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In certain three-dimensional (3D) applications of photoacoustic computed tomography (PACT), including textit{in vivo} breast imaging, hemispherical measurement apertures that enclose the object within their convex hull are employed for data acquisition. Data acquired with such measurement geometries are referred to as textit{half-scan} data, as only half of a complete spherical measurement aperture is employed. Although previous studies have demonstrated that half-scan data can uniquely and stably reconstruct the sought-after object, no closed-form reconstruction formula for use with half-scan data has been reported. To address this, a semi-analytic reconstruction method in the form of filtered backprojection (FBP), referred to as the half-scan FBP method, is developed in this work. Because the explicit form of the filtering operation in the half-scan FBP method is not currently known, a learning-based method is proposed to approximate it. The proposed method is systematically investigated by use of virtual imaging studies of 3D breast PACT that employ ensembles of numerical breast phantoms and a physics-based model of the data acquisition process. The method is subsequently applied to experimental data acquired in an textit{in vivo} breast PACT study. The results confirm that the half-scan FBP method can accurately reconstruct 3D images from half-scan data. Importantly, because the sought-after inverse mapping is well-posed, the reconstruction method remains accurate even when applied to data that differ considerably from those employed to learn the filtering operation.

Motivation: With the rapid expansion of large-scale biological datasets, DNA and protein sequence alignments have become essential for comparative genomics and proteomics. These alignments facilitate the exploration of sequence similarity patterns, providing valuable insights into sequence conservation, evolutionary relationships and for functional analyses. Typically, sequence alignments are stored in formats such as the Multiple Alignment Format (MAF). Counting k-mer occurrences is a crucial task in many computational biology applications, but currently, there is no algorithm designed for k-mer counting in alignment files.

Results: We have developed MAFcounter, the first k-mer counter dedicated to alignment files. MAFcounter is multithreaded, fast, and memory efficient, enabling k-mer counting in DNA and protein sequence alignment files.

Availability: The MAFcounter package and its Python bindings are released under GPL license as a multi-platform application and are available at: https://github.com/Georgakopoulos-Soares-lab/MAFcounter.

Magnetic resonance (MR)-guided radiation therapy (RT) is enhancing head and neck cancer (HNC) treatment through superior soft tissue contrast and longitudinal imaging capabilities. However, manual tumor segmentation remains a significant challenge, spurring interest in artificial intelligence (AI)-driven automation. To accelerate innovation in this field, we present the Head and Neck Tumor Segmentation for MR-Guided Applications (HNTS-MRG) 2024 Challenge, a satellite event of the 27th International Conference on Medical Image Computing and Computer Assisted Intervention. This challenge addresses the scarcity of large, publicly available AI-ready adaptive RT datasets in HNC and explores the potential of incorporating multi-timepoint data to enhance RT auto-segmentation performance. Participants tackled two HNC segmentation tasks: automatic delineation of primary gross tumor volume (GTVp) and gross metastatic regional lymph nodes (GTVn) on pre-RT (Task 1) and mid-RT (Task 2) T2-weighted scans. The challenge provided 150 HNC cases for training and 50 for testing, hosted on grand-challenge.org using a Docker submission framework. In total, 19 independent teams from across the world qualified by submitting both their algorithms and corresponding papers, resulting in 18 submissions for Task 1 and 15 submissions for Task 2. Evaluation using the mean aggregated Dice Similarity Coefficient showed top-performing AI methods achieved scores of 0.825 in Task 1 and 0.733 in Task 2. These results surpassed clinician interobserver variability benchmarks, marking significant strides in automated tumor segmentation for MR-guided RT applications in HNC.

Empirical investigation of the quintillion-scale, functionally diverse antibody repertoires that can be generated synthetically or naturally is critical for identifying potential biotherapeutic leads, yet remains burdensome. We present high-throughput nanophotonics- and bioprinter-enabled screening (HT-NaBS), a multiplexed assay for large-scale, sample-efficient, and rapid characterization of antibody libraries. Our platform is built upon independently addressable pixelated nanoantennas exhibiting wavelength-scale mode volumes, high-quality factors (high-Q) exceeding 5000, and pattern densities exceeding one million sensors per square centimeter. Our custom-built acoustic bioprinter enables individual sensor functionalization via the deposition of picoliter droplets from a library of capture antigens at rates up to 25,000 droplets per second. We detect subtle differentiation in the target binding signature through spatially-resolved spectral imaging of hundreds of resonators simultaneously, elucidating antigen-antibody binding kinetic rates, affinity constant, and specificity. We demonstrate HT-NaBS on a panel of antibodies targeting SARS-CoV-2, Influenza A, and Influenza B antigens, with a sub-picomolar limit of detection within 30 minutes. Furthermore, through epitope binning analysis, we demonstrate the competence and diversity of a library of native antibodies targeting functional epitopes on a priority pathogen (H5N1 bird flu) and on glycosylated therapeutic Cetuximab antibodies against epidermal growth factor receptor. With a roadmap to image tens of thousands of sensors simultaneously, this high-throughput, resource-efficient, and label-free platform can rapidly screen for high-affinity and broad epitope coverage, accelerating biotherapeutic discovery and de novo protein design.

User engagement, cognitive participation, and motivation during task execution in physical human-robot interaction are crucial for motor learning. These factors are especially important in contexts like robotic rehabilitation, where neuroplasticity is targeted. However, traditional robotic rehabilitation systems often face challenges in maintaining user engagement, leading to unpredictable therapeutic outcomes. To address this issue, various techniques, such as assist-as-needed controllers, have been developed to prevent user slacking and encourage active participation. In this paper, we introduce a new direction through a novel multi-modal robotic interaction designed to enhance user engagement by synergistically integrating visual, motor, cognitive, and auditory (speech recognition) tasks into a single, comprehensive activity. To assess engagement quantitatively, we compared multiple electroencephalography (EEG) biomarkers between this multi-modal protocol and a traditional motor-only protocol. Fifteen healthy adult participants completed 100 trials of each task type. Our findings revealed that EEG biomarkers, particularly relative alpha power, showed statistically significant improvements in engagement during the multi-modal task compared to the motor-only task. Moreover, while engagement decreased over time in the motor-only task, the multi-modal protocol maintained consistent engagement, suggesting that users could remain engaged for longer therapy sessions. Our observations on neural responses during interaction indicate that the proposed multi-modal approach can effectively enhance user engagement, which is critical for improving outcomes. This is the first time that objective neural response highlights the benefit of a comprehensive robotic intervention combining motor, cognitive, and auditory functions in healthy subjects.

Networks of excitatory and inhibitory (EI) neurons form a canonical circuit in the brain. Seminal theoretical results on dynamics of such networks are based on the assumption that synaptic strengths depend on the type of neurons they connect, but are otherwise statistically independent. Recent synaptic physiology datasets however highlight the prominence of specific connectivity patterns that go well beyond what is expected from independent connections. While decades of influential research have demonstrated the strong role of the basic EI cell type structure, to which extent additional connectivity features influence dynamics remains to be fully determined. Here we examine the effects of pair-wise connectivity motifs on the linear dynamics in excitatory-inhibitory networks using an analytical framework that approximates the connectivity in terms of low-rank structures. This low-rank approximation is based on a mathematical derivation of the dominant eigenvalues of the connectivity matrix, and predicts the impact on responses to external inputs of connectivity motifs and their interactions with cell-type structure. Our results reveal that a particular pattern of connectivity, chain motifs, have a much stronger impact on dominant eigenmodes than other pair-wise motifs. In particular, an over-representation of chain motifs induces a strong positive eigenvalue in inhibition-dominated networks and generates a potential instability that requires revisiting the classical excitation-inhibition balance criteria. Examining effects of external inputs, we show that chain motifs can on their own induce paradoxical responses, where an increased input to inhibitory neurons leads to a decrease in their activity due to the recurrent feedback. These findings have direct implications for the interpretation of experiments in which responses to optogenetic perturbations are measured and used to infer the dynamical regime of cortical circuits.

The seasonal human influenza virus undergoes rapid evolution, leading to significant changes in circulating viral strains from year to year. These changes are typically driven by adaptive mutations, particularly in the antigenic epitopes, the regions of the viral surface protein haemagglutinin targeted by human antibodies. Here we describe a consistent set of methods for data-driven predictive analysis of viral evolution. Our pipeline integrates four types of data: (1) sequence data of viral isolates collected on a worldwide scale, (2) epidemiological data on incidences, (3) antigenic characterization of circulating viruses, and (4) intrinsic viral phenotypes. From the combined analysis of these data, we obtain estimates of relative fitness for circulating strains and predictions of clade frequencies for periods of up to one year. Furthermore, we obtain comparative estimates of protection against future viral populations for candidate vaccine strains, providing a basis for pre-emptive vaccine strain selection. Continuously updated predictions obtained from the prediction pipeline for influenza and SARS-CoV-2 are available on the website previr.app.

Understanding biological functions requires identifying the physical limits and system-specific constraints that have shaped them. In Escherichia coli chemotaxis, gradient-climbing speed is information-limited, bounded by the sensory information they acquire from real-time measurements of their environment. However, it remains unclear what limits this information. Past work conjectured that E. coli's chemosensing is limited by the physics of molecule arrivals at their sensors. Here, we derive the physical limit on behaviorally-relevant information, and then perform single-cell experiments to quantify how much information E. coli's signaling pathway encodes. We find that E. coli encode two orders of magnitude less information than the physical limit due to their stochastic signal processing. Thus, system-specific constraints, rather than the physical limit, have shaped the evolution of this canonical sensory-motor behavior.

Background: Intensity-modulated proton therapy (IMPT) using pencil beam technique scans tumor in a layer by layer, then spot by spot manner. It can provide highly conformal dose to tumor targets and spare nearby organs-at-risk (OAR). Fast delivery of IMPT can improve patient comfort and reduce motion-induced uncertainties. Since energy layer switching time dominants the plan delivery time, reducing the number of energy layers is important for improving delivery efficiency. Although various energy layer optimization (ELO) methods exist, they are rarely experimentally validated or clinically implemented, since it is technically challenging to integrate these methods into commercially available treatment planning system (TPS) that is not open-source.

Purpose: This work develops and experimentally validates an in-house TPS (IH-TPS) that incorporates a novel ELO method for the purpose of fast IMPT.

Methods: The dose calculation accuracy of IH-TPS is verified against the measured beam data and the RayStation TPS. For treatment planning, a novel ELO method via greed selection algorithm is proposed to reduce energy layer switching time and total plan delivery time. To validate the planning accuracy of IH-TPS, the 3D gamma index is calculated between IH-TPS plans and RayStation plans for various scenarios. Patient-specific quality-assurance (QA) verifications are conducted to experimentally verify the delivered dose from the IH-TPS plans for several clinical cases.

Results: Dose distributions in IH-TPS matched with those from RayStation TPS, with 3D gamma index results exceeding 95% (2mm, 2%). The ELO method significantly reduced the delivery time while maintaining plan quality. For instance, in a brain case, the number of energy layers was reduced from 78 to 40, leading to a 62% reduction in total delivery time. Patient-specific QA validation with the IBA Proteus^®ONE proton machine confirmed a >95% pass rate for all cases.

Conclusions: An IH-TPS equipped with a novel ELO algorithm is developed and experimentally validated for the purpose of fast IMPT, with enhanced delivery efficiency and preserved plan quality.