Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation
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Introduction to the show: ident: AI Radio. Generated commentary on the latest Artificial Intelligence papers.
Tom: I'm Tom, and with me are Jane, Lu, senior AI researcher at Tsinghua, Meng, lead engineer at a mysterious AI startup and Lalam, the in-house Large Language Model.
Jane: Today's paper: "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation".
Tom: Imaging biomarkers in magnetic resonance imaging (MRI) are crucial for diagnosing, tracking, and treating Alzheimer's disease (AD), particularly because neurofibrillary tau pathology spreads through brain subregions,
Jane: First, who's behind it and why it matters.
Title and authors: Tom: Welcome back everyone! Today we’re talking about a paper that really tackles a massive headache in Alzheimer's imaging: getting accurate measurements of the Medial Temporal Lobe subregions when your scans are all over the place. We’ve got some incredible insights coming from this work.
Jane: It sounds like they are trying to fix a problem where the way MRI scans, especially T2-weighted ones, are taken makes it really hard to measure things consistently across different patients. This paper is about using an implicit neural representation, or INR, to sort out that geometric mess and get better data for diagnosing Alzheimer's disease.
Lu: I think the core idea here is addressing that anisotropy mentioned in page one of "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation." Since T2w images have such a huge difference between in-plane and out-of-plane resolution, modeling those subregions geometrically becomes really tricky, which is why they are focusing on creating an isotropic training set.
Meng: From an engineering standpoint, that sounds computationally intensive. How do you actually handle the process of generating this super-resolution atlas mentioned in the methodology? We need to know if this INR approach is feasible for real-world clinical data processing pipelines or if it stays mostly theoretical for now.
Lalam: I see a potential cultural impact here, Meng; imagine being able to analyze brain atrophy biomarkers with such high fidelity across different scanners without needing massive manual annotation efforts for every single scan. That level of automated consistency could really streamline how researchers work on AD pathology in the long run.
Tom: Exactly, Lalam! And what this paper does is propose a two-phase training process: first, using an INR superresolution network to build that isotropic high-resolution atlas, and then using that atlas to train a multi-modality segmentation model with nnU-Net. That’s a smart way to combine the strengths of different imaging types.
Jane: So, essentially, they're taking low-resolution data and using an INR network to synthesize a much higher resolution isotropic training set before they even start training the main segmentation model on that set. It simplifies things significantly for the subsequent steps.
Lu: Page two explains that this approach is designed to overcome the difficulty of geometric modeling caused by the T2w MRI's anisotropy, which is why they are using this INR superresolution network specifically to create a resolution-invariant atlas, as detailed in "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation."
Meng: It’s interesting how they use that synthesized atlas for training the second phase, the nnU-Net model. Does the method maintain enough fidelity when moving from that synthesized data back to actual clinical scans? I mean, if we lose too much detail in that upsampling process, we lose the advantage.
Title and authors: Lalam: The results suggest it holds up quite well because they used specific loss functions like Soft Dice loss and cross-entropy loss during the training of the multi-modality segmentation model, which helps prevent overdependence on any single image type.
Tom: And what they found in their evaluation is pretty compelling: the morphological measures extracted from this new isotropic model showed stronger effect sizes when distinguishing participants with mild cognitive impairment from those who were cognitively unimpaired compared to models trained on anisotropic data. That’s a big win for diagnostic accuracy.
Jane: Plus, they also demonstrated that these measurements exhibit greater stability over time when tracking participants longitudinally, which addresses a real weakness in many previous segmentation methods we've seen.
Lu: The paper shows that the isotropic model achieved "the highest Dice score in six out of nine subregions," which speaks directly to the quality of the anatomical segmentation it produces, as mentioned on page two of "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation."
Meng: For practical implementation, I’m curious about the trade-off between training time and inference speed. Since they use INR-upsampled segmentations instead of raw INR images for the nnU-Net training, they managed to keep it practical, but what is the actual computational cost when running that final segmentation model on a new patient scan?
Lalam: That improved speed is critical because it means this powerful segmentation capability could become much more accessible in routine clinical settings, making high-resolution biomarker extraction standard practice.
Tom: And the implications for AD tracking are huge. If we can get more reliable measurements of hippocampal subfield volumes and cortical subregion thicknesses, as they test on page two of "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation," it gives clinicians much better tools to monitor disease progression.
Jane: It really moves us closer to having a consistent way to quantify the structural changes associated with tau pathology spreading through the MTL, which is central to understanding AD.
Lu: The authors are also testing the stability of these measurements over two years for cognitively unimpaired participants, showing "greater stability than both ASHS and the linear upsampling model" in calculating biomarkers across most subfields and subregions.
Meng: That stability is what grounds this work in reality; it means we aren't just getting a good result on one scan, but we’re getting consistent data over time, which is what longitudinal studies need.
Title and authors: Lalam: If this technique becomes standard, it could fundamentally improve how we track the spread of pathology in the brain over a person's lifetime, offering much more reliable data for researchers to build on.
Tom: So, to wrap up this discussion on "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation," we see a method that tackles the resolution issues head-on by synthesizing an isotropic training set through INR.
Jane: This results in a multi-modality model that provides more accurate and stable morphological measurements for diagnosing and tracking AD pathology.
Lu: It’s a solid methodological contribution because it specifically targets the geometric modeling constraints of anisotropic T2w MRI data, as discussed throughout the paper.
Meng: Practically, it suggests that we can build more robust AI tools for structural biomarkers by focusing on creating resolution-invariant training data rather than just feeding models raw, noisy input.
Lalam: This paper has the potential to significantly improve our ability to track disease progression in a way that is both accurate and consistent across different scans.
Tom: Absolutely. We’ve seen how this work moves beyond just getting a high Dice score; it focuses on making those scores translate into statistically meaningful clinical differences between groups and over time.
Jane: It’s about turning complex, messy imaging data into reliable biomarkers that clinicians can actually use to make informed decisions about patient care.
Lu: The future work mentioned suggests further exploration of how this framework can be extended to other neuroimaging modalities beyond T1w and T2w, which opens up a lot of avenues for broader application.
Meng: And from an engineering perspective, extending it means figuring out how to integrate this INR pre-processing step smoothly into existing high-throughput imaging workflows without creating major bottlenecks.
Lalam: I think the cultural impact lies in making these sophisticated diagnostic tools available to more diverse clinical settings where high-end MRI infrastructure might not be everywhere.
Tom: Well, that’s what we have been hearing today about "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation." It’s a paper that shows how smart modeling choices can yield much more reliable clinical insights.
Jane: It really gives us a concrete path forward for improving the accuracy of structural brain biomarkers related to Alzheimer's disease.
Lu: The work solidifies the idea that using advanced generative models like INR can be very effective at creating data that is inherently less sensitive to input noise and image acquisition variability.
Meng: We’re excited to see how this specific technique translates into a production-ready tool for structural brain analysis in the coming years.
Lalam: This paper contributes a vital piece to the AI toolkit for neuroimaging, making AD assessment more precise and consistent across the board.
The paper's summary: Tom: So, to summarize what we've been diving into about this paper, they’re essentially taking messy MRI data from the Medial Temporal Lobe—the part of the brain crucial for Alzheimer's diagnosis—and using an implicit neural representation to build a perfect, high-resolution training set that’s isotropic.
Jane: That means they’re solving the problem where T2w scans have huge differences in resolution between directions, which makes accurately measuring things like cortical thickness really difficult for segmentation models. Think of it like trying to measure a surface when your ruler only works well in one direction; this AI is building a universal ruler.
Lu: Exactly! The core innovation is that they use an INR super-resolution network to synthesize this isotropic training atlas from lower-resolution, anisotropic data, which then feeds into the nnU-Net segmentation framework. It’s a clever way to create resolution invariance across different imaging modalities like T1w and T2w.
Meng: From an engineering standpoint, that synthesis step sounds pretty heavy computationally; how much time does it actually take to generate this super-resolution atlas before we can even start training the main model?
Lalam: I think the real impact here is that we get a way to automate high-quality segmentation without relying on hours of manual atlas creation for every single scan, which could really streamline clinical workflows down the line.
Tom: And when they talk about their results, it’s not just about getting a high Dice score; they show that these new morphological measurements are much better at telling the difference between people with mild cognitive impairment and those who aren't. That’s a huge step for diagnostic AI accuracy.
Jane: Plus, they also highlighted that these measurements stay more stable over time when tracking patients longitudinally, which is really important for monitoring how disease progresses in real-world studies.
Lu: The paper shows that the INR-based model achieved the highest Dice scores in several subregions and demonstrated better stability than both standard atlas methods and linear upsampling models across most areas. It solidifies the idea that this approach provides a more robust foundation for extracting reliable structural biomarkers from complex MRI data.
Meng: So, if we translate this into practice, it means our AI systems can start producing highly consistent anatomical measurements that are less likely to be skewed by the inherent noise or resolution issues in any single patient's scan.
Lalam: That consistency is what’s going to improve the culture of medical imaging research by providing a standardized, high-fidelity tool for assessing structural brain changes associated with Alzheimer's disease.
Tom: It really does move us toward having a more reliable way to quantify the structural pathology spreading through the MTL, which is central to understanding AD progression. This is definitely something we need to keep our eyes on as we discuss how this technology can actually be implemented in hospitals.
The paper's improvements: Tom: So, looking at the suggested improvements in this paper, they aren't just stopping at getting better Dice scores; they’re really pushing for a more robust system that handles real-world data variability much better than what we see in current models.
Jane: That makes sense; it sounds like the authors are suggesting ways to make the segmentation process itself more resilient to different types of image quality issues, which is something we always struggle with in medical AI.
Lu: They are focusing on the fact that by training on this synthetic isotropic data, the resulting model will be much more consistent when faced with actual clinical scans that might have different inherent noise or resolution quirks. This creates a multi-modality segmentation model that just works more reliably across various inputs.
Meng: That consistency is key for practical deployment; if we can guarantee that the extracted biomarkers are stable regardless of the scanner used, it drastically reduces the need for intensive pre-processing steps on every new scan.
Lalam: The cultural impact here is significant because this means high-quality structural analysis, which was previously a luxury, could become a standard tool in routine care for tracking disease progression accurately over long periods.
Tom: They also highlighted how the model produces smoother boundaries compared to baseline methods like ASHS or simple linear upsampling, especially for those small subregions that are often fragmented. That’s a real visual improvement we can see.
Jane: Smoother boundaries mean less noise in the measurements derived from them, and that directly translates to more trustworthy data points for tracking atrophy over years of follow-up scans.
Lu: The authors suggest that by using this INR approach, we can create models that are less dependent on any single modality for their training, which is a smart way to avoid overfitting and make the final output more generalizable.
Meng: I'm interested in the practical side of that generalization; how much does this synthetic data help us when we move from testing on one specific dataset to deploying it across a wider variety of patient populations?
Lalam: This paper contributes a vital piece to the AI toolkit for neuroimaging by showing how generative models can create data that is inherently less sensitive to input noise and acquisition variability, which helps improve the overall culture of medical data analysis.
Tom: So, while they’ve shown amazing accuracy improvements in segmentation and discrimination tasks, what's the one limitation they plainly state about this method? We need to be realistic about where this technology stops working right now.
Jane: The authors are clear that their approach is focused on combining T1w and T2w data, so it doesn't address scenarios where we have completely different types of imaging modalities entirely, which is a constraint they admit.
Lu: That’s true; the framework is specifically built around these two modalities to create the isotropic training set, so extending it to other types of imaging would require a completely new architecture.
Meng: So for our current engineering roadmap, this paper suggests we can prioritize building systems that leverage multi-modality training from synthetic data if we want to maximize stability and reduce manual annotation load.
Lalam: Ultimately, this work shows how advanced generative models can create a more reliable foundation for structural biomarker extraction, which is going to improve the culture of medical imaging research by providing a standardized, high-fidelity tool for assessing structural brain changes associated with Alzheimer's disease.
Conclusion: Tom: So, to wrap up on "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation," this research shows a really solid path toward making structural biomarker measurements in Alzheimer's disease much more reliable and consistent across different scans.
Jane: That’s right; by using an implicit neural representation to create that resolution-invariant training set, the authors are giving us tools that are far less sensitive to the inherent geometric mess of anisotropic MRI data.
Lu: It really highlights how creative we can be with generative models; they're not just analyzing existing data, they’re synthesizing a new type of 'ground truth' training material that bridges the gap between different imaging characteristics.
Meng: From an engineering viewpoint, the practical implication is that we can build more robust AI tools for structural biomarkers by focusing on creating resolution-invariant training data rather than just feeding models raw, noisy input.
Lalam: I think this paper’s most impactful vision is how this advance can improve the culture of medical imaging by providing a standardized, high-fidelity tool for assessing structural brain changes associated with Alzheimer's disease, making diagnosis more consistent across settings.
Tom: Absolutely; they’ve shown that these morphological measures have better effect sizes in distinguishing MCI from cognitively unimpaired individuals and offer greater stability over time for longitudinal tracking.
Jane: It’s about turning complex, messy imaging data into reliable biomarkers that clinicians can actually use to make more informed decisions about patient care, which is a huge step forward.
Lu: The future work mentioned suggests exploring how this framework can be extended to other neuroimaging modalities beyond T1w and T2w, opening up a lot of avenues for broader application in neuroimaging.
Meng: And from an engineering side, extending it means figuring out how to integrate this INR pre-processing step smoothly into existing high-throughput imaging workflows without creating major bottlenecks.
Lalam: This paper contributes a vital piece to the AI toolkit for neuroimaging, making AD assessment more precise and consistent across the board.
Tom: So, that’s our rundown on "Achieving detailed medial temporal lobe segmentation with upsampled isotropic training from implicit neural representation," demonstrating a powerful way to tackle geometric modeling constraints in MRI.
Jane: It’s a really exciting piece of research because it shows how smart modeling choices can yield much more reliable clinical insights for diagnosing and tracking AD pathology.
Lu: This work solidifies the idea that using advanced generative models like INR can be very effective at creating data that is inherently less sensitive to input noise and acquisition variability.
Meng: We’re excited to see how this specific technique translates into a production-ready tool for structural brain analysis in the coming years, provided we can solve those computational efficiency hurdles.
Lalam: This paper really moves us closer to having a consistent way to quantify the structural changes associated with tau pathology spreading through the MTL, which is central to understanding AD.
Yue Li, Pulkit Khandelwal, Rohit Jena, Long Xie, Michael Tran Duong, Amanda E. Denning, Christopher A. Brown, Laura E. M. Wisse3, Sandhitsu R. Das1
University of Pennsylvania
cs.CV
Submitted: 2025-08-24
Updated: 2026-09-29
Code: https://github.com/liyue3780/HyperResASHS
License: http://creativecommons.org/licenses/by-nc-nd/4.0/
Importance score: 83/100
The gist: Imaging biomarkers in magnetic resonance imaging (MRI) are crucial for diagnosing, tracking, and treating Alzheimer's disease (AD), particularly because neurofibrillary tau pathology spreads through
Key concepts
- Implicit Neural Representation (INR)
- An INR is used as a network to build a super-resolution atlas from lower-resolution, anisotropic data. This allows the model to synthesize a high-resolution training set that is isotropic, meaning it has consistent resolution in all directions, overcoming the resolution differences found in T2w MRI scans.
- Isotropic Training Set
- This refers to a training set with uniform resolution across all spatial dimensions. The paper uses an INR super-resolution network to create this set from lower-resolution data, which helps model the medial temporal lobe subregions geometrically more accurately than using raw, anisotropic scans.
- nnU-Net
- This is a multi-modality segmentation framework used in the second phase of training. It takes the high-resolution atlas built by the INR and uses it to train a segmentation model, combining information from different imaging types for better results.
- Anisotropy
- Anisotropy refers to the huge difference in resolution between in-plane and out-of-plane dimensions in T2w MRI images. The paper's method specifically targets this anisotropy to create a resolution-invariant atlas, simplifying geometric modeling of brain subregions.
Terminology
Summary
Imaging biomarkers in magnetic resonance imaging (MRI) are crucial for diagnosing, tracking, and treating Alzheimer's disease (AD), particularly because neurofibrillary tau pathology spreads through brain subregions, beginning in the medial temporal lobe (MTL). Accurate segmentation of these MTL subregions is necessary to extract granular biomarkers of AD progression. This study addresses the difficulty in reliably modeling MTL subregions due to the highly anisotropic nature of T2-weighted (T2w) MRI scans, which complicates geometric modeling and morphological measurements like thickness. The research proposes an implicit neural representation (INR) method to combine isotropic T1-weighted (T1w) and anisotropic T2w MRI data to create a multi-modality, high-resolution training set of isotropic data for automatic segmentation using the nnU-Net framework. The findings demonstrate that morphological measures extracted from this isotropic model show stronger effect sizes in distinguishing participants with mild cognitive impairment (MCI) from cognitively unimpaired (CU) individuals and exhibit greater stability over time compared to models trained on anisotropic data, suggesting improved reliability for quantifying AD pathology and brain atrophy.
Problem Addressed
The core challenge lies in the inherent anisotropy of T2w MRI scans used for MTL imaging, which makes reliably modeling subregions geometrically difficult. While T1w images are often isotropic or nearly isotropic, T2w images exhibit significant differences in resolution between in-plane and out-of-plane dimensions (e.g., an in-plane resolution of approximately 0.4 to 0.45 mm! and a slice thickness ranging from 1.2 to 2.6 mm). This anisotropy can reduce accuracy, especially for measuring cortical thickness, because the distance between structure skeleton and boundary varies significantly depending on the direction of measurement. Existing atlas-based methods like ASHS are limited by this resolution constraint in T2w images, where segmentation resolution is limited by image resolution and is anisotropic in typical T2w images.
Methodology: Isotropic High-resolution Atlas Creation
The study employs a two-phase training process. In the first phase, an INR superresolution network (Section 2.2) is trained to generate an isotropic high-resolution ASHS atlas.
This involves:
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Obtaining MTL regions of interest (ROIs) from the original T2w and T1w ASHS atlases, utilizing paired ROIs from the same cohort.
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Performing rigid alignment between the T1w ROI and the T2w ROI using a Greedy registration tool in physical coordinates, ensuring the aligned patch fits the spatial bounding box of both ROIs.
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Using an INR network to establish an implicit mapping between image coordinates and voxel values, trained on coordinate samples including intensity values for T1w or T2w ROIs, as well as one-hot encoded labels for the segmentation ROI.
Methodology: Multi-modality Segmentation Model Training
In the second phase, a multi-modality segmentation model is trained using the INR-upsampled segmentations from phase one. The framework utilized is nnU-Net (Section 2.3). Key aspects of this training include:
-
The segmentation model is trained using
INR-upsampled segmentations
rather than the raw, time-consuming INR images to maintain practical inference speed. -
For training, the T2w image is used as the primary modality, and the T1w image is registered rigidly again in isotropic space to correct subtle misalignments.
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Loss functions used for supervision include Soft Dice loss and cross-entropy loss, along with a modality augmentation scheme to avoid overdependence on any single modality.
Evaluation of Performance
The performance of the proposed method was evaluated through several downstream tasks on independent test sets:
-
Dice Coefficient Calculation: Dice scores were calculated in both the high-resolution isotropic space and the original anisotropic space after resampling the model's validation output back to manual segmentation space to allow for direct comparison. The proposed INR-based model achieved
the highest Dice score in six out of nine subregions.
-
Disease Status Discrimination: General linear models (GLMs) were fitted to measures of interest (hippocampal subfield volumes and cortical subregion thicknesses) from the status-discrimination test set to test their ability to differentiate A-CU and A+MCI groups. The isotropic models achieved
numerically higher AUC values in most subfields and subregions
when compared against ASHS. -
Test-retest Consistency: For CU participants, stability was measured by calculating the percentage difference for volume or the absolute difference for thickness between two scans over a two-year interval. The proposed model demonstrated
greater stability than both ASHS and the linear upsampling model
in calculating biomarkers across most subfields and subregions.
Improvements for AI systems
As a fastidious and diligent researcher, I have analyzed this study, which proposes an isotropic deep learning segmentation method for Medial Temporal Lobe (MTL) subregions using implicit neural representations (INR) to overcome the limitations of anisotropic MRI data.
Here are the specific improvements that can be made to AI systems, derived directly from this research:
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The AI system can perform automated, high-resolution segmentation of MTL subregions in multi-modality MRI scans (T1w and T2w) without requiring manual atlas annotation effort for every new scan.
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The system will generate an isotropic, high-resolution training atlas by applying an Implicit Neural Representation (INR) super-resolution network to low-resolution existing atlases, effectively synthesizing data that is resolution-invariant across modalities.
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The downstream segmentation model (trained using the nnU-Net framework) will be robust against variable image quality and modality differences because it is trained on this synthesized isotropic atlas, ensuring consistent anatomical feature extraction regardless of the input scan's inherent anisotropy or resolution mismatch with the training set.
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The system can extract highly reliable morphological biomarkers—such as volumes of hippocampal subfields (CA1-3, DG, SUB) and median cortical subregion thicknesses (ERC, BA35, BA36, PHC)—with significantly higher accuracy compared to models trained on anisotropic data.
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The resulting biomarker measurements will exhibit superior statistical performance:
Ease the ability to distinguish between cognitively unimpaired (CU) and mild cognitive impairment (MCI) participants by achieving higher Area Under the Curve (AUC) values in General Linear Models (GLMs).
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The AI system will provide enhanced temporal stability for longitudinal tracking of disease progression; measurements derived from this model will show greater consistency over time within the CU group, reducing measurement noise inherent in anisotropic segmentation.
-
The system can produce smoother, more continuous segmentation boundaries compared to baseline methods (like ASHS or linear upsampling), specifically preserving the smooth morphology of small subregions (e.g., CA2 and CA3) that are often fragmented or disconnected in anisotropic segmentations.
Abstract
Imaging biomarkers in magnetic resonance imaging (MRI) are important tools for diagnosing, tracking and treating Alzheimer's disease (AD). Neurofibrillary tau pathology in AD is closely linked to neurodegeneration and generally follows a pattern of spread in the brain, with early stages involving subregions of the medial temporal lobe (MTL). Accurate segmentation of MTL subregions is needed to extract granular biomarkers of AD progression. MTL subregions are often imaged using T2-weighted (T2w) MRI scans that are highly anisotropic due to constraints of MRI physics and image acquisition, making it difficult to reliably model MTL subregions geometrically and extract morphological measures, such as thickness. In this study, we propose a segmentation framework for MTL subregions in isotropic space, in which an implicit neural representation is used to construct the isotropic training atlas from the anisotropic low-resolution T2w data, with T1w MRI as an auxiliary modality to support the INR and segmentation. In an independent test set, the morphological measures extracted using this isotropic model showed stronger effect sizes than those from models trained on anisotropic data in distinguishing participants with mild cognitive impairment (MCI) from cognitively unimpaired individuals. In the test-retest analysis, the morphological measures extracted using the isotropic model showed greater stability than those from the anisotropic segmentation. This study demonstrates improved reliability of MRI-derived MTL subregion biomarkers without additional atlas annotation effort, which may more accurately quantify and track the relationship between AD pathology and brain atrophy for monitoring disease progression.
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