148 results on '"Hirofumi Kobayashi"'
Search Results
2. Neuropilin-1 Mediates SARS-CoV-2 Infection of Astrocytes in Brain Organoids, Inducing Inflammation Leading to Dysfunction and Death of Neurons
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Weili Kong, Mauricio Montano, Michael J. Corley, Ekram Helmy, Hirofumi Kobayashi, Martin Kinisu, Rahul Suryawanshi, Xiaoyu Luo, Loic A. Royer, Nadia R. Roan, Melanie Ott, Lishomwa C. Ndhlovu, and Warner C. Greene
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COVID-19 ,astrocytes ,innate immunity ,inflammation ,neuronal dysfunction ,human iPSC-derived brain organoids ,Microbiology ,QR1-502 - Abstract
ABSTRACT Coronavirus disease 2019 (COVID-19) is frequently associated with neurological deficits, but how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces these effects remains unclear. Here, we show that astrocytes are readily infected by SARS-CoV-2, but surprisingly, neuropilin-1, not angiotensin-converting enzyme 2 (ACE2), serves as the principal receptor mediating cell entry. Infection is further positively modulated by the two-pore segment channel 2 (TPC2) protein that regulates membrane trafficking and endocytosis. Astrocyte infection produces a pathological response closely resembling reactive astrogliosis characterized by elevated type I interferon (IFN) production, increased inflammation, and the decreased expression of transporters of water, ions, choline, and neurotransmitters. These combined events initiated within astrocytes produce a hostile microenvironment that promotes the dysfunction and death of uninfected bystander neurons. IMPORTANCE SARS-CoV-2 infection primarily targets the lung but may also damage other organs, including the brain, heart, kidney, and intestine. Central nervous system (CNS) pathologies include loss of smell and taste, headache, delirium, acute psychosis, seizures, and stroke. Pathological loss of gray matter occurs in SARS-CoV-2 infection, but it is unclear whether this is due to direct viral infection, indirect effects associated with systemic inflammation, or both. Here, we used induced pluripotent stem cell (iPSC)-derived brain organoids and primary human astrocytes from the cerebral cortex to study direct SARS-CoV-2 infection. Our findings support a model where SARS-CoV-2 infection of astrocytes produces a panoply of changes in the expression of genes regulating innate immune signaling and inflammatory responses. The deregulation of these genes in astrocytes produces a microenvironment within the CNS that ultimately disrupts normal neuron function, promoting neuronal cell death and CNS deficits.
- Published
- 2022
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3. Basic locomotor muscle synergies used in land walking are finely tuned during underwater walking
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Hikaru Yokoyama, Tatsuya Kato, Naotsugu Kaneko, Hirofumi Kobayashi, Motonori Hoshino, Takanori Kokubun, and Kimitaka Nakazawa
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Medicine ,Science - Abstract
Abstract Underwater walking is one of the most common hydrotherapeutic exercises. Therefore, understanding muscular control during underwater walking is important for optimizing training regimens. The effects of the water environment on walking are mainly related to the hydrostatic and hydrodynamic theories of buoyancy and drag force. To date, muscular control during underwater walking has been investigated at the individual muscle level. However, it is recognized that the human nervous system modularly controls multiple muscles through muscle synergies, which are sets of muscles that work together. We found that the same set of muscle synergies was shared between the two walking tasks. However, some task-dependent modulation was found in the activation combination across muscles and temporal activation patterns of the muscle synergies. The results suggest that the human nervous system modulates activation of lower-limb muscles during water walking by finely tuning basic locomotor muscle synergies that are used during land walking to meet the biomechanical requirements for walking in the water environment.
- Published
- 2021
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- View/download PDF
4. Effort-dependent effects on uniform and diverse muscle activity features in skilled pitching
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Tsubasa Hashimoto, Ken Takiyama, Takeshi Miki, Hirofumi Kobayashi, Daiki Nasu, Tetsuya Ijiri, Masumi Kuwata, Makio Kashino, and Kimitaka Nakazawa
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Medicine ,Science - Abstract
Abstract How do skilled players change their motion patterns depending on motion effort? Pitchers commonly accelerate wrist and elbow joint rotations via proximal joint motions. Contrastingly, they show individually different pitching motions, such as in wind-up or follow-through. Despite the generality of the uniform and diverse features, effort-dependent effects on these features are unclear. Here, we reveal the effort dependence based on muscle activity data in natural three-dimensional pitching performed by skilled players. We extract motor modules and their effort dependence from the muscle activity data via tensor decomposition. Then, we reveal the unknown relations among motor modules, common features, unique features, and effort dependence. The current study clarifies that common features are obvious in distinguishing between low and high effort and that unique features are evident in differentiating high and highest efforts.
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- 2021
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5. Raman image-activated cell sorting
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Nao Nitta, Takanori Iino, Akihiro Isozaki, Mai Yamagishi, Yasutaka Kitahama, Shinya Sakuma, Yuta Suzuki, Hiroshi Tezuka, Minoru Oikawa, Fumihito Arai, Takuya Asai, Dinghuan Deng, Hideya Fukuzawa, Misa Hase, Tomohisa Hasunuma, Takeshi Hayakawa, Kei Hiraki, Kotaro Hiramatsu, Yu Hoshino, Mary Inaba, Yuki Inoue, Takuro Ito, Masataka Kajikawa, Hiroshi Karakawa, Yusuke Kasai, Yuichi Kato, Hirofumi Kobayashi, Cheng Lei, Satoshi Matsusaka, Hideharu Mikami, Atsuhiro Nakagawa, Keiji Numata, Tadataka Ota, Takeichiro Sekiya, Kiyotaka Shiba, Yoshitaka Shirasaki, Nobutake Suzuki, Shunji Tanaka, Shunnosuke Ueno, Hiroshi Watarai, Takashi Yamano, Masayuki Yazawa, Yusuke Yonamine, Dino Di Carlo, Yoichiroh Hosokawa, Sotaro Uemura, Takeaki Sugimura, Yasuyuki Ozeki, and Keisuke Goda
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Science - Abstract
Most current cell sorting methods are based on fluorescence detection with no imaging capability. Here the authors generate and use Raman image-activated cell sorting with a throughput of around 100 events per second, providing molecular images with no need for labeling.
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- 2020
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6. ZAF, the first open source fully automated feeder for aquatic facilities
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Merlin Lange, AhmetCan Solak, Shruthi Vijay Kumar, Hirofumi Kobayashi, Bin Yang, and Loïc Alain Royer
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zebrafish ,open-source ,feeder ,automatic ,zaf ,aquatic ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
In the past few decades, aquatic animals have become popular model organisms in biology, spurring a growing need for establishing aquatic facilities. Zebrafish are widely studied and relatively easy to culture using commercial systems. However, a challenging aspect of maintaining aquatic facilities is animal feeding, which is both time- and resource-consuming. We have developed an open-source fully automatic daily feeding system, Zebrafish Automatic Feeder (ZAF). ZAF is reliable, provides a standardized amount of food to every tank, is cost-efficient and easy to build. The advanced version, ZAF+, allows for the precise control of food distribution as a function of fish density per tank, and has a user-friendly interface. Both ZAF and ZAF+ are adaptable to any laboratory environment and facilitate the implementation of aquatic colonies. Here, we provide all blueprints and instructions for building the mechanics, electronics, fluidics, as well as to setup the control software and its user-friendly graphical interface. Importantly, the design is modular and can be scaled to meet different user needs. Furthermore, our results show that ZAF and ZAF+ do not adversely affect zebrafish culture, enabling fully automatic feeding for any aquatic facility.
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- 2021
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7. Intelligent classification of platelet aggregates by agonist type
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Yuqi Zhou, Atsushi Yasumoto, Cheng Lei, Chun-Jung Huang, Hirofumi Kobayashi, Yunzhao Wu, Sheng Yan, Chia-Wei Sun, Yutaka Yatomi, and Keisuke Goda
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platelet ,blood ,deep learning ,imaging flow cytometry ,thrombosis ,microfluidics ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.
- Published
- 2020
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8. Influence of Release Parameters on Pitch Location in Skilled Baseball Pitching
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Ayane Kusafuka, Hirofumi Kobayashi, Takeshi Miki, Masumi Kuwata, Kazutoshi Kudo, Kimitaka Nakazawa, and Shinji Wakao
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baseball ,pitch location ,release parameter ,accuracy ,simulation ,Sports ,GV557-1198.995 - Abstract
This study explored the mechanical factors that determine accuracy of a baseball pitching. In particular, we focused on the mechanical parameters at ball release, referred to as release parameters. The aim was to understand which parameter has the most deterministic influence on pitch location by measuring the release parameters during actual pitching and developing a simulation that predicts the pitch location from given release parameters. By comparing the fluctuation of the simulated pitch location when varying each release parameter, it was found that the elevation pitching angle and speed significantly influenced the vertical pitch location, and the azimuth pitching angle significantly influenced the horizontal pitch location. Moreover, a regression model was obtained to predict the pitch location, and it became clear that the significant predictors for the vertical pitch location were the elevation pitching angle, the speed, and spin axis, and those for the horizontal pitch location were the azimuth pitching angle, the spin axis, and horizontal release point. Therefore, it was suggested that the parameter most affecting pitch location weas pitching angle. On the other hand, multiple regression analyses revealed that the relation between release parameters varied between pitchers. The result is expected to contribute to an understanding of the mechanisms underlying accurate ball control skill in baseball pitching.
- Published
- 2020
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9. GHz Optical Time-Stretch Microscopy by Compressive Sensing
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Cheng Lei, Yi Wu, Aswin C. Sankaranarayanan, Shih-Min Chang, Baoshan Guo, Naoto Sasaki, Hirofumi Kobayashi, Chia-Wei Sun, Yasuyuki Ozeki, and Keisuke Goda
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Compressive sensing (CS) ,time-stretch microscopy ,image processing. ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
Optical time-stretch microscopy has recently attracted intensive attention for its capability of acquiring images at an ultrahigh frame rate. Unfortunately, its achievable frame rate is limited by the requirement of having no overlap between consecutive frames, which leads to a tradeoff between the frame rate (pulse repetition rate) and the amount of the temporal dispersion used for optical image serialization. In this paper, we demonstrate compressive sensing on the platform of optical time-stretch microscopy to overcome the tradeoff between frame rate and temporal dispersion (time stretch) and achieve 50 times higher frame rate than conventional optical time-stretch microscopy. Specifically, we computationally perform compressed optical time-stretch microscopy with an experimental dataset acquired by conventional optical time-stretch microscopy and demonstrate its effects in terms of spatial resolution and cell classification accuracy. Our results indicate that the spatial resolution and cell classification accuracy reach 780 nm and 95% at a line scan rate of 675 MHz and 6.75 GHz, respectively, which correspond to five times and 50 times higher frame rates than what conventional optical time-stretch microscopy can achieve with the same dispersion amount and digitizer sampling rate.
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- 2017
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10. Mechanisms of post-contraction activation in skeletal muscle
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Azusa Uematsu, Hirofumi Sekiguchi, Hirofumi Kobayashi, Kazushi Tsuchiya, Tibor Hortobágyi, and Shuji Suzuki
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voluntary muscle contraction ,spinal excitability ,corticospinal excitability ,post activation potentiation ,post activation depression ,Sports medicine ,RC1200-1245 ,Physiology ,QP1-981 - Abstract
This review provides evidence for the task-, intensity-, and duration-specific modulation of twitch, spinal, corticospinal and cortical responses recorded up to ~18 min after the end of a muscle contraction produced by artificial and voluntary muscle activation in animal and human experimental models. Animal data revealed facilitation in spinal excitability after tetanic contraction; a phenomenon confirmed by human experiments using artificial, as well as voluntary, activation of muscle. There is evidence for a strong task-specific potentiation of spinal excitability associated with shortening and high intensity isometric contractions in contrast to depression after lengthening contractions. Contraction duration-specific effects suggest that when a contraction is performed to fatigue, post-exercise spinal excitability tends to decrease. Data from a limited number of transcranial magnetic brain stimulation studies suggest that, akin to spinal excitability, voluntary muscle contraction produces corticospinal and cortical excitability-associated changes. Of possible functional relevance, concerning these data, is that potentiation and depression in neural excitability can shape the mechanisms of how acute responses to exercise accumulate and convert to chronic adaptations. Of clinical relevance is that an even better understanding of the post-contraction effects would provide the opportunity for therapists to set exercise parameters according to the goals of therapy and need of patients and athletes to up/ down-regulate spinal, corticospinal, and cortical activity.
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- 2012
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11. A behavioral mechanism of how increases in leg strength improve old adults' gait speed.
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Azusa Uematsu, Kazushi Tsuchiya, Norio Kadono, Hirofumi Kobayashi, Takamasa Kaetsu, Tibor Hortobágyi, and Shuji Suzuki
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Medicine ,Science - Abstract
We examined a behavioral mechanism of how increases in leg strength improve healthy old adults' gait speed. Leg press strength training improved maximal leg press load 40% (p = 0.001) and isometric strength in 5 group of leg muscles 32% (p = 0.001) in a randomly allocated intervention group of healthy old adults (age 74, n = 15) but not in no-exercise control group (age 74, n = 8). Gait speed increased similarly in the training (9.9%) and control (8.6%) groups (time main effect, p = 0.001). However, in the training group only, in line with the concept of biomechanical plasticity of aging gait, hip extensors and ankle plantarflexors became the only significant predictors of self-selected and maximal gait speed. The study provides the first behavioral evidence regarding a mechanism of how increases in leg strength improve healthy old adults' gait speed.
- Published
- 2014
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12. Image Deconvolution via Noise-Tolerant Self-Supervised Inversion.
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Hirofumi Kobayashi, Ahmet Can Solak, Joshua Batson, and Loïc Alain Royer
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- 2020
13. Self-supervised deep learning encodes high-resolution features of protein subcellular localization
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Hirofumi Kobayashi, Keith C. Cheveralls, Manuel D. Leonetti, and Loic A. Royer
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Cell Biology ,Molecular Biology ,Biochemistry ,Biotechnology - Abstract
Explaining the diversity and complexity of protein localization is essential to fully understand cellular architecture. Here we present cytoself, a deep-learning approach for fully self-supervised protein localization profiling and clustering. Cytoself leverages a self-supervised training scheme that does not require preexisting knowledge, categories or annotations. Training cytoself on images of 1,311 endogenously labeled proteins from the OpenCell database reveals a highly resolved protein localization atlas that recapitulates major scales of cellular organization, from coarse classes, such as nuclear and cytoplasmic, to the subtle localization signatures of individual protein complexes. We quantitatively validate cytoself’s ability to cluster proteins into organelles and protein complexes, showing that cytoself outperforms previous self-supervised approaches. Moreover, to better understand the inner workings of our model, we dissect the emergent features from which our clustering is derived, interpret them in the context of the fluorescence images, and analyze the performance contributions of each component of our approach.
- Published
- 2022
14. Use of R-mini-CHP in combination with polatuzumab vedotin (pola-R-mini-CHP) as the primary treatment in ≥80-year-old cases with diffuse large B-cell lymphoma.
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Yasunobu Sekiguchi, Hiroki Tsutsumi, Ayumi Gomyo, Masahisa Kudo, Yoshie Iizaki, Nobuo Maseki, Machiko Kawamura, Kazuhiko Kobayashi, Yu Nishimura, Hiroaki Kanda, Hideaki Nitta, Masaaki Noguchi, and Hirofumi Kobayashi
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- 2023
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15. Long‐term follow‐up after <scp>R‐High CHOP</scp> / <scp>CHASER</scp> / <scp>LEED</scp> with <scp>Auto‐PBSCT</scp> in untreated mantle cell lymphoma—Final analysis of <scp>JCOG0406</scp>
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Michinori Ogura, Kazuhito Yamamoto, Yasuo Morishima, Masashi Wakabayashi, Kensei Tobinai, Kiyoshi Ando, Naokuni Uike, Mitsutoshi Kurosawa, Hiroshi Gomyo, Masafumi Taniwaki, Kisato Nosaka, Norifumi Tsukamoto, Tatsu Shimoyama, Noriko Fukuhara, Yoshihiro Yakushijin, Kazunori Ohnishi, Kana Miyazaki, Yoshihiro Kameoka, Nobuyuki Takayama, Ichiro Hanamura, Hirofumi Kobayashi, Kensuke Usuki, Naoki Kobayashi, Kazuma Ohyashiki, Takahiko Utsumi, Kyoya Kumagai, Dai Maruyama, Ken Ohmachi, Yoshihiro Matsuno, Shigeo Nakamura, Tomomitsu Hotta, Kunihiro Tsukasaki, and Hirokazu Nagai
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Cancer Research ,Oncology ,General Medicine - Published
- 2023
16. Modeling the Biological Pathology Continuum with HSIC-regularized Wasserstein Auto-encoders.
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Denny Wu, Hirofumi Kobayashi, Charles Ding, Cheng Lei, Keisuke Goda, and Marzyeh Ghassemi
- Published
- 2019
17. Zebrahub – Multimodal Zebrafish Developmental Atlas Reveals the State Transition Dynamics of Late Vertebrate Pluripotent Axial Progenitors
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Merlin Lange, Alejandro Granados, Shruthi VijayKumar, Jordao Bragantini, Sarah Ancheta, Sreejith Santhosh, Michael Borja, Hirofumi Kobayashi, Erin McGeever, Ahmet Can Solak, Bin Yang, Xiang Zhao, Yang Liu, Angela Detweiler, Sheryl Paul, Honey Mekonen, Tiger Lao, Rachel Banks, Adrian Jacobo, Keir Balla, Kyle Awayan, Samuel D’Souza, Robert Haase, Alexandre Dizeux, Olivier Pourquie, Rafael Gómez-Sjöberg, Greg Huber, Mattia Serra, Norma Neff, Angela Oliveira Pisco, and Loïc A. Royer
- Abstract
Elucidating the developmental process of an organism will require the complete cartography of cellular lineages in the spatial, temporal, and molecular domains. We present Zebrahub, a comprehensive dynamic atlas of zebrafish embryonic development that combines single-cell sequencing time course data with light-sheet microscopy-based lineage reconstructions. Zebrahub is a foundational resource to study developmental processes at both transcriptional and spatiotemporal levels. It is publicly accessible as a web-based resource, providing an open-access collection of datasets and tools. Using this resource we shed new light on the pluripotency of Neuro-Mesodermal Progenitors (NMPs). We find that NMPs are pluripotent only during early axis elongation before becoming exclusively mesodermal progenitors. We attribute this restriction in NMP cell fate to emerging morphodynamic features that compartmentalize tissue motion.
- Published
- 2023
18. DaXi—high-resolution, large imaging volume and multi-view single-objective light-sheet microscopy
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Bin Yang, Merlin Lange, Alfred Millett-Sikking, Xiang Zhao, Jordão Bragantini, Shruthi VijayKumar, Mason Kamb, Rafael Gómez-Sjöberg, Ahmet Can Solak, Wanpeng Wang, Hirofumi Kobayashi, Matthew N. McCarroll, Lachlan W. Whitehead, Reto P. Fiolka, Thomas B. Kornberg, Andrew G. York, and Loic A. Royer
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Cell Biology ,Molecular Biology ,Biochemistry ,Biotechnology - Abstract
The promise of single-objective light-sheet microscopy is to combine the convenience of standard single-objective microscopes with the speed, coverage, resolution and gentleness of light-sheet microscopes. We present DaXi, a single-objective light-sheet microscope design based on oblique plane illumination that achieves: (1) a wider field of view and high-resolution imaging via a custom remote focusing objective; (2) fast volumetric imaging over larger volumes without compromising image quality or necessitating tiled acquisition; (3) fuller image coverage for large samples via multi-view imaging and (4) higher throughput multi-well imaging via remote coverslip placement. Our instrument achieves a resolution of 450 nm laterally and 2 μm axially over an imaging volume of 3,000 × 800 × 300 μm. We demonstrate the speed, field of view, resolution and versatility of our instrument by imaging various systems, including Drosophila egg chamber development, zebrafish whole-brain activity and zebrafish embryonic development – up to nine embryos at a time.
- Published
- 2022
19. Exploring the Deep Feature Space of a Cell Classification Neural Network.
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Ezra Webb, Cheng Lei, Chun-Jung Huang, Hirofumi Kobayashi, Hideharu Mikami, and Keisuke Goda
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- 2018
20. A Case of Diffuse Large B-Cell Lymphoma Complicated by Helicobacter Pylori-Negative Russell Body Gastritis
- Author
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Yasunobu, Sekiguchi, You, Nishimura, Hiroaki, Kanda, Machiko, Kawamura, Kazuhiko, Kobayashi, Yukiko, Misaki, Yutaka, Takazawa, and Hirofumi, Kobayashi
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Helicobacter pylori ,Gastritis ,Humans ,Female ,Lymphoma, Large B-Cell, Diffuse ,Rituximab ,Aged ,Helicobacter Infections - Abstract
A 76-year-old woman with a past history of diabetes mellitus and Hashimoto's disease, in regard to her personal history, she did not smoke or drink alcohol. In March, year X-1, she became aware of cervical lymphadenopathy. Based on the findings of lymph node biopsy, she was diagnosed as having diffuse large B-cell lymphoma(DLBCL). An upper gastrointestinal endoscopy(U-GIE)revealed white granular prominences in the gastric fornix, and biopsy of these lesions revealed the diagnosis of Russell body gastritis(RBG). Neither lymphoma infiltration nor other malignant findings were found. Diagnostic tests for Helicobacter pylori were negative. The clinical stage of the DLBCL was determined as stage ⅢA, and the International Prognostic Index was"high intermediate". She received 6 cycles of R-CHOP therapy, with concomitant use of a proton pump inhibitor. Complete remission was confirmed in November, year X-1. An U-GIE performed again no longer showed the white granular prominences in the gastric fornix. The present report is the first of DLBCL complicated by RBG; our findings suggested that the two diseases were associated with each other.
- Published
- 2022
21. Basic locomotor muscle synergies used in land walking are finely tuned during underwater walking
- Author
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Kimitaka Nakazawa, Takanori Kokubun, Naotsugu Kaneko, Tatsuya Kato, Hirofumi Kobayashi, Hikaru Yokoyama, and Motonori Hoshino
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Adult ,Male ,medicine.medical_specialty ,Multidisciplinary ,Computer science ,Science ,Work (physics) ,Water ,Walking ,Electromyography - EMG ,Article ,Biomechanical Phenomena ,Physical medicine and rehabilitation ,Motor control ,Immersion ,Central Pattern Generators ,Water environment ,medicine ,Humans ,Medicine ,Underwater ,Muscle, Skeletal ,human activities - Abstract
Underwater walking is one of the most common hydrotherapeutic exercises. Therefore, understanding muscular control during underwater walking is important for optimizing training regimens. The effects of the water environment on walking are mainly related to the hydrostatic and hydrodynamic theories of buoyancy and drag force. To date, muscular control during underwater walking has been investigated at the individual muscle level. However, it is recognized that the human nervous system modularly controls multiple muscles through muscle synergies, which are sets of muscles that work together. We found that the same set of muscle synergies was shared between the two walking tasks. However, some task-dependent modulation was found in the activation combination across muscles and temporal activation patterns of the muscle synergies. The results suggest that the human nervous system modulates activation of lower-limb muscles during water walking by finely tuning basic locomotor muscle synergies that are used during land walking to meet the biomechanical requirements for walking in the water environment.
- Published
- 2021
22. Specific Brain Reorganization Underlying Superior Upper Limb Motor Function After Spinal Cord Injury: A Multimodal MRI Study
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Tomoya Nakanishi, Kimitaka Nakazawa, Kazutoshi Kudo, Hirofumi Kobayashi, and Kento Nakagawa
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Adult ,Male ,Brain reorganization ,Superior parietal lobule ,Motor function ,050105 experimental psychology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Parietal Lobe ,medicine ,Humans ,0501 psychology and cognitive sciences ,Gray Matter ,Spinal cord injury ,Spinal Cord Injuries ,Aged ,Brain Mapping ,Neuronal Plasticity ,Hand Strength ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Motor Cortex ,Magnetic resonance imaging ,General Medicine ,Anatomy ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Upper limb ,Female ,Primary motor cortex ,Grip force ,business ,030217 neurology & neurosurgery ,Muscle Contraction - Abstract
Background We recently discovered that individuals with complete spinal cord injury (SCI) have a higher grip force control ability in their intact upper limbs than able-bodied subjects. However, the neural basis for this phenomenon is unknown. Objective This study aimed to investigate the neural basis of the higher grip force control in the brains of individuals with SCI using multimodal magnetic resonance imaging (MRI). Methods Eight SCI subjects and 10 able-bodied subjects performed hand grip force control tasks at 10%, 20%, and 30% of their maximal voluntary contraction during functional MRI (fMRI). Resting-state fMRI and T1-weighted structural images were obtained to investigate changes in brain networks and structures after SCI. Results SCI subjects showed higher grip force steadiness than able-bodied subjects ( P < .05, corrected), smaller activation in the primary motor cortex ( P < .05, corrected), and deactivation of the visual cortex ( P < .001, uncorrected). Furthermore, SCI subjects had stronger functional connectivity between the superior parietal lobule and the left primary motor cortex ( P < .001, uncorrected), as well as larger gray matter volume in the bilateral superior parietal lobule ( P < .001, uncorrected). Conclusions The structural and functional reorganization observed in the superior parietal lobule of SCI subjects may represent the neural basis underlying the observed higher grip force control, and is likely responsible for the smaller activation in the primary motor cortex observed in these individuals. These findings could have applications in the fields of neurorehabilitation for improvement of intact limb functions after SCI.
- Published
- 2021
23. Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma Associated with Nephrotic Syndrome during Hemodialysis, Treated Successfully with Tirabrutinib
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Yasunobu Sekiguchi, You Nishimura, Hiroaki Kanda, Machiko Kawamura, Kazuhiko Kobayashi, and Hirofumi Kobayashi
- Subjects
Nephrotic Syndrome ,Pyrimidines ,Lymphoma ,Renal Dialysis ,Internal Medicine ,Imidazoles ,Humans ,Female ,General Medicine ,Waldenstrom Macroglobulinemia ,Rituximab ,Aged - Abstract
A 74-year-old woman was diagnosed with Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) in X-18. Fludarabine plus rituximab (FR) was started, and she showed remission. In July X-7, the serum creatinine (Cr) level increased to 1.67 mg/dL, and bendamustine plus rituximab (BR) was started. By November X-7, the Cr level had increased to 8.41 mg/dL, so she was started on hemodialysis (HD). In September X-1, she developed nephrotic syndrome. She was started on tirabrutinib at 480 mg. In July X, her nephrotic syndrome had improved, and a complete response (CR) was achieved. This is the first case of the administration of tirabrutinib in a patient undergoing HD.
- Published
- 2022
24. OpenCell: Endogenous tagging for the cartography of human cellular organization
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Nathan H. Cho, Keith C. Cheveralls, Andreas-David Brunner, Kibeom Kim, André C. Michaelis, Preethi Raghavan, Hirofumi Kobayashi, Laura Savy, Jason Y. Li, Hera Canaj, James Y. S. Kim, Edna M. Stewart, Christian Gnann, Frank McCarthy, Joana P. Cabrera, Rachel M. Brunetti, Bryant B. Chhun, Greg Dingle, Marco Y. Hein, Bo Huang, Shalin B. Mehta, Jonathan S. Weissman, Rafael Gómez-Sjöberg, Daniel N. Itzhak, Loïc A. Royer, Matthias Mann, and Manuel D. Leonetti
- Subjects
Proteomics ,Spatial Analysis ,Microscopy, Confocal ,Multidisciplinary ,Proteome ,Datasets as Topic ,Proteins ,RNA-Binding Proteins ,Mass Spectrometry ,Machine Learning ,HEK293 Cells ,Protein Interaction Mapping ,Cluster Analysis ,Humans ,Immunoprecipitation ,CRISPR-Cas Systems ,Fluorescent Dyes - Abstract
Elucidating the wiring diagram of the human cell is a central goal of the postgenomic era. We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. Our approach provides a data-driven description of the molecular and spatial networks that organize the proteome. Unsupervised clustering of these networks delineates functional communities that facilitate biological discovery. We found that remarkably precise functional information can be derived from protein localization patterns, which often contain enough information to identify molecular interactions, and that RNA binding proteins form a specific subgroup defined by unique interaction and localization properties. Paired with a fully interactive website (opencell.czbiohub.org), our work constitutes a resource for the quantitative cartography of human cellular organization.
- Published
- 2022
25. R‐CHOP‐14 versus R‐CHOP‐14/CHASER for upfront autologous transplantation in diffuse large B‐cell lymphoma: JCOG0908 study
- Author
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Ryo Tominaga, Koichiro Minauchi, Yasuo Morishima, Yoshitoyo Kagami, Kazuhito Yamamoto, Michihide Tokuhira, Satoko Morishima, Shigeru Kusumoto, Shigeo Nakamura, Taro Shibata, Kisato Nosaka, Hirokazu Nagai, Shinichiro Yoshida, Kensei Tobinai, Junya Kuroda, Youko Suehiro, Nobuhiko Yamauchi, Michinori Ogura, Yasushi Kubota, Kunihiro Tsukasaki, Kazuyuki Shimada, Dai Maruyama, Noriko Fukuhara, Yoshihiro Yakushijin, Akira Hangaishi, Hideki Tsujimura, Hirofumi Kobayashi, Yasushi Takamatsu, Yoshiko Inoue, Tomomitsu Hotta, Toshiki Uchida, Yoshitaka Imaizumi, and Sachiko Suzuki
- Subjects
Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Phases of clinical research ,Transplantation, Autologous ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,International Prognostic Index ,autologous stem‐cell transplantation ,Clinical Research ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Autologous transplantation ,Medicine ,Cyclophosphamide ,induction chemotherapy ,Aged ,business.industry ,diffuse large B‐cell lymphoma ,Hematopoietic Stem Cell Transplantation ,Induction chemotherapy ,General Medicine ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Progression-Free Survival ,Transplantation ,Regimen ,030104 developmental biology ,Oncology ,Doxorubicin ,Vincristine ,030220 oncology & carcinogenesis ,high‐dose chemotherapy ,Prednisone ,Original Article ,Female ,Lymphoma, Large B-Cell, Diffuse ,Rituximab ,business ,Diffuse large B-cell lymphoma ,JCOG‐LSG - Abstract
The efficiency of upfront consolidation with high‐dose chemotherapy/autologous stem‐cell transplantation (HDCT/ASCT) for newly diagnosed high‐risk diffuse large B‐cell lymphoma (DLBCL) may be influenced by induction chemotherapy. To select better induction chemotherapy regimens for HDCT/ASCT, a randomized phase II study was conducted in high‐risk DLBCL patients having an age‐adjusted International Prognostic Index (aaIPI) score of 2 or 3. As induction chemotherapy, 6 cycles of R‐CHOP‐14 (arm A) or 3 cycles of R‐CHOP‐14 followed by 3 cycles of CHASER (arm B) were planned, and patients who responded proceeded to HDCT with LEED and ASCT. The primary endpoint was 2‐y progression‐free survival (PFS), and the main secondary endpoints included overall survival, overall response rate, and adverse events (AEs). In total, 71 patients were enrolled. With a median follow‐up of 40.3 mo, 2‐y PFS in arms A and B were 68.6% (95% confidence interval [CI], 50.5%‐81.2%) and 66.7% (95% CI: 48.8%‐79.5%), respectively. Overall survival at 2 y in arms A and B was 74.3% (95% CI: 56.4%‐85.7%) and 83.3% (95% CI: 66.6%‐92.1%). Overall response rates were 82.9% in arm A and 69.4% in arm B. During induction chemotherapy, 45.7% and 75.0% of patients in arms A and B, respectively, had grade ≥ 3 non‐hematologic toxicities. One patient in arm A and 6 in arm B discontinued induction chemotherapy due to AEs. In conclusion, R‐CHOP‐14 showed higher 2‐y PFS and less toxicity compared with R‐CHOP‐14/CHASER in patients with high‐risk DLBCL, suggesting the former to be a more promising induction regimen for further investigations (UMIN‐CTR, UMIN000003823)., The efficiency of upfront consolidation with high‐dose chemotherapy/autologous stem‐cell transplantation (HDCT/ASCT) for newly diagnosed high‐risk diffuse large B‐cell lymphoma (DLBCL) may be influenced by induction chemotherapy. To select better induction chemotherapy regimens for HDCT/ASCT, a randomized phase II study was conducted in patients with high‐risk DLBCL who had an age‐adjusted International Prognostic Index (aaIPI) score of 2 or 3. R‐CHOP‐14 showed higher 2‐y PFS and less toxicity compared with R‐CHOP‐14/CHASER in patients with high‐risk DLBCL, suggesting the former to be a more promising induction regimen for further investigations.
- Published
- 2020
26. Raman image-activated cell sorting
- Author
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Takeshi Hayakawa, Yu Hoshino, Shunnosuke Ueno, Yusuke Kasai, Hiroshi Karakawa, Minoru Oikawa, Yuki Inoue, Dino Di Carlo, Shunji Tanaka, Takanori Iino, Yuichi Kato, Yuta Suzuki, Mary Inaba, Yasuyuki Ozeki, Cheng Lei, Hiroshi Tezuka, Kotaro Hiramatsu, Takeaki Sugimura, Takashi Yamano, Yasutaka Kitahama, Kei Hiraki, Hideya Fukuzawa, Takuya Asai, Hideharu Mikami, Atsuhiro Nakagawa, Yoichiroh Hosokawa, Fumihito Arai, Misa Hase, Yusuke Yonamine, Keisuke Goda, Akihiro Isozaki, Tadataka Ota, Satoshi Matsusaka, Hirofumi Kobayashi, Takuro Ito, Yoshitaka Shirasaki, Takeichiro Sekiya, Hiroshi Watarai, Nao Nitta, Dinghuan Deng, Nobutake Suzuki, Mai Yamagishi, Tomohisa Hasunuma, Sotaro Uemura, Shinya Sakuma, Kiyotaka Shiba, Masayuki Yazawa, Masataka Kajikawa, and Keiji Numata
- Subjects
Sorting algorithm ,Computer science ,Science ,General Physics and Astronomy ,Nanotechnology ,Cell Separation ,Spectrum Analysis, Raman ,Article ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,Imaging ,symbols.namesake ,law ,Microscopy ,Animals ,Humans ,lcsh:Science ,Multidisciplinary ,Lab-on-a-chip ,Sorting ,High-throughput screening ,General Chemistry ,Cell sorting ,Raman spectroscopy ,symbols ,Isolation, separation and purification ,lcsh:Q ,Intracellular ,Raman scattering - Abstract
The advent of image-activated cell sorting and imaging-based cell picking has advanced our knowledge and exploitation of biological systems in the last decade. Unfortunately, they generally rely on fluorescent labeling for cellular phenotyping, an indirect measure of the molecular landscape in the cell, which has critical limitations. Here we demonstrate Raman image-activated cell sorting by directly probing chemically specific intracellular molecular vibrations via ultrafast multicolor stimulated Raman scattering (SRS) microscopy for cellular phenotyping. Specifically, the technology enables real-time SRS-image-based sorting of single live cells with a throughput of up to ~100 events per second without the need for fluorescent labeling. To show the broad utility of the technology, we show its applicability to diverse cell types and sizes. The technology is highly versatile and holds promise for numerous applications that are previously difficult or undesirable with fluorescence-based technologies., Most current cell sorting methods are based on fluorescence detection with no imaging capability. Here the authors generate and use Raman image-activated cell sorting with a throughput of around 100 events per second, providing molecular images with no need for labeling.
- Published
- 2020
27. Effects of Flow‐Induced Microfluidic Chip Wall Deformation on Imaging Flow Cytometry
- Author
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Nobutoshi Ota, Hector E. Muñoz, Cheng Lei, Baoshan Guo, Dino Di Carlo, Keisuke Goda, Yaxiaer Yalikun, Tao Tang, Hirofumi Kobayashi, Yoichiroh Hosokawa, Yo Tanaka, Yuqi Zhou, and Ming Li
- Subjects
0301 basic medicine ,Histology ,Materials science ,Instrumentation ,Microfluidics ,Flow (psychology) ,Deformation (meteorology) ,Pathology and Forensic Medicine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Lab-On-A-Chip Devices ,Microscopy ,Microchannel ,Polydimethylsiloxane ,business.industry ,Cell Biology ,Microfluidic Analytical Techniques ,Flow Cytometry ,030104 developmental biology ,chemistry ,Flow velocity ,030220 oncology & carcinogenesis ,Hydrodynamics ,Optoelectronics ,business - Abstract
Imaging flow cytometry is a powerful tool by virtue of its capability for high-throughput cell analysis. The advent of high-speed optical imaging methods on a microfluidic platform has significantly improved cell throughput and brought many degrees of freedom to instrumentation and applications over the last decade, but it also poses a predicament on microfluidic chips. Specifically, as the throughput increases, the flow speed also increases (currently reaching 10 m/s): consequently, the increased hydrodynamic pressure on the microfluidic chip deforms the wall of the microchannel and produces detrimental effects lead to defocused and blur image. Here, we present a comprehensive study of the effects of flow-induced microfluidic chip wall deformation on imaging flow cytometry. We fabricated three types of microfluidic chips with the same geometry and different degrees of stiffness made of polydimethylsiloxane (PDMS) and glass to investigate material influence on image quality. First, we found the maximum deformation of a PDMS microchannel was >60 μm at a pressure of 0.6 MPa, while no appreciable deformation was identified in a glass microchannel at the same pressure. Second, we found the deviation of lag time that indicating velocity difference of migrating microbeads due to the deformation of the microchannel was 29.3 ms in a PDMS microchannel and 14.9 ms in a glass microchannel. Third, the glass microchannel focused cells into a slightly narrower stream in the X-Y plane and a significantly narrower stream in the Z-axis direction (focusing percentages were increased 30%, 32%, and 5.7% in the glass channel at flow velocities of 0.5, 1.5, and 3 m/s, respectively), and the glass microchannel showed stabler equilibrium positions of focused cells regardless of flow velocity. Finally, we achieved the world's fastest imaging flow cytometry by combining a glass microfluidic device with an optofluidic time-stretch microscopy imaging technique at a flow velocity of 25 m/s. © 2019 International Society for Advancement of Cytometry.
- Published
- 2019
28. Author response: ZAF, the first open source fully automated feeder for aquatic facilities
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Merlin Lange, AhmetCan Solak, Shruthi Vijay Kumar, Hirofumi Kobayashi, Bin Yang, and Loïc Alain Royer
- Published
- 2021
29. ZAF, the first open source fully automated feeder for aquatic facilities
- Author
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Loic Royer, Merlin Lange, Shruthi Vijay Kumar, AhmetCan Solak, Hirofumi Kobayashi, and Bin Yang
- Subjects
QH301-705.5 ,Interface (computing) ,Science ,Control software ,Aquaculture ,General Biochemistry, Genetics and Molecular Biology ,Automation ,zaf ,Animals ,Biology (General) ,User needs ,open-source ,Graphical user interface ,General Immunology and Microbiology ,business.industry ,Data Collection ,General Neuroscience ,aquatic ,Feeding Behavior ,General Medicine ,Modular design ,zebrafish ,Animal Feed ,feeder ,Open source ,Fully automated ,Fully automatic ,automatic ,Medicine ,business ,Software engineering ,Software ,Research Article ,Developmental Biology - Abstract
In the past few decades, aquatic animals have become popular model organisms in biology, spurring a growing need for establishing aquatic facilities. Zebrafish are widely studied and relatively easy to culture using commercial systems. However, a challenging aspect of maintaining aquatic facilities is animal feeding, which is both time- and resource-consuming. We have developed an open-source fully automatic daily feeding system, Zebrafish Automatic Feeder (ZAF). ZAF is reliable, provides a standardized amount of food to every tank, is cost-efficient and easy to build. The advanced version, ZAF+, allows for the precise control of food distribution as a function of fish density per tank, and has a user-friendly interface. Both ZAF and ZAF+ are adaptable to any laboratory environment and facilitate the implementation of aquatic colonies. Here, we provide all blueprints and instructions for building the mechanics, electronics, fluidics, as well as to setup the control software and its user-friendly graphical interface. Importantly, the design is modular and can be scaled to meet different user needs. Furthermore, our results show that ZAF and ZAF+ do not adversely affect zebrafish culture, enabling fully automatic feeding for any aquatic facility.
- Published
- 2021
30. Author Reply to Peer Reviews of ZAF – The First Open Source Fully Automated Feeder for Aquatic Facilities
- Author
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Loic A. Royer, Bin Yang, Hirofumi Kobayashi, Shruthi Vijay Kumar, AhmetCan Solak, and Merlin Lange
- Published
- 2021
31. Self-supervised deep learning encodes high-resolution features of protein subcellular localization
- Author
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Hirofumi, Kobayashi, Keith C, Cheveralls, Manuel D, Leonetti, and Loic A, Royer
- Subjects
Organelles ,Protein Transport ,Deep Learning ,Cluster Analysis ,Proteins - Abstract
Explaining the diversity and complexity of protein localization is essential to fully understand cellular architecture. Here we present cytoself, a deep-learning approach for fully self-supervised protein localization profiling and clustering. Cytoself leverages a self-supervised training scheme that does not require preexisting knowledge, categories or annotations. Training cytoself on images of 1,311 endogenously labeled proteins from the OpenCell database reveals a highly resolved protein localization atlas that recapitulates major scales of cellular organization, from coarse classes, such as nuclear and cytoplasmic, to the subtle localization signatures of individual protein complexes. We quantitatively validate cytoself's ability to cluster proteins into organelles and protein complexes, showing that cytoself outperforms previous self-supervised approaches. Moreover, to better understand the inner workings of our model, we dissect the emergent features from which our clustering is derived, interpret them in the context of the fluorescence images, and analyze the performance contributions of each component of our approach.
- Published
- 2021
32. Assessing the sealing quality of submarine mass transport complexes and deposits
- Author
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Sebastian Cardona, Hirofumi Kobayashi, Lesli Wood, Brandon Dugan, and Alexei V. Milkov
- Subjects
Geophysics ,Stratigraphy ,Economic Geology ,Geology ,Oceanography - Published
- 2022
33. DaXi-high-resolution, large imaging volume and multi-view single-objective light-sheet microscopy
- Author
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Bin, Yang, Merlin, Lange, Alfred, Millett-Sikking, Xiang, Zhao, Jordão, Bragantini, Shruthi, VijayKumar, Mason, Kamb, Rafael, Gómez-Sjöberg, Ahmet Can, Solak, Wanpeng, Wang, Hirofumi, Kobayashi, Matthew N, McCarroll, Lachlan W, Whitehead, Reto P, Fiolka, Thomas B, Kornberg, Andrew G, York, and Loic A, Royer
- Subjects
Microscopy, Fluorescence ,Animals ,Brain ,Embryonic Development ,Drosophila ,Zebrafish - Abstract
The promise of single-objective light-sheet microscopy is to combine the convenience of standard single-objective microscopes with the speed, coverage, resolution and gentleness of light-sheet microscopes. We present DaXi, a single-objective light-sheet microscope design based on oblique plane illumination that achieves: (1) a wider field of view and high-resolution imaging via a custom remote focusing objective; (2) fast volumetric imaging over larger volumes without compromising image quality or necessitating tiled acquisition; (3) fuller image coverage for large samples via multi-view imaging and (4) higher throughput multi-well imaging via remote coverslip placement. Our instrument achieves a resolution of 450 nm laterally and 2 μm axially over an imaging volume of 3,000 × 800 × 300 μm. We demonstrate the speed, field of view, resolution and versatility of our instrument by imaging various systems, including Drosophila egg chamber development, zebrafish whole-brain activity and zebrafish embryonic development - up to nine embryos at a time.
- Published
- 2021
34. Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial
- Author
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Masashi Wakabayashi, Takahiko Utsumi, Yasuo Morishima, Yoshifusa Takatsuka, Kazutaka Sunami, Hiroshi Gomyo, Shinya Rai, Kenji Ishitsuka, Takaki Shimada, Hideki Tsujimura, Sawako Nakachi, Naoki Kobayashi, Isao Yoshida, Takashi Terauchi, Takashi Watanabe, Naoto Takahashi, Yurie Saitoh, Hidenori Sasaki, Kazuma Ohyashiki, Takashi Tokunaga, Yoshihiro Yakushijin, Tsutomu Kobayashi, Jo Kanasugi, Tomohiro Kinoshita, Takaaki Chou, Kazuyuki Shimada, Kisato Nosaka, Yukiyoshi Moriuchi, Masako Yokoo, Makoto Yoshimitsu, Yoshihiro Kameoka, Hiroaki Asai, Shinsuke Iida, Shigeru Kusumoto, Akihiko Yokohama, Kensei Tobinai, Koichiro Minauchi, Tadashi Yoshino, Junichi Tsukada, Hirokazu Nagai, Tatsuro Jo, Naokuni Uike, Yoshitaka Imaizumi, Nobuhiko Yamauchi, Tatsu Shimoyama, Eiichi Ohtsuka, Hirofumi Kobayashi, Takahiro Yamauchi, Yoshitoyo Kagami, Harumi Kato, Shinya Kimura, Yasushi Takamatsu, Tomomitsu Hotta, Junya Kuroda, Yoko Ushijima, Michinori Ogura, Nobuyuki Takayama, Naoko Harada, Kunihiro Tsukasaki, Youko Suehiro, Masafumi Taniwaki, Tohru Murayama, Satoshi Yamasaki, Masanori Makita, Yosuke Minami, Fumiaki Sano, Yasushi Miyazaki, Kyoya Kumagai, Shin Matsuda, Kazuhito Yamamoto, Yutaro Kamiyama, Kayo Yamagishi, Noriko Fukuhara, Toshiki Uchida, Izumi Wasada, Takuro Ishiguro, Daigo Akahane, Nobuaki Dobashi, Ichiro Hanamura, Noriyasu Fukushima, Sigeru Nawano, Michihiro Hidaka, Koji Izutsu, Hiro Tatetsu, Kiyoshi Ando, Shinichiro Yoshida, Itaru Matsumura, Tatsuo Ichinohe, Madoka Takimoto, Kana Miyazaki, Junji Hiraga, Yasufumi Masaki, Ilseung Choi, Hiroaki Morimoto, Norifumi Tsukamoto, Atae Utsunomiya, Mitsutoshi Kurosawa, Dai Maruyama, Takaaki Ono, Takayo Suzuki, Motoko Yamaguchi, Satoko Morishima, Hideo Harigae, and Nobuko Kubota
- Subjects
Male ,medicine.medical_specialty ,Follicular lymphoma ,Antibodies, Monoclonal, Murine-Derived ,03 medical and health sciences ,0302 clinical medicine ,Prednisone ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,medicine ,Humans ,Cumulative incidence ,Cyclophosphamide ,Lymphoma, Follicular ,business.industry ,Standard treatment ,Hazard ratio ,Hematology ,Middle Aged ,medicine.disease ,Clinical trial ,Treatment Outcome ,Doxorubicin ,Vincristine ,030220 oncology & carcinogenesis ,Female ,Rituximab ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Summary Background Standard treatment for untreated advanced-stage follicular lymphoma is rituximab plus chemotherapy. The incidence of histological transformation of follicular lymphoma has been reported only in heterogeneously treated populations and rarely with long-term follow-up. Additionally, the incidence of secondary malignancies after treatment, without high-dose therapy for follicular lymphoma, is largely unknown. The aim of our study was to assess progression-free survival, overall survival, incidence of secondary malignancies, and incidence of histological transformation in a 10-year follow-up analysis of the JCOG0203 trial. Methods In the phase 2–3 randomised JCOG0203 trial, previously untreated patients with stage III or IV indolent B-cell lymphoma, including grades 1–3 follicular lymphoma, from 44 hospital centres in Japan, were randomly assigned (1:1) by use of a minimisation method to receive six cycles of R-CHOP (rituximab [375 mg/m2], given on day 1, plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2, capped at 2·0 mg] given intravenously on day 3, and oral prednisone [100 mg once daily on days 3–7]) every 3 weeks (R-CHOP-21) or every 2 weeks (enabled by mandatory granulocyte-colony stimulating factor administration once daily for 6 days, starting on day 8; R-CHOP-14) without rituximab maintenance. Age, bulky disease (nodal or extranodal mass ≥10 cm in diameter on CT), and institution were used as adjustment factors. Investigators enrolled participants, and assignment to trial groups was done with a computer-assisted randomisation allocation sequence that took place centrally at the Japan Clinical Oncology Group Data Center, without the intervention of investigators. Interventions were not masked for patients or investigators. Data were collected 10 years after enrolment of the last patient. The primary endpoint of the phase 3 part of the study was progression-free survival, and the primary endpoint of the phase 2 part of the study was the proportion of patients who achieved a complete response. Accrual was 4·5 years, and follow-up was 3 years after registration was closed. Data were updated on the cutoff date of Feb 28, 2017. Intention-to-treat analyses (ie, progression-free survival, overall survival, and incidence of secondary malignancies) were predefined, to be done at 10 years after the last patient was enrolled. An additional analysis of the incidence of histological transformation was defined 15 years after the protocol, on May 8, 2017, in a supplementary analysis plan, and assessed at 10 years after the last patient was enrolled. Follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00147121. Findings Between Sept 1, 2002, and Feb 28, 2007, 300 patients were enrolled, and 149 (50%) were assigned to the R-CHOP-21 group and 151 (50%) were assigned to the R-CHOP-14 group. After eligibility was assessed, one patient was excluded from the R-CHOP-21 group. 10-year progression-free survival was not different between groups (R-CHOP-21 33%, 95% CI 25–41; R-CHOP-14 39%, 31–47; hazard ratio 0·89, 95% CI 0·67–1·17). In 248 patients with grade 1–3a follicular lymphoma, progression-free survival was 39% (33–45) at 8 years and 36% (30–42) at 10 years. The cumulative incidence of histological transformation was 3·2% (95% CI 1·5–6·0) at 5 years, 8·5% (5·4–12·4) at 8 years, and 9·3% (6·1–13·4) at 10 years after enrolment. At 10 years, the cumulative incidence of secondary malignancies was 8·1% (5·1–12·0) and the cumulative incidence of haematological secondary malignancies was 2·9% (1·3–5·5). Interpretation R-CHOP is a viable option for first-line treatment in patients with newly diagnosed advanced follicular lymphoma. Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death. Funding National Cancer Center and Ministry of Health, Labour and Welfare of Japan.
- Published
- 2018
35. Self-Supervised Deep Learning Encodes High-Resolution Features of Protein Subcellular Localization
- Author
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Hirofumi Kobayashi, Cheveralls Kc, Leonetti, and Loic Royer
- Subjects
Profiling (computer programming) ,Cellular architecture ,Basis (linear algebra) ,Computer science ,business.industry ,Deep learning ,Context (language use) ,Computational biology ,Subcellular localization ,Protein subcellular localization prediction ,ComputingMethodologies_PATTERNRECOGNITION ,Artificial intelligence ,Cluster analysis ,business - Abstract
Elucidating the diversity and complexity of protein localization is essential to fully understand cellular architecture. Here, we present cytoself, a deep-learning approach for fully self-supervised protein localization profiling and clustering. cytoself leverages a self-supervised training scheme that does not require pre-existing knowledge, categories, or annotations. Training cytoself on images of 1,311 endogenously labeled proteins from the OpenCell database reveals a highly resolved protein localization atlas that recapitulates major scales of cellular organization, from coarse classes such as nuclear, cytoplasmic and vesicular, to the subtle localization signatures of individual protein complexes. We quantitatively validate cytoself’s ability to cluster proteins into organelles and protein complex clusters using a clustering score, and show that cytoself attains higher scores than previous unsupervised or self-supervised approaches. Finally, to better understand the inner workings of our model, we dissect the emergent features from which our clustering is derived, interpret these features in the context of the fluorescence images, and analyze the performance contributions of the different components of our approach.
- Published
- 2021
36. OpenCell: proteome-scale endogenous tagging enables the cartography of human cellular organization
- Author
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Matthias Mann, Hera Canaj, Andreas-David Brunner, Bo Huang, Rachel M. Brunetti, Bryant B. Chhun, Cabrera Jp, Savy L, Nathan H. Cho, Jonathan S. Weissman, Daniel N. Itzhak, Kim Jy, Kim K, Loic Royer, Hirofumi Kobayashi, McCarthy F, Leonetti, Marco Y. Hein, Cheveralls Kc, Christian Gnann, Preethi Raghavan, André C. Michaelis, Rafael Gomez-Sjoberg, Shalin B. Mehta, Stewart Em, Dingle G, and Li Jy
- Subjects
Cellular architecture ,Computer science ,Scale (chemistry) ,Proteome ,Human proteome project ,ENCODE ,Protein subcellular localization prediction ,Cartography ,Genome engineering ,Protein–protein interaction - Abstract
Elucidating the wiring diagram of the human cell is one of the central goals of the post-genomic era. Here, we integrate genome engineering, confocal imaging, mass spectrometry and data science to systematically map protein localization in live cells and protein interactions under endogenous expression conditions. For this, we generated a library of 1,311 CRISPR-edited cell lines harboring fluorescent tags that also serve as handles for affinity capture, and applied a new machine learning framework to encode the interaction and localization profiles of each protein. Our approach provides a data-driven description of the molecular and spatial networks that organize the human proteome. We show that unsupervised clustering of these networks delineates functional groups and facilitates biological discovery, while hierarchical analyses uncover the core features that template cellular architecture. Furthermore, we discover that localization signatures are remarkably predictive of protein function, and often contain enough information to identify molecular interactions. Paired with a fully interactive website (opencell.czbiohub.org), OpenCell is a resource for the quantitative cartography of human cellular organization.
- Published
- 2021
37. Cross-sectional comparison of the probabilistic structure in the distribution of pitching location among baseball pitchers of different ages
- Author
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Tetsuya Ogawa, Takeshi Miki, Hirofumi Kobayashi, Masumi Kuwata, Kimitaka Nakazawa, Tetsuya Ijiri, Hiroki Obata, and Masahiro Shinya
- Subjects
0206 medical engineering ,Probabilistic logic ,Physical Therapy, Sports Therapy and Rehabilitation ,030229 sport sciences ,02 engineering and technology ,Ellipse ,020601 biomedical engineering ,Correlation ,03 medical and health sciences ,0302 clinical medicine ,Distribution (mathematics) ,Reflection (mathematics) ,Age groups ,Statistics ,Trajectory ,Orthopedics and Sports Medicine ,Throwing ,Mathematics - Abstract
The present study was a cross-sectional comparison of probabilistic structure in the distribution of pitching location among baseball pitchers of various age groups (25 elementary school (ES), 20 junior high school (JH), 15 high school (HS), and 18 college students (CL)). In the results, despite the general age-dependent variations in pitching precision, the difference was reflected not only in error 'size' but also in the 'shape' of error as it was shown by fitting 95% confidence ellipse to the two dimensional distribution of pitch location. While the precision measure as a reflection of trial-by-trial variability of release timing (major axis length of the ellipse) was constant, minor axis length of the ellipse as a reflection of variability in the pitching form of each participant demonstrated significant differences among the groups. In the ES group particularly, the trial-by-trial variability in the trajectory angle of the throwing arm was significantly correlated with the minor axis length; this correlation was far greater than those in older groups. The present study is the first to demonstrate the detailed structure of the variability of pitching location of baseball dependent on age.
- Published
- 2020
38. Effort-dependent effects on uniform and diverse muscle activity features in skilled pitching
- Author
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Masumi Kuwata, Takeshi Miki, Daiki Nasu, Kimitaka Nakazawa, Ken Takiyama, Hirofumi Kobayashi, Makio Kashino, Tetsuya Ijiri, and Tsubasa Hashimoto
- Subjects
Adult ,Male ,Wrist Joint ,Computer science ,Science ,Acceleration ,Musculoskeletal Physiological Phenomena ,Physical Exertion ,Motor Activity ,Baseball ,Motion (physics) ,Article ,Young Adult ,Motor control ,Elbow Joint ,Human behaviour ,Tensor decomposition ,Humans ,Muscle activity ,Range of Motion, Articular ,Multidisciplinary ,business.industry ,Shoulder Joint ,Pattern recognition ,Middle Aged ,Biomechanical Phenomena ,Athletes ,Medicine ,Artificial intelligence ,business - Abstract
How do skilled players change their motion patterns depending on motion effort? Pitchers commonly accelerate wrist and elbow joint rotations via proximal joint motions. Contrastingly, they show individually different pitching motions, such as in wind-up or follow-through. Despite the generality of the uniform and diverse features, effort-dependent effects on these features are unclear. Here, we reveal the effort dependence based on muscle activity data in natural three-dimensional pitching performed by skilled players. We extract motor modules and their effort dependence from the muscle activity data via tensor decomposition. Then, we reveal the unknown relations among motor modules, common features, unique features, and effort dependence. The current study clarifies that common features are obvious in distinguishing between low and high effort and that unique features are evident in differentiating high and highest efforts.
- Published
- 2020
39. High-Resolution, Large Imaging Volume, and Multi-View Single Objective Light-Sheet Microscopy
- Author
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Merlin Lange, Reto Fiolka, Lachlan Whitehead, Bin Yang, Ahmet Can Solak, Andrew York, Matthew N McCarroll, Hirofumi Kobayashi, Loic Royer, Wanpeng Wang, Shruthi Vijay Kumar, Alfred Millett-Sikking, and Thomas B. Kornberg
- Subjects
Microscope ,Materials science ,business.industry ,Orientation (computer vision) ,Image quality ,Resolution (electron density) ,Volume (computing) ,Field of view ,law.invention ,Optics ,law ,Light sheet fluorescence microscopy ,Microscopy ,business - Abstract
Recent developments in Oblique Plane Microscopy (OPM) have shown that it can achieve high spatio-temporal resolution. Here we describe a single objective light-sheet microscope based on oblique plane illumination that achieves: (i) large field of view and high-resolution imaging via a custom remote focusing objective; (ii) fast volumetric imaging by means of light-sheet stabilised stage scanning – a novel scanning modality that extends the imaging volume without compromising imaging speed nor quality; (iii) multi-view imaging by alternating the orientation of light-sheet illumination and detection to improve the image quality on large samples; (iv) simpler design and ergonomics by remote placement of coverslips to allow inverted imaging, enabling imaging across scales in a high-throughput format. Overall, we achieved a resolution of 450 nm laterally and 2 μm axially and a field of view of 3000 μm × 800 μm × 300 μm. We demonstrate the speed, field of view, resolution and versatility of our novel instrument by imaging various systems, including zebrafish whole brain activity, Drosophila egg chamber development, and zebrafish development – up to nine embryos simultaneously.
- Published
- 2020
40. Intelligent classification of platelet aggregates by agonist type
- Author
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Chun-Jung Huang, Yunzhao Wu, Atsushi Yasumoto, Cheng Lei, Chia-Wei Sun, Yuqi Zhou, Sheng Yan, Hirofumi Kobayashi, Keisuke Goda, and Yutaka Yatomi
- Subjects
0301 basic medicine ,Agonist ,Platelet Aggregation ,QH301-705.5 ,medicine.drug_class ,Science ,Short Report ,microfluidics ,Inflammation ,030204 cardiovascular system & hematology ,General Biochemistry, Genetics and Molecular Biology ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,blood ,Lab-On-A-Chip Devices ,medicine ,Humans ,Platelet ,Platelet activation ,Biology (General) ,Human Biology and Medicine ,thrombosis ,platelet ,General Immunology and Microbiology ,medicine.diagnostic_test ,Chemistry ,General Neuroscience ,deep learning ,Cell Biology ,General Medicine ,Microfluidic Analytical Techniques ,imaging flow cytometry ,Flow Cytometry ,Platelet Activation ,medicine.disease ,Thrombosis ,Pharmacometrics ,030104 developmental biology ,Hemostasis ,Medicine ,Neural Networks, Computer ,medicine.symptom ,Neuroscience ,Human - Abstract
Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics., eLife digest Platelets are small cells in the blood that primarily help stop bleeding after an injury by sticking together with other blood cells to form a clot that seals the broken blood vessel. Blood clots, however, can sometimes cause harm. For example, if a clot blocks the blood flow to the heart or the brain, it can result in a heart attack or stroke, respectively. Blood clots have also been linked to harmful inflammation and the spread of cancer, and there are now preliminary reports of remarkably high rates of clotting in COVID-19 patients in intensive care units. A variety of chemicals can cause platelets to stick together. It has long been assumed that it would be impossible to tell apart the clots formed by different chemicals (which are also known as agonists). This is largely because these aggregates all look very similar under a microscope, making it incredibly time consuming for someone to look at enough microscopy images to reliably identify the subtle differences between them. However, finding a way to distinguish the different types of platelet aggregates could lead to better ways to diagnose or treat blood vessel-clogging diseases. To make this possible, Zhou, Yasumoto et al. have developed a method called the “intelligent platelet aggregate classifier” or iPAC for short. First, numerous clot-causing chemicals were added to separate samples of platelets taken from healthy human blood. The method then involved using high-throughput techniques to take thousands of images of these samples. Then, a sophisticated computer algorithm called a deep learning model analyzed the resulting image dataset and “learned” to distinguish the chemical causes of the platelet aggregates based on subtle differences in their shapes. Finally, Zhou, Yasumoto et al. verified iPAC method’s accuracy using a new set of human platelet samples. The iPAC method may help scientists studying the steps that lead to clot formation. It may also help clinicians distinguish which clot-causing chemical led to a patient’s heart attack or stroke. This could help them choose whether aspirin or another anti-platelet drug would be the best treatment. But first more studies are needed to confirm whether this method is a useful tool for drug selection or diagnosis.
- Published
- 2020
41. Influence of Release Parameters on Pitch Location in Skilled Baseball Pitching
- Author
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Masumi Kuwata, Takeshi Miki, Kimitaka Nakazawa, Shinji Wakao, Kazutoshi Kudo, Ayane Kusafuka, and Hirofumi Kobayashi
- Subjects
lcsh:Sports ,Ball release ,baseball ,accuracy ,Release point ,Acoustics ,pitch location ,Horizontal pitch ,Regression analysis ,Spin axis ,release parameter ,simulation ,humanities ,Azimuth ,lcsh:GV557-1198.995 ,Computer Science::Sound ,Sports and Active Living ,Linear regression ,otorhinolaryngologic diseases ,psychological phenomena and processes ,Mathematics ,Original Research - Abstract
This study explored the mechanical factors that determine accuracy of a baseball pitching. In particular, we focused on the mechanical parameters at ball release, referred to as release parameters. The aim was to understand which parameter has the most deterministic influence on pitch location by measuring the release parameters during actual pitching and developing a simulation that predicts the pitch location from given release parameters. By comparing the fluctuation of the simulated pitch location when varying each release parameter, it was found that the elevation pitching angle and speed significantly influenced the vertical pitch location, and the azimuth pitching angle significantly influenced the horizontal pitch location. Moreover, a regression model was obtained to predict the pitch location, and it became clear that the significant predictors for the vertical pitch location were the elevation pitching angle, the speed, and spin axis, and those for the horizontal pitch location were the azimuth pitching angle, the spin axis, and horizontal release point. Therefore, it was suggested that the parameter most affecting pitch location weas pitching angle. On the other hand, multiple regression analyses revealed that the relation between release parameters varied between pitchers. The result is expected to contribute to an understanding of the mechanisms underlying accurate ball control skill in baseball pitching.
- Published
- 2020
42. Intelligent frequency-shifted optofluidic time-stretch quantitative phase imaging (Conference Presentation)
- Author
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Chia-Wei M. Sun, Hirofumi Kobayashi, Sheng Yan, Chun-Jung Huang, Yuqi Zhou, Keisuke Goda, Cheng Lei, Yunzhao Wu, and Yasuyuki Ozeki
- Subjects
Computer science ,business.industry ,Deep learning ,media_common.quotation_subject ,Pattern recognition ,medicine.disease ,Convolutional neural network ,Phase image ,Leukemia ,Presentation ,medicine.anatomical_structure ,Phase imaging ,medicine ,Bone marrow ,Artificial intelligence ,business ,Throughput (business) ,media_common - Abstract
The traditional diagnosis of leukemia relies on pathologists to observe and classify cells on bone marrow smears, which is low-throughput, time-consuming, and subject to human bias. To overcome these limitations, we demonstrate intelligent frequency-shifted optofluidic time-stretch quantitative phase imaging (OTS-QPI) that acquires bright-field and quantitative phase images of white blood cells (WBCs) containing leukemia cells with high throughput (15,000 cells/s) for deep-learning-based classification. After trained with 64,000 images, a convolutional neural network (CNN) distinguishes three different types of leukemia cells from WBCs with an accuracy of over 96%. Our method provides new possibilities for high-throughput, label-free, and intelligent leukemia diagnosis.
- Published
- 2020
43. Simple, rapid and cost-effective drug-susceptibility testing of leukemia by intelligent whole-blood imaging flow cytometry (Conference Presentation)
- Author
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Hirofumi Kobayashi, Yi Wu, Yaxiaer Yalikun, Makoto Yamada, Keisuke Goda, Masahiro Jona, Atsushi Yasumoto, Yutaka Yatomi, Cheng Lei, Baoshan Guo, Chun-Jung Huang, Chia-Wei Sun, Yo Tanaka, and Wenxuan Li
- Subjects
Imaging flow cytometry ,Leukemia ,Presentation ,business.industry ,Simple (abstract algebra) ,media_common.quotation_subject ,Medicine ,Drug susceptibility ,business ,medicine.disease ,Whole blood ,Biomedical engineering ,media_common - Published
- 2020
44. Classification of platelet aggregates by intelligent imaging flow cytometry (Conference Presentation)
- Author
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Sheng Yan, Yuqi Zhou, Yunzhao Wu, Chia-Wei Sun, Yutaka Yatomi, Chun-Jung Huang, Atsushi Yasumoto, Keisuke Goda, Cheng Lei, and Hirofumi Kobayashi
- Subjects
Imaging flow cytometry ,Platelet Morphology ,Platelet aggregation ,Computer science ,Hemostasis ,Platelet ,Neuroscience - Abstract
Platelets participate in both physiological hemostasis and pathological thrombosis by forming aggregates activated by various agonists. However, it has been considered impossible to identify the stimuli and classify the aggregates. Here we present an intelligent method for classifying platelet aggregates by agonist type based on the combination of high-throughput imaging flow cytometry and a convolutional neural network. It morphologically identifies the contributions of different agonists to platelet aggregation with high accuracy. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to develop a new class of clinical diagnostics and therapeutics.
- Published
- 2020
45. Author response: Intelligent classification of platelet aggregates by agonist type
- Author
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Yuqi Zhou, Chia-Wei Sun, Keisuke Goda, Yutaka Yatomi, Cheng Lei, Atsushi Yasumoto, Chun-Jung Huang, Yunzhao Wu, Sheng Yan, and Hirofumi Kobayashi
- Subjects
Agonist ,Chemistry ,medicine.drug_class ,medicine ,Platelet ,Pharmacology - Published
- 2020
46. Long-term QiGong practice is associated with improved self-perceived health and quality of life
- Author
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Azusa Uematsu, Tibor Hortobágyi, Masataka Kiryu, Takashi Shimazaki, Hirofumi Kobayashi, Madoka Nakamura, Shuji Suzuki, and SMART Movements (SMART)
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Gerontology ,exercise ,Social Psychology ,05 social sciences ,exercise, physiology ,Self perceived health ,030229 sport sciences ,self-perceived ,050105 experimental psychology ,Perceived health ,Term (time) ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,quality of life ,physiology ,Self perceived ,0501 psychology and cognitive sciences ,QiGong ,Exercise physiology ,Psychology ,human activities ,Applied Psychology - Abstract
In cross-sectional studies, we examined the long-term practice effects of QiGong exercise on perceived health and quality of life (QoL) in middle-aged (over 50 years) Japanese individuals. In Study 1, Japanese adults (n = 320) who practised QiGong responded to a questionnaire concerning the perceived benefits of QiGong practice and QoL. In Study 2, we collected data from QiGong participants who attended a QiGong conference (n = 799). Participants in Study 1 perceived that QiGong affords physical, psychological, and social benefits and QiGong duration in years correlated strongly with QoL. In Study 2, those who practised QiGong for 0–3 years vs. 13+ years reported a greater likelihood of perceived palpitation, insomnia, a lack of vigour, and attention deficit (odd ratios 1.56–2.60, all p .05). QiGong is a multi-component form of physical activity, which – if practised for prolonged periods – affords motor, cognitive, social, and QoL benefits.
- Published
- 2018
47. Optofluidic time-stretch quantitative phase microscopy
- Author
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Takuro Ito, Yaxiaer Yalikun, Yiyue Jiang, Cheng Lei, Baoshan Guo, Yutaka Yatomi, Dino Di Carlo, Yi Wu, Ming Li, Atsushi Yasumoto, Akihiro Isozaki, Yasuyuki Ozeki, Sangwook Lee, Yo Tanaka, Keisuke Goda, and Hirofumi Kobayashi
- Subjects
0301 basic medicine ,Microscopy ,Materials science ,Quantitative phase microscopy ,Microfluidics ,Nanotechnology ,Microfluidic Analytical Techniques ,Signal ,General Biochemistry, Genetics and Molecular Biology ,Characterization (materials science) ,law.invention ,03 medical and health sciences ,Interferometry ,030104 developmental biology ,Interference (communication) ,Optical microscope ,law ,Humans ,Microscopy, Phase-Contrast ,Molecular Biology ,Throughput (business) - Abstract
Innovations in optical microscopy have opened new windows onto scientific research, industrial quality control, and medical practice over the last few decades. One of such innovations is optofluidic time-stretch quantitative phase microscopy - an emerging method for high-throughput quantitative phase imaging that builds on the interference between temporally stretched signal and reference pulses by using dispersive properties of light in both spatial and temporal domains in an interferometric configuration on a microfluidic platform. It achieves the continuous acquisition of both intensity and phase images with a high throughput of more than 10,000 particles or cells per second by overcoming speed limitations that exist in conventional quantitative phase imaging methods. Applications enabled by such capabilities are versatile and include characterization of cancer cells and microalgal cultures. In this paper, we review the principles and applications of optofluidic time-stretch quantitative phase microscopy and discuss its future perspective.
- Published
- 2018
48. High-throughput, label-free, single-cell, microalgal lipid screening by machine-learning-equipped optofluidic time-stretch quantitative phase microscopy
- Author
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Yasuyuki Ozeki, Keisuke Goda, Takuro Ito, Yo Tanaka, Hirofumi Kobayashi, Cheng Lei, Baoshan Guo, Yiyue Jiang, and Yaxiaer Yalikun
- Subjects
0301 basic medicine ,Histology ,Microscope ,business.industry ,Microfluidics ,Cell Biology ,Biology ,Machine learning ,computer.software_genre ,Optofluidics ,Pathology and Forensic Medicine ,law.invention ,03 medical and health sciences ,030104 developmental biology ,Single-cell analysis ,law ,High-Throughput Screening Assays ,Microscopy ,Artificial intelligence ,business ,Throughput (business) ,computer ,Cytometry - Abstract
The development of reliable, sustainable, and economical sources of alternative fuels to petroleum is required to tackle the global energy crisis. One such alternative is microalgal biofuel, which is expected to play a key role in reducing the detrimental effects of global warming as microalgae absorb atmospheric CO2 via photosynthesis. Unfortunately, conventional analytical methods only provide population-averaged lipid amounts and fail to characterize a diverse population of microalgal cells with single-cell resolution in a non-invasive and interference-free manner. Here high-throughput label-free single-cell screening of lipid-producing microalgal cells with optofluidic time-stretch quantitative phase microscopy was demonstrated. In particular, Euglena gracilis, an attractive microalgal species that produces wax esters (suitable for biodiesel and aviation fuel after refinement), within lipid droplets was investigated. The optofluidic time-stretch quantitative phase microscope is based on an integration of a hydrodynamic-focusing microfluidic chip, an optical time-stretch quantitative phase microscope, and a digital image processor equipped with machine learning. As a result, it provides both the opacity and phase maps of every single cell at a high throughput of 10,000 cells/s, enabling accurate cell classification without the need for fluorescent staining. Specifically, the dataset was used to characterize heterogeneous populations of E. gracilis cells under two different culture conditions (nitrogen-sufficient and nitrogen-deficient) and achieve the cell classification with an error rate of only 2.15%. The method holds promise as an effective analytical tool for microalgae-based biofuel production. © 2017 International Society for Advancement of Cytometry.
- Published
- 2017
49. GHz Optical Time-Stretch Microscopy by Compressive Sensing
- Author
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Yasuyuki Ozeki, Cheng Lei, Baoshan Guo, Chia-Wei Sun, Yi Wu, Naoto Sasaki, Aswin C. Sankaranarayanan, Shih-Min Chang, Keisuke Goda, and Hirofumi Kobayashi
- Subjects
lcsh:Applied optics. Photonics ,time-stretch microscopy ,Digital image correlation ,Materials science ,Compressive sensing (CS) ,02 engineering and technology ,01 natural sciences ,010309 optics ,Optics ,image processing ,0103 physical sciences ,Microscopy ,Dispersion (optics) ,lcsh:QC350-467 ,Electrical and Electronic Engineering ,Image resolution ,business.industry ,lcsh:TA1501-1820 ,021001 nanoscience & nanotechnology ,Frame rate ,Atomic and Molecular Physics, and Optics ,Light sheet fluorescence microscopy ,Digital holographic microscopy ,Near-field scanning optical microscope ,0210 nano-technology ,business ,lcsh:Optics. Light - Abstract
Optical time-stretch microscopy has recently attracted intensive attention for its capability of acquiring images at an ultrahigh frame rate. Unfortunately, its achievable frame rate is limited by the requirement of having no overlap between consecutive frames, which leads to a tradeoff between the frame rate (pulse repetition rate) and the amount of the temporal dispersion used for optical image serialization. In this paper, we demonstrate compressive sensing on the platform of optical time-stretch microscopy to overcome the tradeoff between frame rate and temporal dispersion (time stretch) and achieve 50 times higher frame rate than conventional optical time-stretch microscopy. Specifically, we computationally perform compressed optical time-stretch microscopy with an experimental dataset acquired by conventional optical time-stretch microscopy and demonstrate its effects in terms of spatial resolution and cell classification accuracy. Our results indicate that the spatial resolution and cell classification accuracy reach 780 nm and 95% at a line scan rate of 675 MHz and 6.75 GHz, respectively, which correspond to five times and 50 times higher frame rates than what conventional optical time-stretch microscopy can achieve with the same dispersion amount and digitizer sampling rate.
- Published
- 2017
50. Radiotherapy for localized gastric mucosa–associated lymphoid tissue lymphoma: long-term outcomes over 10 years
- Author
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Nobuko Kubota, Hiroki Ushijima, Jun-ichi Saitoh, Tomoko Kazumoto, Yu Ohkubo, Hirofumi Kobayashi, Masafumi Kurosumi, Yoshihiro Saito, Yu Nishimura, Masahiro Onishi, and Nobuo Maseki
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Time Factors ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,complication ,Kaplan-Meier Estimate ,Gastroenterology ,Disease-Free Survival ,MALT ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Internal medicine ,Regular Paper ,gastric lymphoma ,medicine ,Gastric mucosa ,Humans ,Radiology, Nuclear Medicine and imaging ,Neoplasm Metastasis ,radiotherapy ,Aged ,Aged, 80 and over ,Radiation ,business.industry ,Lymphoma, Non-Hodgkin ,Gastric lymphoma ,Dose-Response Relationship, Radiation ,MALT lymphoma ,Middle Aged ,medicine.disease ,Lymphoma ,Radiation therapy ,Treatment Outcome ,Lymphatic system ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,Tomography, X-Ray Computed ,Complication ,business - Abstract
This study aimed to assess the long-term outcomes of radiotherapy in patients with localized gastric mucosa–associated lymphoid tissue (MALT) lymphoma. Twenty-seven patients with Stage I gastric MALT lymphoma were treated with radiotherapy from 1999 to 2010. The median age was 65 years (range: 31–84). Fifteen patients were Helicobacter pylori–negative. Thirteen patients were treated with definitive radiotherapy alone. The other 14 patients who had refractory or residual disease following a prior treatment received salvage radiotherapy. The median dose of the radiotherapy was 30 Gy in 20 fractions (range: 30–39.5 Gy). The median follow-up period was 121 months (range: 8–176 months). The 5- and 10-year overall survival rates for all patients were 92% and 87%, respectively. No patients died from MALT lymphoma. Three patients died of other diseases at 8, 33 and 74 months after radiotherapy (myocardial infarction, pneumonia and hepatocellular carcinoma, respectively). No cases of local recurrence were observed during the follow-up period. There were no serious late gastric, liver or kidney complications during a median follow-up period of over 10 years. Two patients remain alive with distant metastases: a lung metastasis and an abdominal lymph node metastasis at 104 months and 21 months after radiotherapy, respectively. Excellent long-term local control was observed in patients with localized gastric MALT lymphoma after radiotherapy. However, lifelong follow-up should be conducted to detect cases of late recurrence, especially distant metastases.
- Published
- 2017
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