ArXiv最新文献

Bacterial swarming is a complex phenomenon in which thousands of self-propelled rod-shaped cells move coherently on surfaces, providing an excellent example of active matter. However, bacterial swarming is different from most studied examples of active systems because single isolated cells do not move, while clusters do. The biophysical aspects underlying this behavior are unclear. In this work we explore the case of low local cell densities, where single cells become temporarily immobile. We show that immobility is related to local depletion of liquid. In addition, it is also associated with the state of the flagella. Specifically, the flagellar bundles at (temporarily) liquid depleted regions are completely spread-out. Our results suggest that dry models of self-propelled agents, which only consider steric alignments and neglect hydrodynamic effects, are oversimplified and are not sufficient to describe swarming bacteria.

Objective: Proton spot-scanning arc therapy (ARC) is an emerging modality that can improve the high-dose conformity to targets compared with standard intensity-modulated proton therapy (IMPT). However, the efficient treatment delivery of ARC is challenging due to the required frequent energy changes during the continuous gantry rotation. This work proposes a novel method that delivers a multiple IMPT (multi-IMPT) plan that is equivalent to ARC in terms of biologically effective dose (BED).

Approach: The proposed multi-IMPT method utilizes a different subset of limited number of beam angles in each fraction for dose delivery. Due to the different dose delivered to organs at risk (OAR) in each fraction, we optimize biologically effective dose (BED) for OAR and the physical dose delivered for target in each fraction. The BED-based multi-IMPT inverse optimization problem is solved via the iterative convex relaxation method and the alternating direction method of multipliers. The effectiveness of the proposed multi-IMPT method is evaluated in terms of dose objectives in comparison with ARC.

Main results: Multi-IMPT provided similar plan quality with ARC. For example, multi-IMPT provided better OAR sparing and slightly better target dose coverage for the prostate case; similar dose distribution for the lung case; slightly worse dose coverage for the brain case; better dose coverage but slightly higher BED in OAR for the head-and-neck case.

Significance: We have proposed a multi-IMPT approach to deliver ARC-equivalent plan quality.

Motivation: A major challenge in metabolomics is annotation: assigning molecular structures to mass spectral fragmentation patterns. Despite recent advances in molecule-to-spectra and in spectra-to-molecular fingerprint prediction (FP), annotation rates remain low.

Results: We introduce in this paper a novel paradigm (JESTR) for annotation. Unlike prior approaches that explicitly construct molecular fingerprints or spectra, JESTR leverages the insight that molecules and their corresponding spectra are views of the same data and effectively embeds their representations in a joint space. Candidate structures are ranked based on cosine similarity between the embeddings of query spectrum and each candidate. We evaluate JESTR against mol-to-spec and spec-to-FP annotation tools on three datasets. On average, for rank@[1-5], JESTR outperforms other tools by 23.6% - 71.6%. We further demonstrate the strong value of regularization with candidate molecules during training, boosting rank@1 performance by 11.4% and enhancing the model's ability to discern between target and candidate molecules. Through JESTR, we offer a novel promising avenue towards accurate annotation, therefore unlocking valuable insights into the metabolome.

Availability: Code and dataset available at https://github.com/HassounLab/JESTR1/.

Purpose: Deformable image registration (DIR) plays a critical role in adaptive radiation therapy (ART) to accommodate anatomical changes. However, conventional intensity-based DIR methods face challenges when registering images with unequal image intensities. In these cases, DIR accuracy can be improved using a hybrid image similarity metric which matches both image intensities and the location of known structures. This study aims to assess DIR accuracy using a hybrid similarity metric and leveraging CycleGAN-based intensity correction and auto-segmentation and comparing performance across three DIR workflows.

Methods: The proposed approach incorporates a hybrid image similarity metric combining a point-to-distance (PD) score and intensity similarity score. Synthetic CT (sCT) images were generated using a 2D CycleGAN model trained on unpaired CT and CBCT images, improving soft-tissue contrast in CBCT images. The performance of the approach was evaluated by comparing three DIR workflows: (1) traditional intensity-based (No PD), (2) auto-segmented contours on sCT (CycleGAN PD), and (3) expert manual contours (Expert PD). A 3D U-Net model was then trained on two datasets comprising 56 3D images and validated on 14 independent cases to segment the prostate, bladder, and rectum. DIR accuracy was assessed using Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD), and fiducial separation metrics.

Results: The hybrid similarity metric significantly improved DIR accuracy. For the prostate, DSC increased from 0.61 ± 0.18 (No PD) to 0.82 ± 0.13 (CycleGAN PD) and 0.89 ± 0.05 (Expert PD), with corresponding reductions in 95% HD from 11.75 mm to 4.86 mm and 3.27 mm, respectively. Fiducial separation was also reduced from 8.95 mm to 4.07 mm (CycleGAN PD) and 4.11 mm (Expert PD) (p < 0.05). Improvements in alignment were also observed for the bladder and rectum, highlighting the method's robustness.

Conclusion: A hybrid similarity metric that uses CycleGAN-based auto-segmentation presents a promising avenue for advancing DIR accuracy in ART. The study's findings suggest the potential for substantial enhancements in DIR accuracy by combining AI-based image correction and auto-segmentation with classical DIR.

Objectives: The vast and complex nature of human genomic sequencing data presents challenges for effective analysis. This review aims to investigate the application of Natural Language Processing (NLP) techniques, particularly Large Language Models (LLMs) and transformer architectures, in deciphering genomic codes, focusing on tokenization, transformer models, and regulatory annotation prediction. This review aims to assess data and model accessibility in the most recent literature, gaining a better understanding of the existing capabilities and constraints of these tools in processing genomic sequencing data.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, our scoping review was conducted across PubMed, Medline, Scopus, Web of Science, Embase, and ACM Digital Library. Studies were included if they focused on NLP methodologies applied to genomic sequencing data analysis, without restrictions on publication date or article type.

Results: A total of 26 studies published between 2021 and April 2024 were selected for review. The review highlights that tokenization and transformer models enhance the processing and understanding of genomic data, with applications in predicting regulatory annotations like transcription-factor binding sites and chromatin accessibility.

Discussion: The application of NLP and LLMs to genomic sequencing data interpretation is a promising field that can help streamline the processing of large-scale genomic data while providing a better understanding of its complex structures. It can potentially drive advancements in personalized medicine by offering more efficient and scalable solutions for genomic analysis. Further research is needed to discuss and overcome limitations, enhancing model transparency and applicability.

Deep generative models that produce novel molecular structures have the potential to facilitate chemical discovery. Flow matching is a recently proposed generative modeling framework that has achieved impressive performance on a variety of tasks including those on biomolecular structures. The seminal flow matching framework was developed only for continuous data. However, de novo molecular design tasks require generating discrete data such as atomic elements or sequences of amino acid residues. Several discrete flow matching methods have been proposed recently to address this gap. In this work we benchmark the performance of existing discrete flow matching methods for 3D de novo small molecule generation and provide explanations of their differing behavior. As a result we present FlowMol-CTMC, an open-source model that achieves state of the art performance for 3D de novo design with fewer learnable parameters than existing methods. Additionally, we propose the use of metrics that capture molecule quality beyond local chemical valency constraints and towards higher-order structural motifs. These metrics show that even though basic constraints are satisfied, the models tend to produce unusual and potentially problematic functional groups outside of the training data distribution. Code and trained models for reproducing this work are available at url{https://github.com/dunni3/FlowMol}.

Purpose: To identify the predominant source of the $T_1$ variability described in the literature, which ranges from 0.6-1.1 s for brain white matter at 3 T.

Methods: 25 $T_1$ -mapping methods from the literature were simulated with a mono-exponential and various magnetization-transfer (MT) models, each followed by mono-exponential fitting. A single set of model parameters was assumed for the simulation of all methods, and these parameters were estimated by fitting the simulation based to the corresponding literature $T_1$ values of white matter at 3 T. In vivo MT parameter maps were further used to synthesize MR images for 3 $T_1$ -mapping methods. A mono-exponential model was fitted to the synthesized and corresponding experimental MR images.

Results: Mono-exponential simulations suggest good inter-method reproducibility and fail to explain the highly variable $T_1$ estimates in the literature. In contrast, MT simulations suggest that a mono-exponential fit results in a variable $T_1$ and explain up to 62% of the literature's variability. In our own in vivo experiments, MT explains 70% of the observed variability.

Conclusion: The results suggest that a mono-exponential model does not adequately describe longitudinal relaxation in biological tissue. Therefore, $T_1$ in biological tissue should be considered only a semi-quantitative metric that is inherently contingent upon the imaging methodology; and comparisons between different $T_1$ -mapping methods and the use of simplistic spin systems-such as doped-water phantoms-for validation should be viewed with caution.

Morphological variations in the left atrial appendage (LAA) are associated with different levels of ischemic stroke risk for patients with atrial fibrillation (AF). Studying LAA morphology can elucidate mechanisms behind this association and lead to the development of advanced stroke risk stratification tools. However, current categorical descriptions of LAA morphologies are qualitative in nature, and inconsistent across studies, which impedes advancements in our understanding of stroke pathogenesis in AF. To mitigate these issues, we introduce a quantitative pipeline that combines elastic shape analysis with unsupervised learning for the categorization of LAA morphology in AF patients. We demonstrate that our method reliably clusters LAAs based on their geometric features, and thus provides an avenue to overcome the limitations of current qualitative LAA categorization systems.

Virtual staining streamlines traditional staining procedures by digitally generating stained images from unstained or differently stained images. While conventional staining methods involve time-consuming chemical processes, virtual staining offers an efficient and low infrastructure alternative. Leveraging microscopy-based techniques, such as confocal microscopy, researchers can expedite tissue analysis without the need for physical sectioning. However, interpreting grayscale or pseudo-color microscopic images remains a challenge for pathologists and surgeons accustomed to traditional histologically stained images. To fill this gap, various studies explore digitally simulating staining to mimic targeted histological stains. This paper introduces a novel network, In-and-Out Net, specifically designed for virtual staining tasks. Based on Generative Adversarial Networks (GAN), our model efficiently transforms Reflectance Confocal Microscopy (RCM) images into Hematoxylin and Eosin (H&E) stained images. We enhance nuclei contrast in RCM images using aluminum chloride preprocessing for skin tissues. Training the model with virtual H&E labels featuring two fluorescence channels eliminates the need for image registration and provides pixel-level ground truth. Our contributions include proposing an optimal training strategy, conducting a comparative analysis demonstrating state-of-the-art performance, validating the model through an ablation study, and collecting perfectly matched input and ground truth images without registration. In-and-Out Net showcases promising results, offering a valuable tool for virtual staining tasks and advancing the field of histological image analysis.

How ecosystems respond to environmental perturbations is a fundamental question in ecology, made especially challenging due to the strong coupling between species and their environment. Here, we introduce a theoretical framework for calculating the steady-state response of ecosystems to environmental perturbations in generalized consumer-resource. Our construction is applicable to a wide class of systems, including models with non-reciprocal interactions, cross-feeding, and non-linear growth/consumption rates. Within our framework, all ecological variables are embedded into four distinct vector spaces and ecological interactions are represented by geometric transformations between these spaces. We show that near a steady state, such geometric transformations directly map environmental perturbations - in resource availability and mortality rates - to shifts in niche structure. We illustrate these ideas in a variety of settings including a minimal model for pH-induced toxicity in bacterial denitrification. We end by discussing the biological implications of our framework. In particular, we show that it is extremely difficult to distinguish cooperative and competitive interactions by measuring species' responses to external perturbations.