中口 俊哉

Tongue diagnosis is one of the important diagnostic methods in Kampo (traditional Japanese) medicine, in which the color and shape of the tongue are used to determine the patient’s constitution and systemic symptoms. Tongue diagnosis is performed with the patient in the sitting or supine positions; however, the differences in tongue color in these two different positions have not been analyzed. We developed tongue image analyzing system (TIAS), which can quantify tongue color by capturing tongue images in the sitting and supine positions. We analyzed the effects on tongue color in two different body positions. Tongue color was quantified as L∗a∗b∗ from tongue images of 18 patients in two different body positions by taking images with TIAS. The CIEDE 2000 color difference equation (ΔE00) was used to assess the difference in tongue color in two different body positions. Correlations were also determined between ΔE00, physical characteristics, and laboratory test values. The mean and median ΔE00 for 18 patients were 2.85 and 2.34, respectively. Of these patients, 77.8% had a ΔE00 < 4.1. A weak positive correlation was obtained between ΔE00 and systolic blood pressure and fasting plasma glucose. Approximately 80% of patients’ tongue color did not change between the sitting and supine positions. This indicates that the diagnostic results of tongue color are trustworthy even if medical professionals perform tongue diagnosis in two different body positions.

An educational augmented reality auscultation system (EARS) is proposed to enhance the reality of auscultation training using a simulated patient. The conventional EARS cannot accurately reproduce breath sounds according to the breathing of a simulated patient because the system instructs the breathing rhythm. In this study, we propose breath measurement methods that can be integrated into the chest piece of a stethoscope. We investigate methods using the thoracic variations and frequency characteristics of breath sounds. An accelerometer, a magnetic sensor, a gyro sensor, a pressure sensor, and a microphone were selected as the sensors. For measurement with the magnetic sensor, we proposed a method by detecting the breathing waveform in terms of changes in the magnetic field accompanying the surface deformation of the stethoscope based on thoracic variations using a magnet. During breath sound measurement, the frequency spectra of the breath sounds acquired by the built-in microphone were calculated. The breathing waveforms were obtained from the difference in characteristics between the breath sounds during exhalation and inhalation. The result showed the average value of the correlation coefficient with the reference value reached 0.45, indicating the effectiveness of this method as a breath measurement method. And the evaluations suggest more accurate breathing waveforms can be obtained by selecting the measurement method according to breathing method and measurement point.

Abstract Background Optical coherence tomography (OCT) is the most important and commonly utilized imaging modality in ophthalmology and is especially crucial for the diagnosis and management of macular diseases. Each OCT volume is typically only available as a series of cross-sectional images (B-scans) that are accessible through proprietary software programs which accompany the OCT machines. To maximize the potential of OCT imaging for machine learning purposes, each OCT image should be analyzed en bloc as a 3D volume, which requires aligning all the cross-sectional images within a particular volume. Methods A dataset of OCT B-scans obtained from 48 age-related macular degeneration (AMD) patients and 50 normal controls was used to evaluate five registration algorithms. After alignment of B-scans from each patient, an en face surface map was created to measure the registration quality, based on an automatically generated Laplace difference of the surface map–the smoother the surface map, the smaller the average Laplace difference. To demonstrate the usefulness of B-scan alignment, we trained a 3D convolutional neural network (CNN) to detect age-related macular degeneration (AMD) on OCT images and compared the performance of the model with and without B-scan alignment. Results The mean Laplace difference of the surface map before registration was 27 ± 4.2 pixels for the AMD group and 26.6 ± 4 pixels for the control group. After alignment, the smoothness of the surface map was improved, with a mean Laplace difference of 5.5 ± 2.7 pixels for Advanced Normalization Tools Symmetric image Normalization (ANTs-SyN) registration algorithm in the AMD group and a mean Laplace difference of 4.3 ± 1.4.2 pixels for ANTs in the control group. Our 3D CNN achieved superior performance in detecting AMD, when aligned OCT B-scans were used (AUC 0.95 aligned vs. 0.89 unaligned). Conclusions We introduced a novel metric to quantify OCT B-scan alignment and compared the effectiveness of five alignment algorithms. We confirmed that alignment could be improved in a statistically significant manner with readily available alignment algorithms that are available to the public, and the ANTs algorithm provided the most robust performance overall. We further demonstrated that alignment of OCT B-scans will likely be useful for training 3D CNN models.

Since side-effects of drugs are one of the primary reasons for their failure in clinical trials, predicting their side-effects can help reduce drug development costs. We proposed a method based on heterogeneous graph transformer and capsule networks for side-effect-drug-association prediction (TCSD). The method encodes and integrates attributes from multiple types of neighbor nodes, connection semantics, and multi-view pairwise information. In each drug-side-effect heterogeneous graph, a target node has two types of neighbor nodes, the drug nodes and the side-effect ones. We proposed a new heterogeneous graph transformer-based context representation learning module. The module is able to encode specific topology and the contextual relations among multiple kinds of nodes. There are similarity and association connections between the target node and its various types of neighbor nodes, and these connections imply semantic diversity. Therefore, we designed a new strategy to measure the importance of a neighboring node to the target node and incorporate different semantics of the connections between the target node and its multi-type neighbors. Furthermore, we designed attentions at the neighbor node type level and at the graph level, respectively, to obtain enhanced informative neighbor node features and multi-graph features. Finally, a pairwise multi-view feature learning module based on capsule networks was built to learn the pairwise attributes from the heterogeneous graphs. Our prediction model was evaluated using a public dataset, and the cross-validation results showed it achieved superior performance to several state-of-the-art methods. Ablation experiments undertaken demonstrated the effectiveness of heterogeneous graph transformer-based context encoding, the position enhanced pairwise attribute learning, and the neighborhood node category-level attention. Case studies on five drugs further showed TCSD’s ability in retrieving potential drug-related side-effect candidates, and TCSD inferred the candidate side-effects for 708 drugs.

Lung cancer is the second most common cancer in the world, with an average five-year survival rate of 15 percent. Approximately 238,340 people were diagnosed in the US in 2023 based on the estimation of the American Cancer Society, and 127,070 people died from it. Cancer has always been a big problem for scientists. There has never been a good solution. So, the early detection of cancer is particularly important. In recent years, endobronchial ultrasonography (EBUS) images have been used more and more in the diagnosis of lung cancer because of their advantages of good real-time performance, no radiation, and superior performance. This research aims to develop a computer-aided diagnosis (CAD) system to differentiate benign and malignant peripheral pulmonary lesions (PPLs). The efficacy of this framework was evaluated on a dataset comprising 69 cases of lung carcinoma, encompassing 59 malignant instances and 10 benign cases. The final experimental results of accuracy, F1-Score, AUC, PPV, NPV, sensitivity, and specificity were 0.7, 0.63, 0.75, 0.84, 0.68, 0.56, and 0.85, respectively. From the experiment results, the developed CAD system has the potential ability to diagnose PPLs by using the EBUS images based on Deep Learning.

Precisely detecting puncture times has long posed a challenge in medical education. This challenge is attributable not only to the subjective nature of human evaluation but also to the insufficiency of effective detection techniques, resulting in many medical students lacking full proficiency in injection skills upon entering clinical practice. To address this issue, we propose a novel detection method that enables automatic detection of puncture times during injection without needing wearable devices. In this study, we utilized a hardware system and the YOLOv7 algorithm to detect critical features of injection motion, including puncture time and injection depth parameters. We constructed a sample of 126 medical injection training videos of medical students, and skilled observers were employed to determine accurate puncture times. Our experimental results demonstrated that the mean puncture time of medical students was 2.264 s and the mean identification error was 0.330 s. Moreover, we confirmed that there was no significant difference (p = 0.25 with a significance level of α = 0.05) between the predicted value of the system and the ground truth, which provides a basis for the validity and reliability of the system. These results show our system’s ability to automatically detect puncture times and provide a novel approach for training healthcare professionals. At the same time, it provides a key technology for the future development of injection skill assessment systems.

INTRODUCTION: Capillary refill time (CRT) is an indicator of peripheral circulation and is recommended in the 2021 guidelines for treating and managing sepsis. STUDY OBJECTIVE: This study developed a portable device to realize objective CRT measurement. Assuming that peripheral blood flow obstruction by the artery occlusion test (AOT) or venous occlusion test (VOT) increases the CRT, the cut-off value for peripheral circulatory failure was studied by performing a comparative analysis with CRT with no occlusion test (No OT). METHODS: Fourteen (14) healthy adults (age: 20-26 years) participated in the study. For the vascular occlusion test, a sphygmomanometer was placed on the left upper arm of the participant in the supine position, and a pressure of 30mmHg higher than the systolic pressure was applied for AOT, a pressure of 60mmHg was applied for VOT, respectively, and no pressure was applied for No OT. The CRT was measured from the index finger of the participant's left hand. RESULTS: Experimental results revealed that CRT was significantly longer in the AOT and did not differ significantly in the VOT. The cut-off value for peripheral circulatory failure was found to be 2.88 seconds based on Youden's index by using receiver operating characteristic (ROC) analysis with AOT as positive and No OT as negative. CONCLUSION: Significant results were obtained in a previous study on the evaluation of septic shock patients when CRT > three seconds was considered abnormal, and the cut-off value for peripheral circulatory failure in the current study validated this.

Abstract Objective. Accurate and automated segmentation of lung tumors from computed tomography (CT) images is critical yet challenging. Lung tumors are of various sizes and locations and have indistinct boundaries adjacent to other normal tissues. Approach. We propose a new segmentation model that can integrate the topological structure and global features of image region nodes to address the challenges. Firstly, we construct a weighted graph with image region nodes. The graph topology reflects the complex spatial relationships among these nodes, and each node has its specific attributes. Secondly, we propose a node-wise topological feature learning module based on a new graph convolutional autoencoder (GCA). Meanwhile, a node information supplementation (GNIS) module is established by integrating specific features of each node extracted by a convolutional neural network (CNN) into each encoding layer of GCA. Afterwards, we construct a global feature extraction model based on multi-layer perceptron (MLP) to encode the features learnt from all the image region nodes which are crucial complementary information for tumor segmentation. Main results. Ablation study results over the public lung tumor segmentation dataset demonstrate the contributions of our major technical innovations. Compared with other segmentation methods, our new model improves the segmentation performance and has generalization ability on different 3D image segmentation backbones. Our model achieved Dice of 0.7827, IoU of 0.6981, and HD of 32.1743 mm on the public dataset 2018 Medical Segmentation Decathlon challenge, and Dice of 0.7004, IoU of 0.5704 and HD of 64.4661 mm on lung tumor dataset from Shandong Cancer Hospital. Significance. The novel model improves automated lung tumor segmentation performance especially the challenging and complex cases using topological structure and global features of image region nodes. It is of great potential to apply the model to other CT segmentation tasks.

Abstract Motivation Accurate identification of proteins interacted with drugs helps reduce the time and cost of drug development. Most of previous methods focused on integrating multisource data about drugs and proteins for predicting drug–target interactions (DTIs). There are both similarity connection and interaction connection between two drugs, and these connections reflect their relationships from different perspectives. Similarly, two proteins have various connections from multiple perspectives. However, most of previous methods failed to deeply integrate these connections. In addition, multiple drug-protein heterogeneous networks can be constructed based on multiple kinds of connections. The diverse topological structures of these networks are still not exploited completely. Results We propose a novel model to extract and integrate multi-type neighbor topology information, diverse similarities and interactions related to drugs and proteins. Firstly, multiple drug–protein heterogeneous networks are constructed according to multiple kinds of connections among drugs and those among proteins. The multi-type neighbor node sequences of a drug node (or a protein node) are formed by random walks on each network and they reflect the hidden neighbor topological structure of the node. Secondly, a module based on graph neural network (GNN) is proposed to learn the multi-type neighbor topologies of each node. We propose attention mechanisms at neighbor node level and at neighbor type level to learn more informative neighbor nodes and neighbor types. A network-level attention is also designed to enhance the context dependency among multiple neighbor topologies of a pair of drug and protein nodes. Finally, the attribute embedding of the drug-protein pair is formulated by a proposed embedding strategy, and the embedding covers the similarities and interactions about the pair. A module based on three-dimensional convolutional neural networks (CNN) is constructed to deeply integrate pairwise attributes. Extensive experiments have been performed and the results indicate GCDTI outperforms several state-of-the-art prediction methods. The recall rate estimation over the top-ranked candidates and case studies on 5 drugs further demonstrate GCDTI’s ability in discovering potential drug-protein interactions.

The role of multi-parametric magnetic resonance imaging (mp-MRI) is becoming increasingly important in the diagnosis of the clinical severity of prostate cancer (PCa). However, mp-MRI images usually contain several unaligned 3D sequences, such as DWI image sequences and T2-weighted image sequences, and there are many images among the entirety of 3D sequence images that do not contain cancerous tissue, which affects the accuracy of large-scale prostate cancer detection. Therefore, there is a great need for a method that uses accurate computer-aided detection of mp-MRI images and minimizes the influence of useless features. Our proposed PCa detection method is divided into three stages: (i) multimodal image alignment, (ii) automatic cropping of the sequence images to the entire prostate region, and, finally, (iii) combining multiple modal images of each patient into novel 3D sequences and using 3D convolutional neural networks to learn the newly composed 3D sequences with different modal alignments. We arrange the different modal methods to make the model fully learn the cancerous tissue features; then, we predict the clinical severity of PCa and generate a 3D cancer response map for the 3D sequence images from the last convolution layer of the network. The prediction results and 3D response map help to understand the features that the model focuses on during the process of 3D-CNN feature learning. We applied our method to Toho hospital prostate cancer patient data; the AUC (=0.85) results were significantly higher than those of other methods.

内視鏡検査では,医師が検査の記録として診断内容,検査臓器,実施処置などを記入した所見を作成する.しかし,内視鏡操作のため検査中の所見作成は困難であり,医師は検査後の時間を利用して記入する.医師の作業負担軽減のため,所見作成の効率化が求められる.また,所見は医師の記憶に基づくため,記載漏れの発生も課題である.診療報酬点数の申告漏れや医療安全の観点からも,正確な検査記録が求められる.本研究では,内視鏡動画解析による所見作成の効率化と記載漏れ防止を目的とし,第一段階として,検査臓器の判別手法を提案する.提案手法では,CNNとLSTMを組み合わせ,時間情報を利用した臓器分類を行う.さらに,分類結果に対して検査開始時と終了時の双方向からSliding Window(SW)によって臓器境界を探索し誤分類フレームを除去する.17症例の内視鏡動画で学習した提案手法を別の7症例で評価した結果,LSTMとSWを導入することの有効性が示唆された.(著者抄録)

Abstract Motivation Computerized methods for drug-related side effect identification can help reduce costs and speed up drug development. Multisource data about drug and side effects are widely used to predict potential drug-related side effects. Heterogeneous graphs are commonly used to associate multisourced data of drugs and side effects which can reflect similarities of the drugs from different perspectives. Effective integration and formulation of diverse similarities, however, are challenging. In addition, the specific topology of each heterogeneous graph and the common topology of multiple graphs are neglected. Results We propose a drug-side effect association prediction model, GCRS, to encode and integrate specific topologies, common topologies and pairwise attributes of drugs and side effects. First, multiple drug-side effect heterogeneous graphs are constructed using various kinds of similarities and associations related to drugs and side effects. As each heterogeneous graph has its specific topology, we establish separate module based on graph convolutional autoencoder (GCA) to learn the particular topology representation of each drug node and each side effect node, respectively. Since multiple graphs reflect the complex relationships among the drug and side effect nodes and contain common topologies, we construct a module based on GCA with sharing parameters to learn the common topology representations of each node. Afterwards, we design an attention mechanism to obtain more informative topology representations at the representation level. Finally, multi-layer convolutional neural networks with attribute-level attention are constructed to deeply integrate the similarity and association attributes of a pair of drug-side effect nodes. Comprehensive experiments show that GCRS’s prediction performance is superior to other comparing state-of-the-art methods for predicting drug-side effect associations. The recall rates in top-ranked candidates and case studies on five drugs further demonstrate GCRS’s ability in discovering potential drug-related side effects. Contact zhang@hlju.edu.cn

Abstract Motivation Identifying new uses of approved drugs is an effective way to reduce the time and cost of drug development. Recent computational approaches for predicting drug–disease associations have integrated multi-sourced data on drugs and diseases. However, neighboring topologies of various scales in multiple heterogeneous drug–disease networks have yet to be exploited and fully integrated. Results We propose a novel method for drug–disease association prediction, called MGPred, used to encode and learn multi-scale neighboring topologies of drug and disease nodes and pairwise attributes from heterogeneous networks. First, we constructed three heterogeneous networks based on multiple kinds of drug similarities. Each network comprises drug and disease nodes and edges created based on node-wise similarities and associations that reflect specific topological structures. We also propose an embedding mechanism to formulate topologies that cover different ranges of neighbors. To encode the embeddings and derive multi-scale neighboring topology representations of drug and disease nodes, we propose a module based on graph convolutional autoencoders with shared parameters for each heterogeneous network. We also propose scale-level attention to obtain an adaptive fusion of informative topological representations at different scales. Finally, a learning module based on a convolutional neural network with various receptive fields is proposed to learn multi-view attribute representations of a pair of drug and disease nodes. Comprehensive experiment results demonstrate that MGPred outperforms other state-of-the-art methods in comparison to drug-related disease prediction, and the recall rates for the top-ranked candidates and case studies on five drugs further demonstrate the ability of MGPred to retrieve potential drug–disease associations.

Identifying new disease indications for existing drugs can help facilitate drug development and reduce development cost. The previous drug–disease association prediction methods focused on data about drugs and diseases from multiple sources. However, they did not deeply integrate the neighbor topological information of drug and disease nodes from various meta-path perspectives. We propose a prediction method called NAPred to encode and integrate meta-path-level neighbor topologies, multiple kinds of drug attributes, and drug-related and disease-related similarities and associations. The multiple kinds of similarities between drugs reflect the degrees of similarity between two drugs from different perspectives. Therefore, we constructed three drug–disease heterogeneous networks according to these drug similarities, respectively. A learning framework based on fully connected neural networks and a convolutional neural network with an attention mechanism is proposed to learn information of the neighbor nodes of a pair of drug and disease nodes. The multiple neighbor sets composed of different kinds of nodes were formed respectively based on meta-paths with different semantics and different scales. We established the attention mechanisms at the neighbor-scale level and at the neighbor topology level to learn enhanced neighbor feature representations and enhanced neighbor topological representations. A convolutional-autoencoder-based module is proposed to encode the attributes of the drug–disease pair in three heterogeneous networks. Extensive experimental results indicated that NAPred outperformed several state-of-the-art methods for drug–disease association prediction, and the improved recall rates demonstrated that NAPred was able to retrieve more actual drug–disease associations from the top-ranked candidates. Case studies on five drugs further demonstrated the ability of NAPred to identify potential drug-related disease candidates.

千葉大学で2020-2021年に実施したオンラインでの大規模IPEについて、4段階の段階的プログラムのうち初学年を対象とした"Step1"での協働学習と体験学習に焦点を当てて報告する。協働学習では、オンデマンド型ツールのみ使用したグループと同時双方向性ツールと併用したグループ間の比較で、学生のグループワーク自己評価得点の平均が併用グループの方が有意に高い結果であった(p<0.05)。教員評価得点には有意差はなく、オンデマンド型ツールを用いた学習では特に教員からの肯定的フィードバックが必要と思われた。体験学習に関しては、患者・サービス利用者とのメールおよび同時双方向性ツールを用いたインタビュー学習について実施上の課題を報告した。学生の各種ICTツールへのリテラシー状況のアセスメント、患者・サービス利用者の個人情報保護のさらなる徹底が課題である。(著者抄録)

舌診は舌特徴を捉え,簡便かつ非侵襲的に健康状態を把握する診断法であるが,医師の主観や経験に依存するため,定量化が求められている.本研究ではドライマウスや口腔疾患を誘発するシェーグレン症候群(SS)について,診断支援を目的に舌画像に基づく解析を行った.SS患者19名を含む,計60名において舌画像を取得した.舌形状規格化のため,舌を5角形に近似し同一の解析領域を指定した.舌色をCIELAB空間で取得しSupport Vector Machine,Random Forest,Logistic Regressionを訓練した.SVMが最も高い性能を示し,交差検証における平均精度71.3%,感度57.5%,特異度78.1%となった.本手法は現行の診断基準の一つである唾液量検査と比較し同等の診断性能を示しており,衛生面と簡便性において優位であるため,コロナ禍に適した新たな診断法となることが示唆された.(著者抄録)

千葉大学で2020-2021年に実施したオンラインでの大規模IPEについて、4段階の段階的プログラムのうち初学年を対象とした"Step1"での協働学習と体験学習に焦点を当てて報告する。協働学習では、オンデマンド型ツールのみ使用したグループと同時双方向性ツールと併用したグループ間の比較で、学生のグループワーク自己評価得点の平均が併用グループの方が有意に高い結果であった(p<0.05)。教員評価得点には有意差はなく、オンデマンド型ツールを用いた学習では特に教員からの肯定的フィードバックが必要と思われた。体験学習に関しては、患者・サービス利用者とのメールおよび同時双方向性ツールを用いたインタビュー学習について実施上の課題を報告した。学生の各種ICTツールへのリテラシー状況のアセスメント、患者・サービス利用者の個人情報保護のさらなる徹底が課題である。(著者抄録)