidating molecular and genetic mechanisms that control the nervous system.

Classification of Motor-Imagery Tasks using a Large EEG Dataset by Fusing Classifiers Learning on Wavelet-Scattering Features.

Brain-computer or brain-machine interface technology allows humans to control machines using their thoughts via brain signals. In particular, these interfaces can assist people with neurological diseases for speech understanding or physical disabilities for operating devices such as wheelchairs. Motor-imagery tasks play a basic role in brain-computer interfaces. This study introduces an approach for classifying motor-imagery tasks in a brain-computer interface environment, which remains a challenge for rehabilitation technology using electroencephalogram sensors. Methods used and developed for addressing the classification include wavelet time and image scattering networks, fuzzy recurrence plots, support vector machines, and classifier fusion. The rationale for combining outputs from two classifiers learning on wavelet-time and wavelet-image scattering features of brain signals, respectively, is that they are complementary and can be effectively fused using a novel fuzzy rule-based system. A large-scale challenging electroencephalogram dataset of motor imagery-based brain-computer interface was used to test the efficacy of the proposed approach. Experimental results obtained from within-session classification show the potential application of the new model that achieves an improvement of 7% in classification accuracy over the best existing classifier using state-of-the-art artificial intelligence (76% versus 69%, respectively). For the cross-session experiment, which imposes a more challenging and practical classification task, the proposed fusion model improves the accuracy by 11% (54% versus 65%). The technical novelty presented herein and its further exploration are promising for developing a reliable sensor-based intervention for assisting people with neurodisability to improve their quality of life.

Prediction of Five-Year Survival Rate for Rectal Cancer Using Markov Models of Convolutional Features of RhoB Expression on Tissue Microarray.

The ability to predict survival in cancer is clinically important because the finding can help patients and physicians make optimal treatment decisions. Artificial intelligence in the context of deep learning has been increasingly realized by the informatics-oriented medical community as a powerful machine-learning technology for cancer research, diagnosis, prediction, and treatment. This paper presents the combination of deep learning, data coding, and probabilistic modeling for predicting five-year survival in a cohort of patients with rectal cancer using images of RhoB expression on biopsies. Using about one-third of the patients' data for testing, the proposed approach achieved 90% prediction accuracy, which is much higher than the direct use of the best pretrained convolutional neural network (70%) and the best coupling of a pretrained model and support vector machines (70%).

Wavelet scattering networks in deep learning for discovering protein markers in a cohort of Swedish rectal cancer patients.

BACKGROUND: Cancer biomarkers play a pivotal role in the diagnosis, prognosis, and treatment response prediction of the disease. In this study, we analyzed the expression levels of RhoB and DNp73 proteins in rectal cancer, as captured in immunohistochemical images, to predict the 5-year survival time of two patient groups: one with preoperative radiotherapy and one without. METHODS: The utilization of deep convolutional neural networks in medical research, particularly in clinical cancer studies, has been gaining substantial attention. This success primarily stems from their ability to extract intricate image features that prove invaluable in machine learning. Another innovative method for extracting features at multiple levels is the wavelet-scattering network. Our study combines the strengths of these two convolution-based approaches to robustly extract image features related to protein expression. RESULTS: The efficacy of our approach was evaluated across various tissue types, including tumor, biopsy, metastasis, and adjacent normal tissue. Statistical assessments demonstrated exceptional performance across a range of metrics, including prediction accuracy, classification accuracy, precision, and the area under the receiver operating characteristic curve. CONCLUSION: These results underscore the potential of dual convolutional learning to assist clinical researchers in the timely validation and discovery of cancer biomarkers.

A review on artificial intelligence for the diagnosis of fractures in facial trauma imaging.

Patients with facial trauma may suffer from injuries such as broken bones, bleeding, swelling, bruising, lacerations, burns, and deformity in the face. Common causes of facial-bone fractures are the results of road accidents, violence, and sports injuries. Surgery is needed if the trauma patient would be deprived of normal functioning or subject to facial deformity based on findings from radiology. Although the image reading by radiologists is useful for evaluating suspected facial fractures, there are certain challenges in human-based diagnostics. Artificial intelligence (AI) is making a quantum leap in radiology, producing significant improvements of reports and workflows. Here, an updated literature review is presented on the impact of AI in facial trauma with a special reference to fracture detection in radiology. The purpose is to gain insights into the current development and demand for future research in facial trauma. This review also discusses limitations to be overcome and current important issues for investigation in order to make AI applications to the trauma more effective and realistic in practical settings. The publications selected for review were based on their clinical significance, journal metrics, and journal indexing.

Artificial intelligence fusion for predicting survival of rectal cancer patients using immunohistochemical expression of Ras homolog family member B in biopsy.

Aim: The process of biomarker discovery is being accelerated with the application of artificial intelligence (AI), including machine learning. Biomarkers of diseases are useful because they are indicators of pathogenesis or measures of responses to therapeutic treatments, and therefore, play a key role in new drug development. Proteins are among the candidates for biomarkers of rectal cancer, which need to be explored using state-of-the-art AI to be utilized for prediction, prognosis, and therapeutic treatment. This paper aims to investigate the predictive power of Ras homolog family member B (RhoB) protein in rectal cancer. Methods: This study introduces the integration of pretrained convolutional neural networks and support vector machines (SVMs) for classifying biopsy samples of immunohistochemical expression of protein RhoB in rectal-cancer patients to validate its biologic measure in biopsy. Features of the immunohistochemical expression images were extracted by the pretrained networks and used for binary classification by the SVMs into two groups of less and more than 5-year survival rates. Results: The fusion of neural search architecture network (NASNet)-Large for deep-layer feature extraction and classifier using SVMs provided the best average classification performance with a total accuracy = 85%, prediction of survival rate of more than 5 years = 90%, and prediction of survival rate of less than 5 years = 75%. Conclusions: The finding obtained from the use of AI reported in this study suggest that RhoB expression on rectal-cancer biopsy can be potentially used as a biomarker for predicting survival outcomes in rectal-cancer patients, which can be informative for clinical decision making if the patient would be recommended for preoperative therapy.

Classification of IHC Images of NATs With ResNet-FRP-LSTM for Predicting Survival Rates of Rectal Cancer Patients.

BACKGROUND: Over a decade, tissues dissected adjacent to primary tumors have been considered "normal" or healthy samples (NATs). However, NATs have recently been discovered to be distinct from both tumorous and normal tissues. The ability to predict the survival rate of cancer patients using NATs can open a new door to selecting optimal treatments for cancer and discovering biomarkers. METHODS: This paper introduces an artificial intelligence (AI) approach that uses NATs for predicting the 5-year survival of pre-operative radiotherapy patients with rectal cancer. The new approach combines pre-trained deep learning, nonlinear dynamics, and long short-term memory to classify immunohistochemical images of RhoB protein expression on NATs. RESULTS: Ten-fold cross-validation results show 88% accuracy of prediction obtained from the new approach, which is also higher than those provided from baseline methods. CONCLUSION: Preliminary results not only add objective evidence to recent findings of NATs' molecular characteristics using state-of-the-art AI methods, but also contribute to the discovery of RhoB expression on NATs in rectal-cancer patients. CLINICAL IMPACT: The ability to predict the survival rate of cancer patients is extremely important for clinical decision-making. The proposed AI tool is promising for assisting oncologists in their treatments of rectal cancer patients.

Homeodomain interacting protein kinase 2 regulates postnatal development of enteric dopaminergic neurons and glia via BMP signaling.

Trophic factor signaling is important for the migration, differentiation, and survival of enteric neurons during development. The mechanisms that regulate the maturation of enteric neurons in postnatal life, however, are poorly understood. Here, we show that transcriptional cofactor HIPK2 (homeodomain interacting protein kinase 2) is required for the maturation of enteric neurons and for regulating gliogenesis during postnatal development. Mice lacking HIPK2 display a spectrum of gastrointestinal (GI) phenotypes, including distention of colon and slowed GI transit time. Although loss of HIPK2 does not affect the enteric neurons in prenatal development, a progressive loss of enteric neurons occurs during postnatal life in Hipk2(-/-) mutant mice that preferentially affects the dopaminergic population of neurons in the caudal region of the intestine. The mechanism by which HIPK2 regulates postnatal enteric neuron development appears to involve the response of enteric neurons to bone morphogenetic proteins (BMPs). Specifically, compared to wild type mice, a larger proportion of enteric neurons in Hipk2(-/-) mutants have an abnormally high level of phosphorylated Smad1/5/8. Consistent with the ability of BMP signaling to promote gliogenesis, Hipk2(-/-) mutants show a significant increase in glia in the enteric nervous system. In addition, numbers of autophagosomes are increased in enteric neurons in Hipk2(-/-) mutants, and synaptic maturation is arrested. These results reveal a new role for HIPK2 as an important transcriptional cofactor that regulates the BMP signaling pathway in the maintenance of enteric neurons and glia, and further suggest that HIPK2 and its associated signaling mechanisms may be therapeutically altered to promote postnatal neuronal maturation.