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| 1 | Detection for disease tipping points by landscape dynamic network biomarkers显示文摘A new model-free method has been developed and termed the landscape dynamic network biomarker(l-DNB) methodology. The method is based on bifurcation theory, which can identify tipping points prior to serious disease deterioration using only single-sample omics data. Here, we show that l-DNB provides early-warning signals of disease deterioration on a single-sample basis and also detects critical genes or network biomarkers(i.e. DNB members) that promote the transition from normal to disease states. As a case study, l-DNB was used to predict severe influenza symptoms prior to the actual symptomatic appearance in influenza virus infections. The l-DNB approach was then also applied to three tumor disease datasets from the TCGA and was used to detect critical stages prior to tumor deterioration using an individual DNB for each patient. The individual DNBs were further used as individual biomarkers in the analysis of physiological data, which led to the identification of two biomarker types that were surprisingly effective in predicting the prognosis of tumors. The biomarkers can be considered as common biomarkers for cancer, wherein one indicates a poor prognosis and the other indicates a good prognosis. | Xiaoping Liu Xiao Chang Siyang Leng Hui Tang Kazuyuki Aihara Luonan Chen | 2019 | National Science Review2019，6，4： | 12 |
| 2 | Hunt for the tipping point during endocrine resistance process in breast cancer by dynamic network biomarkers显示文摘Acquired drug resistance is the major reason why patients fail to respond to cancer therapies.It is a challenging task to deter.mine the tipping point of endocrine resistance and detect the associated molecules.Derived from new systems biology theory, the dynamic network biomarker (DNB) method is designed to quantitatively identify the tipping point of a drastic system transition and can theoretically identify DNB genes that play key roles in acquiring drug resistance.We analyzed time-course mRNA sequence data generated from the tamoxifen-treated estrogen receptor (ER)-positive MCF-7 cell line, and identified the tipping point of endocrine resistance with its leading molecules.The results show that there is interplay between gene mutations and DNB genes, in which the accumulated mutations eventually affect the DNB genes that subsequently cause the change of transcriptional landscape, enabling full-blown drug resistance. Survival analyses based on clinical datasets validated that the DNB genes were associated with the poor survival of breast cancer patients.The results provided the detection for the pre-resistance state or early signs of endocrine resistance.Our predictive method may greatly benefit the scheduling of treatments for complex diseases in which patients are exposed to considerably different drugs and may become drug resistant. | Rui Liu Jinzeng Wang Masao Ukai Ki Sewon Pei Chen Yutaka Suzuki Haiyun Wang Kazuyuki Aihara Mariko Okada-Hatakeyama Luonan Chen | 2019 | Journal of Molecular Cell Biology2019，11，8： | 7 |
| 3 | Serum angiotensin-converting enzyme level for evaluating significant fibrosis in chronic hepatitis B显示文摘AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy in our hospital were enrolled,and 70 patients except for 30 patients with hypertension,fatty liver or habitual alcoholic consumption were analyzed.We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase(AST)-to-platelet ratio index(APRI),the fibrosis index based on four factors(FIB-4),the Mac-2 binding protein glycosylation isomer(M2BPGi)level and the number of platelets(Plt). RESULTS Serum ACE levels showed moderately positive correlation with liver fibrotic stages(R2=0.181).Patients with significant,advanced fibrosis and cirrhosis(F2-4)had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis(F0-1).For significant fibrosis(≥F2),the 12.8 U/L cut-off value of ACE showed 91.7%sensitivity and 75.0%specificity.The receiver-operating characteristic(ROC)curves analysis revealed that the area under the curve(AUC)value of ACE was 0.871,which was higher than that of APRI,FIB-4,M2BPGi and Plt. CONCLUSION The serum ACE level could be a novel noninvasive,easy,accurate,and inexpensive marker of significant fibrosis stage in patients with CHB. | Ryuichi Noguchi Kosuke Kaji Tadashi Namisaki Kei Moriya Mitsuteru Kitade Kosuke Takeda Hideto Kawaratani Yasushi Okura Yosuke Aihara Masanori Furukawa Akira Mitoro Hitoshi Yoshiji | 2017 | World Journal of Gastroenterology2017，23，36： | 6 |
| 4 | Efficacy of a novel auto-fluorescence imaging system with computer-assisted color analysis for assessment of colorectal lesions显示文摘AIM:To evaluate the efficacy of computer-assisted color analysis of colorectal lesions using a novel auto-fluorescence imaging(AFI)system to distinguish neoplastic lesions from non-neoplastic lesions and to predict the depth of invasion.METHODS:From January 2013 to April 2013,consecutive patients with known polyps greater than 5 mm in size who were scheduled to undergo endoscopic treatment at The Jikei University Hospital were prospectively recruited for this study.All lesions were evaluated using a novel AFI system,and color-tone sampling was performed in a region of interest determined from narrow band imaging or from chromoendoscopy findings without magnification.The green/red(G/R)ratio for each lesion on the AFI images was calculated automatically using a computer-assisted color analysis system that permits real-time color analysis during endoscopic procedures.RESULTS:A total of 88 patients with 163 lesions were enrolled in this study.There were significant differences in the G/R ratios of hyperplastic polyps(non-neoplastic lesions),adenoma/intramucosal cancer/submucosal(SM)superficial cancer,and SM deep cancer(P<0.0001).The mean±SD G/R ratios were 0.984±0.118in hyperplastic polyps and 0.827±0.081 in neoplastic lesions.The G/R ratios of hyperplastic polyps were significantly higher than those of neoplastic lesions(P<0.001).When a G/R ratio cut-off value of>0.89 was applied to determine non-neoplastic lesions,the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and accuracy were 83.9%,82.6%,53.1%,95.6%and 82.8%,respectively.For neoplastic lesions,the mean G/R ratio was 0.834±0.080 in adenoma/intramucosal cancer/SM superficial cancer and 0.746±0.045 in SM deep cancer.The G/R ratio of adenoma/intramucosal cancer/SM superficial cancer was significantly higher than that of SM deep cancer(P<0.01).When a G/R ratio cut-off value of<0.77 was applied to distinguish SM deep cancers,the sensitivity,specificity,PPV,NPV,and accuracy were80.0%,84.4%,29.6%,98.1%and 84.1%,respectively.CONCLUSION:The novel AFI system with color analysis was effective in distinguishing non-neoplastic lesions from neoplastic lesions and might allow determination of the depth of invasion. | Hiroko Inomata Naoto Tamai Hiroyuki Aihara Kazuki Sumiyama Shoichi Saito Tomohiro Kato Hisao Tajiri | 2013 | World Journal of Gastroenterology2013，19，41： | 5 |
| 5 | Dynamical network biomarkers for identifying critical transitions and their driving networks of biologic processes显示文摘 | Rui Liu Kazuyuki Aihara Luonan Chen | 2013 | Frontiers of Electrical and Electronic Engineering in China2013，8，2： | 5 |
| 6 | Dynamics-based data science in biology显示文摘Life science has long been a rich subject for research,and continues to develop at high speed.One of the major aims of life science is to study the mechanisms of various biological processes on the basis of biological big-data.Many statistics-based methods have been proposed to catch the essence by mining such data,including the popular category classification,variables regression,group clustering,statistical comparison,dimensionality reduction,and component analysis. | Jifan Shi Kazuyuki Aihara Luonan Chen | 2021 | National Science Review2021，8，5： | 4 |
| 7 | 基于景观网络熵的局部新冠肺炎暴发和传染病流行预警显示文摘新型冠状病毒肺炎(COVID-19)的迅速传播对全人类构成了巨大的威胁.为了及时采取相应的控制措施,制定有效的策略来检测COVID-19疫情的预警信号是非常必要的.然而,与时间序列预测不同,流行病的暴发事件通常是高度非线性的,具有从缓慢变化到剧烈转变的动力学特征,因此很难预测.通过综合利用地理区域网络的高维动态信息和每日新增病例的实时数据,本研究开发了一种非线性、无模型的计算方法,即景观网络熵(LNE)方法,来探测COVID-19暴发前的预警信号及预测流感暴发. LNE方法成功应用于中国湖北省、西欧、日本关东地区、韩国、美国17个州和意大利的新冠疫情,以及日本东京流感疫情,探测到了传染病暴发前的预警信号.此外,本研究还基于LNE方法开发了一个在线分析平台,用于实时预警疫情暴发. | 刘锐 钟佳元 洪仁豪 Ely Chen Kazuyuki Aihara 陈培 陈洛南 | 2021 | Science Bulletin2021，66，22： | 3 |
| 8 | Predicting future dynamics from short-term time series using an Anticipated Learning Machine显示文摘Predicting time series has significant practical applications over different disciplines.Here,we propose an Anticipated Learning Machine(ALM)to achieve precise future-state predictions based on short-term but high-dimensional data.From non-linear dynamical systems theory,we show that ALM can transform recent correlation/spatial information of high-dimensional variables into future dynamical/temporal information of any target variable,thereby overcoming the small-sample problem and achieving multistep-ahead predictions.Since the training samples generated from high-dimensional data also include information of the unknown future values of the target variable,it is called anticipated learning.Extensive experiments on real-world data demonstrate significantly superior performances of ALM over all of the existing 12 methods.In contrast to traditional statistics-based machine learning,ALM is based on non-linear dynamics,thus opening a new way for dynamics-based machine learning. | Chuan Chen Rui Li Lin Shu Zhiyu He Jining Wang Chengming Zhang Huanfei Ma Kazuyuki Aihara Luonan Chen | 2020 | National Science Review2020，7，6： | 3 |
| 9 | 不同硫载体对轮胎用NR胶料性能的影响显示文摘研究了添加不同硫载体化合物二辛基多硫代磷酸酯 (SDT/S)、二丁基二硫代磷酸锌 (TP/S)、二硫代己内酰胺 (S/G)、二硫代二吗啡啉 (M /G)以及SDT/S的用量对轮胎用NR胶料的加工性能、硫化特性、拉伸性能、动态生热和压缩永久变形等性能的影响规律 ,并与传统硫黄硫化体系进行了比较。结果表明 ,加入SDT/S和TP/S会缩短门尼焦烧时间 ,但能提高硫化平坦模量和改善抗硫化返原能力 ;较低硫化温度 (145℃ )下 ,传统硫化体系赋予NR硫化胶较低的拉伸强度和 30 0 %定伸应力 ,提高硫化温度 (175℃ ) ,会使加入硫载体的NR硫化胶具有较高的拉伸性能保持率 ;加入SDT/S和提高其用量 ,可提高NR胶料的抗硫化返原性能 。 | 苘辉刚 范汝良 张青凯 Aihara T 纪奎江 | 2001 | 轮胎工业2001，21，6： | 2 |
| 10 | Esophageal Capsule Endoscopy for Screening Esophageal Varices among Japanese Patients with Liver Cirrhosis显示文摘 | Haruya Ishiguro Shoichi Saito Hiroo Imazu Hiroyuki Aihara Tomohiro Kato Hisao Tajiri Cristiano Spada | 2011 | Gastroenterology Research and Practice2011，，： | 2 |
| 11 | Effectiveness of impedance monitoring during radiofrequency ablation for predicting popping显示文摘AIM:To retrospectively evaluate the effectiveness of impedance monitoring for predicting popping during radiofrequency ablation(RFA) using internally cooled electrodes.METHODS:We reviewed 140 patients(94 males,46 females;age range 73.0 ± 11.1 year) who underwent RFA between February 2006 and November 2008 with a modified protocol using a limited power delivery rather than a conventional one to avoid popping.All the patients provided their written informed consent,and the study was approved by the institutional review board.Intraprocedural impedances were measured for the study subjects,and the tumors were classified into three types according to the characteristics of their impedance curves:increasing,flat,or decreasing.The tumors were further sorted into seven subtypes(A-G) depending on the curvature of the impedance curve' s increase or decrease.Relative popping rates were determined for the three types and seven subtypes.A chi-square test was performed to estimate statistical significance.RESULTS:A total of 148 nodules treated by RFA were analyzed.The study samples included 132 nodules of hepatocellular carcinoma,14 nodules of metastatic liver cancer,and two nodules of intrahepatic cholangiocarcinoma.The numbers of nodules with each impedance curve type were as follows:37 increasing-type nodules,43 flat-type nodules,and 68 decreasing-type nodules.Popping occurrence rates were 24.3%,46.5% and 64.7%,respectively.Flat-type nodules exhibited a significantly higher rate of popping compared to increasing-type nodules(P = 0.039).Decreasing-type nodules exhibited a significantly higher rate of popping compared to increasing-type nodules(P < 0.0001).Notably,nodules that showed a sharp decrease in impedance in the latter ablation period(subtype E) exhibited a significantly higher rate of popping compared to other subtypes.CONCLUSION:Intraprocedural impedance monitoring can be a useful tool to predict the occurrence of popping during liver tumor RFA performed with internally cooled electrodes. | Hiroya Iida Tsukasa Aihara Shinichi Ikuta Naoki Yamanaka | 2012 | World Journal of Gastroenterology2012，18，41： | 2 |
| 12 | Blinded nonrandomized comparative study of gastric examination with a magnetically guided capsule endoscope and standard videoendoscope显示文摘 | Jean-Francois Rey Haruhiko Ogata Naoki Hosoe Kazuo Ohtsuka Noriyuki Ogata Keiichi Ikeda Hiroyuki Aihara Ileana Pangtay Toshifumi Hibi Shin-Ei Kudo Hisao Tajiri | 2012 | Gastrointestinal Endoscopy2012，，2： | 2 |
| 13 | Laparoscopically assisted total gastrectomy with lymph node dissection for upper and middle gastric cancer显示文摘 | Erito Mochiki Yoshitaka Toyomasu Kyouichi Ogata Hiroyuki Andoh Tetsuro Ohno Ryusuke Aihara Takayuki Asao Hiroyuki Kuwano | 2008 | Surgical Endoscopy2008，，9： | 2 |
| 14 | Decrease of CD56 + T Cells and Natural Killer Cells in Cirrhotic Livers With Hepatitis C May Be Involved in Their Susceptibility to Hepatocellular Carcinoma显示文摘 | Nobuaki Kawarabayashi Shuhji Seki Kazuo Hatsuse Takashi Ohkawa Yuji Koike Tsukasa Aihara Yoshiko Habu Ryusuke Nakagawa Katsunori Ami Hoshio Hiraide Hidetaka Mochizuki | 2000 | Hepatology2000，，5： | 2 |
| 15 | Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma显示文摘AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RESULTS: The G-related mucin phenotypes were highly expressed in all the histological subtypes of AGA. The expression of the GI phenotype in SIG patients was lower than that in DAC patients (P = 0.02), and this phenotype was observed in 56% of the non-SIG patients in the intramucosal layer. Among non-SIG cases, the expression of the GI phenotype was significantly higherin patients with extended adenocarcinomas and those with positive rates of lymph node metastasis. There was no difference between the expressions of the G and other GI phenotypes factors. Among DAC and non-SIG patients, there were no differences between the survival rates of the corresponding patient groups. CONCLUSION: The GI phenotype might possess more invasive characteristics than the G phenotype in nonSIG. Neither of the phenotypes indicated a poor prognosis of DAC and non-SIG. | Fumiaki Toki Atsushi Takahashi Ryusuke Aihara Kyoichi Ogata Hiroyuki Ando Tetsuro Ohno Erito Mochiki Hiroyuki Kuwano | 2010 | World Journal of Gastroenterology2010，16，22： | 2 |
| 16 | Laparoscopic assisted distal gastrectomy for early gastric cancer:five years'experience显示文摘 | Mochiki E Kamiyama Y Aihara R | | 0，，03： | 2 |
| 17 | Development of thermal spraying-sintering Technology for solid oxide fuel cells 显示文摘 | OKUMURA K AIHARA Y ITO S | 2000 | Journal of Thermal Spray Technology2000，9，： | 2 |
| 18 | Energy landscape decomposition for cell differentiation with proliferation effect显示文摘Complex interactions between genes determine the development and differentiation of cells.We establish a landscape theory for cell differentiation with proliferation effect,in which the developmental process is modeled as a stochastic dynamical system with a birth-death term.We find that two different energy landscapes,denoted U and V,collectively contribute to the establishment of non-equilibrium steady differentiation.The potential U is known as the energy landscape leading to the steady distribution,whose metastable states stand for cell types,while V indicates the differentiation direction from pluripotent to differentiated cells.This interpretation of cell differentiation is different from the previous landscape theory without the proliferation effect.We propose feasible numerical methods and a mean-field approximation for constructing landscapes U and V.Successful applications to typical biological models demonstrate the energy landscape decomposition’s validity and reveal biological insights into the considered processes. | Jifan Shi Kazuyuki Aihara Tiejun Li Luonan Chen | 2022 | National Science Review2022，9，8： | 2 |
| 19 | Bifurcation and resonance of a mathematical model for non-linear motion of a flooded ship in waves显示文摘 | MURASHIGE S AIHARA K | 1999 | Journal of sound and vibration1999，220，1： | 1 |
| 20 | Chaotic simulated annealing by a neural network model with transient chaos显示文摘 | CHEN L AIHARA K | 1995 | Neural Networks1995，8，6： | 1 |
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