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Introduction: Real-time, non-invasive monitoring of thrombus formation in extracorporeal circuits has yet to be achieved. To address the challenges of conventional optical thrombus detection methods requiring large devices that limit detection capacity, we developed a micro-optical thrombus sensor. Methods: The proposed micro-optical thrombus sensor can detect the intensity of light scattered by blood at wavelengths of 660 and 855 nm. Two thrombus sensors were installed on in vitro circuit: one at the rotary blood pump and one at a flow channel. To evaluate the variation in the ratio of incident light intensity at each wavelength of the two sensors, Rfluct (for 660 nm) and Ifluct (for 855 nm) were defined. Using fresh porcine blood as a working fluid, we performed in vitro tests of haematocrit (Hct) and oxygen saturation (SaO2) variation and thrombus detection. Thrombus tests were terminated after Rfluct or Ifluct showed a larger change than the maximum range of those in the Hct and SaO2 variation test. Results: In all three thrombus detection tests, Ifluct showed a larger change than the maximum range of those in the Hct and SaO2 variation test. After the tests, thrombus formation was confirmed in the pump, and there was no thrombus in the flow channel. The results indicate that Ifluct is an effective parameter for identifying the presence of a thrombus. Conclusion: Thrombus detection in an extracorporeal circuit using the developed micro-optical sensors was successfully demonstrated in an in vitro test.

Phylogenetic profiling is a powerful computational method for revealing the functions of function-unknown genes. Although conventional similarity evaluation measures in phylogenetic profiling showed high prediction accuracy, they have two estimation biases: an evolutionary bias and a spurious correlation bias. Existing studies have focused on the evolutionary bias, but the spurious correlation bias has not been analyzed. To eliminate the spurious correlation bias, we applied an evaluation measure based on the inverse Potts model (IPM) to phylogenetic profiling. We also proposed an evaluation measure to remove both the evolutionary and spurious correlation biases using the IPM. In an empirical dataset analysis, we demonstrated that these IPM-based evaluation measures improved the prediction performance of phylogenetic profiling. In addition, we found that the integration of several evaluation measures, including the IPM-based evaluation measures, had superior performance to a single evaluation measure. The source code is freely available at https://github.com/fukunagatsu/Ipm.

Summary Accessing enormous uncultivated microorganisms (microbial dark matter) in various Earth environments requires accurate, nondestructive classification, and molecular understanding of the microorganisms in in situ and at the single-cell level. Here we demonstrate a combined approach of random forest (RF) machine learning and single-cell Raman microspectroscopy for accurate classification of phylogenetically diverse prokaryotes (three bacterial and three archaeal species from different phyla). Our RF classifier achieved a 98.8 ± 1.9% classification accuracy among the six species in pure populations and 98.4% for three species in an artificially mixed population. Feature importance scores against each wavenumber reveal that the presence of carotenoids and structure of membrane lipids play key roles in distinguishing the prokaryotic species. We also find unique Raman markers for an ammonia-oxidizing archaeon. Our approach with moderate data pretreatment and intuitive visualization of feature importance is easy to use for non-spectroscopists, and thus offers microbiologists a new single-cell tool for shedding light on microbial dark matter., Graphical abstract, Highlights • Random forest models classify prokaryotic species with high accuracy of >98% • Both bacteria and archaea are classified using minimally preprocessed Raman data • Feature importance reveals what biomolecules contribute to species classification • Raman marker bands for some archaeal species are discovered, Molecular spectroscopy techniques; Microbiology; Machine learning

A characteristic clinical feature of COVID-19 is the frequent occurrence of thrombotic events. Furthermore, many cases of multiorgan failure are thrombotic in nature. Since the outbreak of COVID-19, D-dimer testing has been used extensively to evaluate COVID-19-associated thrombosis, but does not provide a complete view of the disease because it probes blood coagulation, but not platelet activity. Due to this limitation, D-dimer testing fails to account for thrombotic events which occur despite low D-dimer levels, such as sudden stroke in young patients and autopsy-identified widespread microthrombi in multiple organs. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by large-scale single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients, including those who were not clinically diagnosed with thrombosis and those with low D-dimer levels (≤1 µg/mL). Additionally, results indicate a strong link between the concentration of platelet aggregates and the severity and mortality of COVID-19. Finally, high-dimensional analysis and comparison with other diseases reveal that COVID-19 behaves as a product of thrombosis (localized) and infectious diseases (systemic), as a cause of systemic thrombosis.

A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we present a method for massive image-based profiling, temporal monitoring, and big data analysis of circulating platelets and platelet aggregates in the blood of COVID-19 patients at single-cell resolution, to provide previously unattainable insights into the disease. In fact, our analysis of the image data from 110 hospitalized patients shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, and respiratory condition of patients with COVID-19. Finally, high-dimensional analysis based on deep learning shows that the disease behaves as systemic thrombosis.

Motivation Orthology inference constitutes a common base of many genome-based studies, as a pre-requisite for annotating new genomes, finding target genes for biotechnological applications and revealing the evolutionary history of life. Although its importance keeps rising with the ever-growing number of sequenced genomes, existing tools are computationally demanding and difficult to employ. Results Here, we present SonicParanoid, which is faster than, but comparably accurate to, the well-established tools with a balanced precision-recall trade-off. Furthermore, SonicParanoid substantially relieves the difficulties of orthology inference for those who need to construct and maintain their own genomic datasets. Availability and implementation SonicParanoid is available with a GNU GPLv3 license on the Python Package Index and BitBucket. Documentation is available at http://iwasakilab.bs.s.u-tokyo.ac.jp/sonicparanoid. Supplementary information Supplementary data are available at Bioinformatics online.

We present a case in which the accidental ingestion of a toothpick caused duodenal perforation and small intestinal obstruction. A 58-year-old man visited our emergency room with acute abdominal pain. Computed tomography (CT) showed obstructive ileus as well as a foreign body penetrating the duodenum, which was identified as a toothpick and removed endoscopically. Unenhanced CT was superior in detecting the object. The patient has been doing well since the operation.

It is expected that IoT technology can make a breakthrough in livestock management by connecting biological information of livestock and environmental information obtained by IoT sensors to farmers who are in remote location from the farm via cloud. It will help to improve efficiency of livestock production and reduce physical labor and labor cost. There are some requirements for IoT sensors for smart livestock monitoring, which is a little different from the case of IoT sensors for humans. In this chapter, we explain these requirements. In addition, representative IoT sensors for livestock monitoring including commercialized sensors and prototypes in research stage are introduced and their advantages and disadvantages are discussed.

The reconstruction of ancestral scenarios is widely used to study the evolution of characters along phylogenetic trees. One commonly uses the marginal posterior probabilities of the character states, or the joint reconstruction of the most likely scenario. However, marginal reconstructions provide users with state probabilities, which are difficult to interpret and visualize, whereas joint reconstructions select a unique state for every tree node and thus do not reflect the uncertainty of inferences. We propose a simple and fast approach, which is in between these two extremes. We use decision-theory concepts (namely, the Brier score) to associate each node in the tree to a set of likely states. A unique state is predicted in tree regions with low uncertainty, whereas several states are predicted in uncertain regions, typically around the tree root. To visualize the results, we cluster the neighboring nodes associated with the same states and use graph visualization tools. The method is implemented in the PastML program and web server. The results on simulated data demonstrate the accuracy and robustness of the approach. PastML was applied to the phylogeography of Dengue serotype 2 (DENV2), and the evolution of drug resistances in a large HIV data set. These analyses took a few minutes and provided convincing results. PastML retrieved the main transmission routes of human DENV2 and showed the uncertainty of the human-sylvatic DENV2 geographic origin. With HIV, the results show that resistance mutations mostly emerge independently under treatment pressure, but resistance clusters are found, corresponding to transmissions among untreated patients.

Here, we report the development of an integrated laser Doppler blood flow micrometer for chickens. This sensor weighs only 18 g and is one of the smallest-sized blood flow meters, with no wired line, these are features necessary for attaching the sensor to the chicken. The structure of the sensor chip consists of two silicon cavities with a photo diode and a laser diode, which was achieved using the microelectromechanical systems technique, resulting in its small size and significantly low power consumption. In addition, we introduced an intermittent measuring arrangement in the measuring system to reduce power consumption and to enable the sensor to work longer. We were successfully able to measure chicken blood flow for five consecutive days, and discovered that chicken blood flow shows daily fluctuations.

Clouds play an important role in creating realistic images of outdoor scenes. Many methods have therefore been proposed for displaying realistic clouds. However, the realism of the resulting images depends on many parameters used to render them and it is often difficult to adjust those parameters manually. This paper proposes a method for addressing this problem by solving an inverse rendering problem: given a non-uniform synthetic cloud density distribution, the parameters for rendering the synthetic clouds are estimated using photographs of real clouds. The objective function is defined as the difference between the color histograms of the photograph and the synthetic image. Our method searches for the optimal parameters using genetic algorithms. During the search process, we take into account the multiple scattering of light inside the clouds. The search process is accelerated by precomputing a set of intermediate images. After ten to twenty minutes of precomputation, our method estimates the optimal parameters within a minute.

小腸軸捻転症は比較的まれな疾患であり，今回，空腸憩室が原因と考えられた1例を経験した．症例は90歳，女性．上腹部痛を自覚し，数日後上腹部痛が増強したため来院した．腹部造影CTでは上腸間膜動脈を中心としたwhirl signを認め，小腸軸捻転症と診断し同日緊急手術を行った．手術所見では，小腸は全体が上腸間膜動脈を中心として反時計回りに720度捻転していた．腸管壊死はなく用手的に軸捻転を整復した．この際，Treitz靱帯より30cm肛門側の空腸の腸間膜対側に憩室を認め，その位置的関連から，軸捻転の原因と考えられた．このため憩室基部を楔形に切除し縫合閉鎖した．原因不明の腸閉塞症例では小腸軸捻転症も念頭に置き精査を行い，術中憩室を認めた場合には憩室の切除を行って，軸捻転の再発を防止すべきと考えられた．

We have developed the first and the smallest blood flow sensor composed of integrated circuits (ICs) fused with an optical microelectromechanical systems (MEMS) chip using system-in-package (SiP) technologies for application in a healthcare monitoring system. The probe of this blood flow sensor consists of three layers, and the optical MEMS chip is stacked as the top layer. Through silicon via (TSV), vertical-cavity surface-emitting laser (VCSEL) and cavities enable wafer-level packaging of the optical MEMS chip. The other two layers consisting of ICs are highly densified by SiP technology, and the volume of the probe is miniaturized to about one-sixth of our previously reported integrated laser Doppler blood flowmeter, an MEMS blood flow sensor to which SiP technology was not applied. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

症例は70歳,男性.発熱,嘔吐,心窩部痛を主訴に救急搬送.来院時,心窩部に圧痛を認め,腹部は軽度膨隆していた.血液所見でBUN 41.2mg/dl, Cr 2.7mg/dlと腎障害・脱水があり,また, CPK 9418IU/l, BE-1.2と代謝性アシドーシスを呈しており腸管虚血を疑った.腹部単純CT検査では,門脈左枝領域に門脈ガス血症を認めた.以上より上腸間膜動脈血栓症と診断し,上腸間膜動脈造影を施行.末梢動脈の造影不良と動脈の狭小化と拡張を交互に認め,非閉塞性小腸虚血と判断し,血管拡張薬動注したが血行改善ないため,緊急手術施行.空腸は非連続性広範に壊死していた.術中小腸内視鏡を行い切除範囲決定し,空腸125cmを切除した.術後肝不全を呈したが術後1カ月退院した.腸管壊死を伴う非閉塞性腸管虚血症を経験したので報告した.切除範囲決定には術中小腸内視鏡検査が有用であった.

Quantitative analysis of behaviors shown by interacting multiple animals can provide a key for revealing high-order functions of their nervous systems. To resolve these complex behaviors, a video tracking system that preserves individual identity even under severe overlap in positions, i.e., occlusion, is needed. We developed GroupTracker, a multiple animal tracking system that accurately tracks individuals even under severe occlusion. As maximum likelihood estimation of Gaussian mixture model whose components can severely overlap is theoretically an ill-posed problem, we devised an expectation-maximization scheme with additional constraints on the eigenvalues of the covariance matrix of the mixture components. Our system was shown to accurately track multiple medaka (Oryzias latipes) which freely swim around in three dimensions and frequently overlap each other. As an accurate multiple animal tracking system, GroupTracker will contribute to revealing unexplored structures and patterns behind animal interactions. The Java source code of GroupTracker is available at https://sites.google.com/site/fukunagatsu/software/group-tracker.

Exchanging ideas with like-minded, enthusiastic people interested in the same topic is crucial for the advancement of a scientist's career. Several Regional Student Groups (RSGs) of the International Society for Computational Biology (ISCB) Student Council have cooperated in the last six years to organize scientific workshops and conferences. With motivated students, it is possible to create a memorable event for fellow scientists; in doing so, the organizers gain valuable experiences. While collaborating across borders and time zones can be difficult, feedback from event organizers was always positive. When limited resources are juxtaposed with great ideas and a network of contacts, the outcome is always an amazing experience, despite organizers being separated geographically across different countries.

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed. ispartof: Journal of Biomedical Semantics vol:5 issue:5 pages:1-13 ispartof: location:England status: published

We demonstrated a Nd3+ complex doped solid-state polymer laser. The laser threshold was reduced to 334 μJ with a new solid-state host matrix and a short laser cavity. Its low threshold enables LD pumping operation.

We obtained the slope efficiency of 20% and the maximum output energy of 5.3mJ by Nd3+ complex laser. To the best of knowledge, this is the highest slope efficiency in bulky lasers using Nd3+ complex.

Using Micro Electro Mechanical Systems (MEMS) technologies, we have developed the world's smallest, lightest, and least power-consuming integrated laser Doppler blood flow sensor. Unlikely commercial optical fiber type blood flow instruments, the structure of our sensor need not optical fiber, which is also invulnerable to any movements of the person wearing it. Therefore our sensor enables stable measurement the person raising an arm with our sensor attached to a finger-tip (arm-raising test). In this paper, we present a new structure of an integrated laser Doppler blood flow sensor and its application to dehydration prevention using our sensor and arm-raising test.

This article describes a new technique for retracting the rectum upward during laparoscopic surgery using the pulling force created between two magnets. A magnet and a colonoscope were inserted into the rectal cavity of a swine model, and a second magnet was placed on the abdominal wall creating a magnetic anchor or retraction that pulled the rectum upward. Subsequently, a laparoscopic anterior resection of the rectosigmoid colon was performed. The magnetic anchor transferred an electromagnetic force through the abdominal wall, creating effective organ retraction without the need of a trocar. Surgery without the use of trocars allows for increased flexibility in the angle, distance, and location of the retraction. Since retraction was achieved without a shaft device that can impede visibility within the abdominal cavity, the surgeons achieved excellent endoscopic views. Because the intraluminal magnetic anchor was placed directly on the inside wall of the target organ, tracking target organ movement closely with the movement of the extracorporeal control magnet was possible and synchronizing their movements was not difficult. The technique presented in this article might be less invasive and could provide more effective manageability for laparoscopic surgery.

We designed a method for remote-controlled endoscopic surgery using magnet-retracting forceps. To evaluate the feasibility of this technique, laparoscopic cholecystectomy was attempted in a swine model. This method takes advantage of the attractive force between two magnets, one inserted into the peritoneal cavity and the other located outside the abdominal wall. An intra-peritoneal magnet was fixed to the fundus of the gallbladder using an endovascular clip. Laparoscopic cholecystectomy was accomplished by magnetic retraction of the gallbladder. This magnet-retracting forceps provided port-less access to the abdominal cavity. Since the direction and range of retraction were unrestricted by the location of access-ports fixed on the abdominal wall, surgery could be less invasive. In addition, this procedure provided surgeons with excellent endoscopic views, as retraction force was supplied without any shaft device in the abdomen. This operation system using magnetic retraction appears promising.

In the trial and research phases, the fabrication of micro electro mechanical systems (MEMS) devices and integrated circuits (ICs) is both lengthy and costly, owing to the demands imposed by the use of photomasks. Maskless lithography techniques, such as electron beam (EB), laser scanning, and digital mirror device (DMD) lithography techniques, are widely used. In the MEMS field, submicron and wiring patterns are often created on uneven structures. We have developed a maskless lithography technique by modifying a DMD with two automatically switchable lenses. The first lens with a magnification power of 10× and a numerical aperture (NA) of 0.3 was used to rapidly expose wide areas, and the second lens with a magnification power of 100× and an NA of 0.9 was used for fine patterning. In the present study, we fabricated submicron patterns, wiring patterns, and alignment marks on slanted and deeply etched surfaces, and three-dimensional photoresist structures using our developed DMD lithography technique.

Nd3+ complex doped polymer liquid laser have been demonstrated and the threshold of the laser was also calculated. The calculation results that a laser media with 2 mm length is suitable for low threshold laser oscillation. We obtained the slope efficiency of 20% and the maximum output energy of 5.3 mJ at the pumping energy of 31 mJ by the method of the side pumping. To the best of knowledge, this is the highest slope efficiency of the bulky laser using Nd3+ complex.

In this paper, we describe a server/client literature management system specialized for the life science domain, the TogoDoc system (Togo, pronounced Toe-Go, is a romanization of a Japanese word for integration). The server and the client program cooperate closely over the Internet to provide life scientists with an effective literature recommendation service and efficient literature management. The content-based and personalized literature recommendation helps researchers to isolate interesting papers from the "tsunami" of literature, in which, on average, more than one biomedical paper is added to MEDLINE every minute. Because researchers these days need to cover updates of much wider topics to generate hypotheses using massive datasets obtained from public databases or omics experiments, the importance of having an effective literature recommendation service is rising. The automatic recommendation is based on the content of personal literature libraries of electronic PDF papers. The client program automatically analyzes these files, which are sometimes deeply buried in storage disks of researchers' personal computers. Just saving PDF papers to the designated folders makes the client program automatically analyze and retrieve metadata, rename file names, synchronize the data to the server, and receive the recommendation lists of newly published papers, thus accomplishing effortless literature management. In addition, the tag suggestion and associative search functions are provided for easy classification of and access to past papers (researchers who read many papers sometimes only vaguely remember or completely forget what they read in the past). The TogoDoc system is available for both Windows and Mac OS X and is free. The TogoDoc Client software is available at http://tdc.cb.k.u-tokyo.ac.jp/, and the TogoDoc server is available at https://docman.dbcls.jp/pubmed_recom.

In this study, we developed a micropyramid array electrode that facilitates contact between a nitrocellulose membrane and electrode, which is important to realize a quantitative and sensitive electrochemical detection system for immunochromatography. We evaluated the micropyamid array electrode with our newly developed detection system that can measure contact forces between a membrane and electrode, and also investigated the relationship between redox current and contact forces. By using normal pulse voltammetry, we observed higher reduction currents over a flat surface electrode at lower contact forces with the micropyramid array.

The overwhelming amount of network data in functional genomics is making its visualization cluttered with jumbling nodes and edges. Such cluttered network visualization, which is known as "hair-balls", is significantly hindering data interpretation and analysis of researchers. Effective navigation approaches that can always abstract network data properly and present them insightfully are hence required, to help researchers interpret the data and acquire knowledge efficiently. Cytoscape is a de facto standard platform for network visualization and analysis, which has many users around the world. Apart from its core sophisticated features, it easily allows for extension of the functionalities by loading extra plug-ins. We developed NaviClusterCS, which enables researchers to interactively navigate large biological networks of ~100,000 nodes in a "Google Maps-like" manner in the Cytoscape environment. NaviClusterCS rapidly and automatically identifies biologically meaningful clusters in large networks, e.g., proteins sharing similar biological functions in protein-protein interaction networks. Then, it displays not all nodes but only preferable numbers of those clusters at any magnification to avoid creating the cluttered network visualization, while its zooming and re-centering functions still enable researchers to interactively analyze the networks in detail. Its application to a real Arabidopsis co-expression network dataset illustrated a practical use of the tool for suggesting knowledge that is hidden in large biological networks and difficult to be obtained using other visualization methods. NaviClusterCS provides interactive and multi-scale network navigation to a wide range of biologists in the big data era, via the de facto standard platform for network visualization. It can be freely downloaded at http://navicluster.cb.k.u-tokyo.ac.jp/cs/ and installed as a plug-in of Cytoscape.