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Exploratory digital outcome measures of motor sign progression in Parkinson's disease patients treated with prasinezumab

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NPJ digital medicine 2025年第1期8卷 365页

作者： Kirsten I Taylor Florian Lipsmeier Marzia A Scelsi Ekaterina Volkova-Volkmar Daria Rukina Werner Popp Stefan Lambrecht Judith Anzures-Cabrera David Summers Markus Abt Annabelle Monnet Timothy Kilchenmann Jens Schjodt-Eriksen Laurent Essioux Thomas Kustermann Wagner Zago Hanno Svoboda Tania Nikolcheva Ronald B Postuma Gennaro Pagano Michael Lindemann Roche Pharma Research and Early Development (pRED) Neuroscience & Rare Diseases Data & Analytics Pharmaceutical Sciences Clinical Pharmacology Roche Innovation Center Basel F. Hoffmann-La Roche Ltd. Basel Switzerland. kirsten.taylor@***. Roche Pharma Research and Early Development (pRED) Neuroscience & Rare Diseases Data & Analytics Pharmaceutical Sciences Clinical Pharmacology Roche Innovation Center Basel F. Hoffmann-La Roche Ltd. Basel Switzerland. Roche Information Solutions (RIS) Data & Analytics Roche Diagnostics F. Hoffmann-La Roche Ltd. Basel Switzerland. Product Development Data Sciences Roche Products Ltd Welwyn Garden City UK. Chiesi Group Manchester United Kingdom. Product Development Data Sciences Hoffmann-La Roche Ltd. Basel Switzerland. Computer Science Resource and Research Center Institut Pasteur Paris France. Prothena Biosciences Inc South San Francisco California USA. Roche Innovation Center Basel and Product Development Neuroscience F. Hoffmann-La Roche Ltd. Basel Switzerland. Department of Neurology McGill University Montreal General Hospital Montreal Quebec Canada. University of Exeter Medical School London United Kingdom.

Digital health technology (DHT) tools for Parkinson's disease (PD) e.g., smartphones and wearables were used for remote and frequent measurement of motor signs in the phase 2 PASADENA study of the anti-alpha-synuclein monoclonal antibody prasinezumab. 316 early-stage PD participants were randomized to placebo, 1500 mg, or 4500 mg prasinezumab for 52 weeks; placebo participants were re-randomized to prasinezumab for the ensuing 52 weeks. Patients performed daily smartphone motor "active tests", and were passively monitored by smartphone/smartwatch throughout the day over 2 y. Change from baseline analyses censored data at dopaminergic treatment start. Bilateral speeded tapping variability and hand-turning, U-turn speed, passively monitored hand movement power, and summary Simple Sum scores progressed numerically less in prasinezumab-treated vs placebo at week 52. All findings except hand-turning persisted at week 104. DHT sensor-based outcome measures may contribute to quantifying disease progression in clinical research of early-stage, dopaminergic treatment-naïve PD. Clinical Trial Registry Name: ***; Clinical Trial Registry ID: NCT03100149; registered 2017-03-29.

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Why is the Winner the Best?

Why is the Winner the Best?

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Conference on computer Vision and Pattern Recognition (CVPR)

作者： M. Eisenmann A. Reinke V. Weru M. D. Tizabi F. Isensee T. J. Adler S. Ali V. Andrearczyk M. Aubreville U. Baid S. Bakas N. Balu S. Bano J. Bernal S. Bodenstedt A. Casella V. Cheplygina M. Daum M. De Bruijne A. Depeursinge R. Dorent J. Egger D. G. Ellis S. Engelhardt M. Ganz N. Ghatwary G. Girard P. Godau A. Gupta L. Hansen K. Harada M. Heinrich N. Heller A. Hering A. Huaulmé P. Jannin A. E. Kavur O. Kodym M. Kozubek J. Li H. Li J. Ma C. Martín-Isla B. Menze A. Noble V. Oreiller N. Padoy S. Pati K. Payette T. Rädsch J. Rafael-Patiño V. Singh Bawa S. Speidel C. H. Sudre K. Van Wijnen M. Wagner D. Wei A. Yamlahi M. H. Yap C. Yuan M. Zenk A. Zia D. Zimmerer D. Aydogan B. Bhattarai L. Bloch R. Brüngel J. Cho C. Choi Q. Dou I. Ezhov C. M. Friedrich C. Fuller R. R. Gaire A. Galdran Á. García Faura M. Grammatikopoulou S. Hong M. Jahanifar I. Jang A. Kadkhodamohammadi I. Kang F. Kofler S. Kondo H. Kuijf M. Li M. Luu T. Martinčič P. Morais M. A. Naser B. Oliveira D. Owen S. Pang J. Park S. Park S. Płotka E. Puybareau N. Rajpoot K. Ryu N. Saeed A. Shephard P. Shi D. Štepec R. Subedi G. Tochon H. R. Torres H. Urien J. L. Vilaça K. A. Wahid H. Wang J. Wang L. Wang X. Wang B. Wiestler M. Wodzinski F. Xia J. Xie Z. Xiong S. Yang Y. Yang Z. Zhao K. Maier-Hein P. F. Jäger A. Kopp-Schneider L. Maier-Hein Division of Intelligent Medical Systems German Cancer Research Center (DKFZ) Heidelberg Germany Helmholtz Imaging German Cancer Research Center (DKFZ) Heidelberg Germany Faculty of Mathematics and Computer Science Heidelberg University Heidelberg Germany Division of Biostatistics German Cancer Research Center (DKFZ) Heidelberg Germany Division of Medical Image Computing German Cancer Research Center (DKFZ) Heidelberg Germany Faculty of Engineering and Physical Sciences School of Computing University of Leeds Leeds UK Institute of Informatics School of Management HES-SO Valais-Wallis University of Applied Sciences and Arts Western Switzerland Sierre Switzerland Department of Nuclear Medicine and Molecular Imaging Lausanne University Hospital Lausanne Switzerland Technische Hochschule Ingolstadt Ingolstadt Germany Center for Artificial Intelligence and Data Science for Integrated Diagnostics (AI2D) and Center for Biomedical Image Computing and Analytics (CBICA) University of Pennsylvania Philadelphia PA USA Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Department of Radiology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Department of Radiology University of Washington Seattle WA USA Department of Computer Science Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS) University College London London UK Universitat Autònoma de Barcelona & Computer Vision Center Barcelona Spain Division of Translational Surgical Oncology National Center for Tumor Diseases (NCT/UCC) Dresden Dresden Germany Department of Advanced Robotics Istituto Italiano di Tecnologia Italy Department of Electronics Information and Bioengineering Politecnico di Milano Milan Italy IT University of Copenhagen Copenhagen Denmark Department of General Visceral and Transplantation Surgery Heidelberg University Hospital Heidelberg Germany Department of Radiology and Nuc

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multicenter study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and post-processing (66%). The “typical” lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.

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Ranking-based convolutional neural network models for peptide-MHC binding prediction

arXiv

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arXiv 2020年

作者： Chen, Ziqi Min, Martin Renqiang Ning, Xia Computer Science and Engineering Department Ohio State University ColumbusOH United States Machine Learning Department NEC Labs America PrincetonNJ United States Biomedical Informatics Department Ohio State University ColumbusOH United States Translational Data Analytics Institute Ohio State University ColumbusOH United States

T-cell receptors can recognize foreign peptides bound to major histocompatibility complex (MHC) class-I proteins, and thus trigger the adaptive immune response. Therefore, identifying peptides that can bind to MHC class-I molecules plays a vital role in the design of peptide vaccines. Many computational methods, for example, the state-of-the-art allele-specific method MHCflurry, have been developed to predict the binding affinities between peptides and MHC molecules. In this manuscript, we develop two allele-specific Convolutional Neural Network (CNN)based methods named ConvM and SpConvM to tackle the binding prediction problem. Specifically, we formulate the problem as to optimize the rankings of peptide-MHC bindings via ranking-based learning objectives. Such optimization is more robust and tolerant to the measurement inaccuracy of binding affinities, and therefore enables more accurate prioritization of binding peptides. In addition, we develop a new position encoding method in ConvM and SpConvM to better identify the most important amino acids for the binding events. We conduct a comprehensive set of experiments using the latest Immune Epitope database (IEDB) datasets. Our experimental results demonstrate that our models significantly outperform the state-of-the-art methods including MHCflurry with an average percentage improvement of 6.70% on AUC and 17.10% on ROC5 across 128 alleles. © 2020, CC BY.

关键词： Peptides

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Deep reinforcement learning for motion planning of mobile robots

arXiv

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arXiv 2019年

作者： Butyrev, Leonid Edelhäußer, Thorsten Mutschler, Christopher Fraunhofer Institute for Integrated Circuits Iis Precise Positioning and Analytics Department Machine Learning and Information Fusion Group Nuremberg Germany Computer Science Department Machine Learning and Data Analytics Lab Erlangen Germany

This paper presents a novel motion and trajectory planning algorithm for nonholonomic mobile robots that uses recent advances in deep reinforcement learning. Starting from a random initial state, i.e., position, velocity and orientation, the robot reaches an arbitrary target state while taking both kinematic and dynamic constraints into account. Our deep reinforcement learning agent not only processes a continuous state space it also executes continuous actions, i.e., the acceleration of wheels and the adaptation of the steering angle. We evaluate our motion and trajectory planning on a mobile robot with a differential drive in a simulation environment. Copyright © 2019, The Authors. All rights reserved.

关键词： Deep learning

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Synchronized sensor insoles for clinical gait analysis in home-monitoring applications

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Current Directions in Biomedical Engineering 2018年第1期4卷 433-437页

作者： Roth, Nils Martindale, Christine F. Gaßner, Heiko Kohl, Zacharias Klucken, Jochen Eskofer, Bjoern M. Machine Learning and Data Analytics Lab. Department of Computer Science Friedrich-Alexander-University Erlangen-Nürnberg (FAU) Erlangen Germany Department of Molecular Neurology University Hospital Erlangen Germany

Wearable sensor systems are of increasing interest in clinical gait analysis. However, little information about gait dynamics of patients under free living conditions is available, due to the challenges of integrating such systems unobtrusively into a patient's everyday live. To address this limitation, new, fully integrated low power sensor insoles are proposed, to target applications particularly in home-monitoring scenarios. The insoles combine inertial as well as pressure sensors and feature wireless synchronization to acquire biomechanical data of both feet with a mean timing offset of 15.0 μs. The proposed system was evaluated on 15 patients with mild to severe gait disorders against the GAITRite® system as reference. Gait events based on the insoles' pressure sensors were manually extracted to calculate temporal gait features such as double support time and double support. Compared to the reference system a mean error of 0.06 s ± 0.06 s and 3.89 % ± 2.61 % was achieved, respectively. The proposed insoles proved their ability to acquire synchronized gait parameters and address the requirements for home-monitoring scenarios, pushing the boundaries of clinical gait analysis. © 2018 Nils Roth et al.

关键词： Synchronization

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Metric-based few-shot learning for video action recognition

arXiv

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arXiv 2019年

作者： Careaga, Chris Hutchinson, Brian Hodas, Nathan Phillips, Lawrence Computer Science Department Western Washington University BellinghamWA United States Data Science and Analytics Pacific Northwest National Laboratory RichlandWA United States

In the few-shot scenario, a learner must effectively generalize to unseen classes given a small support set of labeled examples. While a relatively large amount of research has gone into few-shot learning for image classification, little work has been done on few-shot video classification. In this work, we address the task of few-shot video action recognition with a set of two-stream models. We evaluate the performance of a set of convolutional and recurrent neural network video encoder architectures used in conjunction with three popular metric-based few-shot algorithms. We train and evaluate using a few-shot split of the Kinetics 600 dataset. Our experiments confirm the importance of the two-stream setup, and find prototypical networks and pooled long short-term memory network embeddings to give the best performance as few-shot method and video encoder, respectively. For a 5-shot 5-way task, this setup obtains 84.2% accuracy on the test set and 59.4% on a special "challenge" test set, composed of highly confusable classes. Copyright © 2019, The Authors. All rights reserved.

关键词： Classification (of information)

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Generating Approximate Ground States of Molecules Using Quantum Machine Learning

arXiv

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arXiv 2022年

作者： Ceroni, Jack Stetina, Torin F. Kieferová, Mária Marrero, Carlos Ortiz Arrazola, Juan Miguel Wiebe, Nathan Xanadu TorontoONM5G 2C8 Canada Department of Mathematics University of Toronto TorontoONM5S 3E1 Canada Simons Institute for the Theory of Computing BerkeleyCA94704 United States Berkeley Quantum Information and Computation Center University of California BerkeleyCA94720 United States Centre for Quantum Computation and Communication Technology Centre for Quantum Software and Information University of Technology SydneyNSW2007 Australia AI & Data Analytics Division Pacific Northwest National Laboratory RichlandWA99354 United States Department of Electrical & Computer Engineering North Carolina State University RaleighNC27607 United States Department of Computer Science University of Toronto ONM5S 1A1 Canada High Performance Computing Group Pacific Northwest National Laboratory RichlandWA99354 United States

The potential energy surface (PES) of molecules with respect to their nuclear positions is a primary tool in understanding chemical reactions from first principles. However, obtaining this information is complicated by the fact that sampling a large number of ground states over a high-dimensional PES can require a vast number of state preparations. In this work, we propose using a generative quantum machine learning model to prepare quantum states at arbitrary points on the PES. The model is trained using quantum data consisting of ground-state wavefunctions associated with different classical nuclear coordinates. Our approach uses a classical neural network to convert the nuclear coordinates of a molecule into quantum parameters of a variational quantum circuit. The model is trained using a fidelity loss function to optimize the neural network parameters. We show that gradient evaluation is efficient and numerically demonstrate our method’s ability to prepare wavefunctions on the PES of hydrogen chains, water, and beryllium hydride. In all cases, we find that a small number of training points are needed to achieve very high overlap with the groundstates in practice. From a theoretical perspective, we further prove limitations on these protocols by showing that if we were able to learn across an avoided crossing using a small number of samples, then we would be able to violate Grover’s lower bound. Additionally, we prove lower bounds on the amount of quantum data needed to learn a locally optimal neural network function using arguments from quantum Fisher information. This work further identifies that quantum chemistry can be an important use case for quantum machine learning. © 2022, CC BY.

关键词： Molecules

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DoT-Net: Document Layout Classification Using Texture-Based CNN

DoT-Net: Document Layout Classification Using Texture-Based ...

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International Conference on Document Analysis and Recognition

作者： Sai Chandra Kosaraju Mohammed Masum Nelson Zange Tsaku Pritesh Patel Tanju Bayramoglu Girish Modgil Mingon Kang Department of Computer Science Kennesaw State University Marietta USA Analytics and Data Science Institute Kennesaw State University Kennesaw USA GE power Atlanta USA

Document Layout Analysis (DLA) is a segmentation process that decomposes a scanned document image into its blocks of interest and classifies them. DLA is essential in a large number of applications, such as Information Retrieval, Machine Translation, Optical Character Recognition (OCR) systems, and structured data extraction from documents. However, identification of document blocks in DLA is challenging due to variations of block locations, inter-and intra-class variability, and background noises. In this paper, we propose a novel texture-based convolutional neural network for document layout analysis, called DoT-Net. DoT-Net is a multiclass classifier that can effectively identify document component blocks such as text, image, table, mathematical expression, and line-diagram, whereas most related methods have focused on the text vs. non-text block classification problem. DoT-Net can capture textural variations among the multiclass regions of documents. Our proposed method DoT-Net achieved promising results outperforming state-of-the-art document layout classifiers on accuracy, F1 score, and AUC. The open-source code of DoT-Net is available at https://***/datax-lab/DoTNet.

关键词： Feature extraction Layout Text analysis Shape Kernel Optical character recognition software Support vector machines

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Learning physically consistent differential equation models from data using group sparsity

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Physical Review E 2021年第4期103卷 042310-042310页

作者： Suryanarayana Maddu Bevan L. Cheeseman Christian L. Müller Ivo F. Sbalzarini Technische Universität Dresden Faculty of Computer Science 01069 Dresden Germany Max Planck Institute of Molecular Cell Biology and Genetics 01307 Dresden Germany Center for Systems Biology Dresden 01307 Dresden Germany Center for Scalable Data Analytics and Artificial Intelligence ScaDS.AI Dresden/Leipzig Germany Center for Computational Mathematics Flatiron Institute New York New York 10010 USA Department of Statistics LMU München 80539 Munich Germany Institute of Computational Biology Helmholtz Zentrum München 85764 Neuherberg Germany Cluster of Excellence Physics of Life TU Dresden 01307 Dresden Germany

We propose a statistical learning framework based on group-sparse regression that can be used to (i) enforce conservation laws, (ii) ensure model equivalence, and (iii) guarantee symmetries when learning or inferring differential-equation models from data. Directly learning interpretable mathematical models from data has emerged as a valuable modeling approach. However, in areas such as biology, high noise levels, sensor-induced correlations, and strong intersystem variability can render data-driven models nonsensical or physically inconsistent without additional constraints on the model structure. Hence, it is important to leverage prior knowledge from physical principles to learn biologically plausible and physically consistent models rather than models that simply fit the data best. We present the group iterative hard thresholding algorithm and use stability selection to infer physically consistent models with minimal parameter tuning. We show several applications from systems biology that demonstrate the benefits of enforcing priors in data-driven modeling.

关键词： data analysis data mining Machine learning

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When crowds give you lemons: Filtering innovative ideas using a diverse-bag-of-lemons strategy

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Proceedings of the ACM on Human-computer Interaction 2018年第CSCW期2卷 1-23页

作者： Lykourentzou, Ioanna Ahmed, Faez Papastathis, Costas Sadien, Irwyn Papangelis, Konstantinos Utrecht University Netherlands University of Maryland United States University of Peloponnese Greece Research Institute of Big Data Analytics Department of Computer Science and Software Engineering Xi’an Joaoton-Liverpool University China

Following successful crowd ideation contests, organizations in search of the "next big thing" are left with hundreds of ideas. Expert-based idea filtering is lengthy and costly;therefore, crowd-based strategies are often employed. Unfortunately, these strategies typically (1) do not separate the mediocre from the excellent, and (2) direct all the attention to certain idea concepts, while others starve. We introduce DBLemons – a crowd-based idea filtering strategy that addresses these issues by (1) asking voters to identify the worst rather than the best ideas using a "bag of lemons" voting approach, and (2) by exposing voters to a wider idea spectrum, thanks to a dynamic diversity-based ranking system balancing idea quality and coverage. We compare DBLemons against two state-of-the-art idea filtering strategies in a real-world setting. Results show that DBLemons is more accurate, less time-consuming, and reduces the idea space in half while still retaining 94% of the top ideas. © 2018 Association for Computing Machinery.

关键词： Citrus fruits

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