Gastroesophageal reflux disease (GERD) is caused by gastric acid flowing from the stomach into the esophagus. Under healthy conditions, a physiologic barrier called the lower esophageal sphincter (LES) prevents pathologic reflux of stomach contents into the esophagus. GERD is an extremely common disease, affecting between 60 and 70 million people in the United States [2]. Chronic and extreme cases of GERD in infants can cause failure to thrive and damage the esophagus. When medical management fails, a surgical procedure called a fundoplication is performed. The most common fundoplication is the Nissen fundoplication, in which the fundus of the stomach is wrapped around the lower esophagus 360 degrees. This procedure is often performed using laparoscopic (minimally-invasive) surgical techniques. The procedure is not perfect and there is a recurrence rate of 10-15%, especially in infants. The surgeons at Emory Children's Hospital would like to improve the long-term results [2] of fundoplication using low risk system for testing first. We have formed an interdisciplinary team to design such system to meet the medical needs.
Purpose: A new and exciting breakthrough due to Maynard establishes that there exist infinitely many pairs of distinct primes p1, p2 with |p1-p2| ≤ 600 as a consequence of the Bombieri-Vinogradov Theorem. In this paper, we apply his general method to the setting of Chebotarev sets of primes.
Methods: We use recent developments in sieve theory due to Maynard and Tao in conjunction with standard results in algebraic number theory.
Results: Given a Galois extension, we prove the existence of bounded gaps between primes p having the same Artin symbol.
Conclusions: We study applications of these bounded gaps with an emphasis on ranks of prime quadratic twists of elliptic curves over congruence properties of the Fourier coefficients of normalized Hecke eigenforms, and representations of primes by binary quadratic forms.
INTRODUCTION: There has been a rapid development of deep learning (DL) models for medical imaging. However, DL requires a large labeled dataset for training the models. Getting large-scale labeled data remains a challenge, and multi-center datasets suffer from heterogeneity due to patient diversity and varying imaging protocols. Domain adaptation (DA) has been developed to transfer the knowledge from a labeled data domain to a related but unlabeled domain in either image space or feature space. DA is a type of transfer learning (TL) that can improve the performance of models when applied to multiple different datasets. OBJECTIVE: In this survey, we review the state-of-the-art DL-based DA methods for medical imaging. We aim to summarize recent advances, highlighting the motivation, challenges, and opportunities, and to discuss promising directions for future work in DA for medical imaging. METHODS: We surveyed peer-reviewed publications from leading biomedical journals and conferences between 2017-2020, that reported the use of DA in medical imaging applications, grouping them by methodology, image modality, and learning scenarios. RESULTS: We mainly focused on pathology and radiology as application areas. Among various DA approaches, we discussed domain transformation (DT) and latent feature-space transformation (LFST). We highlighted the role of unsupervised DA in image segmentation and described opportunities for future development. CONCLUSION: DA has emerged as a promising solution to deal with the lack of annotated training data. Using adversarial techniques, unsupervised DA has achieved good performance, especially for segmentation tasks. Opportunities include domain transferability, multi-modal DA, and applications that benefit from synthetic data.
The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.
The extraction of common and distinct biomedical signatures among different populations allows for a more detailed study of the group-specific as well as distinct information of different populations. A number of subspace analysis algorithms have been developed and successfully applied to data fusion, however they are limited to joint analysis of only a couple of datasets. Since subspace analysis is very promising for analysis of multi-subject medical imaging data as well, we focus on this problem and propose a new method based on independent vector analysis (IVA) for common subspace extraction (IVA-CS) for multi-subject data analysis. IVA-CS leverages the strength of IVA in identification of a complete subspace structure across multiple datasets along with an efficient solution that uses only second-order statistics. We propose a subset analysis approach within IVA-CS to mitigate issues in estimation in IVA due to high dimensionality, both in terms of components estimated and the number of datasets. We introduce a scheme to determine a desirable size for the subset that is high enough to exploit the dependence across datasets and is not affected by the high dimensionality issue. We demonstrate the success of IVA-CS in extracting complex subset structures and apply the method to analysis of functional magnetic resonance imaging data from 179 subjects and show that it successfully identifies shared and complementary brain patterns from patients with schizophrenia (SZ) and healthy controls group. Two components with linked resting-state networks are identified to be unique to the SZ group providing evidence of functional dysconnectivity. IVA-CS also identifies subgroups of SZs that show significant differences in terms of their brain networks and clinical symptoms.
Association rule mining has been utilized extensively in many areas because it has the ability to discover relationships among variables in large databases. However, one main drawback of association rule mining is that it attempts to generate a large number of rules and does not guarantee that the rules are meaningful in the real world. Many visualization techniques have been proposed for association rules. These techniques were designed to provide a global overview of all rules so as to identify the most meaningful rules. However, using these visualization techniques to search for specific rules becomes challenging especially when the volume of rules is extremely large.
In this study, we have developed an interactive association rule visualization technique, called InterVisAR, specifically designed for effective rule search. We conducted a user study with 24 participants, and the results demonstrated that InterVisAR provides an efficient and accurate visualization solution. We also verified that InterVisAR satisfies a non-factorial property that should be guaranteed in performing rule search. All participants also expressed high preference towards InterVisAR as it provides a more comfortable and pleasing visualization in association rule search comparing with table-based rule search.
Advances in imaging acquisition techniques allow multiple imaging modalities to be collected from the same subject. Each individual modality offers limited yet unique views of the functional, structural, or dynamic temporal features of the brain. Multimodal fusion provides effective ways to leverage these complementary perspectives from multiple modalities. However, the majority of current multimodal fusion approaches involving functional magnetic resonance imaging (fMRI) are limited to 3D feature summaries that do not incorporate its rich temporal information. Thus, we propose a novel three-way parallel group independent component analysis (pGICA) fusion method that incorporates the first-level 4D fMRI data (temporal information included) by parallelizing group ICA into parallel ICA via a unified optimization framework.
A new variability matrix was defined to capture subject-wise functional variability and then link it to the mixing matrices of the other two modalities. Simulation results show that the three-way pGICA provides highly accurate cross-modality linkage estimation under both weakly and strongly correlated conditions, as well as comparable source estimation under different noise levels. Results using real brain imaging data identified one linked functional–structural–diffusion component associated to differences between schizophrenia and controls. This was replicated in an independent cohort, and the identified components were also correlated with major cognitive domains. Functional network connectivity revealed visual–subcortical and default mode-cerebellum pairs that discriminate between schizophrenia and controls. Overall, both simulation and real data results support the use of three-way pGICA to identify multimodal spatiotemporal links and to pursue the study of brain disorders under a single unifying multimodal framework.
It is becoming increasingly common to collect multiple related neuroimaging datasets either from different modalities or from different tasks and conditions. In addition, we have non-imaging data such as cognitive or behavioral variables, and it is through the association of these two sets of data—neuroimaging and non-neuroimaging—that we can understand and explain the evolution of neural and cognitive processes, and predict outcomes for intervention and treatment. Multiple methods for the joint analysis or fusion of multiple neuroimaging datasets or modalities exist; however, methods for the joint analysis of imaging and non-imaging data are still in their infancy. Current approaches for identifying brain networks related to cognitive assessments are still largely based on simple one-to-one correlation analyses and do not use the cross information available across multiple datasets. This work proposes two approaches based on independent vector analysis (IVA) to jointly analyze the imaging datasets and behavioral variables such that multivariate relationships across imaging data and behavioral features can be identified. The simulation results show that our proposed methods provide better accuracy in identifying associations across imaging and behavioral components than current approaches. With functional magnetic resonance imaging (fMRI) task data collected from 138 healthy controls and 109 patients with schizophrenia, results reveal that the central executive network (CEN) estimated in multiple datasets shows a strong correlation with the behavioral variable that measures working memory, a result that is not identified by traditional approaches. Most of the identified fMRI maps also show significant differences in activations across healthy controls and patients potentially providing a useful signature of mental disorders.
Background
Schizophrenia is a brain disorder characterized by diffuse, diverse, and wide-spread changes in gray matter volume (GM) and white matter structure (fractional anisotropy, FA), as well as cognitive impairments that greatly impact an individual’s quality of life. While the relationship of each of these image modalities and their links to schizophrenia status and cognitive impairment has been investigated separately, a multimodal fusion via parallel independent component analysis (pICA) affords the opportunity to explore the relationships between the changes in GM and FA, and the implications these network changes have on cognitive performance.
Methods
Images from 73 subjects with schizophrenia (SZ) and 82 healthy controls (HC) were drawn from an existing dataset. We investigated 12 components from each feature (FA and GM). Loading coefficients from the images were used to identify pairs of features that were significantly correlated and showed significant group differences between HC and SZ. MANCOVA analysis uncovered the relationships the identified spatial maps had with age, gender, and a global cognitive performance score.
Results
Three component pairs showed significant group differences (HC > SZ) in both gray and white matter measurements. Two of the component pairs identified networks of gray matter that drove significant relationships with cognition (HC > SZ) after accounting for age and gender. The gray and white matter structural networks identified in these three component pairs pull broadly from many regions, including the right and left thalamus, lateral occipital cortex, multiple regions of the middle temporal gyrus, precuneus cortex, postcentral gyrus, cingulate gyrus/cingulum, lingual gyrus, and brain stem.
Conclusion
The results of this multimodal analysis adds to our understanding of how the relationship between GM, FA, and cognition differs between HC and SZ by highlighting the correlated intermodal covariance of these structural networks and their differential relationships with cognitive performance. Previous unimodal research has found similar areas of GM and FA differences between these groups, and the cognitive deficits associated with SZ have been well documented. This study allowed us to evaluate the intercorrelated covariance of these structural networks and how these networks are involved the differences in cognitive performance between HC and SZ.
Dynamic muscle fascicle length measurements through B-mode ultrasound have become popular for the non-invasive physiological insights they provide regarding musculoskeletal structure-function. However, current practices typically require time consuming post-processing to track muscle length changes from B-mode images. A real-time measurement tool would not only save processing time but would also help pave the way toward closed-loop applications based on feedback signals driven by in vivo muscle length change patterns. In this paper, we benchmark an approach that combines traditional machine learning (ML) models with B-mode ultrasound recordings to obtain muscle fascicle length changes in real-time. To gauge the utility of this framework for ‘in-the-loop’ applications, we evaluate accuracy of the extracted muscle length change signals against time-series’ derived from a standard, post-hoc automated tracking algorithm.