Tinnitus classification based on resting-state functional connectivity using a convolutional neural network architecture.

OBJECTIVES: Many studies have investigated aberrant functional connectivity (FC) using resting-state functional MRI (rs-fMRI) in subjective tinnitus patients. However, no studies have verified the efficacy of resting-state FC as a diagnostic imaging marker. We established a convolutional neural network (CNN) model based on rs-fMRI FC to distinguish tinnitus patients from healthy controls, providing guidance and fast diagnostic tools for the clinical diagnosis of subjective tinnitus. METHODS: A CNN architecture was trained on rs-fMRI data from 100 tinnitus patients and 100 healthy controls using an asymmetric convolutional layer. Additionally, a traditional machine learning model and a transfer learning model were included for comparison with the CNN, and each of the three models was tested on three different brain atlases. RESULTS: Of the three models, the CNN model outperformed the other two models with the highest area under the curve, especially on the Dos_160 atlas (AUC = 0.944). Meanwhile, the model with the best classification performance highlights the crucial role of the default mode network, salience network, and sensorimotor network in distinguishing between normal controls and patients with subjective tinnitus. CONCLUSION: Our CNN model could appropriately tackle the diagnosis of tinnitus patients using rs-fMRI and confirmed the diagnostic value of FC as measured by rs-fMRI.

Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

Associations of serum uric acid variability with neuroimaging metrics and cognitive decline: a population-based cohort study.

BACKGROUND: The relationship between variation in serum uric acid (SUA) levels and brain health is largely unknown. This study aimed to examine the associations of long-term variability in SUA levels with neuroimaging metrics and cognitive function. METHODS: This study recruited 1111 participants aged 25-83 years from a multicenter, community-based cohort study. The SUA concentrations were measured every two years from 2006 to 2018. We measured the intraindividual SUA variability, including the direction and magnitude of change by calculating the slope value. The associations of SUA variability with neuroimaging markers (brain macrostructural volume, microstructural integrity, white matter hyperintensity, and the presence of cerebral small vessel disease) and cognitive function were examined using generalized linear models. Mediation analyses were performed to assess whether neuroimaging markers mediate the relationship between SUA variation and cognitive function. RESULTS: Compared with the stable group, subjects with increased or decreased SUA levels were all featured by smaller brain white matter volume (beta = - 0.25, 95% confidence interval [CI] - 0.39 to - 0.11 and beta = - 0.15, 95% CI - 0.29 to - 0.02). Participants with progressively increased SUA exhibited widespread disrupted microstructural integrity, featured by lower global fractional anisotropy (beta = - 0.24, 95% CI - 0.38 to - 0.10), higher mean diffusivity (beta = 0.16, 95% CI 0.04 to 0.28) and radial diffusivity (beta = 0.19, 95% CI 0.06 to 0.31). Elevated SUA was also associated with cognitive decline (beta = - 0.18, 95% CI - 0.32 to - 0.04). White matter atrophy and impaired brain microstructural integrity mediated the impact of SUA increase on cognitive decline. CONCLUSIONS: It is the magnitude of SUA variation rather than the direction that plays a critical negative role in brain health, especially for participants with hyperuricemia. Smaller brain white matter volume and impaired microstructural integrity mediate the relationship between increased SUA level and cognitive function decline. Long-term stability of SUA level is recommended for maintaining brain health and preventing cognitive decline.

Cerebral Sinus Hemodynamics in Adults Revealed by 4D Flow MRI.

BACKGROUND: The hemodynamics of the cerebral sinuses play a vital role in understanding blood flow-related diseases, yet the hemodynamics of the cerebral sinuses in normal adults remains an unresolved issue. PURPOSE: To evaluate hemodynamics in the cerebral sinus of adults using 4-dimensional flow MRI (4D Flow MRI). STUDY TYPE: Cross-sectional. POPULATION: Ninety-nine healthy volunteers (mean age, 42.88 ± 13.16 years old; females/males, 55/44). FIELD STRENGTH/SEQUENCE: 3 T/4D Flow MRI. ASSESSMENT: The blood flow velocity, average blood flow rate (Q), and vortexes at the superior sagittal sinus (SSS), straight sinus (STS), transverse sinus, sigmoid sinus, and jugular bulb of each volunteer were evaluated by two independent neuroradiologists. The relationship between the total cerebral Q and sex and age was also assessed. Twelve volunteers underwent two scans within a month. STATISTICAL TESTS: The intraclass correlation coefficient (ICC) evaluated the inter-observer agreement. Blood flow parameters among volunteers were compared by the independent-sample t-test or Mann-Whitney U test. The multiple linear regression equation was used to evaluate the relationship between total cerebral Q and age and sex. P < 0.05 indicated statistical significance. RESULTS: The test-retest and interobserver reliability of average velocity and Q were moderate to high (ICC: 0.54-0.99). Cerebral sinus velocity varied by segment and cardiac cycle. The SSS's velocity and Q increased downstream and Q near torcular herophili was 3.5 times that through the STS. The total cerebral Q decreased by 0.06 mL/s per year (ß = -0.06 ± 0.013) and was sex-independent within the group. Vortexes were found in 12.12%, 8.9%, and 59.8% of torcular herophili, transverse-sigmoid junction, and jugular bulb, respectively, and were related to higher upstream flow. DATA CONCLUSION: Cerebral sinuses could be measured visually and quantitatively in vivo by 4D Flow MRI, providing a basis for future research on pulsating tinnitus, multiple sclerosis, and other related diseases. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Standardized reporting for Head CT Scans in patients suspected of traumatic brain injury (TBI): An international expert endeavor.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) is a major source of health loss and disability worldwide. Accurate and timely diagnosis of TBI is critical for appropriate treatment and management of the condition. Neuroimaging plays a crucial role in the diagnosis and characterization of TBI. Computed tomography (CT) is the first-line diagnostic imaging modality typically utilized in patients with suspected acute mild, moderate and severe TBI. Radiology reports play a crucial role in the diagnostic process, providing critical information about the location and extent of brain injury, as well as factors that could prevent secondary injury. However, the complexity and variability of radiology reports can make it challenging for healthcare providers to extract the necessary information for diagnosis and treatment planning. METHODS/RESULTS/CONCLUSION: In this article, we report the efforts of an international group of TBI imaging experts to develop a clinical radiology report template for CT scans obtained in patients suspected of TBI and consisting of fourteen different subdivisions (CT technique, mechanism of injury or clinical history, presence of scalp injuries, fractures, potential vascular injuries, potential injuries involving the extra-axial spaces, brain parenchymal injuries, potential injuries involving the cerebrospinal fluid spaces and the ventricular system, mass effect, secondary injuries, prior or coexisting pathology).

Ocular biomarkers of cognitive decline based on deep-learning retinal vessel segmentation.

BACKGROUND: The current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition. METHODS: We included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P < 0.05 was considered statistically significant. The correlation between the CI and RMPs were explored, then the correlation coefficients between CI and RMPs were analyzed. Random Forest nonlinear classification model was used to predict whether one having cognitive decline or not. The assessment criterion was the AUC value derived from the working characteristic curve. RESULTS: The fractal dimension (FD) and global vein width were significantly correlated with the CI (P < 0.05). Age (0.193), BMI (0.154), global vein width (0.106), retinal vessel FD (0.099), and CRAE (0.098) were the variables in this model that were ranked in order of feature importance. The AUC values of the model were 0.799. CONCLUSIONS: Establishment of a predictive model based on the extraction of vascular features from fundus images has a high recognizability and predictive power for cognitive function and can be used as a screening method for CI.

Gray matter volume mediates the association of long-term blood pressure variability with cognitive function in an adult population.

INTRODUCTION: We delineated the associations among long-term blood pressure variability (BPV), brain structure, and cognitive function. METHODS: We included 1254 adult participants from the Kailuan study. BPV was calculated from 2006 to 2020. Brain magnetic resonance imaging (MRI) and Montreal Cognitive Assessment (MoCA) were conducted in 2020. RESULTS: Higher systolic BPV (SBPV) and diastolic BPV (DBPV) were associated with lower total and frontal gray matter (GM) volume, and higher SBPV was associated with lower temporal GM volume. Elevated DBPV was associated with lower volume of total brain and parietal GM, and higher white matter hyperintensity (WMH) volume. Higher SBPV and DBPV were associated with lower MoCA scores. Decreased total and regional GM volume and increased WMH volume were associated with lower MoCA scores. The association between SBPV and cognitive function was mediated by total, frontal, and temporal GM volume. DISCUSSION: GM volume may play key roles in the association between SBPV and cognitive function. HIGHLIGHTS: SBPV and DBPV were negatively associated with total and regional brain volume. SBPV and DBPV were negatively associated with cognitive function. Decreased brain volume was associated with cognitive decline. GM volume mediated the negative association between SBPV and cognitive function.

A bimetallic peroxidase-mimicking nanozyme with antifouling property for construction of sensor array to identify phosphoproteins and diagnose cancers.

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.

Mendelian randomization analyses support causal relationships between tinnitus of different stages and severity and structural characteristics of specific brain regions.

This study aims to delineate the causal relationships between idiopathic tinnitus in different stages and severity and the morphological properties in specific brain regions. We utilized a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal effects of brain structural attributes on varying severities and stages of tinnitus. Our approach involved harnessing genetic variables derived from extensive genome-wide association studies as instrumental variables, centered mainly on pertinent single-nucleotide polymorphisms associated with tinnitus. Subsequently, we integrated this data with brain structural imaging inputs to facilitate the MR analysis. We also applied reverse MR analysis to pinpoint the critical brain regions implicated in the onset of tinnitus. Our analysis revealed a demonstrable causal relationship between tinnitus and brain structural alterations, including changes primarily within the auditory cortex and hub regions of the limbic system, as well as portions of the frontal-temporal-occipital circuit. We found that individuals exhibiting cortical thickness alterations in the bilateral peri-calcarine and right superior occipital gyrus might have previously experienced tinnitus. Changes in the cortical areas of the right rectus, left inferior frontal gyrus, and right pars-orbitalis appeared unrelated to tinnitus. Furthermore, moderate tinnitus patients showed more pronounced structural alterations. This study substantiates that tinnitus could instigate substantial structural alterations mainly within the auditory-limbic-frontal-visual system, while the reciprocal causality was not supported. Moreover, the data underscores that moderate, rather than severe, tinnitus precipitates the most significant structural changes. Morphological alterations in several specific brain areas either indicate a history of tinnitus or bear no relation to it.

Plasma-activated water: Candidate hand disinfectant for SARS-CoV-2 transmission disruption.

The global epidemic caused by SARS-CoV-2 has brought about worldwide burden and a sense of danger for more than two years, leading to a wide range of social, public health, economic and environmental issues. Self-inoculation through hands has been the primary way for environmental transmission of SARS-CoV-2. Plasma-activated water (PAW) has been reported as an effective, safe and environmentally friendly disinfectant against SARS-CoV-2. However, the inactivating effect of PAW on SARS-CoV-2 located on skin surface and its underlying mechanism of action have not been elucidated. In this study, PAW was prepared using an air-pressure plasma jet device. The antiviral efficiency of PAW1, PAW3, and PAW5 on the SARS-CoV-2 pseudovirus was 8.20 % (±2.88 %), 46.24 % (±1.79 %), and 91.71 % (±0.47 %), respectively. Additionally, determination of PAW's physicochemical properties, identification of major sterile effector in PAW, transmission electron microscopy analysis, malondialdehyde (MDA) assessment, SDS-PAGE, ELISA, and qPCR were conducted to reveal the virucidal mechanism of PAW. Our experimental results suggested that peroxynitrite, which was generated by the synergism of acidic environment and reactive species, was the major sterile effector of PAW. Furthermore, we found that PAW treatment significantly inactivated SARS-CoV-2 pseudovirus through the destruction of its structure of and the degradation of the viral RNA. Therefore, the possible mechanism for the structural destruction of SARS-COV-2 by PAW is through the action of peroxynitrite generated by the synergism of acidic environment and reactive species, which might react with and destroy the lipid envelope of SARS-CoV-2 pseudovirus. Nevertheless, further studies are required to shed light on the interaction mechanism of PAW-inherent RONS and viral components, and to confirm the determinant factors for virus inactivation of SARS-COV-2 by PAW. Therefore, PAW may be a candidate hand disinfectant used to disrupt the transmission of SARS-CoV-2.

Treatment outcomes in tinnitus patients are associated with brain functional network: Evidence from connectome gradient and gene expression analysis.

The neuroimaging mechanisms underlying differences in the outcomes of sound therapy for tinnitus patients remain unclear. We hypothesize that abnormal hierarchical architecture is the neuro-biomarker for treatment outcome explanation. We conducted functional connectome gradient analyses on resting-state functional MRI images that acquired before intervention to investigate differences among the patients with effective treatment (ET, n = 27), ineffective treatment (IT, n = 41), and healthy controls (HC, n = 59). General linear models were used to analyze the associations between intergroup differential regions and clinical characteristics. Partial least squares regression was employed to reveal correlations with gene expression. Compared to HC, both ET and IT groups displayed significant differences in the default mode network. Moreover, the ET group exhibited wider gradient range and greater gradient variance. Also, the gradient scores of the differential regions between the ET and HC groups were significantly correlated with Self-rating Anxiety Scale and Self-rating Depression Scale scores, and exhibited positive correlations with the transcriptional profiles of genes related to depression and anxiety. Our results indicated that the abnormalities of ET group, may be more relevant to psychiatric disorders, bringing a higher possible therapeutic potential due to the plasticity of the nervous system. Connectome gradient dysfunction with genetic evidence may serve as an indicator for identifying diverse treatment outcomes of the sound therapy for tinnitus patients before treatment.

Causal relationship between multiparameter brain MRI phenotypes and age: evidence from Mendelian randomization.

To explore the causal relationship between age and brain health (cortical atrophy, white matter integrity, white matter hyperintensities and cerebral microbleeds in various brain regions) related multiparameter imaging features using two-sample Mendelian randomization. Age was determined as chronological age of the subject. Cortical volume, white matter micro-integrity, white matter hyperintensity volume and cerebral microbleeds of each brain region were included as phenotypes for brain health. Age and imaging of brain health related genetic data were analysed to determine the causal relationship using inverse-variance weighted model, validated by heterogeneity and horizontal pleiotropy variables. Age is causally related to increased volumes of white matter hyperintensities (ß = 0.151). For white matter micro-integrity, fibres of the inferior cerebellar peduncle (axial diffusivity ß = -0.128, orientation dispersion index ß = 0.173), cerebral peduncle (axial diffusivity ß = -0.136), superior fronto-occipital fasciculus (isotropic volume fraction ß = 0.163) and fibres within the limbic system were causally deteriorated. We also detected decreased cortical thickness of multiple frontal and temporal regions (P < 0.05). Microbleeds were not related with aging (P > 0.05). Aging is a threat of brain health, leading to cortical atrophy mainly in the frontal lobes, as well as the white matter degeneration especially abnormal hyperintensity and deteriorated white matter integrity around the hippocampus.

Brain Network Evaluation by Functional-Guided Effective Connectivity Reinforcement Learning Method Indicates Therapeutic Effect for Tinnitus.

Using functional connectivity (FC) or effective connectivity (EC) alone cannot effectively delineate brain networks based on functional magnetic resonance imaging (fMRI) data, limiting the understanding of the mechanism of tinnitus and its treatment. Investigating brain FC is a foundational step in exploring EC. This study proposed a functionally guided EC (FGEC) method based on reinforcement learning (FGECRL) to enhance the precision of identifying EC between distinct brain regions. An actor-critic framework with an encoder-decoder model was adopted as the actor network. The encoder utilizes a transformer model; the decoder employs a bidirectional long short-term memory network with attention. An FGEC network was constructed for the enrolled participants per fMRI scan, including 65 patients with tinnitus and 28 control participants healthy at the enrollment time. After 6 months of sound therapy for tinnitus and prospective follow-up, fMRI data were acquired again and retrospectively categorized into an effective group (EG) and an ineffective group (IG) according to the treatment effect. Compared with FC and EC, the FGECRL method demonstrated better accuracy in discriminating between different groups, highlighting the advantage of FGECRL in identifying brain network features. For the FGEC network of the EG and IG per state (before and after treatment) and healthy controls, effective therapy is characterized by a similar pattern of FGEC network between patients with tinnitus after treatment and healthy controls. Deactivated information output in the motor network, somatosensory network, and medioventral occipital cortex may biologically indicate effective treatment. The maintenance of decreased EC in the primary auditory cortex may represent a failure of sound therapy, further supporting the Bayesian inference theory for tinnitus perception. The FGEC network can provide direct evidence for the mechanism of sound therapy in patients with tinnitus with distinct outcomes.

Quantitative Comparison of Liver Volume, Proton Density Fat Fraction, and Time Burden between Automatic Whole Liver Segmentation and Manual Sampling MRI Strategies for Diagnosing Metabolic Dysfunction-associated Steatotic Liver Disease in Obese Patients.

BACKGROUND: The performance of automatic liver segmentation and manual sampling MRI strategies needs be compared to determine interchangeability. OBJECTIVE: To compare automatic liver segmentation and manual sampling strategies (manual whole liver segmentation and standardized manual region of interest) for performance in quantifying liver volume and MRI-proton density fat fraction (MRI-PDFF), identifying steatosis grade, and time burden. METHODS: Fifty patients with obesity who underwent liver biopsy and MRI between December 2017 and November 2018 were included. Sampling strategies included automatic and manual whole liver segmentation and 4 and 9 large regions of interest. Intraclass correlation coefficient (ICC), Bland-Altman, linear regression, receiver operating characteristic curve, and Pearson correlation analyses were performed. RESULTS: Automatic whole liver segmentation liver volume and manual whole liver segmentation liver volume showed excellent agreement (ICC=0.97), high correlation (R2=0.96), and low bias (3.7%, 95% limits of agreement, -4.8%, 12.2%) in liver volume. There was the best agreement (ICC=0.99), highest correlation (R2=1.00), and minimum bias (0.84%, 95% limits of agreement, -0.20%, 1.89%) between automated whole liver segmentation MRI-PDFF and manual whole liver segmentation MRI-PDFF. There was no difference of each paired comparison of receiver operating characteristic curves for detecting steatosis (P=0.07-1.00). The minimum time burden for automatic whole liver segmentation was 0.32 s (0.32-0.33 s). CONCLUSION: Automatic measurement has similar effects to manual measurement in quantifying liver volume, MRI-PDFF, and detecting steatosis. Time burden of automatic whole liver segmentation is minimal among all sampling strategies. Manual measurement can be replaced by automatic measurement to improve quantitative efficiency.

Protective effect of short-chain fructo-oligosaccharides from chicory on alcohol-induced injury in GES-1 cells via Keap1/Nrf2 and NLRP3 inflammasome signaling pathways.

Numerous studies have demonstrated that polysaccharides derived from chicory possess the ability to regulate host signaling and modify mucosal damage. Yet, the effect and mechanism of short-chain fructo-oligosaccharides (scFOS) on gastric mucosa remain unclear. Hence, the protective effect of three scFOS (1-Kestose, Nystose, and 1F-Fructofuranosylnystose) against ethanol-induced injury in gastric epithelial (GES-1) cells, and the underlying molecular mechanism involved was investigated in this study. Treatment with 7% ethanol decreased the cell viability of GES-1 cells, resulting in oxidative stress and inflammation. However, pretreatment with scFOS exhibited significant improvements in cell viability, and mitigated oxidative stress and inflammation. scFOS markedly elevated the protein expression of Nrf2, HO-1, SOD1 and SOD2, while suppressing the expression of Keap1. scFOS pretreatment could also maintain mitochondrial membrane potential balance and reduce apoptosis. In addition, scFOS was observed to reduce the protein level of NLRP3, Caspase-1 and ASC. In conclusion, scFOS served a preventive function in mitigating oxidative stress and inflammation in ethanol-exposed GES-1 cells through modulation of the Keap1/Nrf2 and NLRP3 inflammasome signaling pathways. Collectively, the results indicated that scFOS could significantly mitigate ethanol-induced gastric cell damage, suggesting its potential for safeguarding gastrointestinal health.

Site-specific pegylated IL2 mutein with biased IL2 receptor binding for cancer immunotherapy.

While Interleukin 2 (IL2) has the capability to activate both NK and T cells robustly, its limited in vivo half-life, considerable toxicity, and tendency to boost Treg cells pose significant challenges, restricting its widespread application in cancer therapy. In this investigation, we engineered a novel IL2 variant (IL2-4M-PEG) with reduced CD25 binding activity and an extended half-life by substituting amino acids associated with CD25 binding and implementing site-directed PEGylation. IL2-4M-PEG notably amplifies effector cells over Treg cells. Furthermore, our findings reveal that IL2-4M-PEG, characterized by an extended half-life, exhibits anti-tumor effects in a mouse model. Consequently, this innovative IL2 holds the potential for enhancing combined cancer therapies in the future.

Sub-features orthogonal decoupling: Detecting bone wall absence via a small number of abnormal examples for temporal CT images.

The absence of bone wall located in the jugular bulb and sigmoid sinus of the temporal bone is one of the important reasons for pulsatile tinnitus. Automatic and accurate detection of these abnormal singes in CT slices has important theoretical significance and clinical value. Due to the shortage of abnormal samples, imbalanced samples, small inter-class differences, and low interpretability, existing deep-learning methods are greatly challenged. In this paper, we proposed a sub-features orthogonal decoupling model, which can effectively disentangle the representation features into class-specific sub-features and class-independent sub-features in a latent space. The former contains the discriminative information, while, the latter preserves information for image reconstruction. In addition, the proposed method can generate image samples using category conversion by combining the different class-specific sub-features and the class-independent sub-features, achieving corresponding mapping between deep features and images of specific classes. The proposed model improves the interpretability of the deep model and provides image synthesis methods for downstream tasks. The effectiveness of the method was verified in the detection of bone wall absence in the temporal bone jugular bulb and sigmoid sinus.

Association of variability in body size with neuroimaging metrics of brain health: a population-based cohort study.

Background: The relationship between the fluctuation in body size and brain health is poorly understood. This study aimed to examine the associations of long-term variability in body mass index (BMI) and waist-to-hip ratio (WHR) with neuroimaging metrics that approximate brain health. Methods: This cohort study recruited 1114 participants aged 25-83 years from a multicenter, community-based cohort study in China. We modeled the BMI and WHR trajectories of participants during 2006-2018 and assessed the BMI and WHR variability (direction and speed of change) by calculating the slope. Generalized linear models were applied to investigate the associations of BMI and WHR variability with MRI markers of brain tissue volume, white matter microstructural integrity, white matter hyperintensity (WMH), and cerebral small vessel disease (CSVD). Findings: Progressive weight gain during follow-up was associated with lower global fractional anisotropy (beta = -0.18, 95% confidence interval [CI] -0.34 to -0.02), higher mean diffusivity (beta = 0.15, 95% CI 0.01-0.30) and radial diffusivity (beta = 0.17, 95% CI 0.02-0.32). Weight loss was also associated with a lower burden of periventricular WMH (beta = -0.26, 95% CI -0.48 to -0.03) and a lower risk of moderate-to-severe basal ganglia enlarged perivascular spaces (BG-EPVS, odds ratio [OR] = 0.41, 95% CI 0.20-0.83). Among overweight populations, weight loss was linked with smaller volumes of WMH (beta = -0.47, 95% CI -0.79 to -0.15), periventricular WMH (beta = -0.57, 95% CI -0.88 to -0.26), and deep WMH (beta = -0.36, 95% CI -0.69 to -0.03), as well as lower risk of CSVD (OR = 0.22, 95% CI 0.08-0.62), lacune (OR = 0.12, 95% CI 0.01-0.91) and moderate-to-severe BG-EPVS (OR = 0.24, 95% CI 0.09-0.61). In adults with central obesity, WHR loss was positively associated with larger gray matter volume (beta = 0.50, 95% CI 0.11-0.89), hippocampus volume (beta = 0.62, 95% CI 0.15-1.09), and parahippocampal gyrus volume (beta = 0.85, 95% CI 0.34-1.37). The sex-stratification and age-stratification analyses revealed similar findings with the main results, with the pattern of associations significantly presented in the individuals at mid-life and late-life. Interpretation: Long-term stability of BMI level is essential for maintaining brain health. Progressive weight gain is associated with impaired white matter microstructural integrity. Weight and WHR losses are associated with improved general brain health. Our results contribute to a better understanding of the integrated associations between variations in obesity measures and brain health. Funding: This study was supported by grants No. 62171297 (Han Lv) and 61931013 (Zhenchang Wang) from the National Natural Science Foundation of China, No. 7242267 from the Beijing Natural Science Foundation (Han Lv), and No. [2015] 160 from the Beijing Scholars Program (Zhenchang Wang).

Association between Body Mass Index and Brain Health in Adults: A 16-Year Population-Based Cohort and Mendelian Randomization Study.

Background: The cumulative effect of body mass index (BMI) on brain health remains ill-defined. The effects of overweight on brain health across different age groups need clarification. We analyzed the effect of cumulative BMI on neuroimaging features of brain health in adults of different ages. Methods: This study was based on a multicenter, community-based cohort study. We modeled the trajectories of BMI over 16 years to evaluate cumulative exposure. Multimodality neuroimaging data were collected once for volumetric measurements of the brain macrostructure, white matter hyperintensity (WMH), and brain microstructure. We used a generalized linear model to evaluate the association between cumulative BMI and neuroimaging features. Two-sample Mendelian randomization analysis was performed using summary level of BMI genetic data from 681,275 individuals and neuroimaging genetic data from 33,224 individuals to analyze the causal relationships. Results: Clinical and neuroimaging data were obtained from 1,074 adults (25 to 83 years). For adults aged under 45 years, brain volume differences in participants with a cumulative BMI of >26.2 kg/m2 corresponded to 12.0 years [95% confidence interval (CI), 3.0 to 20.0] of brain aging. Differences in WMH were statistically substantial for participants aged over 60 years, with a 6.0-ml (95% CI, 1.5 to 10.5) larger volume. Genetic analysis indicated causal relationships between high BMI and smaller gray matter and higher fractional anisotropy in projection fibers. Conclusion: High cumulative BMI is associated with smaller brain volume, larger volume of white matter lesions, and abnormal microstructural integrity. Adults younger than 45 years are suggested to maintain their BMI below 26.2 kg/m2 for better brain health. Trial Registration: This study was registered on clinicaltrials.gov (Clinical Indicators and Brain Image Data: A Cohort Study Based on Kailuan Cohort; No. NCT05453877; https://clinicaltrials.gov/ct2/show/NCT05453877).

Hemodynamic assessments of unilateral pulsatile tinnitus with jugular bulb wall dehiscence using 4D flow magnetic resonance imaging.

Background: Pulsatile tinnitus (PT) is a type of tinnitus characterized by a rhythmic sound that is synchronous with the heartbeat. One of the possible causes of PT is the jugular bulb wall dehiscence (JBWD). However, the hemodynamics of this condition are not well understood. To elucidate this issue, the present study aimed to compare the blood flow of PT patients with JBWD, PT patients with sigmoid sinus wall dehiscence (SSWD), and volunteers. Methods: A retrospective case-control study was conducted, which enrolled patients with unilateral PT who had undergone both computed tomography angiography (CTA) and four-dimensional (4D) flow magnetic resonance imaging (MRI) examinations at the Department of Otolaryngology-Head and Neck Surgery of Beijing Friendship Hospital affiliated to Capital Medical University between January 2019 and July 2023. After excluding the possible causes of PT, the patients were divided into the JBWD group and SSWD group according to the presence or absence of JBWD and/or SSWD. Finally, 11 female unilateral PT patients with JBWD (JBWD group, 11sides), 22 age- and side-matched female patients with SSWD (SSWD group, 22 sides), and 22 age-matched female volunteers (volunteer group, 36 sides) were enrolled. The area, maximum voxel velocity (Vv-max), maximum velocity (Vmax), average velocity (Vavg), and average blood flow rate (Q) were measured in the transverse sinuses (TSs), sigmoid sinuses (SSs), and jugular bulb (JB). The vortex flow pattern was also assessed. Fisher's exact test and Bonferroni correction were used for count data, with P<0.017 was considered statistically significant. Shapiro-Wilk test, one-way analysis of variance (ANOVA), Kruskal-Wallis H test, paired-samples t-test, and Wilcoxon matched-pairs signed-rank test were used for continuous variables depending on the distribution and variance of the data. The P<0.05 and corrected P<0.05 was considered statistically significant. Results: The area and Q of TSs and JB on the symptomatic side were higher than those on the contralateral side in the JBWD group (TSs: Parea=0.004, Pflow=0.002; JB: Parea=0.034, Pflow=0.018). The area was larger and velocities were lower in the JBWD group at the TSs than the SSWD group (Parea=0.004, PVv-max=0.009, PVmax=0.021, PVavg=0.026), and velocities were higher at the distal TSs and SSs than the volunteer group (TSs: PVv-max=0.042, PVmax=0.046, PVavg=0.040; SSs: PVv-max=0.007, PVmax=0.001, PVavg=0.001). At the JB, the JBWD group also had higher Vv-max than the volunteer group (P=0.012). The occurrence rate of vortex at JB in the JBWD group was higher than both the JBWD and the volunteer groups (P=0.002<0.017 and P=0.009<0.017, respectively). Conclusions: The blood flow of the intracranial venous sinus was different between the JBWD group and the SSWD group. The indicators that can differentiate include Vv-max, Vmax, Vavg, vortex, and TSs cross-sectional area.