The role of shear forces in primary and secondary nucleation of amyloid fibrils.

Shear forces affect self-assembly processes ranging from crystallization to fiber formation. Here, the effect of mild agitation on amyloid fibril formation was explored for four peptides and investigated in detail for A[Formula: see text]42, which is associated with Alzheimer's disease. To gain mechanistic insights into the effect of mild agitation, nonseeded and seeded aggregation reactions were set up at various peptide concentrations with and without an inhibitor. First, an effect on fibril fragmentation was excluded by comparing the monomer-concentration dependence of aggregation kinetics under idle and agitated conditions. Second, using a secondary nucleation inhibitor, Brichos, the agitation effect on primary nucleation was decoupled from secondary nucleation. Third, an effect on secondary nucleation was established in the absence of inhibitor. Fourth, an effect on elongation was excluded by comparing the seeding potency of fibrils formed under idle or agitated conditions. We find that both primary and secondary nucleation steps are accelerated by gentle agitation. The increased shear forces facilitate both the detachment of newly formed aggregates from catalytic surfaces and the rate at which molecules are transported in the bulk solution to encounter nucleation sites on the fibril and other surfaces. Ultrastructural evidence obtained with cryogenic transmission electron microscopy and free-flow electrophoresis in microfluidics devices imply that agitation speeds up the detachment of nucleated species from the fibril surface. Our findings shed light on the aggregation mechanism and the role of detachment for efficient secondary nucleation. The results inform on how to modulate the relative importance of different microscopic steps in drug discovery and investigations.

Atherosclerotic Plaque Epigenetic Age Acceleration Predicts a Poor Prognosis and Is Associated With Endothelial-to-Mesenchymal Transition in Humans.

BACKGROUND: Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques is predictive for the risk of cardiovascular events. METHODS: Whole-genome DNA methylation of human carotid atherosclerotic plaques (n=485) and of blood (n=93) from the Athero-Express endarterectomy cohort was used to calculate epigenetic age acceleration (EAA). EAA was linked to clinical characteristics, plaque histology, and future cardiovascular events (n=136). We studied whole-genome DNA methylation and bulk and single-cell transcriptomics to uncover molecular mechanisms of plaque EAA. We experimentally confirmed our in silico findings using in vitro experiments in primary human coronary endothelial cells. RESULTS: Male and female patients with severe atherosclerosis had a median chronological age of 69 years. The median epigenetic age was 65 years in females (median EAA, -2.2 [interquartile range, -4.3 to 2.2] years) and 68 years in males (median EAA, -0.3 [interquartile range, -2.9 to 3.8] years). Patients with diabetes and a high body mass index had higher plaque EAA. Increased EAA of plaque predicted future events in a 3-year follow-up in a Cox regression model (univariate hazard ratio, 1.7; P=0.0034) and adjusted multivariate model (hazard ratio, 1.56; P=0.02). Plaque EAA predicted outcome independent of blood EAA (hazard ratio, 1.3; P=0.018) and of plaque hemorrhage (hazard ratio, 1.7; P=0.02). Single-cell RNA sequencing in plaque samples from 46 patients in the same cohort revealed smooth muscle and endothelial cells as important cell types in plaque EAA. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally confirmed by TGFß-triggered endothelial-to-mesenchymal transition inducing rapid epigenetic aging in coronary endothelial cells. CONCLUSIONS: Plaque EAA is a strong and independent marker of poor outcome in patients with severe atherosclerosis. Plaque EAA was linked to mesenchymal endothelial and smooth muscle cells. Endothelial-to-mesenchymal transition was associated with EAA, which was experimentally validated. Epigenetic aging mechanisms may provide new targets for treatments that reduce atherosclerosis complications.

Self-similar Rayleigh-Taylor mixing with accelerations varying in time and space.

As a ubiquitous paradigm of instabilities and mixing that occur in instances as diverse as supernovae, plasma fusion, oil recovery, and nanofabrication, the Rayleigh-Taylor (RT) problem is rightly regarded as important. The acceleration of the fluid medium in these instances often depends on time and space, whereas most past studies assume it to be constant or impulsive. Here, we analyze the symmetries of RT mixing for variable accelerations and obtain the scaling of correlations and spectra for classes of self-similar dynamics. RT mixing is shown to retain the memory of deterministic conditions for all accelerations, with the dynamics ranging from superballistic to subdiffusive. These results contribute to our understanding and control of the RT phenomena and reveal specific conditions under which Kolmogorov turbulence might be realized in RT mixing.

Hydration-Accelerated Crown Ether Diffusion within Single Three-Dimensional Covalent Organic Frameworks.

In this contribution, we report on the visualization of 12-crown-4 molecular diffusion behavior within a single-crystal particle of covalent organic framework-300 (COF-300) using operando dark-field optical microscopy. The diffusion area and front of 12-crown-4 are directly tracked in real time, offering key information for quantifying the diffusion coefficient (D). The direction of the diffusion and variation of D reveal intraparticle and interparticle heterogeneity. Notably, an unexpected hydration-accelerated diffusion process of 12-crown-4 within the pore channels of COF-300 is captured, in which a relatively low concentration of 12-crown-4 aqueous solution induces a fast diffusion, whereas the pure 12-crown-4 liquid cannot access the framework. The observed acceleration diffusion is demonstrated to arise from the hydrogen-bonding interactions between surface water molecules of hydrated 12-crown-4 and the imine groups of COF-300. These findings expand the mechanistic understanding of the noncovalent interactions between COFs and crown ethers (CEs), which will help to design and prepare CE-based COFs with improved performance.

DNA methyltransferase 1 (DNMT1) promotes cyst growth and epigenetic age acceleration in autosomal dominant polycystic kidney disease.

Alteration of DNA methylation leads to diverse diseases, and the dynamic changes of DNA methylation (DNAm) on sets of CpG dinucleotides in mammalian genomes are termed "DNAm age" and "epigenetic clocks" that can predict chronological age. However, whether and how dysregulation of DNA methylation promotes cyst progression and epigenetic age acceleration in autosomal dominant polycystic kidney disease (ADPKD) remains elusive. Here, we show that DNA methyltransferase 1 (DNMT1) is upregulated in cystic kidney epithelial cells and tissues and that knockout of Dnmt1 and targeting DNMT1 with hydralazine, a safe demethylating agent, delays cyst growth in Pkd1 mutant kidneys and extends life span of Pkd1 conditional knockout mice. With methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), DNMT1 chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing analysis, we identified two novel DNMT1 targets, PTPRM and PTPN22 (members of the protein tyrosine phosphatase family). PTPRM and PTPN22 function as mediators of DNMT1 and the phosphorylation and activation of PKD-associated signaling pathways, including ERK, mTOR and STAT3. With whole-genome bisulfide sequencing in kidneys of patients with ADPKD versus normal individuals, we found that the methylation of epigenetic clock-associated genes was dysregulated, supporting that epigenetic age is accelerated in the kidneys of patients with ADPKD. Furthermore, five epigenetic clock-associated genes, including Hsd17b14, Itpkb, Mbnl1, Rassf5 and Plk2, were identified. Thus, the diverse biological roles of these five genes suggest that their methylation status may not only predict epigenetic age acceleration but also contribute to disease progression in ADPKD.

Percent duration of heart rate acceleration within the respiratory cycle: a novel approach to assess heart rate asymmetry.

Accelerations and decelerations of heart rate are nonsymmetrical in the magnitude and number of beat-to-beat changes. The asymmetric features of heart rate variability are related to respiratory durations. To explore the link between respiration and heart rate asymmetry (HRA), we evaluated 14 seated, healthy young adults who breathed with nine combinations of inspiration duration (TI) and expiration duration (TE), chosen respectively from 2, 4, and 6 s. A 5-min R-R interval (RRI) time series was obtained from each study period to construct an averaged pattern waveform relative to the respiratory cycle. We observed that the time interval between inspiration onset and RRI minimum progressively lengthened as TI and TE increased. The time interval between expiration onset and RRI maximum also lengthened when TE increased but shortened when TI increased. Consequently, TI and TE had different effects on the acceleration time (AT; from RRI maximum to RRI minimum) and deceleration time (DT; from RRI minimum to RRI maximum). The percentage of AT within the respiratory cycle showed a strong correlation with traditional Guzik's (r = 0.862, P < 0.001) and Porta's (r = 0.878, P < 0.001) indexes of HRA assessed in a Poincaré plot analysis. These findings suggest that, in addition to considering the magnitude and number of beat-to-beat changes, HRA can also be assessed based on another aspect: the duration of consecutive changes. The stepwise link between the duration of heart rate change and respiratory duration provides insight into the mechanisms connecting respiration to HRA.NEW & NOTEWORTHY In healthy adults who regulated their breathing across nine combinations of inspiration and expiration durations, we used averaged pattern waveform technique to quantify the durations of heart rate acceleration and deceleration within the respiratory cycle. The percent duration of acceleration showed a strong correlation with traditional heart rate asymmetry indexes, which evaluate the magnitude and number of beat-to-beat changes. This new approach opens a window to explore the asymmetric features of heart rate variability.

Clustering one million molecular structures on GPU within seconds.

Structure clustering is a general but time-consuming work in the study of life science. Up to now, most published tools do not support the clustering analysis on graphics processing unit (GPU) with root mean square deviation metric. In this work, we specially write codes to do the work. It supports multiple threads on multiple GPUs. To show the performance, we apply the program to a 33-residue fragment in protein Pin1 WW domain mutant. The dataset contains 1,400,000 snapshots, which are extracted from an enhanced sampling simulation and distribute widely in the conformational space. Various testing results present that our program is quite efficient. Particularly, with two NVIDIA RTX4090 GPUs and single precision data type, the clustering calculation on 1 million snapshots is completed in a few seconds (including the uploading time of data from memory to GPU and neglecting the reading time from hard disk). This is hundreds of times faster than central processing unit. Our program could be a powerful tool for fast extraction of representative states of a molecule among its thousands to millions of candidate structures.

Perfluorinated Amines: Accelerating Lithium Electrodeposition by Tailoring Interfacial Structure and Modulated Solvation for High-Performance Batteries.

Modulating interfacial electrochemistry represents a prevalent approach for mitigating lithium dendrite growth and enhancing battery performance. Nevertheless, while most additives exhibit inhibitory characteristics, the accelerating effects on interfacial electrochemistry have garnered limited attention. In this work, perfluoromorpholine (PFM) with facilitated kinetics is utilized to preferentially adsorb on the lithium metal interface. The PFM molecules disrupt the solvation structure of Li+ and enhance the migration of Li+. Combined with the benzotrifluoride, a synergistic acceleration-inhibition system is formed. The ab initio molecular dynamics (AIMD) and density functional theory (DFT) calculation of the loose outer solvation clusters and the key adsorption-deposition step supports the fast diffusion and stable interface electrochemistry with an accelerated filling mode with C─F and C─H groups. The approach induces the uniform lithium deposition. Excellent cycling performance is achieved in Li||Li symmetric cells, and even after 200 cycles in Li||NCM811 full cells, 80% of the capacity is retained. This work elucidates the accelerated electrochemical processes at the interface and expands the design strategies of acceleration fluorinated additives for lithium metal batteries.

Efficient end-to-end simulation of time-dependent coherent X-ray scattering experiments.

Physical optics simulations for beamlines and experiments allow users to test experiment feasibility and optimize beamline settings ahead of beam time in order to optimize valuable beam time at synchrotron light sources like NSLS-II. Further, such simulations also help to develop and test experimental data processing methods and software in advance. The Synchrotron Radiation Workshop (SRW) software package supports such complex simulations. We demonstrate how recent developments in SRW significantly improve the efficiency of physical optics simulations, such as end-to-end simulations of time-dependent X-ray photon correlation spectroscopy experiments with partially coherent undulator radiation (UR). The molecular dynamics simulation code LAMMPS was chosen to model the sample: a solution of silica nanoparticles in water at room temperature. Real-space distributions of nanoparticles produced by LAMMPS were imported into SRW and used to simulate scattering patterns of partially coherent hard X-ray UR from such a sample at the detector. The partially coherent UR illuminating the sample can be represented by a set of orthogonal coherent modes obtained by simulation of emission and propagation of this radiation through the coherent hard X-ray (CHX) scattering beamline followed by a coherent-mode decomposition. GPU acceleration is added for several key functions of SRW used in propagation from sample to detector, further improving the speed of the calculations. The accuracy of this simulation is benchmarked by comparison with experimental data.

Evaluation of different computational methods for DNA methylation-based biological age.

In recent years there has been a widespread interest in researching biomarkers of aging that could predict physiological vulnerability better than chronological age. Aging, in fact, is one of the most relevant risk factors for a wide range of maladies, and molecular surrogates of this phenotype could enable better patients stratification. Among the most promising of such biomarkers is DNA methylation-based biological age. Given the potential and variety of computational implementations (epigenetic clocks), we here present a systematic review of such clocks. Furthermore, we provide a large-scale performance comparison across different tissues and diseases in terms of age prediction accuracy and age acceleration, a measure of deviance from physiology. Our analysis offers both a state-of-the-art overview of the computational techniques developed so far and a heterogeneous picture of performances, which can be helpful in orienting future research.

A mathematical model for velocity-selective arterial spin labeling.

PURPOSE: To present a theoretical framework that rigorously defines and analyzes key concepts and quantities for velocity selective arterial spin labeling (VSASL). THEORY AND METHODS: An expression for the VSASL arterial delivery function is derived based on (1) labeling and saturation profiles as a function of velocity and (2) physiologically plausible approximations of changes in acceleration and velocity across the vascular system. The dependence of labeling efficiency on the amplitude and effective bolus width of the arterial delivery function is defined. Factors that affect the effective bolus width are examined, and timing requirements to minimize quantitation errors are derived. RESULTS: The model predicts that a flow-dependent negative bias in the effective bolus width can occur when velocity selective inversion (VSI) is used for the labeling module and velocity selective saturation (VSS) is used for the vascular crushing module. The bias can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal cutoff velocity of the vascular crushing module. CONCLUSION: The elements of the model are specified in a general fashion such that future advances can be readily integrated. The model can facilitate further efforts to understand and characterize the performance of VSASL and provide critical theoretical insights that can be used to design future experiments and develop novel VSASL approaches.

Fast cardiac T1ρ,adiab mapping using slice-selective adiabatic spin-lock preparation pulses.

PURPOSE: Myocardial T1ρ mapping techniques commonly acquire multiple images in one breathhold to calculate a single-slice T1ρ map. Recently, non-selective adiabatic pulses have been used for robust spin-lock preparation (T1ρ,adiab). The objective of this study was to develop a fast multi-slice myocardial T1ρ,adiab mapping approach. METHODS: The proposed-sequence reduces the number of breathholds required for whole-heart 2D T1ρ,adiab mapping by acquiring multiple interleaved slices in each breathhold using slice-selective T1ρ,adiab preparation pulses. The proposed-sequence was implemented with two interleaved slices per breathhold scan and was quantitatively evaluated in phantom experiments and 10 healthy-volunteers against a single-slice T1ρ,adiab mapping sequence. The sequence was demonstrated in two patients with myocardial scar. RESULTS: The phantom experiments showed the proposed-sequence had slice-to-slice variation of 1.62% ± 1.05% and precision of 4.51 ± 0.68 ms. The healthy volunteer cohort subject-wise mean relaxation time was lower for the proposed-sequence than the single-slice sequence (137.7 ± 5.3 ms vs. 148.4 ± 8.3 ms, p < 0.001), and spatial-standard-deviation was better (18.7 ± 1.8 ms vs. 21.8 ± 3.4 ms, p < 0.018). The mean within-subject, coefficient of variation was 5.93% ± 1.57% for the proposed-sequence and 6.31% ± 1.92% for the single-slice sequence (p = 0.35) and the effect of slice variation (0.81 ± 4.87 ms) was not significantly different to zero (p = 0.61). In both patient examples increased T1ρ,adiab (maximum American Heart Association-segment mean = 174 and 197 ms) was measured within the myocardial scar. CONCLUSION: The proposed sequence provides a twofold acceleration for myocardial T1ρ,adiab mapping using a multi-slice approach. It has no significant difference in within-subject variability, and significantly better precision, compared to a 2D T1ρ,adiab mapping sequence based on non-selective adiabatic spin-lock preparations.

Movienet: Deep space-time-coil reconstruction network without k-space data consistency for fast motion-resolved 4D MRI.

PURPOSE: To develop a novel deep learning approach for 4D-MRI reconstruction, named Movienet, which exploits space-time-coil correlations and motion preservation instead of k-space data consistency, to accelerate the acquisition of golden-angle radial data and enable subsecond reconstruction times in dynamic MRI. METHODS: Movienet uses a U-net architecture with modified residual learning blocks that operate entirely in the image domain to remove aliasing artifacts and reconstruct an unaliased motion-resolved 4D image. Motion preservation is enforced by sorting the input image and reference for training in a linear motion order from expiration to inspiration. The input image was collected with a lower scan time than the reference XD-GRASP image used for training. Movienet is demonstrated for motion-resolved 4D MRI and motion-resistant 3D MRI of abdominal tumors on a therapeutic 1.5T MR-Linac (1.5-fold acquisition acceleration) and diagnostic 3T MRI scanners (2-fold and 2.25-fold acquisition acceleration for 4D and 3D, respectively). Image quality was evaluated quantitatively and qualitatively by expert clinical readers. RESULTS: The reconstruction time of Movienet was 0.69 s (4 motion states) and 0.75 s (10 motion states), which is substantially lower than iterative XD-GRASP and unrolled reconstruction networks. Movienet enables faster acquisition than XD-GRASP with similar overall image quality and improved suppression of streaking artifacts. CONCLUSION: Movienet accelerates data acquisition with respect to compressed sensing and reconstructs 4D images in less than 1 s, which would enable an efficient implementation of 4D MRI in a clinical setting for fast motion-resistant 3D anatomical imaging or motion-resolved 4D imaging.

Fast and High-Resolution T2 Mapping Based on Echo Merging Plus k-t Undersampling with Reduced Refocusing Flip Angles (TEMPURA) as Methods for Human Renal MRI.

PURPOSE: To develop a highly accelerated multi-echo spin-echo method, TEMPURA, for reducing the acquisition time and/or increasing spatial resolution for kidney T2 mapping. METHODS: TEMPURA merges several adjacent echoes into one k-space by either combining independent echoes or sharing one echo between k-spaces. The combined k-space is reconstructed based on compressed sensing theory. Reduced flip angles are used for the refocusing pulses, and the extended phase graph algorithm is used to correct the effects of indirect echoes. Two sequences were developed: a fast breath-hold sequence; and a high-resolution sequence. The performance was evaluated prospectively on a phantom, 16 healthy subjects, and two patients with different types of renal tumors. RESULTS: The fast TEMPURA method reduced the acquisition time from 3-5 min to one breath-hold (18 s). Phantom measurements showed that fast TEMPURA had a mean absolute percentage error (MAPE) of 8.2%, which was comparable to a standardized respiratory-triggered sequence (7.4%), but much lower than a sequence accelerated by purely k-t undersampling (21.8%). High-resolution TEMPURA reduced the in-plane voxel size from 3 × 3 to 1 × 1 mm2, resulting in improved visualization of the detailed anatomical structure. In vivo T2 measurements demonstrated good agreement (fast: MAPE = 1.3%-2.5%; high-resolution: MAPE = 2.8%-3.3%) and high correlation coefficients (fast: R = 0.85-0.98; high-resolution: 0.82-0.96) with the standardized method, outperforming k-t undersampling alone (MAPE = 3.3-4.5%, R = 0.57-0.59). CONCLUSION: TEMPURA provides fast and high-resolution renal T2 measurements. It has the potential to improve clinical throughput and delineate intratumoral heterogeneity and tissue habitats at unprecedented spatial resolution.

Diagnostic accuracy of the maximal systolic acceleration to detect peripheral arterial disease.

BACKGROUND: Diagnosing peripheral arterial disease (PAD) can be challenging owing to medial arterial calcification (MAC) in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). Current bedside tests, such as the ankle-brachial index and toe-brachial index, are often insufficient. The maximal systolic acceleration (ACCmax) is a velocimetric Doppler-derived parameter and could be a new promising test in the diagnostic workup of these patients. The primary aim of this study was to evaluate the diagnostic performance of the ACCmax to detect PAD. METHODS: A retrospective cohort study was performed in a tertiary referral hospital. Patients ≥18 years old with suspected PAD who underwent ACCmax measurement(s) along with computed tomography angiography of the abdominal aorta and lower extremities (reference test) were eligible for inclusion. ACCmax measurements of the posterior tibial artery, anterior tibial artery and peroneal artery were collected. Diagnostic performance was assessed by using sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve (AUC). RESULTS: In total, 340 patients (618 limbs) were included. Approximately 40% suffered from DM and 30% had CKD. Diagnostic performance of the ACCmax to detect PAD for the posterior tibial artery showed a sensitivity of 90%, specificity of 93%, positive likelihood ratio of 12.83, and negative likelihood ratio of 0.11 (AUC, 0.953). For the anterior tibial artery, these results were 94%, 97%, 32.06, and 0.06 (same sequence as presented before) with an AUC of 0.984. The peroneal artery had a performance of 86%, 89%, 7.51, and 0.16, respectively (AUC, 0.893). Diagnostic accuracy of the ACCmax did not diminish in subgroup analysis for patients with DM or CKD. CONCLUSIONS: The ACCmax showed excellent diagnostic performance to detect PAD, independent of patients prone to medial arterial calcification.

Epigenetic age acceleration in follicular fluid and markers of ovarian response among women undergoing IVF.

STUDY QUESTION: Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation? SUMMARY ANSWER: Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes. WHAT IS KNOWN ALREADY: In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes. STUDY DESIGN, SIZE, DURATION: Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006-2016). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol. MAIN RESULTS AND ROLE OF CHANCE: Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (-819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: -1265.7, -373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: -21.8%; 95% CI: -37.1%, -2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: -23.8%; 95% CI: -39.9%, -3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response. LIMITATIONS, REASONS FOR CAUTION: Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types. WIDER IMPLICATIONS OF THE FINDINGS: Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870). TRIAL REGISTRATION NUMBER: N/A.

High Spatial-Resolution and Acquisition-Efficiency Cardiac MR T1 Mapping Based on Radial bSSFP and a Low-Rank Tensor Constraint.

BACKGROUND: Cardiac T1 mapping is valuable for evaluating myocardial fibrosis, yet its resolution and acquisition efficiency are limited, potentially obscuring visualization of small pathologies. PURPOSE: To develop a technique for high-resolution cardiac T1 mapping with a less-than-100-millisecond acquisition window based on radial MOdified Look-Locker Inversion recovery (MOLLI) and a calibrationless space-contrast-coil locally low-rank tensor (SCC-LLRT) constrained reconstruction. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Sixteen healthy subjects (age 25 ± 3 years, 44% females) and 12 patients with suspected cardiomyopathy (age 57 ± 15 years, 42% females), NiCl2-agar phantom. FIELD STRENGTH/SEQUENCE: 3-T, standard MOLLI, radial MOLLI, inversion-recovery spin-echo, late gadolinium enhancement. ASSESSMENT: SCC-LLRT was compared to a conventional locally low-rank (LLR) method through simulations using Normalized Root-Mean-Square Error (NRMSE) and Structural Similarity Index Measure (SSIM). Radial MOLLI was compared to standard MOLLI across phantom, healthy subjects, and patients. Three independent readers subjectively evaluated the quality of T1 maps using a 5-point scale (5 = best). STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, intraclass correlation coefficient analysis, linear regression, Bland-Altman analysis. P < 0.05 was considered statistically significant. RESULTS: In simulations, SCC-LLRT demonstrated a significant improvement in NRMSE and SSIM compared to LLR. In phantom, both radial MOLLI and standard MOLLI provided consistent T1 estimates across different heart rates. In healthy subjects, radial MOLLI exhibited a significantly lower mean T1 (1115 ± 39 msec vs. 1155 ± 36 msec), similar T1 SD (74 ± 14 msec vs. 67 ± 23 msec, P = 0.20), and similar T1 reproducibility (28 ± 18 msec vs. 22 ± 15 msec, P = 0.34) compared to standard MOLLI. In patients, the proposed method significantly improved the sharpness of myocardial boundaries (4.50 ± 0.65 vs. 3.25 ± 0.43), the conspicuity of papillary muscles and fine structures (4.33 ± 0.74 vs. 3.33 ± 0.47), and artifacts (4.75 ± 0.43 vs. 3.83 ± 0.55). The reconstruction time for a single slice was 5.2 hours. DATA CONCLUSION: The proposed method enables high-resolution cardiac T1 mapping with a short acquisition window and improved image quality. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Detection of focal to bilateral tonic-clonic seizures using a connected shirt.

OBJECTIVE: This study was undertaken to develop and evaluate a machine learning-based algorithm for the detection of focal to bilateral tonic-clonic seizures (FBTCS) using a novel multimodal connected shirt. METHODS: We prospectively recruited patients with epilepsy admitted to our epilepsy monitoring unit and asked them to wear the connected shirt while under simultaneous video-electroencephalographic monitoring. Electrocardiographic (ECG) and accelerometric (ACC) signals recorded with the connected shirt were used for the development of the seizure detection algorithm. First, we used a sliding window to extract linear and nonlinear features from both ECG and ACC signals. Then, we trained an extreme gradient boosting algorithm (XGBoost) to detect FBTCS according to seizure onset and offset annotated by three board-certified epileptologists. Finally, we applied a postprocessing step to regularize the classification output. A patientwise nested cross-validation was implemented to evaluate the performances in terms of sensitivity, false alarm rate (FAR), time in false warning (TiW), detection latency, and receiver operating characteristic area under the curve (ROC-AUC). RESULTS: We recorded 66 FBTCS from 42 patients who wore the connected shirt for a total of 8067 continuous hours. The XGBoost algorithm reached a sensitivity of 84.8% (56/66 seizures), with a median FAR of .55/24 h and a median TiW of 10 s/alarm. ROC-AUC was .90 (95% confidence interval = .88-.91). Median detection latency from the time of progression to the bilateral tonic-clonic phase was 25.5 s. SIGNIFICANCE: The novel connected shirt allowed accurate detection of FBTCS with a low false alarm rate in a hospital setting. Prospective studies in a residential setting with a real-time and online seizure detection algorithm are required to validate the performance and usability of this device.

Accelerating breast MRI acquisition with generative AI models.

OBJECTIVES: To investigate the use of the score-based diffusion model to accelerate breast MRI reconstruction. MATERIALS AND METHODS: We trained a score-based model on 9549 MRI examinations of the female breast and employed it to reconstruct undersampled MRI images with undersampling factors of 2, 5, and 20. Images were evaluated by two experienced radiologists who rated the images based on their overall quality and diagnostic value on an independent test set of 100 additional MRI examinations. RESULTS: The score-based model produces MRI images of high quality and diagnostic value. Both T1- and T2-weighted MRI images could be reconstructed to a high degree of accuracy. Two radiologists rated the images as almost indistinguishable from the original images (rating 4 or 5 on a scale of 5) in 100% (radiologist 1) and 99% (radiologist 2) of cases when the acceleration factor was 2. This fraction dropped to 88% and 70% for an acceleration factor of 5 and to 5% and 21% with an extreme acceleration factor of 20. CONCLUSION: Score-based models can reconstruct MRI images at high fidelity, even at comparatively high acceleration factors, but further work on a larger scale of images is needed to ensure that diagnostic quality holds. CLINICAL RELEVANCE STATEMENT: The number of MRI examinations of the breast is expected to rise with MRI screening recommended for women with dense breasts. Accelerated image acquisition methods can help in making this examination more accessible. KEY POINTS: Accelerating breast MRI reconstruction remains a significant challenge in clinical settings. Score-based diffusion models can achieve near-perfect reconstruction for moderate undersampling factors. Faster breast MRI scans with maintained image quality could revolutionize clinic workflows and patient experience.

The association between weekly exercise patterns and acceleration of aging: Evidence from a population-based study.

BACKGROUND: Acceleration of aging is a major challenge in public health. Previous studies have focused on the associations between specific types of exercise or overall levels of physical activity with accelerated aging, with less attention given to the weekly exercise patterns. OBJECTIVE: To explore the relationship between weekly exercise patterns and acceleration of aging among American adults. METHODS: We extracted data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES), involving 9850 participants aged ≥20 with comprehensive records on exercise and phenotypic age. Hierarchical clustering categorized participants into three groups based on weekly exercise time and days: cluster 1 (Rare or No Exercise), cluster 2 (Moderate Frequency, Moderate Duration) and cluster 3 (Moderate Frequency, Long Duration). Acceleration of aging was defined as the phenotypic age advance >0. RESULTS: After full adjustment, weekly exercise time and days showed the significant non-linear negative correlation with accelerated aging. The risk of accelerated aging was lowest when weekly exercise days reached five and the weekly exercise time reached three hours. Both cluster 2 and cluster 3 were significantly negatively correlated with acceleration of aging. No significant differences were observed in the association with accelerated aging between cluster 2 and cluster 3. CONCLUSIONS: These findings highlight the importance of targeted exercise programs for healthy aging. They also emphasize the need for public health initiatives to integrate regular physical activity into daily routines to improve the longevity and well-being of American adults.