Search

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, significantly impacting cost, mortality, and burden worldwide. The advent of high-throughput omics technologies, such as genomics, transcriptomics, proteomics, and epigenomics, has revolutionized the molecular understanding of AD. Conventional AI approaches typically require the completion of all omics data at the outset to achieve optimal AD diagnosis, which are inefficient and may be unnecessary. To reduce the clinical cost and improve the accuracy of AD diagnosis using multi-omics data, we propose a novel staged graph convolutional network with uncertainty quantification (SGUQ). SGUQ begins with mRNA and progressively incorporates DNA methylation and miRNA data only when necessary, reducing overall costs and exposure to harmful tests. Experimental results indicate that 46.23% of the samples can be reliably predicted using only single-modal omics data (mRNA), while an additional 16.04% of the samples can achieve reliable predictions when combining two omics data types (mRNA + DNA methylation). In addition, the proposed staged SGUQ achieved an accuracy of 0.858 on ROSMAP dataset, which outperformed existing methods significantly. The proposed SGUQ can not only be applied to AD diagnosis using multi-omics data but also has the potential for clinical decision-making using multi-viewed data. Our implementation is publicly available at https://github.com/chenzhao2023/multiomicsuncertainty., Comment: 20 pages, 2 figures

For object detection detectors, enhancing model performance hinges on the ability to simultaneously consider inconsistencies across tasks and focus on difficult-to-train samples. Achieving this necessitates incorporating information from both the classification and regression tasks. However, prior work tends to either emphasize difficult-to-train samples within their respective tasks or simply compute classification scores with IoU, often leading to suboptimal model performance. In this paper, we propose a Hybrid Classification-Regression Adaptive Loss, termed as HCRAL. Specifically, we introduce the Residual of Classification and IoU (RCI) module for cross-task supervision, addressing task inconsistencies, and the Conditioning Factor (CF) to focus on difficult-to-train samples within each task. Furthermore, we introduce a new strategy named Expanded Adaptive Training Sample Selection (EATSS) to provide additional samples that exhibit classification and regression inconsistencies. To validate the effectiveness of the proposed method, we conduct extensive experiments on COCO test-dev. Experimental evaluations demonstrate the superiority of our approachs. Additionally, we designed experiments by separately combining the classification and regression loss with regular loss functions in popular one-stage models, demonstrating improved performance.

Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors. We propose a novel staged model that combines advanced imaging and clinical data to improve predictive performance. By using CNNs to extract features from hip DXA images, along with clinical variables, shape measurements, and texture features, our method provides a comprehensive framework for assessing fracture risk. A staged machine learning-based model was developed using two ensemble models: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and DXA imaging features). This staged approach used uncertainty quantification from Ensemble 1 to decide if DXA features are necessary for further prediction. Ensemble 2 exhibited the highest performance, achieving an AUC of 0.9541, an accuracy of 0.9195, a sensitivity of 0.8078, and a specificity of 0.9427. The staged model also performed well, with an AUC of 0.8486, an accuracy of 0.8611, a sensitivity of 0.5578, and a specificity of 0.9249, outperforming Ensemble 1, which had an AUC of 0.5549, an accuracy of 0.7239, a sensitivity of 0.1956, and a specificity of 0.8343. Furthermore, the staged model suggested that 54.49% of patients did not require DXA scanning. It effectively balanced accuracy and specificity, offering a robust solution when DXA data acquisition is not always feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of the advanced modeling strategies. Our staged approach could identify individuals at risk with a high accuracy but reduce the unnecessary DXA scanning. It has great promise to guide interventions to prevent hip fractures with reduced cost and radiation., Comment: 29 pages, 5 figures, 6 tables

Objective: fMRI and derived measures such as functional connectivity (FC) have been used to predict brain age, general fluid intelligence, psychiatric disease status, and preclinical neurodegenerative disease. However, it is not always clear that all demographic confounds, such as age, sex, and race, have been removed from fMRI data. Additionally, many fMRI datasets are restricted to authorized researchers, making dissemination of these valuable data sources challenging. Methods: We create a variational autoencoder (VAE)-based model, DemoVAE, to decorrelate fMRI features from demographics and generate high-quality synthetic fMRI data based on user-supplied demographics. We train and validate our model using two large, widely used datasets, the Philadelphia Neurodevelopmental Cohort (PNC) and Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP). Results: We find that DemoVAE recapitulates group differences in fMRI data while capturing the full breadth of individual variations. Significantly, we also find that most clinical and computerized battery fields that are correlated with fMRI data are not correlated with DemoVAE latents. An exception are several fields related to schizophrenia medication and symptom severity. Conclusion: Our model generates fMRI data that captures the full distribution of FC better than traditional VAE or GAN models. We also find that most prediction using fMRI data is dependent on correlation with, and prediction of, demographics. Significance: Our DemoVAE model allows for generation of high quality synthetic data conditioned on subject demographics as well as the removal of the confounding effects of demographics. We identify that FC-based prediction tasks are highly influenced by demographic confounds., Comment: 12 pages

The best way to treat chronic hepatitis B is with pegylated interferon alone or with oral antiviral drugs. There is limited research comparing the renal safety of entecavir and tenofovir when used with pegylated interferon. This study will compare changes in renal function in chronic hepatitis B patients treated with pegylated interferon and either entecavir or tenofovir. The study included a cohort of 836 patients with chronic hepatitis B (CHB) who received treatment with pegylated interferon (IFN) either alone or in combination with entecavir (ETV) and tenofovir (TDF) between the years 2018 and 2021. Of these patients, 713 were included in a matched analysis comparing outcomes between those who were cured and those who were uncured, while 123 patients received IFN alone as a control group for comparison with the ETV and TDF treatment groups. The primary outcome measured was the change in renal function, specifically estimated glomerular filtration rate (eGFR), cystatin C (CysC), and inorganic phosphorus (IPHOS). Patients were categorized into stage 1 or stage 2 based on a baseline eGFR of less than 90 ml/min/m^2 Results: 125 CHB patients were matched 1:1 in both the combined treatment and cured groups. Baseline eGFR, CysC, and IPHOS levels were similar between the groups. Renal function in stage 1 and stage 2 groups showed a decreasing trend at 48 weeks after an initial increase.Correlation analysis showed significant relationships between changes in ALT and eGFR values at 12 weeks in both non-cured and cured groups. Conclusions: Over the 48-week duration of combined treatment in patients with chronic hepatitis B (CHB), it was found that both Tenofovir Disoproxil Fumarate (TDF) and Entecavir (ETV) did not lead to an increase in renal injury., Comment: Over the 48-week duration of combined treatment in patients with chronic hepatitis B (CHB), it was found that both Tenofovir Disoproxil Fumarate (TDF) and Entecavir (ETV) did not lead to an increase in renal injury

The explosion of data volume in communications, AI training, and cloud computing requires efficient data handling, which is typically stored as digital electrical information and transmitted as wireless radio frequency (RF) signals or light waves in optical fibres. Today's communications systems mostly treat the RF and optical signals separately, which results in unnecessary conversion losses and increased cost. In this work, we report the first fully on-chip signal processor for high-speed RF and optical signals based on a silicon photonic circuit. Our chip is capable of both generation and detection of analog electrical and optical signals, and can program a user-defined filter response in both domains. The single silicon photonic chip integrates all essential components like modulators, optical filters, and photodetectors, as well as tunable lasers enabled by transfer-printed Indium Phosphide (InP) optical amplifiers. The system's configuration is locally programmed through thermo-optic phase shifters and monitored by photodetectors. We demonstrate our chip's capabilities with different combinations of RF and optical signal processing functions, including optical and RF signal generation and filtering. This represents a key step towards compact microwave photonic systems for future wireless communication and sensing applications.

Schizophrenia (SCZ), as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk (CHR), first-episode psychosis (FEP), and long-term SCZ, using meta-analyses of functional magnetic resonance imaging (fMRI) studies. Following a systematic literature search, fifty-six whole-brain task-based fMRI studies (15 for CHR, 16 for FEP, 25 for long-term SCZ) were included. The separate and pooled neurofunctional mechanisms among CHR, FEP and long-term SCZ were generated by Seed-based d Mapping toolbox. The CHR and FEP groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of SCZ. Individuals with FEP showed lower activation in left inferior parietal lobule than those with long-term SCZ, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.

Background: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies. Method: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-view variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information. Results: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved R^2-scores > 0.01 for 71.55% of metabolites. Conclusion: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research., Comment: 19 pages, 3 figures

Purpose: Functional magnetic resonance imaging (fMRI) and functional connectivity (FC) have been used to follow aging in both children and older adults. Robust changes have been observed in children, where high connectivity among all brain regions changes to a more modular structure with maturation. In this work, we examine changes in FC in older adults after two years of aging in the UK Biobank longitudinal cohort. Approach: We process data using the Power264 atlas, then test whether FC changes in the 2,722-subject longitudinal cohort are statistically significant using a Bonferroni-corrected t-test. We also compare the ability of Power264 and UKB-provided, ICA-based FC to determine which of a longitudinal scan pair is older. Results: We find a 6.8\% average increase in SMT-VIS connectivity from younger to older scan (from $\rho=0.39$ to $\rho=0.42$) that occurs in male, female, older subject ($>65$ years old), and younger subject ($<55$ years old) groups. Among all inter-network connections, this average SMT-VIS connectivity is the best predictor of relative scan age, accurately predicting which scan is older 57\% of the time. Using the full FC and a training set of 2,000 subjects, one is able to predict which scan is older 82.5\% of the time using either the full Power264 FC or the UKB-provided ICA-based FC. Conclusions: We conclude that SMT-VIS connectivity increases in the longitudinal cohort, while resting state FC increases generally with age in the cross-sectional cohort. However, we consider the possibility of a change in resting state scanner task between UKB longitudinal data acquisitions., Comment: 11 pages, 12 figures, 4 tables

Functional magnetic resonance (fMRI) is an invaluable tool in studying cognitive processes in vivo. Many recent studies use functional connectivity (FC), partial correlation connectivity (PC), or fMRI-derived brain networks to predict phenotypes with results that sometimes cannot be replicated. At the same time, FC can be used to identify the same subject from different scans with great accuracy. In this paper, we show a method by which one can unknowingly inflate classification results from 61% accuracy to 86% accuracy by treating longitudinal or contemporaneous scans of the same subject as independent data points. Using the UK Biobank dataset, we find one can achieve the same level of variance explained with 50 training subjects by exploiting identifiability as with 10,000 training subjects without double-dipping. We replicate this effect in four different datasets: the UK Biobank (UKB), the Philadelphia Neurodevelopmental Cohort (PNC), the Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP), and an OpenNeuro Fibromyalgia dataset (Fibro). The unintentional improvement ranges between 7% and 25% in the four datasets. Additionally, we find that by using dynamic functional connectivity (dFC), one can apply this method even when one is limited to a single scan per subject. One major problem is that features such as ROIs or connectivities that are reported alongside inflated results may confuse future work. This article hopes to shed light on how even minor pipeline anomalies may lead to unexpectedly superb results., Comment: 8 pages, 11 with references

Integrated photonic reservoir computing has been demonstrated to be able to tackle different problems because of its neural network nature. A key advantage of photonic reservoir computing over other neuromorphic paradigms is its straightforward readout system, which facilitates both rapid training and robust, fabrication variation-insensitive photonic integrated hardware implementation for real-time processing. We present our recent development of a fully-optical, coherent photonic reservoir chip integrated with an optical readout system, capitalizing on these benefits. Alongside the integrated system, we also demonstrate a weight update strategy that is suitable for the integrated optical readout hardware. Using this online training scheme, we successfully solved 3-bit header recognition and delayed XOR tasks at 20 Gbps in real-time, all within the optical domain without excess delays.

Integration of heterogeneous and high-dimensional multi-omics data is becoming increasingly important in understanding genetic data. Each omics technique only provides a limited view of the underlying biological process and integrating heterogeneous omics layers simultaneously would lead to a more comprehensive and detailed understanding of diseases and phenotypes. However, one obstacle faced when performing multi-omics data integration is the existence of unpaired multi-omics data due to instrument sensitivity and cost. Studies may fail if certain aspects of the subjects are missing or incomplete. In this paper, we propose a deep learning method for multi-omics integration with incomplete data by Cross-omics Linked unified embedding with Contrastive Learning and Self Attention (CLCLSA). Utilizing complete multi-omics data as supervision, the model employs cross-omics autoencoders to learn the feature representation across different types of biological data. The multi-omics contrastive learning, which is used to maximize the mutual information between different types of omics, is employed before latent feature concatenation. In addition, the feature-level self-attention and omics-level self-attention are employed to dynamically identify the most informative features for multi-omics data integration. Extensive experiments were conducted on four public multi-omics datasets. The experimental results indicated that the proposed CLCLSA outperformed the state-of-the-art approaches for multi-omics data classification using incomplete multi-omics data., Comment: 21 pages; 5 figures

Most packages for the analysis of fMRI-based functional connectivity (FC) and genomic data are used with a programming language interface, lacking an easy-to-navigate GUI frontend. This exacerbates two problems found in these types of data: demographic confounds and quality control in the face of high dimensionality of features. The reason is that it is too slow and cumbersome to use a programming interface to create all the necessary visualizations required to identify all correlations, confounding effects, or quality control problems in a dataset. To remedy this situation, we have developed ImageNomer, a data visualization and analysis tool that allows inspection of both subject-level and cohort-level demographic, genomic, and imaging features. The software is Python-based, runs in a self-contained Docker image, and contains a browser-based GUI frontend. We demonstrate the usefulness of ImageNomer by identifying an unexpected race confound when predicting achievement scores in the Philadelphia Neurodevelopmental Cohort (PNC) dataset. In the past, many studies have attempted to use FC to identify achievement-related features in fMRI. Using ImageNomer, we find a clear potential for confounding effects of race. Using correlation analysis in the ImageNomer software, we show that FCs correlated with Wide Range Achievement Test (WRAT) score are in fact more highly correlated with race. Investigating further, we find that whereas both FC and SNP (genomic) features can account for 10-15\% of WRAT score variation, this predictive ability disappears when controlling for race. In this work, we demonstrate the advantage of our ImageNomer GUI tool in data exploration and confound detection. Additionally, this work identifies race as a strong confound in FC data and casts doubt on the possibility of finding unbiased achievement-related features in fMRI and SNP data of healthy adolescents., Comment: 11 pages

The application of transformation optics to the development of intriguing electromagnetic devices can produce weakly anisotropic or isotropic media with the assistance of quasi-conformal and/or conformal mapping, as opposed to the strongly anisotropic media produced by general mappings; however, it is typically limited to two-dimensional applications. By addressing the conformal mapping between two manifolds embedded in three-dimensional space, we demonstrate that electromagnetic surface waves can be controlled without introducing singularity and anisotropy into the device parameters. Using fruitful surface conformal parameterization methods, a near-perfect conformal mapping between smooth manifolds with arbitrary boundaries can be obtained. Illustrations of cloaking and illusions, including surface Luneburg and Eaton lenses and black holes for surface waves, are provided. Our work brings the manipulation of surface waves at microwave and optical wavelengths one step closer.