Evaluating the diagnostic and therapeutic significance of KL-6 in patients with interstitial lung diseases.

Background: This study aimed to assess the diagnostic value of Krebs von den Lungen-6 (KL-6), Surfactant protein-A (SP-A), SP-D and molecular matrixmetalloproteinase-7 (MMP-7) in discriminating patients with interstitial lung diseases (ILDs) from disease control subjects. Methods: Serum levels of KL-6, SP-A, SP-D and MMP-7 were measured in both the ILD and non-ILD (NILD) groups. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic potential of these markers and laboratory indices. High-resolution computed tomography (HRCT) fibrosis scores were determined, and their correlation with the serum markers was analyzed. Results: Serum levels of KL-6 and MMP-7 were significantly elevated in the ILD group compared to the control group, while no significant differences were observed for SP-A and SP-D. ROC analysis of KL-6 demonstrated superior diagnostic accuracy, with a sensitivity of 76.36%, specificity of 91.07%, and an area under curve (AUC) of 0.902 (95%CI 0.866-0.945). These findings were consistent across an additional cohort. Correlation analysis revealed a link between KL-6 levels at initial diagnosis and HRCT fibrosis scores, indicating disease severity. Moreover, a negative correlation was found between KL-6 and pulmonary function indices, reflecting disease progression. Patients with increased 12-month HRCT fibrosis score showed higher lactate dehydrogenase (LDH) levels, with LDH exhibiting an AUC of 0.767 (95% CI: 0.520-0.927) as a predictor of progression. Conclusions: Serum KL-6 detection proves to be a valuable tool for accurately distinguishing ILDs from control subjects. While KL-6 shows a correlation with HRCT fibrosis scores and a negative association with pulmonary function indices, its predictive value for ILDs prognosis is limited. Trial registration: This study received retrospective approval from the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (institutional review board ID: TJ-IRB20210331, date: 2021.03.30).

The changes of oxygen extraction fraction in different types of lesions in relapsing-remitting multiple sclerosis: A cross-sectional and longitudinal study.

OBJECTIVES: To explore the oxygen metabolism level of different types of lesions in relapsing-remitting multiple sclerosis (RRMS) patients by oxygen extraction fraction (OEF) both cross-sectionally and longitudinally. METHODS: Forty-six RRMS patients and forty-one healthy controls (HC) went MRI examination. The quantitative susceptibility mapping (QSM) and OEF map were reconstructed from a 3D multi-echo gradient echo sequence. MS lesions in white matter were classified as contrast-enhancing lesions (CELs) on post-gadolinium T1-weighted sequence, paramagnetic rim lesions (PRLs), hyperintense lesions and non-hyperintense lesions on QSM, respectively. The susceptibility and OEF of different types of lesions were compared. The susceptibility and OEF values were measured and compared among different types of lesions. Among these RRMS patients, seventeen had follow-up MRI and 232 lesions, and baseline to follow-up longitudinal changes in susceptibility and OEF were measured. RESULTS: PRLs had higher susceptibility and lower OEF than CELs, hyperintense lesions, and non-hyperintense lesions. The hyperintense lesions had higher susceptibility and lower OEF than non-hyperintense lesions. In longitudinal changes, PRLs had susceptibility increased (P < 0.001) and OEF decreased (P < 0.001). The hyperintense lesions showed significant decreases in susceptibility (P = 0.020), and non-hyperintense lesions showed significant increases in OEF during follow-up (P = 0.005). Notably, hyperintense lesions may convert to PRLs or non-hyperintense lesions as time progresses, accompanied by changes of OEF and susceptibility in the lesions. CONCLUSION: This study revealed tissue damage and oxygen metabolism level in different types of MS lesions. The OEF may contribute to further understanding the evolution of MS lesions.

Enlarged choroid plexus in relapsing-remitting multiple sclerosis may lead to brain structural changes through the glymphatic impairment.

OBJECTIVES: To investigate the potential link among choroid plexus (CP) volume, glymphatic clearance and brain structural change in relapsing-remitting multiple sclerosis (RRMS) patients. MATERIALS AND METHODS: Sixty-five RRMS patients and 48 healthy controls (HC) underwent MRI examination. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) was calculated to reflect glymphatic system function. The brain structure volume and DTI-ALPS index were compared between RRMS and HC. The mediating effect of the DTI-ALPS index between CP volume and brain structural changes was further investigated. The longitudinal changes of brain structure and DTI-ALPS index were compared in 20 RRMS patients. RESULTS: Compared to HC, CP volume in RRMS was significantly increased (P < 0.001), and DTI-ALPS index was significantly decreased (P = 0.001). The volumes of white matter, thalamus, putamen and pallidum were significantly decreased in RRMS, and the volumes of lateral ventricle and third ventricle were increased. Mediation analysis showed DTI-ALPS index partially mediated the association between CP enlargement and deep gray matter (DGM) atrophy in RRMS, and between CP enlargement and ventricle enlargement. CP volume and DTI-ALPS index were also significantly correlated with Expanded Disability Status Scale (EDSS) (P = 0.006, P = 0.043). Notably, the variation of DTI_ALPS index during the follow-up period were significantly and negatively correlated with the variation of EDSS (P = 0.045). CONCLUSION: Enlarged CP volume and decreased DTI_ALPS index may be closely related to DGM atrophy and ventricular enlargement in RRMS, and may be potential imaging markers of clinical disability.

SR-TTS: a rhyme-based end-to-end speech synthesis system.

Deep learning has significantly advanced text-to-speech (TTS) systems. These neural network-based systems have enhanced speech synthesis quality and are increasingly vital in applications like human-computer interaction. However, conventional TTS models still face challenges, as the synthesized speeches often lack naturalness and expressiveness. Additionally, the slow inference speed, reflecting low efficiency, contributes to the reduced voice quality. This paper introduces SynthRhythm-TTS (SR-TTS), an optimized Transformer-based structure designed to enhance synthesized speech. SR-TTS not only improves phonological quality and naturalness but also accelerates the speech generation process, thereby increasing inference efficiency. SR-TTS contains an encoder, a rhythm coordinator, and a decoder. In particular, a pre-duration predictor within the cadence coordinator and a self-attention-based feature predictor work together to enhance the naturalness and articulatory accuracy of speech. In addition, the introduction of causal convolution enhances the consistency of the time series. The cross-linguistic capability of SR-TTS is validated by training it on both English and Chinese corpora. Human evaluation shows that SR-TTS outperforms existing techniques in terms of speech quality and naturalness of expression. This technology is particularly suitable for applications that require high-quality natural speech, such as intelligent assistants, speech synthesized podcasts, and human-computer interaction.

The impact of paramagnetic rim lesions on cortical thickness and gray to white matter contrast in relapsing-remitting multiple sclerosis.

Background: Paramagnetic rim lesions (PRLs) on susceptibility magnetic resonance sequences have been suggested as an imaging marker of disease progression in multiple sclerosis. This retrospective cross-sectional study aimed to investigate the impact of PRLs on cortical thickness and gray matter (GM) to white matter (WM) contrast in relapsing-remitting multiple sclerosis (RRMS). Methods: A total of 82 RRMS patients (40 patients with at least 1 PRL and 42 patients without PRL) and 43 healthy controls (HC) were included in this study. The T1-weighted images (T1WI) were processed with the FreeSurfer pipeline. GM to WM signal intensity ratio (GWR) was obtained from T1WI by dividing the GM signal intensity by the WM signal intensity for each vertex. Group differences in cortical thickness and GWR were tested on reconstructed cortical surface. Results: Compared to HC, patients with PRL had thinner mean cortical thickness (P<0.001), higher mean GWR (P=0.001), and lower brain structure volumes (cortex volume, P=0.001; WM volume, P<0.001; deep GM volume, P<0.001). Vertex-based analysis found significant cortical thinning in several regions and increased GWR in a wider range of regions in patients with PRL. The two types of clusters had both overlapping regions and independent regions. However, in patients without PRL, only a few regions showed significant cortical thickness changes. Correlation analysis found that in patients with PRL, only PRL volume showed a significant negative correlation with mean cortical thickness (P=0.048), and PRL volume and count, non-PRL count, and total lesion volume were significantly and positively correlated with mean GWR (P<0.05). Conclusions: There were significant changes in cortical thickness, GWR, and brain structure volume in RRMS patients with PRL that may contribute to further understanding of the pathological mechanisms underlying neurological tissue damage.

Ultralow-cost piezoelectric sensor constructed by thermal compression bonding for long-term biomechanical signal monitoring in chronic mental disorders.

Wearable bioelectronic devices, which circumvent issues related to the large size and high cost of clinical equipment, have emerged as powerful tools for the auxiliary diagnosis and long-term monitoring of chronic psychiatric diseases. Current devices often integrate multiple intricate and expensive devices to ensure accurate diagnosis. However, their high cost and complexity hinder widespread clinical application and long-term user compliance. Herein, we developed an ultralow-cost poly(vinylidene fluoride)/zinc oxide nanofiber film-based piezoelectric sensor in a thermal compression bonding process. Our piezoelectric sensor exhibits remarkable sensitivity (13.4 mV N-1), rapid response (8 ms), and exceptional stability over 2000 compression/release cycles, all at a negligibly low fabrication cost. We demonstrate that pulse wave, blink, and speech signals can be acquired by the sensor, proposing a single biomechanical modality to monitor multiple physiological traits associated with bipolar disorder. This ultralow-cost and mass-producible piezoelectric sensor paves the way for extensive long-term monitoring and immediate feedback for bipolar disorder management.

Structural covariance in subcortical regions in multiple sclerosis and neuromyelitis optica spectrum disorders: An MRI-based study with automated brain volumetry.

PURPOSE: This study aimed to investigate the alterations of brain volumetry and associated structural covariance in subcortical regions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). MATERIALS AND METHODS: Fourty MS patients, 35 NMOSD patients and 34 healthy controls (HC) underwent 3D T1-weighted image and 3D T2 FLAIR of MRI. The volume differences in subcortical regions were compared between the MS, NMOSD, and HC groups by automated brain volumetry. Structural covariance analysis was performed with each pair of these regions to investigate the alterations of anatomical connections in MS and NMOSD compared to HC. RESULTS: Compared with HC, MS patients presented significantly smaller volume in some subcortical and infratentorial regions (P<0.05), while NMOSD patients showed no significant difference of volumetry in any of the brain regions (P>0.05), although they had no significant difference in disease duration (MS 3.95±3.73 ys; NMOSD 3.11±4.61 ys; P>0.05). In addition, the structural covariance analyses revealed synergic volume alteration in subcortical regions both in the MS and NMOSD groups. More extensive additional connections compared with HC were found in MS patients and more extensive missing connections compared with HC were found in NMOSD patients. CONCLUSION: This study revealed distinct patterns of brain structural damage and reorganization in MS and NMOSD, which could facilitate a better distinction between these two entities.

Fractional anisotropy helps to differentiate the optic nerve impairment between neuromyelitis optica spectrum disorders and multiple sclerosis.

OBJECTIVES: To assess the characteristics of optic nerve impairment between neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) patients by fractional anisotropy (FA). METHODS: Thirty-one NMOSD patients, 25 MS patients, and 17 heathy controls (HC) who underwent optic nerve DTI were included. The optic nerves of the NMOSD and MS patients were divided into vision-impaired (VI) subgroups and normal-appearing (NA) subgroups according to visual status, respectively. FA values were measured in the anterior, middle, and posterior segments of each intraorbital optic nerve. RESULTS: FA values in VI NMOSD were significantly decreased in the whole optic nerve, especially the posterior segment of the optic nerve (p < 0.001). FA values measured in the anterior and middle segments of the optic nerve in VI MS were significantly decreased as compared to those in the HC (p < 0.05). Between NMOSD and MS, FA values in the posterior segment of the optic nerve showed significant differences (VI NMOSD vs. VI MS, 0.458 ± 0.097 vs. 0.568 ± 0.098, p < 0.001; NA NMOSD vs. NA MS, 0.568 ± 0.098 vs. 0.600 ± 0.085, p = 0.041, respectively). The signal intensity ratio (SIR) in the posterior segment of the optic nerve was significantly increased in VI NMOSD as compared with VI MS (p = 0.002). The combination of SIR and FA for distinguishing VI NMOSD from VI MS resulted in sensitivity, specificity, and positive and negative predictive values of 86.49%, 80.00%, 88.9%, and 76.2%, respectively. CONCLUSION: FA could quantify the characteristics of NMOSD- and MS-related optic nerve impairment. DTI was a simple and effective imaging tool to differentiate between the two. KEY POINTS: • NMOSD-related optic nerve impairment is extensive, often greater than half of the optic nerve, with the most significant involvement of the posterior segment of the optic nerve. • MS-related optic nerve impairment is more limited than NMOSD, and anterior and middle optic nerve involvement is common. • Optic nerve DTI is a convenient and effective imaging tool that can help characterize NMOSD and MS.

Age and anatomical location related hemodynamic changes assessed by 4D flow MRI in the carotid arteries of healthy adults.

PURPOSE: To evaluate hemodynamic changes (volume, velocity, wall shear stress, pressure gradient, and energy loss) in the common carotid artery (CCA) and internal carotid artery (ICA) of healthy adults among different ages and anatomical locations using 4D flow MRI. METHODS: Sixty-two healthy volunteers aged 20-75 years were enrolled in this study. 4D flow MRI examinations were performed for each subject and were analyzed using the CVI42 platform to generate hemodynamic parameters. Hemodynamic parameters were compared among different age groups and anatomical locations (proximal CCA, distal CCA, proximal ICA and distal CCA) using one-way ANOVA. The paired t-test was used to estimate the differences between left and right vessels. The relationship between age and hemodynamic parameters was quantified by Pearson's correlation coefficient. RESULTS: There were no differences between the left and right carotid arteries for any of the hemodynamic parameters (all p values > 0.05), so we set each vessel as an independent sample. The proximal ICA had significantly lower volume, velocity, wall shear stress, and pressure gradient values than the values determined for other locations (p < 0.05), and energy loss was similar among different locations. Wall shear stress (except in the distal ICA), velocity, pressure gradient, and energy loss decreased with age (p < 0.05). CONCLUSIONS: The multiparameter analysis of 4D flow MRI can identify age and anatomical location changes in hemodynamic parameters in the carotid arteries of healthy adults. The lower velocity, wall shear stress, and pressure gradient in the proximal ICA and the reduced trend with age may be associated with disease occurrence.

Fiber Connectivity Density in Cerebral Small-Vessel Disease Patients With Mild Cognitive Impairment and Cerebral Small-Vessel Disease Patients With Normal Cognition.

Abnormal structural connectivity of cerebral small-vessel disease (CSVD) is associated with cognitive impairment. But the different characteristics of structural connectivity have not been elucidated in early CSVD patients. The current study aimed to investigate the potential differences of structural connectivity in CSVD patients with mild cognitive impairment (MCI) and CSVD patients with normal cognition. Twenty-two CSVD patients with MCI, 34 CSVD patients with normal cognition, and 35 controls, who were age, sex, and education matched underwent diffusion tensor imaging and high resolution T1-weighted imaging. Clinical characteristics, lacunar infarct volume, white matter hyperintensity (WMH) volume, and global atrophy were quantitatively evaluated. Maps of fiber connectivity density (FiCD) were constructed and compared across groups in vertex levels. Pearson correlation was used to estimate the imaging-clinical relationships with control of general characteristics. CSVD patients with MCI had higher lesion load of WMH and lacunar infarcts, and correspondingly lower global FiCD value than CSVD patients with normal cognition (P < 0.01). Lacunar infarct (r = -0.318, P < 0.01) and WMH (r = -0.400, P < 0.01), but not global atrophy, age, or sex, were significantly correlated with the global FiCD value. CSVD patients with normal cognition showed decreased FiCD value mainly in the prefrontal areas (P < 0.01 with Monte Carlo correction). Compared with CSVD patients with normal cognition, CSVD patients with MCI showed significantly decreased FiCD value in enlarged frontal and parietal areas (P < 0.01 with Monte Carlo correction). Inter-group comparisons showed regional enhanced impairment of connectivity density in CSVD patients with MCI in the left superior frontal gyrus, the left precuneus, and the orbital part of the right inferior frontal gyrus (P < 0.01 with Monte Carlo correction). Regional FiCD value of frontal and parietal areas was associated with the cognitive function (P < 0.01). In conclusion, cognitively normal CSVD patients already have disruptions of structural connectivity. The extent and intensity of connectivity disruptions in frontal and parietal areas may underlie the mechanism of cognitive impairment in CSVD. Fiber connectivity density measurements may be helpful for quantitative description of structural cortical connectivity.