Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

A Novel Atomic-Level Post-Etch-Surface-Reinforcement Process for High-Performance p-GaN Gate HEMTs Fabrication.

A novel atomic-level post-etch-surface-reinforcement (PESR) process is developed to recover the p-GaN etching induced damage region for high performance p-GaN gate HEMTs fabrication. This process is composed of a self-limited surface modification step with O2 plasma, following by an oxide removal step with BCl3 plasma. With PESR process, the AlGaN surface morphology after p-GaN etching was comparable to the as-epitaxial level by AFM characterization, and the AlGaN lattice crystallization was also recovered which was measured in a confocal Raman system. The electrical measurement further confirmed the significant improvement of AlGaN surface quality, with one-order of magnitude lower surface leakage in a metal-semiconductor (MS) Schottky-diode and 6 times lower interface density of states (Dit) in a MIS C-V characterization. The XPS analysis of Al2O3/AlGaN showed that the p-GaN etching induced F-byproduct and Ga-oxide was well removed and suppressed by PESR process. Finally, the developed PESR process was successfully integrated in p-GaN gate HEMTs fabrication, and the device performance was significantly enhanced with ~20% lower of on-resistance and ~25% less of current collapse at Vds,Q bias of 40 V, showing great potential of leverage p-GaN gate HEMTs reliability.

Non-Buffer Epi-AlGaN/GaN on SiC for High-Performance Depletion-Mode MIS-HEMTs Fabrication.

A systematic study of epi-AlGaN/GaN on a SiC substrate was conducted through a comprehensive analysis of material properties and device performance. In this novel epitaxial design, an AlGaN/GaN channel layer was grown directly on the AlN nucleation layer, without the conventional doped thick buffer layer. Compared to the conventional epi-structures on the SiC and Si substrates, the non-buffer epi-AlGaN/GaN structure had a better crystalline quality and surface morphology, with reliable control of growth stress. Hall measurements showed that the novel structure exhibited comparable transport properties to the conventional epi-structure on the SiC substrate, regardless of the buffer layer. Furthermore, almost unchanged carrier distribution from room temperature to 150 °C indicated excellent two-dimensional electron gas (2DEG) confinement due to the pulling effect of the conduction band from the nucleation layer as a back-barrier. High-performance depletion-mode MIS-HEMTs were demonstrated with on-resistance of 5.84 Ω·mm and an output current of 1002 mA/mm. The dynamic characteristics showed a much smaller decrease in the saturation current (only ~7%), with a quiescent drain bias of 40 V, which was strong evidence of less electron trapping owing to the high-quality non-buffer AlGaN/GaN epitaxial growth.

A Novel Scheme for Full Bottom Dielectric Isolation in Stacked Si Nanosheet Gate-All-Around Transistors.

In this paper, a novel scheme for source/drain-first (S/D-first) full bottom dielectric isolation (BDI), i.e., Full BDI_Last, with integration of a sacrificial Si0.5Ge0.5 layer was proposed and demonstrated in a stacked Si nanosheet gate-all-around (NS-GAA) device structure using TCAD simulations. The proposed full BDI scheme flow is compatible with the main process flow of NS-GAA transistor fabrication and provides a large window for process fluctuations, such as the thickness of the S/D recess. It is an ingenious solution to insert the dielectric material under the source, drain and gate regions to remove the parasitic channel. Moreover, because the S/D-first scheme decreases the problem of high-quality S/D epitaxy, the innovative fabrication scheme introduces full BDI formation after S/D epitaxy to mitigate the difficulty of providing stress engineering in the full BDI formation before S/D epitaxy (Full BDI_First). The electrical performance of Full BDI_Last is demonstrated by a 4.78-fold increase in the drive current compared to Full BDI_First. Furthermore, compared to traditional punch through stoppers (PTSs), the proposed Full BDI_Last technology could potentially provide an improved short channel behavior and good immunity against parasitic gate capacitance in NS-GAA devices. For the assessed inverter ring oscillator (RO), applying the Full BDI_Last scheme allows the operating speed to be increased by 15.2% and 6.2% at the same power, or alternatively enables an 18.9% and 6.8% lower power consumption at the same speed compared with the PTS and Full BDI_First schemes, respectively. The observations confirm that the novel Full BDI_Last scheme incorporated into an NS-GAA device can be utilized to enable superior characteristics to benefit the performance of integrated circuits.

Bioadhesive and electroactive hydrogels for flexible bioelectronics and supercapacitors enabled by a redox-active core-shell PEDOT@PZIF-71 system.

Stretchable and conductive hydrogels are rapidly emerging as new generation candidates for wearable devices. However, the poor electroactivity and bioadhesiveness of traditional conductive hydrogels has limited their applications. Herein, a mussel-inspired strategy is proposed to prepare a specific core-shell redox-active system, consisting of a polydopamine (PDA) modified zeolitic imidazolate framework 71 (ZIF-71) core, and a poly 3,4-ethylenedioxythiopene (PEDOT) shell. Owing to the abundant catechol groups, PEDOT can be assembled on the surface of ZIF-71 to create a redox-active system. The core-shell nanoparticles could act as a redox-active nanofiller to develop a conductive polyacrylamide (PAM) hydrogel with energy-storage properties. The core-shell PEDOT@PZIF-71 system provides a mussel-inspired environment in the hydrogel matrix and endows the hydrogel with stretchability and adhesiveness. The hydrogel can be applied as a functional electrode for both bioelectronics and supercapacitors. Moreover, this hydrogel exhibits favorable biocompatibility and can be implanted in vivo for biosignal measurement without causing inflammation. This redox-active core-shell PEDOT@PZIF-71 system provides a promising strategy for the design of hydrogel-based wearable electronic devices.

Impact of Stress and Dimension on Nanosheet Deformation during Channel Release of Gate-All-Around Device.

In this paper, nanosheet deformation during channel release has been investigated and discussed in Gate-All-Around (GAA) transistors. Structures with different source/drain size and stacked Si nanosheet lengths were designed and fabricated. The experiment of channel release showed that the stress caused serious deformation to suspended nanosheets. With the guidance of the experiment result, based on simulation studies using the COMSOL Multiphysics and Sentaurus tools, it is confirmed that the stress applied on the channel from source/drain plays an important role in nanosheet deformation during the fabrication process. The deformation of Si nanosheets would cause a serious degradation of the device performance due to an inability to control the work function of the metal gate. This study proposed that the uniformly stacked GAA nanosheets structure could be successfully demonstrated with suitable channel stress engineering provided by fitting S/D size and an appropriate channel length. The conclusions provide useful guidelines for future stacked GAA transistors' design and fabrication.

A Novel Si Nanosheet Channel Release Process for the Fabrication of Gate-All-Around Transistors and Its Mechanism Investigation.

The effect of the source/drain compressive stress on the mechanical stability of stacked Si nanosheets (NS) during the process of channel release has been investigated. The stress of the nanosheets in the stacking direction increased first and then decreased during the process of channel release by technology computer-aided design (TCAD) simulation. The finite element simulation showed that the stress caused serious deformation of the nanosheets, which was also confirmed by the experiment. This study proposed a novel channel release process that utilized multi-step etching to remove the sacrificial SiGe layers instead of conventional single-step etching. By gradually releasing the stress of the SiGe layer on the nanosheets, the stress difference in the stacking direction before and after the last step of etching was significantly reduced, thus achieving equally spaced stacked nanosheets. In addition, the plasma-free oxidation treatment was introduced in the multi-step etching process to realize an outstanding selectivity of 168:1 for Si0.7Ge0.3 versus Si. The proposed novel process could realize the channel release of nanosheets with a multi-width from 30 nm to 80 nm with little Si loss, unlocking the full potential of gate-all-around (GAA) technology for digital, analog, and radio-frequency (RF) circuit applications.

CSPP1 stabilizes growing microtubule ends and damaged lattices from the luminal side.

Microtubules are dynamic cytoskeletal polymers, and their organization and stability are tightly regulated by numerous cellular factors. While regulatory proteins controlling the formation of interphase microtubule arrays and mitotic spindles have been extensively studied, the biochemical mechanisms responsible for generating stable microtubule cores of centrioles and cilia are poorly understood. Here, we used in vitro reconstitution assays to investigate microtubule-stabilizing properties of CSPP1, a centrosome and cilia-associated protein mutated in the neurodevelopmental ciliopathy Joubert syndrome. We found that CSPP1 preferentially binds to polymerizing microtubule ends that grow slowly or undergo growth perturbations and, in this way, resembles microtubule-stabilizing compounds such as taxanes. Fluorescence microscopy and cryo-electron tomography showed that CSPP1 is deposited in the microtubule lumen and inhibits microtubule growth and shortening through two separate domains. CSPP1 also specifically recognizes and stabilizes damaged microtubule lattices. These data help to explain how CSPP1 regulates the elongation and stability of ciliary axonemes and other microtubule-based structures.

Altered brain white matter structural motor network in spinocerebellar ataxia type 3.

OBJECTIVES: Spinocerebellar ataxia type 3 is a disorder within the brain network. However, the relationship between the brain network and disease severity is still unclear. This study aims to investigate changes in the white matter (WM) structural motor network, both in preclinical and ataxic stages, and its relationship with disease severity. METHODS: For this study, 20 ataxic, 20 preclinical SCA3 patients, and 20 healthy controls were recruited and received MRI scans. Disease severity was quantified using the SARA and ICARS scores. The WM motor structural network was created using probabilistic fiber tracking and was analyzed using graph theory and network-based statistics at global, nodal, and edge levels. In addition, the correlations between network topological measures and disease duration or clinical scores were analyzed. RESULTS: Preclinical patients showed increasing assortativity of the motor network, altered subnetwork including 12 edges of 11 nodes, and 5 brain regions presenting reduced nodal strength. In ataxic patients assortativity of the motor network also increased, but global efficiency, global strength, and transitivity decreased. Ataxic patients showed a wider altered subnetwork and a higher number of reduced nodal strengths. A negative correlation between the transitivity of the motor network and SARA and ICARS scores was observed in ataxic patients. INTERPRETATION: Changes to the WM motor network in SCA3 start before ataxia onset, and WM motor network involvement increases with disease progression. Global network topological measures of the WM motor network appear to be a promising image biomarker for disease severity. This study provides new insights into the pathophysiology of disease in SCA3/MJD.

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms.

Background: Radiotherapy plays a crucial role in the management of Cervical cancer (CC), as the development of resistance by cancer cells to radiotherapeutic interventions is a significant factor contributing to treatment failure in patients. However, the specific mechanisms that contribute to this resistance remain unclear. Currently, molecular targeted therapy, including mitochondrial genes, has emerged as a new approach in treating different types of cancers, gaining significant attention as an area of research in addressing the challenge of radiotherapy resistance in cancer. Methods: The present study employed a rigorous screening methodology within the TCGA database to identify a cohort of patients diagnosed with CC who had received radiotherapy treatment. The control group consisted of individuals who demonstrated disease stability or progression after undergoing radiotherapy. In contrast, the treatment group consisted of patients who experienced complete or partial remission following radiotherapy. Following this, we identified and examined the differentially expressed genes (DEGs) in the two cohorts. Subsequently, we conducted additional analyses to refine the set of excluded DEGs by employing the least absolute shrinkage and selection operator regression and random forest techniques. Additionally, a comprehensive analysis was conducted in order to evaluate the potential correlation between the expression of core genes and the extent of immune cell infiltration in patients diagnosed with CC. The mitochondrial-associated genes were obtained from the MITOCARTA 3.0. Finally, the verification of increased expression of the mitochondrial gene TMEM38A in individuals with CC exhibiting sensitivity to radiotherapy was conducted using reverse transcription quantitative polymerase chain reaction and immunohistochemistry assays. Results: This process ultimately led to the identification of 7 crucial genes, viz., GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2, which were strongly associated with radiotherapy sensitivity. The enrichment analysis has unveiled a significant association between these 7 crucial genes and prominent signaling pathways, such as the p53 signaling pathway, KRAS signaling pathway, and PI3K/AKT/MTOR pathway. By utilizing these 7 core genes, an unsupervised clustering analysis was conducted on patients with CC, resulting in the categorization of patients into three distinct molecular subtypes. In addition, a predictive model for the sensitivity of CC radiotherapy was developed using a neural network approach, utilizing the expression levels of these 7 core genes. Moreover, the CellMiner database was utilized to predict drugs that are closely linked to these 7 core genes, which could potentially act as crucial agents in overcoming radiotherapy resistance in CC. Conclusion: To summarize, the genes GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2 were found to be closely correlated with the sensitivity of CC to radiotherapy. Notably, TMEM38A, a mitochondrial gene, exhibited the highest degree of correlation, indicating its potential as a crucial biomarker for the modulation of radiotherapy sensitivity in CC.

Isolation and characterization of cellulose nanocrystals from Chinese medicine residues.

Nanocellulose has become a vital material with excellent and crucial properties in the field of nanotechnology and advanced materials science. Plant-based traditional Chinese medicines are mostly plant rhizomes, which contain a large amount of cellulose, hemicellulose, and lignin. In this study, carboxylated cellulose nanocrystals (CNCs) were prepared from traditional Chinese medicine residues (CMR) by sequential periodate-chlorite oxidation without mechanical treatment. The obtained nanocelluloses were analyzed by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and X-ray diffractometry (XRD); the carboxyl content and specific surface area were also measured, simultaneously. XRD results revealed that the crystallinity index decreased after sequential oxidation; however, the cellulose I structure was maintained. From the morphology analysis, the average length and width of CNCs were 139.3 and 10 nm, respectively. From the FTIR analysis, with the particle size decreasing, hydrogen bonds were broken and recombined. TGA results showed that the thermal property was decreased with a reduction of nanocellulose particle size and crystallinity index. This study is the first to refine utilization of traditional Chinese medicine residues as a potential source of cellulose, that is, to prepare nanocellulose efficiently with high carboxyl content which finds its application in nanomaterials.

Functional imaging of brain organoids using high-density microelectrode arrays.

Abstract: Studies have provided evidence that human cerebral organoids (hCOs) recapitulate fundamental milestones of early brain development, but many important questions regarding their functionality and electrophysiological properties persist. High-density microelectrode arrays (HD-MEAs) represent an attractive analysis platform to perform functional studies of neuronal networks at the cellular and network scale. Here, we use HD-MEAs to derive large-scale electrophysiological recordings from sliced hCOs. We record the activity of hCO slices over several weeks and probe observed neuronal dynamics pharmacologically. Moreover, we present results on how the obtained recordings can be spike-sorted and subsequently studied across scales. For example, we show how to track single neurons across several days on the HD-MEA and how to infer axonal action potential velocities. We also infer putative functional connectivity from hCO recordings. The introduced methodology will contribute to a better understanding of developing neuronal networks in brain organoids and provide new means for their functional characterization. Impact statement: Human cerebral organoids (hCOs) represent an attractive in vitro model system to study key physiological mechanisms underlying early neuronal network formation in tissue with healthy or disease-related genetic backgrounds. Despite remarkable advances in the generation of brain organoids, knowledge on the functionality of their neuronal circuits is still scarce. Here, we used complementary metal-oxide-semiconductor (CMOS)-based high-density microelectrode arrays (HD-MEAs) to perform large-scale recordings from sliced hCOs over several weeks and quantified their activity across scales. Using single-cell and network metrics, we were able to probe aspects of hCO neurophysiology that are more difficult to obtain with other techniques, such as patch clamping (lower yield) and calcium imaging (lower temporal resolution). These metrics included, for example, extracellular action potential (AP) waveform features and axonal AP velocity at the cellular level, as well as functional connectivity at the network level. Analysis was enabled by the large sensing area and the high spatiotemporal resolution provided by HD-MEAs, which allowed recordings from hundreds of neurons and spike sorting of their activity. Our results demonstrate that HD-MEAs provide a multi-purpose platform for the functional characterization of hCOs, which will be key in improving our understanding of this model system and assessing its relevance for translational research. Supplementary Information: The online version contains supplementary material available at 10.1557/s43577-022-00282-w.

Improved Generation of Human Induced Pluripotent Stem Cell-Derived Cardiac Pacemaker Cells Using Novel Differentiation Protocols.

Current protocols for the differentiation of human-induced pluripotent stem cells (hiPSC) into cardiomyocytes only generate a small amount of cardiac pacemaker cells. In previous work, we reported the generation of high amounts of cardiac pacemaker cells by co-culturing hiPSC with mouse visceral endoderm-like (END2) cells. However, potential medical applications of cardiac pacemaker cells generated according to this protocol, comprise an incalculable xenogeneic risk. We thus aimed to establish novel protocols maintaining the differentiation efficiency of the END2 cell-based protocol, yet eliminating the use of END2 cells. Three protocols were based on the activation and inhibition of the Wingless/Integrated (Wnt) signaling pathway, supplemented either with retinoic acid and the Wnt activator CHIR99021 (protocol B) or with the NODAL inhibitor SB431542 (protocol C) or with a combination of all three components (protocol D). An additional fourth protocol (protocol E) was used, which was originally developed by the manufacturer STEMCELL Technologies for the differentiation of hiPSC or hESC into atrial cardiomyocytes. All protocols (B, C, D, E) were compared to the END2 cell-based protocol A, serving as reference, in terms of their ability to differentiate hiPSC into cardiac pacemaker cells. Our analysis revealed that protocol E induced upregulation of 12 out of 15 cardiac pacemaker-specific genes. For comparison, reference protocol A upregulated 11, while protocols B, C and D upregulated 9, 10 and 8 cardiac pacemaker-specific genes, respectively. Cells differentiated according to protocol E displayed intense fluorescence signals of cardiac pacemaker-specific markers and showed excellent rate responsiveness to adrenergic and cholinergic stimulation. In conclusion, we characterized four novel and END2 cell-independent protocols for the differentiation of hiPSC into cardiac pacemaker cells, of which protocol E was the most efficient.

Assessment of hypokalemia and clinical prognosis in Patients with COVID-19 in Yangzhou, China.

BACKGROUND: Hypokalemia is a frequent electrolyte imbalance in patients with COVID-19. The aim of this study was to estimate the association between hypokalemia and clinical prognosis in patients with moderate COVID-19. METHODS: A single-center, retrospective, observational study was conducted on 81 non-ICU admitted patients with moderate COVID-19 according to the criteria issued by the Chinese Health Bureau in the Third People's Hospital of Yangzhou (Northern Jiangsu People's Hospital New District Branch) from 4th to 25th August 2021. The demographic, clinical, and laboratory data were reviewed and collected, then the correlation between hypokalemia and prognosis was determined. RESULTS: The level of serum potassium of patients ranged from 2.80 mmol/L to 4.70 mmol/L. Hypokalemia was detected in 39 out of the 81 included patients (48.15%) during hospitalization. Patients with hypokalemia had prolonged days of negative nucleic acid conversion and hospital stay. Correlation analysis showed that the level of serum potassium was negatively correlated with days of negative nucleic acid conversion and length of hospital stay. Bivariate logistic regression analysis proved that hypokalemia was a risk factor for prolonged hospital stay in patients with moderate COVID-19. CONCLUSION: Hypokalemia was prevalent in patients with moderate COVID-19 in Yangzhou, China. Hypokalemia was associated with the prolonged hospital stay in patients with moderate COVID-19.

Quantification of vascular networks in photoacoustic mesoscopy.

Mesoscopic photoacoustic imaging (PAI) enables non-invasive visualisation of tumour vasculature. The visual or semi-quantitative 2D measurements typically applied to mesoscopic PAI data fail to capture the 3D vessel network complexity and lack robust ground truths for assessment of accuracy. Here, we developed a pipeline for quantifying 3D vascular networks captured using mesoscopic PAI and tested the preservation of blood volume and network structure with topological data analysis. Ground truth data of in silico synthetic vasculatures and a string phantom indicated that learning-based segmentation best preserves vessel diameter and blood volume at depth, while rule-based segmentation with vesselness image filtering accurately preserved network structure in superficial vessels. Segmentation of vessels in breast cancer patient-derived xenografts (PDXs) compared favourably to ex vivo immunohistochemistry. Furthermore, our findings underscore the importance of validating segmentation methods when applying mesoscopic PAI as a tool to evaluate vascular networks in vivo.

Structural Covariance of the Ipsilesional Primary Motor Cortex in Subcortical Stroke Patients with Motor Deficits.

The analysis of structural covariance has emerged as a powerful tool to explore the morphometric correlations among broadly distributed brain regions. However, little is known about the interactions between the damaged primary motor cortex (M1) and other brain regions in stroke patients with motor deficits. This study is aimed at investigating the structural covariance pattern of the ipsilesional M1 in chronic subcortical stroke patients with motor deficits. High-resolution T1-weighted brain images were acquired from 58 chronic subcortical stroke patients with motor deficits (29 with left-sided lesions and 29 with right-sided lesions) and 50 healthy controls. Structural covariance patterns were identified by a seed-based structural covariance method based on gray matter (GM) volume. Group comparisons between stroke patients (left-sided or right-sided groups) and healthy controls were determined by a permutation test. The association between alterations in the regional GM volume and motor recovery after stroke was investigated by a multivariate regression approach. Structural covariance analysis revealed an extensive increase in the structural interactions between the ipsilesional M1 and other brain regions in stroke patients, involving not only motor-related brain regions but also non-motor-related brain regions. We also identified a slightly different pattern of structural covariance between the left-sided stroke group and the right-sided stroke group, thus indicating a lesion-side effect of cortical reorganization after stroke. Moreover, alterations in the GM volume of structural covariance brain regions were significantly correlated to the motor function scores in stroke patients. These findings indicated that the structural covariance patterns of the ipsilesional M1 in chronic subcortical stroke patients were induced by motor-related plasticity. Our findings may help us to better understand the neurobiological mechanisms of motor impairment and recovery in patients with subcortical stroke from different perspectives.

High-performance unbiased Ge metal-semiconductor-metal photodetector covered with asymmetric HfSe2 contact geometries.

A Ge metal-semiconductor-metal photodetector covered with asymmetric HfSe2 contact geometries has been proposed to realize high-performance unbiased photodetection at 1550 nm. At -1 V bias, the responsivity of this device shows a 71% improvement compared to the device without HfSe2. Moreover, the responsivity and detectivity of this device at zero bias can reach to 71.2 mA/W and 3.27×1010 Jones, respectively. Furthermore, the fall time of this device is 2.2 µs and 53% shorter than the device without HfSe2. This work provides a feasible way to develop unbiased Ge-based photodetectors in the near-IR communications band.

Pattern of cerebellar grey matter loss associated with ataxia severity in spinocerebellar ataxias type 3: a multi-voxel pattern analysis.

Spinocerebellar ataxias type 3 (SCA3) patients are clinically characterized by progressive cerebellar ataxia combined with degeneration of the cerebellum. Previous neuroimaging studies have indicated ataxia severity associated with cerebellar atrophy using univariate methods. However, whether cerebellar atrophy patterns can be used to quantitatively predict ataxia severity in SCA3 patients at the individual level remains largely unexplored. In this study, a group of 66 SCA3 patients and 58 healthy controls were included. Disease duration and ataxia assessment, including the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS), were collected for SCA3 patients. The high-resolution T1-weighted MRI was obtained, and cerebellar grey matter (GM) was extracted using a spatially unbiased infratentorial template toolbox for all participants. We investigated the association between the pattern of cerebellar grey matter (GM) loss and ataxia assessment in SCA3 by using a multivariate machine learning technique. We found that the application of RVR allowed quantitative prediction of both SARA scores (leave-one-subject-out cross-validation: correlation = 0.56, p-value = 0.001; mean squared error (MSE) = 20.51, p-value = 0.001; ten-fold cross-validation: correlation = 0.52, p-value = 0.001; MSE = 21.00, p-value = 0.001) and ICARS score (leave-one-subject-out cross-validation: correlation = 0.59, p-value = 0.001; MSE = 139.69, p-value = 0.001; ten-fold cross-validation: correlation = 0.57, p-value = 0.001; MSE = 145.371, p-value = 0.001) with statistically significant accuracy. These results provide proof-of-concept that ataxia severity in SCA3 patients can be predicted by the alteration pattern of cerebellar GM using multi-voxel pattern analysis.

Brain structural abnormalities in the preclinical stage of Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3): evaluation by MRI morphometry, diffusion tensor imaging and neurite orientation dispersion and density imaging.

OBJECTIVE: To investigate whether neurite orientation dispersion and density imaging (NODDI) could provide the added value for detecting brain microstructural alterations in the preclinical stage of Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3) compared with MRI morphometry and diffusion tensor imaging (DTI). METHODS: Twenty preclinical MJD/SCA3 patients and 21 healthy controls were enrolled. Three b values DWI and 3D T1-weighted images were acquired at 3.0 T. Tract-based spatial statistics (TBSS) approach was used to investigate the white matter (WM) alterations in the DTI metrics and NODDI metrics. Gray matter-based spatial statistics (GBSS) approach was used to investigate the grey matter (GM) alterations in the NODDI metrics. Voxel-based morphometry (VBM) approach was performed on the 3D T1-weighted images. The relationship between the cytosine-adenine-guanine (CAG) repeat length and brain microstructural alterations of preclinical MJD/SCA3 was identified. RESULTS: Compared with healthy controls, the preclinical MJD/SCA3 patients showed decreased FA and NDI as well as increased MD, AD, and RD in the WM of cerebellum and brainstem (corrected P < 0.05), and decreased NDI in the GM of cerebellar vermis (corrected P < 0.05). The CAG repeat length in preclinical MJD/SCA3 patients was negatively correlated with the reduced FA and NDI of the infratentorial WM and the reduced NDI of the cerebellum, and positively with the increased MD and RD of the infratentorial WM. CONCLUSIONS: NOODI can provide novel quantitative microstructural changes in MJD/SCA3 carriers, expanding our understanding of the gray and white matter (axons and dendrites) degeneration in this frequent ataxia syndrome.

MRI-Based Grading of Clear Cell Renal Cell Carcinoma Using a Machine Learning Classifier.

OBJECTIVE: To develop a machine learning (ML)-based classifier for discriminating between low-grade (ISUP I-II) and high-grade (ISUP III-IV) clear cell renal cell carcinomas (ccRCCs) using MRI textures. MATERIALS AND METHODS: We retrospectively evaluated a total of 99 patients (with 61 low-grade and 38 high-grade ccRCCs), who were randomly divided into a training set (n = 70) and a validation set (n = 29). Regions of interest (ROIs) of all tumors were manually drawn three times by a radiologist at the maximum lesion level of the cross-sectional CMP sequence images. The quantitative texture analysis software, MaZda, was used to extract texture features, including histograms, co-occurrence matrixes, run-length matrixes, gradient models, and autoregressive models. Reproducibility of the texture features was assessed with the intra-class correlation coefficient (ICC). Features were chosen based on their importance coefficients in a random forest model, while the multi-layer perceptron algorithm was used to build a classifier on the training set, which was later evaluated with the validation set. RESULTS: The ICCs of 257 texture features were equal to or higher than 0.80 (0.828-0.998. Six features, namely Kurtosis, 135dr_RLNonUni, Horzl_GLevNonU, 135dr_GLevNonU, S(4,4)Entropy, and S(0,5)SumEntrp, were chosen to develop the multi-layer perceptron classifier. A three-layer perceptron model, which has 229 nodes in the hidden layer, was trained on the training set. The accuracy of the model was 95.7% with the training set and 86.2% with the validation set. The areas under the receiver operating curves were 0.997 and 0.758 for the training and validation sets, respectively. CONCLUSIONS: A machine learning-based grading model was developed that can aid in the clinical diagnosis of clear cell renal cell carcinoma using MRI images.