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A colored de Bruijn graph (also called a set of k-mer sets), is a set of k-mers with every k-mer assigned a set of colors. Colored de Bruijn graphs are used in a variety of applications, including variant calling, genome assembly, and database search. However, their size has posed a scalability challenge to algorithm developers and users. There have been numerous indexing data structures proposed that allow to store the graph compactly while supporting fast query operations. However, disk compression algorithms, which do not need to support queries on the compressed data and can thus be more space-efficient, have received little attention. The dearth of specialized compression tools has been a detriment to tool developers, tool users, and reproducibility efforts. In this paper, we develop a new tool that compresses colored de Bruijn graphs to disk, building on previous ideas for compression of k-mer sets and indexing colored de Bruijn graphs. We test our tool, called ESS-color, on various datasets, including both sequencing data and whole genomes. ESS-color achieves better compression than all evaluated tools and all datasets, with no other tool able to consistently achieve less than 44% space overhead. The software is available at http://github.com/medvedevgroup/ESSColor. [ABSTRACT FROM AUTHOR]

Purpose: String indexes such as the suffix array (sa) and the closely related longest common prefix (lcp) array are fundamental objects in bioinformatics and have a wide variety of applications. Despite their importance in practice, few scalable parallel algorithms for constructing these are known, and the existing algorithms can be highly non-trivial to implement and parallelize. Methods: In this paper we present caps-sa, a simple and scalable parallel algorithm for constructing these string indexes inspired by samplesort and utilizing an LCP-informed mergesort. Due to its design, caps-sa has excellent memory-locality and thus incurs fewer cache misses and achieves strong performance on modern multicore systems with deep cache hierarchies. Results: We show that despite its simple design, caps-sa outperforms existing state-of-the-art parallel sa and lcp-array construction algorithms on modern hardware. Finally, motivated by applications in modern aligners where the query strings have bounded lengths, we introduce the notion of a bounded-context sa and show that caps-sa can easily be extended to exploit this structure to obtain further speedups. We make our code publicly available at https://github.com/jamshed/CaPS-SA. [ABSTRACT FROM AUTHOR]

Purpose: String indexes such as the suffix array (sa) and the closely related longest common prefix (lcp) array are fundamental objects in bioinformatics and have a wide variety of applications. Despite their importance in practice, few scalable parallel algorithms for constructing these are known, and the existing algorithms can be highly non-trivial to implement and parallelize. Methods: In this paper we present caps-sa, a simple and scalable parallel algorithm for constructing these string indexes inspired by samplesort and utilizing an LCP-informed mergesort. Due to its design, caps-sa has excellent memory-locality and thus incurs fewer cache misses and achieves strong performance on modern multicore systems with deep cache hierarchies. Results: We show that despite its simple design, caps-sa outperforms existing state-of-the-art parallel sa and lcp-array construction algorithms on modern hardware. Finally, motivated by applications in modern aligners where the query strings have bounded lengths, we introduce the notion of a bounded-context sa and show that caps-sa can easily be extended to exploit this structure to obtain further speedups. We make our code publicly available at https://github.com/jamshed/CaPS-SA. [ABSTRACT FROM AUTHOR]

Background: We study the problem of finding maximal exact matches (MEMs) between a query string Q and a labeled graph G. MEMs are an important class of seeds, often used in seed-chain-extend type of practical alignment methods because of their strong connections to classical metrics. A principled way to speed up chaining is to limit the number of MEMs by considering only MEMs of length at least κ (κ -MEMs). However, on arbitrary input graphs, the problem of finding MEMs cannot be solved in truly sub-quadratic time under SETH (Equi et al., TALG 2023) even on acyclic graphs. Results: In this paper we show an O (n · L · d L - 1 + m + M κ , L) -time algorithm finding all κ -MEMs between Q and G spanning exactly L nodes in G, where n is the total length of node labels, d is the maximum degree of a node in G, m = | Q | , and M κ , L is the number of output MEMs. We use this algorithm to develop a κ -MEM finding solution on indexable Elastic Founder Graphs (Equi et al., Algorithmica 2022) running in time O (n H 2 + m + M κ) , where H is the maximum number of nodes in a block, and M κ is the total number of κ -MEMs. Our results generalize to the analysis of multiple query strings (MEMs between G and any of the strings). Additionally, we provide some experimental results showing that the number of graph MEMs is an order of magnitude smaller than the number of string MEMs of the corresponding concatenated collection. Conclusions: We show that seed-chain-extend type of alignment methods can be implemented on top of indexable Elastic Founder Graphs by providing an efficient way to produce the seeds between a set of queries and the graph. The code is available in https://github.com/algbio/efg-mems. [ABSTRACT FROM AUTHOR]

Over the last three decades, emergency surgery for perforated sigmoid diverticulitis has evolved dramatically but remains controversial. Diverticulitis is categorized as uncomplicated (amenable to outpatient treatment) versus complicated (requiring hospitalization).Patients with complicated diverticulitis undergo computerized tomography (CT) scanning and the CT findings are used categorize the severity of disease. Treatment of stage I (phlegmon with or without small abscess) and stage II (phlegmon with large abscess) diverticulitis (which includes bowel rest, intravenous antibiotics and percutaneous drainage (PCD) of the larger abscesses) has not changed much over last two decades. On the other hand, treatment of stage III (purulent peritonitis) and stage IV (feculent peritonitis) diverticulitis has evolved dramatically and remains morbid. In the 1980s a two stage procedure (1st--segmental sigmoid resection with end colostomy and 2nd--colostomy closure after three to six months) was standard of care for most general surgeons. However, it was recognized that half of these patients never had their colostomy reversed and that colostomy closure was a morbid procedure. As a result starting in the 1990s colorectal surgical specialists increasing performed a one stage primary resection anastomosis (PRA) and demonstrated similar outcomes to the two stage procedure. In the mid 2000s, the colorectal surgeons promoted this as standard of care. But unfortunately despite advances in perioperative care and their excellent surgical skills, PRA for stage III/IV diverticulitis continued to have a high mortality (10-15%). The survivors require prolonged hospital stays and often do not fully recover. Recent case series indicate that a substantial portion of the patients who previously were subjected to emergency sigmoid colectomy can be successfully treated with less invasive nonoperative management with salvage PCD and/or laparoscopic lavage and drainage. These patients experience a surprisingly lower mortality and more rapid recovery. They are also spared the need for a colostomy and do not appear to benefit from a delayed elective sigmoid colectomy. While we await the final results ongoing prospective randomized clinical trials testing these less invasive alternatives, we have proposed (based primarily on case series and our expert opinions) what we believe safe and rationale management strategy. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking remains the leading cause of preventable disease and death in the United States. Primary care offers an ideal setting to reach adults who smoke cigarettes and improve uptake of evidence-based cessation treatment. Although U.S. Preventive Services Task Force Guidelines recommend the 5As model (Ask, Advise, Assess, Assist, Arrange) in primary care, there are many barriers to its implementation. Automated, comprehensive, and proactive tools are needed to overcome barriers. Our team developed and preliminarily evaluated a proactive electronic visit (e-visit) delivered via the Electronic Health Record patient portal to facilitate evidence-based smoking cessation treatment uptake in primary care, with promising initial feasibility and efficacy. This paper describes the rationale, design, and protocol for an ongoing Hybrid Type I effectiveness-implementation trial that will simultaneously assess effectiveness of the e-visit intervention for smoking cessation as well as implementation potential across diverse primary care settings. Methods: The primary aim of this remote five-year study is to examine the effectiveness of the e-visit intervention vs. treatment as usual (TAU) for smoking cessation via a clinic-randomized clinical trial. Adults who smoke cigarettes are recruited across 18 primary care clinics. Clinics are stratified based on their number of primary care providers and randomized 2:1 to either e-visit or TAU. An initial baseline e-visit gathers information about patient smoking history and motivation to quit, and a clinical decision support algorithm determines the best evidence-based cessation treatment to prescribe. E-visit recommendations are evaluated by a patient's own provider, and a one-month follow-up e-visit assesses cessation progress. Main outcomes include: (1) cessation treatment utilization (medication, psychosocial cessation counseling), (2) reduction in cigarettes per day, and (3) biochemically verified 7-day point prevalence abstinence (PPA) at six-months. We hypothesize that patients randomized to the e-visit condition will have better cessation outcomes (vs. TAU). A secondary aim evaluates e-visit implementation potential at patient, provider, and organizational levels using a mixed-methods approach. Implementation outcomes include acceptability, adoption, fidelity, implementation cost, penetration, and sustainability. Discussion: This asynchronous, proactive e-visit intervention could provide substantial benefits for patients, providers, and primary care practices and has potential to widely improve reach of evidence-based cessation treatment. Trial registration: NCT05493254. [ABSTRACT FROM AUTHOR]

Objective: In this paper, we develop a new root-finding algorithm to solve the given non-linear equations. The proposed root-finding algorithm is based on the exponential method. This algorithm is derivative-free and converges fast. Results: Several numerical examples are presented to illustrate and validation of the proposed methods. Microsoft Excel and Maple implementation of the proposed algorithm is presented with sample computations. [ABSTRACT FROM AUTHOR]

Introduction: Plasmode simulations are a type of simulations that use real data to determine the synthetic data-generating equations. Such simulations thus allow evaluating statistical methods under realistic conditions. As far as we know, no plasmode algorithm has been proposed for simulating longitudinal data. In this paper, we propose a longitudinal plasmode framework to generate realistic data with both a time-varying exposure and time-varying covariates. This work was motivated by the objective of comparing different methods for estimating the causal effect of a cumulative exposure to psychosocial stressors at work over time. Methods: We developed two longitudinal plasmode algorithms: a parametric and a nonparametric algorithms. Data from the PROspective Québec (PROQ) Study on Work and Health were used as an input to generate data with the proposed plasmode algorithms. We evaluated the performance of multiple estimators of the parameters of marginal structural models (MSMs): inverse probability of treatment weighting, g-computation and targeted maximum likelihood estimation. These estimators were also compared to standard regression approaches with either adjustment for baseline covariates only or with adjustment for both baseline and time-varying covariates. Results: Standard regression methods were susceptible to yield biased estimates with confidence intervals having coverage probability lower than their nominal level. The bias was much lower and coverage of confidence intervals was much closer to the nominal level when considering MSMs. Among MSM estimators, g-computation overall produced the best results relative to bias, root mean squared error and coverage of confidence intervals. No method produced unbiased estimates with adequate coverage for all parameters in the more realistic nonparametric plasmode simulation. Conclusion: The proposed longitudinal plasmode algorithms can be important methodological tools for evaluating and comparing analytical methods in realistic simulation scenarios. To facilitate the use of these algorithms, we provide R functions on GitHub. We also recommend using MSMs when estimating the effect of cumulative exposure to psychosocial stressors at work. [ABSTRACT FROM AUTHOR]

Background: Food frequency questionnaires (FFQs) are one of the most useful tools for studying and understanding diet-disease relationships. However, because FFQs are self-reported data, they are susceptible to response bias, social desirability bias, and misclassification. Currently, several methods have been created to combat these issues by modelling the measurement error in diet-disease relationships. Method: In this paper, a novel machine learning method is proposed to adjust for measurement error found in misreported data by using a random forest (RF) classifier to label the responses in the FFQ based on the input dataset and creating an algorithm that adjusts the measurement error. We demonstrate this method by addressing underreporting in selected FFQ responses. Result: According to the results, we have high model accuracies ranging from 78% to 92% in participant collected data and 88% in simulated data. Conclusion: This shows that our proposed method of using a RF classifier and an error adjustment algorithm is efficient to correct most of the underreported entries in the FFQ dataset and could be used independent of diet-disease models. This could help nutrition researchers and other experts to use dietary data estimated by FFQs with less measurement error and create models from the data with minimal noise. [ABSTRACT FROM AUTHOR]

Bayesian phylogenetics is a computationally challenging inferential problem. Classical methods are based on random-walk Markov chain Monte Carlo (MCMC), where random proposals are made on the tree parameter and the continuous parameters simultaneously. Variational phylogenetics is a promising alternative to MCMC, in which one fits an approximating distribution to the unnormalized phylogenetic posterior. Previous work fit this variational approximation using stochastic gradient descent, which is the canonical way of fitting general variational approximations. However, phylogenetic trees are special structures, giving opportunities for efficient computation. In this paper we describe a new algorithm that directly generalizes the Felsenstein pruning algorithm (a.k.a. sum-product algorithm) to compute a composite-like likelihood by marginalizing out ancestral states and subtrees simultaneously. We show the utility of this algorithm by rapidly making point estimates for branch lengths of a multi-tree phylogenetic model. These estimates accord with a long MCMC run and with estimates obtained using a variational method, but are much faster to obtain. Thus, although generalized pruning does not lead to a variational algorithm as such, we believe that it will form a useful starting point for variational inference. [ABSTRACT FROM AUTHOR]

Primary care physicians (PCPs) play an indispensable role in providing comprehensive care and referring patients for specialty care and other medical services. As the COVID-19 outbreak disrupts patient access to care, understanding the quality of primary care is critical at this unprecedented moment to support patients with complex medical needs in the primary care setting and inform policymakers to redesign our primary care system. The traditional way of collecting information from patient surveys is time-consuming and costly, and novel data collection and analysis methods are needed. In this review paper, we describe the existing algorithms and metrics that use the real-world data to qualify and quantify primary care, including the identification of an individual's likely PCP (identification of plurality provider and major provider), assessment of process quality (for example, appropriate-care-model composite measures), and continuity and regularity of care index (including the interval index, variance index and relative variance index), and highlight the strength and limitation of real world data from electronic health records (EHRs) and claims data in determining the quality of PCP care. The EHR audits facilitate assessing the quality of the workflow process and clinical appropriateness of primary care practices. With extensive and diverse records, administrative claims data can provide reliable information as it assesses primary care quality through coded information from different providers or networks. The use of EHRs and administrative claims data may be a cost-effective analytic strategy for evaluating the quality of primary care. [ABSTRACT FROM AUTHOR]

Background: Although digital mobility outcomes (DMOs) can be readily calculated from real-world data collected with wearable devices and ad-hoc algorithms, technical validation is still required. The aim of this paper is to comparatively assess and validate DMOs estimated using real-world gait data from six different cohorts, focusing on gait sequence detection, foot initial contact detection (ICD), cadence (CAD) and stride length (SL) estimates. Methods: Twenty healthy older adults, 20 people with Parkinson's disease, 20 with multiple sclerosis, 19 with proximal femoral fracture, 17 with chronic obstructive pulmonary disease and 12 with congestive heart failure were monitored for 2.5 h in the real-world, using a single wearable device worn on the lower back. A reference system combining inertial modules with distance sensors and pressure insoles was used for comparison of DMOs from the single wearable device. We assessed and validated three algorithms for gait sequence detection, four for ICD, three for CAD and four for SL by concurrently comparing their performances (e.g., accuracy, specificity, sensitivity, absolute and relative errors). Additionally, the effects of walking bout (WB) speed and duration on algorithm performance were investigated. Results: We identified two cohort-specific top performing algorithms for gait sequence detection and CAD, and a single best for ICD and SL. Best gait sequence detection algorithms showed good performances (sensitivity > 0.73, positive predictive values > 0.75, specificity > 0.95, accuracy > 0.94). ICD and CAD algorithms presented excellent results, with sensitivity > 0.79, positive predictive values > 0.89 and relative errors < 11% for ICD and < 8.5% for CAD. The best identified SL algorithm showed lower performances than other DMOs (absolute error < 0.21 m). Lower performances across all DMOs were found for the cohort with most severe gait impairments (proximal femoral fracture). Algorithms' performances were lower for short walking bouts; slower gait speeds (< 0.5 m/s) resulted in reduced performance of the CAD and SL algorithms. Conclusions: Overall, the identified algorithms enabled a robust estimation of key DMOs. Our findings showed that the choice of algorithm for estimation of gait sequence detection and CAD should be cohort-specific (e.g., slow walkers and with gait impairments). Short walking bout length and slow walking speed worsened algorithms' performances. Trial registration ISRCTN – 12246987. [ABSTRACT FROM AUTHOR]

Tracking points in ultrasound (US) videos can be especially useful to characterize tissues in motion. Tracking algorithms that analyze successive video frames, such as variations of Optical Flow and Lucas–Kanade (LK), exploit frame-to-frame temporal information to track regions of interest. In contrast, convolutional neural-network (CNN) models process each video frame independently of neighboring frames. In this paper, we show that frame-to-frame trackers accumulate error over time. We propose three interpolation-like methods to combat error accumulation and show that all three methods reduce tracking errors in frame-to-frame trackers. On the neural-network end, we show that a CNN-based tracker, DeepLabCut (DLC), outperforms all four frame-to-frame trackers when tracking tissues in motion. DLC is more accurate than the frame-to-frame trackers and less sensitive to variations in types of tissue movement. The only caveat found with DLC comes from its non-temporal tracking strategy, leading to jitter between consecutive frames. Overall, when tracking points in videos of moving tissue, we recommend using DLC when prioritizing accuracy and robustness across movements in videos, and using LK with the proposed error-correction methods for small movements when tracking jitter is unacceptable. [ABSTRACT FROM AUTHOR]

Tracking points in ultrasound (US) videos can be especially useful to characterize tissues in motion. Tracking algorithms that analyze successive video frames, such as variations of Optical Flow and Lucas–Kanade (LK), exploit frame-to-frame temporal information to track regions of interest. In contrast, convolutional neural-network (CNN) models process each video frame independently of neighboring frames. In this paper, we show that frame-to-frame trackers accumulate error over time. We propose three interpolation-like methods to combat error accumulation and show that all three methods reduce tracking errors in frame-to-frame trackers. On the neural-network end, we show that a CNN-based tracker, DeepLabCut (DLC), outperforms all four frame-to-frame trackers when tracking tissues in motion. DLC is more accurate than the frame-to-frame trackers and less sensitive to variations in types of tissue movement. The only caveat found with DLC comes from its non-temporal tracking strategy, leading to jitter between consecutive frames. Overall, when tracking points in videos of moving tissue, we recommend using DLC when prioritizing accuracy and robustness across movements in videos, and using LK with the proposed error-correction methods for small movements when tracking jitter is unacceptable. [ABSTRACT FROM AUTHOR]

Background: MiRNA is a class of non-coding single-stranded RNA molecules with a length of approximately 22 nucleotides encoded by endogenous genes, which can regulate the expression of other genes. Therefore, it is very important to predict the associations between miRNA and disease. Predecessors developed a new prediction method of drug-disease association, and it achieved good results.Methods: In this paper, we introduced the method of LAGCN to identify potential miRNA-disease associations. First, we integrate three associations into a heterogeneous network, such as the known miRNA-disease association, miRNA-miRNA similarities and disease-disease similarities, next we apply graph convolution network to learn the embedding of miRNA and disease. We use an attention mechanism to combine embedding from multiple convolution layers. Unobserved miRNA-disease associations are scored based on integrated embedding.Results: After fivefold cross-validations, the value of AUC is reached 0.9091, which is higher than other prediction methods and baseline methods.Conclusions: In this paper, we introduced the method of LAGCN to identify potential miRNA-disease associations. LAGCN has achieved good performance in predicting miRNA-disease associations, and it is superior to other association prediction methods and baseline methods. [ABSTRACT FROM AUTHOR]

Synchronization (insertions–deletions) errors are still a major challenge for reliable information retrieval in DNA storage. Unlike traditional error correction codes (ECC) that add redundancy in the stored information, multiple sequence alignment (MSA) solves this problem by searching the conserved subsequences. In this paper, we conduct a comprehensive simulation study on the error correction capability of a typical MSA algorithm, MAFFT. Our results reveal that its capability exhibits a phase transition when there are around 20% errors. Below this critical value, increasing sequencing depth can eventually allow it to approach complete recovery. Otherwise, its performance plateaus at some poor levels. Given a reasonable sequencing depth (≤ 70), MSA could achieve complete recovery in the low error regime, and effectively correct 90% of the errors in the medium error regime. In addition, MSA is robust to imperfect clustering. It could also be combined with other means such as ECC, repeated markers, or any other code constraints. Furthermore, by selecting an appropriate sequencing depth, this strategy could achieve an optimal trade-off between cost and reading speed. MSA could be a competitive alternative for future DNA storage. [ABSTRACT FROM AUTHOR]

Background: Knowledge graphs (KGs), especially medical knowledge graphs, are often significantly incomplete, so it necessitating a demand for medical knowledge graph completion (MedKGC). MedKGC can find new facts based on the existed knowledge in the KGs. The path-based knowledge reasoning algorithm is one of the most important approaches to this task. This type of method has received great attention in recent years because of its high performance and interpretability. In fact, traditional methods such as path ranking algorithm take the paths between an entity pair as atomic features. However, the medical KGs are very sparse, which makes it difficult to model effective semantic representation for extremely sparse path features. The sparsity in the medical KGs is mainly reflected in the long-tailed distribution of entities and paths. Previous methods merely consider the context structure in the paths of knowledge graph and ignore the textual semantics of the symbols in the path. Therefore, their performance cannot be further improved due to the two aspects of entity sparseness and path sparseness.Methods: To address the above issues, this paper proposes two novel path-based reasoning methods to solve the sparsity issues of entity and path respectively, which adopts the textual semantic information of entities and paths for MedKGC. By using the pre-trained model BERT, combining the textual semantic representations of the entities and the relationships, we model the task of symbolic reasoning in the medical KG as a numerical computing issue in textual semantic representation.Results: Experiments results on the publicly authoritative Chinese symptom knowledge graph demonstrated that the proposed method is significantly better than the state-of-the-art path-based knowledge graph reasoning methods, and the average performance is improved by 5.83% for all relations.Conclusions: In this paper, we propose two new knowledge graph reasoning algorithms, which adopt textual semantic information of entities and paths and can effectively alleviate the sparsity problem of entities and paths in the MedKGC. As far as we know, it is the first method to use pre-trained language models and text path representations for medical knowledge reasoning. Our method can complete the impaired symptom knowledge graph in an interpretable way, and it outperforms the state-of-the-art path-based reasoning methods. [ABSTRACT FROM AUTHOR]

Background: Machine learning can be used to predict the different onset of human cancers. Highly dimensional data have enormous, complicated problems. One of these is an excessive number of genes plus over-fitting, fitting time, and classification accuracy. Recursive Feature Elimination (RFE) is a wrapper method for selecting the best subset of features that cause the best accuracy. Despite the high performance of RFE, time computation and over-fitting are two disadvantages of this algorithm. Random forest for selection (RFS) proves its effectiveness in selecting the effective features and improving the over-fitting problem. Method: This paper proposed a method, namely, positions first bootstrap step (PFBS) random forest selection recursive feature elimination (RFS-RFE) and its abbreviation is PFBS- RFS-RFE to enhance cancer classification performance. It used a bootstrap with many positions included in the outer first bootstrap step (OFBS), inner first bootstrap step (IFBS), and outer/ inner first bootstrap step (O/IFBS). In the first position, OFBS is applied as a resampling method (bootstrap) with replacement before selection step. The RFS is applied with bootstrap = false i.e., the whole datasets are used to build each tree. The importance features are hybrid with RFE to select the most relevant subset of features. In the second position, IFBS is applied as a resampling method (bootstrap) with replacement during applied RFS. The importance features are hybrid with RFE. In the third position, O/IFBS is applied as a hybrid of first and second positions. RFE used logistic regression (LR) as an estimator. The proposed methods are incorporated with four classifiers to solve the feature selection problems and modify the performance of RFE, in which five datasets with different size are used to assess the performance of the PFBS-RFS-RFE. Results: The results showed that the O/IFBS-RFS-RFE achieved the best performance compared with previous work and enhanced the accuracy, variance and ROC area for RNA gene and dermatology erythemato-squamous diseases datasets to become 99.994%, 0.0000004, 1.000 and 100.000%, 0.0 and 1.000, respectively. Conclusion: High dimensional datasets and RFE algorithm face many troubles in cancers classification performance. PFBS-RFS-RFE is proposed to fix these troubles with different positions. The importance features which extracted from RFS are used with RFE to obtain the effective features. [ABSTRACT FROM AUTHOR]

Background: Identifying protein complexes from protein-protein interaction network is one of significant tasks in the postgenome era. Protein complexes, none of which exceeds 10 in size play an irreplaceable role in life activities and are also a hotspot of scientific research, such as PSD-95, CD44, PKM2 and BRD4. And in MIPS, CYC2008, SGD, Aloy and TAP06 datasets, the proportion of small protein complexes is over 75%. But up to now, protein complex identification methods do not perform well in the field of small protein complexes. Results: In this paper, we propose a novel method, called BOPS. It is a three-step procedure. Firstly, it calculates the balanced weights to replace the original weights. Secondly, it divides the graphs larger than MAXP until the original PPIN is divided into small PPINs. Thirdly, it enumerates the connected subset of each small PPINs, identifies potential protein complexes based on cohesion and removes those that are similar. Conclusions: In four yeast PPINs, experimental results have shown that BOPS has an improvement of about 5% compared with the SOTA model. In addition, we constructed a weighted Homo sapiens PPIN based on STRINGdb and BioGRID, and BOPS gets the best result in it. These results give new insights into the identification of small protein complexes, and the weighted Homo sapiens PPIN provides more data for related research. [ABSTRACT FROM AUTHOR]

Biclustering algorithm is an effective tool for processing gene expression datasets. There are two kinds of data matrices, binary data and non-binary data, which are processed by biclustering method. A binary matrix is usually converted from pre-processed gene expression data, which can effectively reduce the interference from noise and abnormal data, and is then processed using a biclustering algorithm. However, biclustering algorithms of dealing with binary data have a poor balance between running time and performance. In this paper, we propose a new biclustering algorithm called the Adjacency Difference Matrix Binary Biclustering algorithm (AMBB) for dealing with binary data to address the drawback. The AMBB algorithm constructs the adjacency matrix based on the adjacency difference values, and the submatrix obtained by continuously updating the adjacency difference matrix is called a bicluster. The adjacency matrix allows for clustering of gene that undergo similar reactions under different conditions into clusters, which is important for subsequent genes analysis. Meanwhile, experiments on synthetic and real datasets visually demonstrate that the AMBB algorithm has high practicability. [ABSTRACT FROM AUTHOR]

Facial paralysis (FP) is an inability to move facial muscles voluntarily, affecting daily activities. There is a need for quantitative assessment and severity level classification of FP to evaluate the condition. None of the available tools are widely accepted. A comprehensive FP evaluation system has been developed by the authors. The system extracts real-time facial animation units (FAUs) using the Kinect V2 sensor and includes both FP assessment and classification. This paper describes the development and testing of the FP classification phase. A dataset of 375 records from 13 unilateral FP patients and 1650 records from 50 control subjects was compiled. Artificial Intelligence and Machine Learning methods are used to classify seven FP categories: the normal case and three severity levels: mild, moderate, and severe for the left and right sides. For better prediction results (Accuracy = 96.8%, Sensitivity = 88.9% and Specificity = 99%), an ensemble learning classifier was developed rather than one weak classifier. The ensemble approach based on SVMs was proposed for the high-dimensional data to gather the advantages of stacking and bagging. To address the problem of an imbalanced dataset, a hybrid strategy combining three separate techniques was used. Model robustness and stability was evaluated using fivefold cross-validation. The results showed that the classifier is robust, stable and performs well for different train and test samples. The study demonstrates that FAUs acquired by the Kinect sensor can be used in classifying FP. The developed FP assessment and classification system provides a detailed quantitative report and has significant advantages over existing grading scales. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis, a common degenerative disease of articular cartilage, is characterized by degeneration of articular cartilage, changes in subchondral bone structure, and formation of osteophytes, with main clinical manifestations including increasingly serious swelling, pain, stiffness, deformity, and mobility deficits of the knee joints. With the advent of the big data era, the processing of mass data has evolved into a hot topic and gained a solid foundation from the steadily developed and improved machine learning algorithms. Aiming to provide a reference for the diagnosis and treatment of osteoarthritis, this paper using machine learning identifies the key feature genes of osteoarthritis and explores its relationship with immune infiltration, thereby revealing its pathogenesis at the molecular level. Methods: From the GEO database, GSE55235 and GSE55457 data were derived as training sets and GSE98918 data as a validation set. Differential gene expressions of the training sets were analyzed, and the LASSO regression model and support vector machine model were established by applying machine learning algorithms. Moreover, their intersection genes were regarded as feature genes, the receiver operator characteristic (ROC) curve was drawn, and the results were verified using the validation set. In addition, the expression spectrum of osteoarthritis was analyzed by immunocyte infiltration and the co-expression correlation between feature genes and immunocytes was construed. Conclusion: EPYC and KLF9 can be viewed as feature genes for osteoarthritis. The silencing of EPYC and the overexpression of KLF9 are associated with the occurrence of osteoarthritis and immunocyte infiltration. [ABSTRACT FROM AUTHOR]

Background: The minimum variance (MV) beamformer can significantly improve the image resolution in ultrasound imaging, but it has limited performance in noise reduction. We recently proposed the covariance matrix-based statistical beamforming (CMSB) for medical ultrasound imaging to reduce sidelobes and incoherent clutter.Methods: In this paper, we aim to improve the imaging performance of the MV beamformer by introducing a new pixel-based adaptive weighting approach based on CMSB, which is named as covariance matrix-based adaptive weighting (CMSAW). The proposed CMSAW estimates the mean-to-standard-deviation ratio (MSR) of a modified covariance matrix reconstructed by adaptive spatial smoothing, rotary averaging, and diagonal reducing. Moreover, adaptive diagonal reducing based on the aperture coherence is introduced in CMSAW to enhance the performance in speckle preservation.Results: The proposed CMSAW-weighted MV (CMSAW-MV) was validated through simulation, phantom experiments, and in vivo studies. The phantom experimental results show that CMSAW-MV obtains resolution improvement of 21.3% and simultaneously achieves average improvements of 96.4% and 71.8% in average contrast and generalized contrast-to-noise ratio (gCNR) for anechoic cyst, respectively, compared with MV. in vivo studies indicate that CMSAW-MV improves the noise reduction performance of MV beamformer.Conclusion: Simulation, experimental, and in vivo results all show that CMSAW-MV can improve resolution and suppress sidelobes and incoherent clutter and noise. These results demonstrate the effectiveness of CMSAW in improving the imaging performance of MV beamformer. Moreover, the proposed CMSAW with a computational complexity of [Formula: see text] has the potential to be implemented in real time using the graphics processing unit. [ABSTRACT FROM AUTHOR]

Background: Image segmentation is considered an important step in image processing. Fuzzy c-means clustering is one of the common methods of image segmentation. However, this method suffers from drawbacks, such as sensitivity to initial values, entrapment in local optima, and the inability to distinguish objects with similar color intensity. This paper proposes the hybrid Fuzzy c-means clustering and Gray wolf optimization for image segmentation to overcome the shortcomings of Fuzzy c-means clustering. The Gray wolf optimization has a high exploration capability in finding the best solution to the problem, which prevents the entrapment of the algorithm in local optima. In this study, breast cytology images were used to validate the methods, and the results of the proposed method were compared to those of c-means clustering. Results: FCMGWO has performed better than FCM in separating the nucleus from the other dark objects in the cell. The clustering was validated using Vpc, Vpe, Davies-Bouldin, and Calinski Harabasz criteria. The FCM and FCMGWO methods have a significant difference with respect to the Vpc and Vpe indexes. However, there is no significant difference between the performances of the two clustering methods with respect to the Calinski-Harabasz and Davies-Bouldin indices. The results indicate the better efficacy of the proposed method. Conclusions: The hybrid FCMGWO algorithm distinguishes the cells better in images with less detail than in images with high detail. However, FCM exhibits unacceptable performance in both low- and high-detail images. [ABSTRACT FROM AUTHOR]

Background: With single-cell RNA sequencing (scRNA-seq) methods, gene expression patterns at the single-cell resolution can be revealed. But as impacted by current technical defects, dropout events in scRNA-seq lead to missing data and noise in the gene-cell expression matrix and adversely affect downstream analyses. Accordingly, the true gene expression level should be recovered before the downstream analysis is carried out. Results: In this paper, a novel low-rank tensor completion-based method, termed as scLRTC, is proposed to impute the dropout entries of a given scRNA-seq expression. It initially exploits the similarity of single cells to build a third-order low-rank tensor and employs the tensor decomposition to denoise the data. Subsequently, it reconstructs the cell expression by adopting the low-rank tensor completion algorithm, which can restore the gene-to-gene and cell-to-cell correlations. ScLRTC is compared with other state-of-the-art methods on simulated datasets and real scRNA-seq datasets with different data sizes. Specific to simulated datasets, scLRTC outperforms other methods in imputing the dropouts closest to the original expression values, which is assessed by both the sum of squared error (SSE) and Pearson correlation coefficient (PCC). In terms of real datasets, scLRTC achieves the most accurate cell classification results in spite of the choice of different clustering methods (e.g., SC3 or t-SNE followed by K-means), which is evaluated by using adjusted rand index (ARI) and normalized mutual information (NMI). Lastly, scLRTC is demonstrated to be also effective in cell visualization and in inferring cell lineage trajectories. Conclusions: a novel low-rank tensor completion-based method scLRTC gave imputation results better than the state-of-the-art tools. Source code of scLRTC can be accessed at https://github.com/jianghuaijie/scLRTC. [ABSTRACT FROM AUTHOR]

Background: Gene expression data play an important role in bioinformatics applications. Although there may be a large number of features in such data, they mainly tend to contain only a few samples. This can negatively impact the performance of data mining and machine learning algorithms. One of the most effective approaches to alleviate this problem is to use gene selection methods. The aim of gene selection is to reduce the dimensions (features) of gene expression data leading to eliminating irrelevant and redundant genes.Methods: This paper presents a hybrid gene selection method based on graph theory and a many-objective particle swarm optimization (PSO) algorithm. To this end, a filter method is first utilized to reduce the initial space of the genes. Then, the gene space is represented as a graph to apply a graph clustering method to group the genes into several clusters. Moreover, the many-objective PSO algorithm is utilized to search an optimal subset of genes according to several criteria, which include classification error, node centrality, specificity, edge centrality, and the number of selected genes. A repair operator is proposed to cover the whole space of the genes and ensure that at least one gene is selected from each cluster. This leads to an increasement in the diversity of the selected genes.Results: To evaluate the performance of the proposed method, extensive experiments are conducted based on seven datasets and two evaluation measures. In addition, three classifiers-Decision Tree (DT), Support Vector Machine (SVM), and K-Nearest Neighbors (KNN)-are utilized to compare the effectiveness of the proposed gene selection method with other state-of-the-art methods. The results of these experiments demonstrate that our proposed method not only achieves more accurate classification, but also selects fewer genes than other methods.Conclusion: This study shows that the proposed multi-objective PSO algorithm simultaneously removes irrelevant and redundant features using several different criteria. Also, the use of the clustering algorithm and the repair operator has improved the performance of the proposed method by covering the whole space of the problem. [ABSTRACT FROM AUTHOR]

Background: The correct identification of pills is very important to ensure the safe administration of drugs to patients. Here, we use three current mainstream object detection models, namely RetinaNet, Single Shot Multi-Box Detector (SSD), and You Only Look Once v3(YOLO v3), to identify pills and compare the associated performance.Methods: In this paper, we introduce the basic principles of three object detection models. We trained each algorithm on a pill image dataset and analyzed the performance of the three models to determine the best pill recognition model. The models were then used to detect difficult samples and we compared the results.Results: The mean average precision (MAP) of RetinaNet reached 82.89%, but the frames per second (FPS) is only one third of YOLO v3, which makes it difficult to achieve real-time performance. SSD does not perform as well on the indicators of MAP and FPS. Although the MAP of YOLO v3 is slightly lower than the others (80.69%), it has a significant advantage in terms of detection speed. YOLO v3 also performed better when tasked with hard sample detection, and therefore the model is more suitable for deployment in hospital equipment.Conclusion: Our study reveals that object detection can be applied for real-time pill identification in a hospital pharmacy, and YOLO v3 exhibits an advantage in detection speed while maintaining a satisfactory MAP. [ABSTRACT FROM AUTHOR]

Background: Developing efficient and successful computational methods to infer potential miRNA-disease associations is urgently needed and is attracting many computer scientists in recent years. The reason is that miRNAs are involved in many important biological processes and it is tremendously expensive and time-consuming to do biological experiments to verify miRNA-disease associations. Methods: In this paper, we proposed a new method to infer miRNA-disease associations using collaborative filtering and resource allocation algorithms on a miRNA-disease-lncRNA tripartite graph. It combined the collaborative filtering algorithm in CFNBC model to solve the problem of imbalanced data and the method for association prediction established multiple types of known associations among multiple objects presented in TPGLDA model. Results: The experimental results showed that our proposed method achieved a reliable performance with Area Under Roc Curve (AUC) and Area Under Precision-Recall Curve (AUPR) values of 0.9788 and 0.9373, respectively, under fivefold-cross-validation experiments. It outperformed than some other previous methods such as DCSMDA and TPGLDA. Furthermore, it demonstrated the ability to derive new associations between miRNAs and diseases among 8, 19 and 14 new associations out of top 40 predicted associations in case studies of Prostatic Neoplasms, Heart Failure, and Glioma diseases, respectively. All of these new predicted associations have been confirmed by recent literatures. Besides, it could discover new associations for new diseases (or miRNAs) without any known associations as demonstrated in the case study of Open-angle glaucoma disease. Conclusion: With the reliable performance to infer new associations between miRNAs and diseases as well as to discover new associations for new diseases (or miRNAs) without any known associations, our proposed method can be considered as a powerful tool to infer miRNA-disease associations. [ABSTRACT FROM AUTHOR]

Background: The historical data of rare disease is very scarce in reality, so how to perform drug repositioning for the rare disease is a great challenge. Most existing methods of drug repositioning for the rare disease usually neglect father-son information, so it is extremely difficult to predict drugs for the rare disease.Method: In this paper, we focus on father-son information mining for the rare disease. We propose GRU-Cooperation-Attention-Network (GCAN) to predict drugs for the rare disease. We construct two heterogeneous networks for information enhancement, one network contains the father-nodes of the rare disease and the other network contains the son-nodes information. To bridge two heterogeneous networks, we set a mapping to connect them. What's more, we use the biased random walk mechanism to collect the information smoothly from two heterogeneous networks, and employ a cooperation attention mechanism to enhance repositioning ability of the network.Result: Comparing with traditional methods, GCAN makes full use of father-son information. The experimental results on real drug data from hospitals show that GCAN outperforms state-of-the-art machine learning methods for drug repositioning.Conclusion: The performance of GCAN for drug repositioning is mainly limited by the insufficient scale and poor quality of the data. In future research work, we will focus on how to utilize more data such as drug molecule information and protein molecule information for the drug repositioning of the rare disease. [ABSTRACT FROM AUTHOR]

Background: Standardized coding of plays an important role in radiology reports' secondary use such as data analytics, data-driven decision support, and personalized medicine. RadLex, a standard radiological lexicon, can reduce subjective variability and improve clarity in radiology reports. RadLex coding of radiology reports is widely used in many countries, but translation and localization of RadLex in China are far from being established. Although automatic RadLex coding is a common way for non-standard radiology reports, the high-accuracy cross-language RadLex coding is hardly achieved due to the limitation of up-to-date auto-translation and text similarity algorithms and still requires further research.Methods: We present an effective approach that combines a hybrid translation and a Multilayer Perceptron weighting text similarity ensemble algorithm for automatic RadLex coding of Chinese structured radiology reports. Firstly, a hybrid way to integrate Google neural machine translation and dictionary translation helps to optimize the translation of Chinese radiology phrases to English. The dictionary is made up of 21,863 Chinese-English radiological term pairs extracted from several free medical dictionaries. Secondly, four typical text similarity algorithms are introduced, which are Levenshtein distance, Jaccard similarity coefficient, Word2vec Continuous bag-of-words model, and WordNet Wup similarity algorithms. Lastly, the Multilayer Perceptron model has been used to synthesize the contextual, lexical, character and syntactical information of four text similarity algorithms to promote precision, in which four similarity scores of two terms are taken as input and the output presents whether the two terms are synonyms.Results: The results show the effectiveness of the approach with an F1-score of 90.15%, a precision of 91.78% and a recall of 88.59%. The hybrid translation algorithm has no negative effect on the final coding, F1-score has increased by 21.44% and 8.12% compared with the GNMT algorithm and dictionary translation. Compared with the single similarity, the result of the MLP weighting similarity algorithm is satisfactory that has a 4.48% increase compared with the best single similarity algorithm, WordNet Wup.Conclusions: The paper proposed an innovative automatic cross-language RadLex coding approach to solve the standardization of Chinese structured radiology reports, that can be taken as a reference to automatic cross-language coding. [ABSTRACT FROM AUTHOR]

Background: Accurate segmentation and recognition algorithm of lung nodules has great important value of reference for early diagnosis of lung cancer. An algorithm is proposed for 3D CT sequence images in this paper based on 3D Res U-Net segmentation network and 3D ResNet50 classification network. The common convolutional layers in encoding and decoding paths of U-Net are replaced by residual units while the loss function is changed to Dice loss after using cross entropy loss to accelerate network convergence. Since the lung nodules are small and rich in 3D information, the ResNet50 is improved by replacing the 2D convolutional layers with 3D convolutional layers and reducing the sizes of some convolution kernels, 3D ResNet50 network is obtained for the diagnosis of benign and malignant lung nodules. Results: 3D Res U-Net was trained and tested on 1044 CT subcases in the LIDC-IDRI database. The segmentation result shows that the Dice coefficient of 3D Res U-Net is above 0.8 for the segmentation of lung nodules larger than 10 mm in diameter. 3D ResNet50 was trained and tested on 2960 lung nodules in the LIDC-IDRI database. The classification result shows that the diagnostic accuracy of 3D ResNet50 is 87.3% and AUC is 0.907. Conclusion: The 3D Res U-Net module improves segmentation performance significantly with the comparison of 3D U-Net model based on residual learning mechanism. 3D Res U-Net can identify small nodules more effectively and improve its segmentation accuracy for large nodules. Compared with the original network, the classification performance of 3D ResNet50 is significantly improved, especially for small benign nodules. [ABSTRACT FROM AUTHOR]

Background: Gene co-expression networks are widely studied in the biomedical field, with algorithms such as WGCNA and lmQCM having been developed to detect co-expressed modules. However, these algorithms have limitations such as insufficient granularity and unbalanced module size, which prevent full acquisition of knowledge from data mining. In addition, it is difficult to incorporate prior knowledge in current co-expression module detection algorithms. Results: In this paper, we propose a novel module detection algorithm based on topology potential and spectral clustering algorithm to detect co-expressed modules in gene co-expression networks. By testing on TCGA data, our novel method can provide more complete coverage of genes, more balanced module size and finer granularity than current methods in detecting modules with significant overall survival difference. In addition, the proposed algorithm can identify modules by incorporating prior knowledge. Conclusion: In summary, we developed a method to obtain as much as possible information from networks with increased input coverage and the ability to detect more size-balanced and granular modules. In addition, our method can integrate data from different sources. Our proposed method performs better than current methods with complete coverage of input genes and finer granularity. Moreover, this method is designed not only for gene co-expression networks but can also be applied to any general fully connected weighted network. [ABSTRACT FROM AUTHOR]

Background: Undernutrition is the main cause of child death in developing countries. This paper aimed to explore the efficacy of machine learning (ML) approaches in predicting under-five undernutrition in Ethiopian administrative zones and to identify the most important predictors.Method: The study employed ML techniques using retrospective cross-sectional survey data from Ethiopia, a national-representative data collected in the year (2000, 2005, 2011, and 2016). We explored six commonly used ML algorithms; Logistic regression, Least Absolute Shrinkage and Selection Operator (L-1 regularization logistic regression), L-2 regularization (Ridge), Elastic net, neural network, and random forest (RF). Sensitivity, specificity, accuracy, and area under the curve were used to evaluate the performance of those models.Results: Based on different performance evaluations, the RF algorithm was selected as the best ML model. In the order of importance; urban-rural settlement, literacy rate of parents, and place of residence were the major determinants of disparities of nutritional status for under-five children among Ethiopian administrative zones.Conclusion: Our results showed that the considered machine learning classification algorithms can effectively predict the under-five undernutrition status in Ethiopian administrative zones. Persistent under-five undernutrition status was found in the northern part of Ethiopia. The identification of such high-risk zones could provide useful information to decision-makers trying to reduce child undernutrition. [ABSTRACT FROM AUTHOR]

Background: Finding significant genes or proteins from gene chip data for disease diagnosis and drug development is an important task. However, the challenge comes from the curse of the data dimension. It is of great significance to use machine learning methods to find important features from the data and build an accurate classification model. Results: The proposed method has proved superior to the published advanced hybrid feature selection method and traditional feature selection method on different public microarray data sets. In addition, the biomarkers selected using our method show a match to those provided by the cooperative hospital in a set of clinical cleft lip and palate data. Method: In this paper, a feature selection algorithm ILRC based on clustering and improved L1 regularization is proposed. The features are firstly clustered, and the redundant features in the sub-clusters are deleted. Then all the remaining features are iteratively evaluated using ILR. The final result is given according to the cumulative weight reordering. Conclusion: The proposed method can effectively remove redundant features. The algorithm's output has high stability and classification accuracy, which can potentially select potential biomarkers. [ABSTRACT FROM AUTHOR]

Background: Undernutrition is the main cause of child death in developing countries. This paper aimed to explore the efficacy of machine learning (ML) approaches in predicting under-five undernutrition in Ethiopian administrative zones and to identify the most important predictors. Method: The study employed ML techniques using retrospective cross-sectional survey data from Ethiopia, a national-representative data collected in the year (2000, 2005, 2011, and 2016). We explored six commonly used ML algorithms; Logistic regression, Least Absolute Shrinkage and Selection Operator (L-1 regularization logistic regression), L-2 regularization (Ridge), Elastic net, neural network, and random forest (RF). Sensitivity, specificity, accuracy, and area under the curve were used to evaluate the performance of those models. Results: Based on different performance evaluations, the RF algorithm was selected as the best ML model. In the order of importance; urban–rural settlement, literacy rate of parents, and place of residence were the major determinants of disparities of nutritional status for under-five children among Ethiopian administrative zones. Conclusion: Our results showed that the considered machine learning classification algorithms can effectively predict the under-five undernutrition status in Ethiopian administrative zones. Persistent under-five undernutrition status was found in the northern part of Ethiopia. The identification of such high-risk zones could provide useful information to decision-makers trying to reduce child undernutrition. [ABSTRACT FROM AUTHOR]

Background: The use of sound to represent sequence data—sonification—has great potential as an alternative and complement to visual representation, exploiting features of human psychoacoustic intuitions to convey nuance more effectively. We have created five parameter-mapping sonification algorithms that aim to improve knowledge discovery from protein sequences and small protein multiple sequence alignments. For two of these algorithms, we investigated their effectiveness at conveying information. To do this we focussed on subjective assessments of user experience. This entailed a focus group session and survey research by questionnaire of individuals engaged in bioinformatics research. Results: For single protein sequences, the success of our sonifications for conveying features was supported by both the survey and focus group findings. For protein multiple sequence alignments, there was limited evidence that the sonifications successfully conveyed information. Additional work is required to identify effective algorithms to render multiple sequence alignment sonification useful to researchers. Feedback from both our survey and focus groups suggests future directions for sonification of multiple alignments: animated visualisation indicating the column in the multiple alignment as the sonification progresses, user control of sequence navigation, and customisation of the sound parameters. Conclusions: Sonification approaches undertaken in this work have shown some success in conveying information from protein sequence data. Feedback points out future directions to build on the sonification approaches outlined in this paper. The effectiveness assessment process implemented in this work proved useful, giving detailed feedback and key approaches for improvement based on end-user input. The uptake of similar user experience focussed effectiveness assessments could also help with other areas of bioinformatics, for example in visualisation. [ABSTRACT FROM AUTHOR]

Background: This paper exploits recent developments in topological data analysis to present a pipeline for clustering based on Mapper, an algorithm that reduces complex data into a one-dimensional graph. Results: We present a pipeline to identify and summarise clusters based on statistically significant topological features from a point cloud using Mapper. Conclusions: Key strengths of this pipeline include the integration of prior knowledge to inform the clustering process and the selection of optimal clusters; the use of the bootstrap to restrict the search to robust topological features; the use of machine learning to inspect clusters; and the ability to incorporate mixed data types. Our pipeline can be downloaded under the GNU GPLv3 license at https://github.com/kcl-bhi/mapper-pipeline. [ABSTRACT FROM AUTHOR]

Background: As a common social phenomenon, nurses' occupational burnout has a high incidence rate, which seriously affects their mental health and nursing level. The current assessment mostly uses the total score model and explores the influence of external factors on burnout, while the correlation between burnout items or dimensions is less explored. Ignoring the correlation between the items or dimensions may result in a limited understanding of nurse occupational burnout. This paper explores the item and dimension network structure of the Maslach Burnout Inventory-General Survey (MBI-GS) in Chinese nurses, so as to gain a deeper understanding of this psychological construct and identify potential targets for clinical intervention. Methods: A total of 493 Chinese nurses were recruited by cluster sampling. All participants were invited to complete the survey on symptoms of burnout. Network analysis was used to investigate the item network of MBI-GS. In addition, community detection was used to explore the communities of MBI-GS, and then network analysis was used to investigate the dimension network of MBI-GS based on the results of community detection. Regularized partial correlation and non-regularized partial correlation were used to describe the association between different nodes of the item network and dimension network, respectively. Expected influence and predictability were used to describe the relative importance and the controllability of nodes in both the item and dimension networks. Results: In the item network, most of the strongly correlated edges were in the same dimension of emotional exhaustion (E), cynicism (C) and reduced professional efficacy (R), respectively. E5 (Item 5 of emotional exhaustion, the same below) "I feel burned out from my work", C1 "I have become more callous toward work since I took this job", and R3 "In my opinion, I am good at my job" had the highest expected influence (z-scores = 0.99, 0.81 and 0.94, respectively), indicating theirs highest importance in the network. E1 "I feel emotionally drained from my work" and E5 had the highest predictability (E1 = 0.74, E5 = 0.74). It shows that these two nodes can be interpreted by their internal neighbors to the greatest extent and have the highest controllability in the network. The spinglass algorithm and walktrap algorithm obtained exactly the same three communities, which are consistent with the original dimensions of MBI-GS. In the dimension network, the emotional exhaustion dimension was closely related to the cynicism dimension (weight = 0.65). Conclusions: The network model is a useful tool to study burnout in Chinese nurses. This study explores the item and domain network structure of nurse burnout from the network perspective. By calculating the relevant indicators, we found that E5, C1, and R3 were the most central nodes in the item network and cynicism was the central node in the domain network, suggesting that interventions aimed at E5, C1, R3 and cynicism might decrease the overall burnout level of Chinese nurses to the greatest extent. This study provides potential targets and a new way of thinking for the intervention of nurse burnout, which can be explored and verified in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Clinical notes record the health status, clinical manifestations and other detailed information of each patient. The International Classification of Diseases (ICD) codes are important labels for electronic health records. Automatic medical codes assignment to clinical notes through the deep learning model can not only improve work efficiency and accelerate the development of medical informatization but also facilitate the resolution of many issues related to medical insurance. Recently, neural network-based methods have been proposed for the automatic medical code assignment. However, in the medical field, clinical notes are usually long documents and contain many complex sentences, most of the current methods cannot effective in learning the representation of potential features from document text.Methods: In this paper, we propose a hybrid capsule network model. Specifically, we use bi-directional LSTM (Bi-LSTM) with forwarding and backward directions to merge the information from both sides of the sequence. The label embedding framework embeds the text and labels together to leverage the label information. We then use a dynamic routing algorithm in the capsule network to extract valuable features for medical code prediction task.Results: We applied our model to the task of automatic medical codes assignment to clinical notes and conducted a series of experiments based on MIMIC-III data. The experimental results show that our method achieves a micro F1-score of 67.5% on MIMIC-III dataset, which outperforms the other state-of-the-art methods.Conclusions: The proposed model employed the dynamic routing algorithm and label embedding framework can effectively capture the important features across sentences. Both Capsule networks and domain knowledge are helpful for medical code prediction task. [ABSTRACT FROM AUTHOR]

Background: The misestimation of surgical risk is a serious threat to the lives of patients when implementing surgical risk calculator. Improving the accuracy of postoperative risk prediction has received much attention and many methods have been proposed to cope with this problem in the past decades. However, those linear approaches are inable to capture the non-linear interactions between risk factors, which have been proved to play an important role in the complex physiology of the human body, and thus may attenuate the performance of surgical risk calculators.Methods: In this paper, we presented a new surgical risk calculator based on a non-linear ensemble algorithm named Gradient Boosting Decision Tree (GBDT) model, and explored the corresponding pipeline to support it. In order to improve the practicability of our approach, we designed three different modes to deal with different data situations. Meanwhile, considering that one of the obstacles to clinical acceptance of surgical risk calculators was that the model was too complex to be used in practice, we reduced the number of input risk factors according to the importance of them in GBDT. In addition, we also built some baseline models and similar models to compare with our approach.Results: The data we used was three-year clinical data from Surgical Outcome Monitoring and Improvement Program (SOMIP) launched by the Hospital Authority of Hong Kong. In all experiments our approach shows excellent performance, among which the best result of area under curve (AUC), Hosmer-Lemeshow test ([Formula: see text]) and brier score (BS) can reach 0.902, 7.398 and 0.047 respectively. After feature reduction, the best result of AUC, [Formula: see text] and BS of our approach can still be maintained at 0.894, 7.638 and 0.060, respectively. In addition, we also performed multiple groups of comparative experiments. The results show that our approach has a stable advantage in each evaluation indicator.Conclusions: The experimental results demonstrate that NL-SRC can not only improve the accuracy of predicting the surgical risk of patients, but also effectively capture important risk factors and their interactions. Meanwhile, it also has excellent performance on the mixed data from multiple surgical fields. [ABSTRACT FROM AUTHOR]

Background: Multifunction surveillance alerting systems have been found to be beneficial for the operating room and labor and delivery. This paper describes a similar system developed for in-hospital acute care environments, AlertWatch Acute Care (AWAC). Results: A decision support surveillance system has been developed which extracts comprehensive electronic health record (EHR) data including live data from physiologic monitors and ventilators and incorporates them into an integrated organ icon-based patient display. Live data retrieved from the hospitals network are processed by presenting scrolling median values to reduce artifacts. A total of 48 possible alerts are generated covering a broad range of critical patient care concerns. Notification is achieved by paging or texting the appropriated member of the critical care team. Alerts range from simple out of range values to more complex programing of impending Ventilator Associated Events, SOFA, qSOFA, SIRS scores and process of care reminders for the management of glucose and sepsis. As with similar systems developed for the operating room and labor and delivery, there are green, yellow, and red configurable ranges for all parameters. A census view allows surveillance of an entire unit with flashing or text to voice alerting and enables detailed information by windowing into an individual patient view including live physiologic waveforms. The system runs via web interface on desktop as well as mobile devices, with iOS native app available, for ease of communication from any location. The goal is to improve safety and adherence to standard management protocols. Conclusions: AWAC is designed to provide a high level surveillance view for multi-bed hospital units with varying acuity from standard floor patients to complex ICU care. Alerts are generated by algorithms running in the background and automatically notify the selected member of the patients care team. Its value has been demonstrated for low acuity patients, further study is required to determine its effectiveness in high acuity patients. [ABSTRACT FROM AUTHOR]

K-mer based methods have become prevalent in many areas of bioinformatics. In applications such as database search, they often work with large multi-terabyte-sized datasets. Storing such large datasets is a detriment to tool developers, tool users, and reproducibility efforts. General purpose compressors like gzip, or those designed for read data, are sub-optimal because they do not take into account the specific redundancy pattern in k-mer sets. In our earlier work (Rahman and Medvedev, RECOMB 2020), we presented an algorithm UST-Compress that uses a spectrum-preserving string set representation to compress a set of k-mers to disk. In this paper, we present two improved methods for disk compression of k-mer sets, called ESS-Compress and ESS-Tip-Compress. They use a more relaxed notion of string set representation to further remove redundancy from the representation of UST-Compress. We explore their behavior both theoretically and on real data. We show that they improve the compression sizes achieved by UST-Compress by up to 27 percent, across a breadth of datasets. We also derive lower bounds on how well this type of compression strategy can hope to do. [ABSTRACT FROM AUTHOR]

Background: In the string correction problem, we are to transform one string into another using a set of prescribed edit operations. In string correction using the Damerau-Levenshtein (DL) distance, the permissible edit operations are: substitution, insertion, deletion and transposition. Several algorithms for string correction using the DL distance have been proposed. The fastest and most space efficient of these algorithms is due to Lowrance and Wagner. It computes the DL distance between strings of length m and n, respectively, in O(mn) time and O(mn) space. In this paper, we focus on the development of algorithms whose asymptotic space complexity is less and whose actual runtime and energy consumption are less than those of the algorithm of Lowrance and Wagner. Results: We develop space- and cache-efficient algorithms to compute the Damerau-Levenshtein (DL) distance between two strings as well as to find a sequence of edit operations of length equal to the DL distance. Our algorithms require O(s min{m,n}+m+n) space, where s is the size of the alphabet and m and n are, respectively, the lengths of the two strings. Previously known algorithms require O(mn) space. The space- and cache-efficient algorithms of this paper are demonstrated, experimentally, to be superior to earlier algorithms for the DL distance problem on time, space, and enery metrics using three different computational platforms. Conclusion: Our benchmarking shows that, our algorithms are able to handle much larger sequences than earlier algorithms due to the reduction in space requirements. On a single core, we are able to compute the DL distance and an optimal edit sequence faster than known algorithms by as much as 73.1% and 63.5%, respectively. Further, we reduce energy consumption by as much as 68.5%. Multicore versions of our algorithms achieve a speedup of 23.2 on 24 cores. [ABSTRACT FROM AUTHOR]

Multiple imputation is a recommended method for handling incomplete data problems. One of the barriers to its successful use is the breakdown of the multiple imputation procedure, often due to numerical problems with the algorithms used within the imputation process. These problems frequently occur when imputation models contain large numbers of variables, especially with the popular approach of multivariate imputation by chained equations. This paper describes common causes of failure of the imputation procedure including perfect prediction and collinearity, focusing on issues when using Stata software. We outline a number of strategies for addressing these issues, including imputation of composite variables instead of individual components, introducing prior information and changing the form of the imputation model. These strategies are illustrated using a case study based on data from the Longitudinal Study of Australian Children. [ABSTRACT FROM AUTHOR]

Background: Hidden Markov models (HMM) are a powerful tool for analyzing biological sequences in a wide variety of applications, from profiling functional protein families to identifying functional domains. The standard method used for HMM training is either by maximum likelihood using counting when sequences are labelled or by expectation maximization, such as the Baum–Welch algorithm, when sequences are unlabelled. However, increasingly there are situations where sequences are just partially labelled. In this paper, we designed a new training method based on the Baum–Welch algorithm to train HMMs for situations in which only partial labeling is available for certain biological problems. Results: Compared with a similar method previously reported that is designed for the purpose of active learning in text mining, our method achieves significant improvements in model training, as demonstrated by higher accuracy when the trained models are tested for decoding with both synthetic data and real data. Conclusions: A novel training method is developed to improve the training of hidden Markov models by utilizing partial labelled data. The method will impact on detecting de novo motifs and signals in biological sequence data. In particular, the method will be deployed in active learning mode to the ongoing research in detecting plasmodesmata targeting signals and assess the performance with validations from wet-lab experiments. [ABSTRACT FROM AUTHOR]

Background: Insomnia as one of the dominant diseases of traditional Chinese medicine (TCM) has been extensively studied in recent years. To explore the novel approaches of research on TCM diagnosis and treatment, this paper presents a strategy for the research of insomnia based on machine learning. Methods: First of all, 654 insomnia cases have been collected from an experienced doctor of TCM as sample data. Secondly, in the light of the characteristics of TCM diagnosis and treatment, the contents of research samples have been divided into four parts: the basic information, the four diagnostic methods, the treatment based on syndrome differentiation and the main prescription. And then, these four parts have been analyzed by three analysis methods, including frequency analysis, association rules and hierarchical cluster analysis. Finally, a comprehensive study of the whole four parts has been conducted by random forest. Results: Researches of the above four parts revealed some essential connections. Simultaneously, based on the algorithm model established by the random forest, the accuracy of predicting the main prescription by the combinations of the four diagnostic methods and the treatment based on syndrome differentiation was 0.85. Furthermore, having been extracted features through applying the random forest, the syndrome differentiation of five zang-organs was proven to be the most significant parameter of the TCM diagnosis and treatment. Conclusions: The results indicate that the machine learning methods are worthy of being adopted to study the dominant diseases of TCM for exploring the crucial rules of the diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: The Damerau-Levenshtein (DL) distance metric has been widely used in the biological science. It tries to identify the similar region of DNA,RNA and protein sequences by transforming one sequence to the another using the substitution, insertion, deletion and transposition operations. Lowrance and Wagner have developed an O(mn) time O(mn) space algorithm to find the minimum cost edit sequence between strings of length m and n, respectively. In our previous research, we have developed algorithms that run in O(mn) time using only O(s∗min{m,n}+m+n) space, where s is the size of the alphabet comprising the strings, to compute the DL distance as well as the corresponding edit sequence. These are so far the fastest and most space efficient algorithms. In this paper, we focus on the development of algorithms whose asymptotic space complexity is linear. Results: We develop linear space algorithms to compute the Damerau-Levenshtein (DL) distance between two strings and determine the optimal trace (corresponding edit operations.)Extensive experiments conducted on three computational platforms–Xeon E5 2603, I7-x980 and Xeon E5 2695–show that, our algorithms, in addition to using less space, are much faster than earlier algorithms. Conclusion: Besides using less space than the previously known algorithms,significant run-time improvement was seen for our new algorithms on all three of our experimental platforms. On all platforms, our linear-space cache-efficient algorithms reduced run time by as much as 56.4% and 57.4% in respect to compute the DL distance and an optimal edit sequences compared to previous algorithms. Our multi-core algorithms reduced the run time by up to 59.3% compared to the best previously known multi-core algorithms. [ABSTRACT FROM AUTHOR]

Background: High resolution 2D whole slide imaging provides rich information about the tissue structure. This information can be a lot richer if these 2D images can be stacked into a 3D tissue volume. A 3D analysis, however, requires accurate reconstruction of the tissue volume from the 2D image stack. This task is not trivial due to the distortions such as tissue tearing, folding and missing at each slide. Performing registration for the whole tissue slices may be adversely affected by distorted tissue regions. Consequently, regional registration is found to be more effective. In this paper, we propose a new approach to an accurate and robust registration of regions of interest for whole slide images. We introduce the idea of multi-scale attention for registration. Results: Using mean similarity index as the metric, the proposed algorithm (mean ± SD 0.84 ± 0.11 ) followed by a fine registration algorithm ( 0.86 ± 0.08 ) outperformed the state-of-the-art linear whole tissue registration algorithm ( 0.74 ± 0.19 ) and the regional version of this algorithm ( 0.81 ± 0.15 ). The proposed algorithm also outperforms the state-of-the-art nonlinear registration algorithm (original: 0.82 ± 0.12 , regional: 0.77 ± 0.22 ) for whole slide images and a recently proposed patch-based registration algorithm (patch size 256: 0.79 ± 0.16 , patch size 512: 0.77 ± 0.16 ) for medical images. Conclusion: Using multi-scale attention mechanism leads to a more robust and accurate solution to the problem of regional registration of whole slide images corrupted in some parts by major histological artifacts in the imaged tissue. [ABSTRACT FROM AUTHOR]

Background: High-throughput sequencing data are widely collected and analyzed in the study of complex diseases in quest of improving human health. Well-studied algorithms mostly deal with single data source, and cannot fully utilize the potential of these multi-omics data sources. In order to provide a holistic understanding of human health and diseases, it is necessary to integrate multiple data sources. Several algorithms have been proposed so far, however, a comprehensive comparison of data integration algorithms for classification of binary traits is currently lacking. Results: In this paper, we focus on two common classes of integration algorithms, graph-based that depict relationships with subjects denoted by nodes and relationships denoted by edges, and kernel-based that can generate a classifier in feature space. Our paper provides a comprehensive comparison of their performance in terms of various measurements of classification accuracy and computation time. Seven different integration algorithms, including graph-based semisupervised learning, graph sharpening integration, composite association network, Bayesian network, semi-definite programming-support vector machine (SDP-SVM), relevance vector machine (RVM) and Ada-boost relevance vector machine are compared and evaluated with hypertension and two cancer data sets in our study. In general, kernel-based algorithms create more complex models and require longer computation time, but they tend to perform better than graph-based algorithms. The performance of graph-based algorithms has the advantage of being faster computationally. Conclusions: The empirical results demonstrate that composite association network, relevance vector machine, and Ada-boost RVM are the better performers. We provide recommendations on how to choose an appropriate algorithm for integrating data from multiple sources. [ABSTRACT FROM AUTHOR]

Background: During gait training, physical therapists continuously supervise stroke survivors and provide physical support to their pelvis when they judge that the patient is unable to keep his balance. This paper is the first in providing quantitative data about the corrective forces that therapists use during gait training. It is assumed that changes in the acceleration of a patient's COM are a good predictor for therapeutic balance assistance during the training sessions Therefore, this paper provides a method that predicts the timing of therapeutic balance assistance, based on acceleration data of the sacrum.Methods: Eight sub-acute stroke survivors and seven therapists were included in this study. Patients were asked to perform straight line walking as well as slalom walking in a conventional training setting. Acceleration of the sacrum was captured by an Inertial Magnetic Measurement Unit. Balance-assisting corrective forces applied by the therapist were collected from two force sensors positioned on both sides of the patient's hips. Measures to characterize the therapeutic balance assistance were the amount of force, duration, impulse and the anatomical plane in which the assistance took place. Based on the acceleration data of the sacrum, an algorithm was developed to predict therapeutic balance assistance. To validate the developed algorithm, the predicted events of balance assistance by the algorithm were compared with the actual provided therapeutic assistance.Results: The algorithm was able to predict the actual therapeutic assistance with a Positive Predictive Value of 87% and a True Positive Rate of 81%. Assistance mainly took place over the medio-lateral axis and corrective forces of about 2% of the patient's body weight (15.9 N (11), median (IQR)) were provided by therapists in this plane. Median duration of balance assistance was 1.1 s (0.6) (median (IQR)) and median impulse was 9.4Ns (8.2) (median (IQR)). Although therapists were specifically instructed to aim for the force sensors on the iliac crest, a different contact location was reported in 22% of the corrections.Conclusions: This paper presents insights into the behavior of therapists regarding their manual physical assistance during gait training. A quantitative dataset was presented, representing therapeutic balance-assisting force characteristics. Furthermore, an algorithm was developed that predicts events at which therapeutic balance assistance was provided. Prediction scores remain high when different therapists and patients were analyzed with the same algorithm settings. Both the quantitative dataset and the developed algorithm can serve as technical input in the development of (robot-controlled) balance supportive devices. [ABSTRACT FROM AUTHOR]