Diffusion Kurtosis Imaging in Diagnosing Parkinson's Disease: A Preliminary Comparison Study Between Kurtosis Metric and Radiomic Features.

RATIONALE AND OBJECTIVES: Parkinson's disease (PD) shows small structural changes in nigrostriatal pathways, which can be sensitively captured through diffusion kurtosis imaging (DKI). However, the value of DKI and its radiomic features in the classification performance of PD still need confirmation. This study aimed to compare the diagnostic efficiency of DKI-derived kurtosis metric and its radiomic features with different machine learning models for PD classification. MATERIALS AND METHODS: 75 people with PD and 80 healthy individuals had their brains scanned using DKI. These images were pre-processed and the standard atlas were non-linearly registered to them. With the labels in atlas, different brain regions in nigrostriatal pathways, including the caudate nucleus, putamen, pallidum, thalamus, and substantia nigra, were chosen as the region of interests (ROIs) to warped to the native space to measure the mean kurtosis (MK). Additionally, new radiomic features were developed for comparison. To handle the large amount of data, a statistical method called Z-score normalization and another method called LASSO regression were used to simplify the information. From this, a few most important features were chosen, and a combined score called Radscore was calculated using LASSO regression. For the comprehensive analyses, three different conventional machine learning models were then created: logistic regression (LR), support vector machine (SVM), and random forest (RF). To ensure the models were accurate, a process called 10-fold cross-validation was used, where the data were split into 10 parts for training and testing. RESULTS: Using MK alone, the models achieved good results in correctly identifying PD in the validation set, with LR at 0.90, RF at 0.93, and SVM at 0.90. When the radiomic features were added, the models performed even better, with LR at 0.92, RF at 0.95, and SVM at 0.91. Additionally, a nomogram combining all the information was created to predict the likelihood of someone having PD, which had an AUC of 0.91. CONCLUSION: These findings suggest that the combination of DKI measurements and radiomic features can effectively diagnose PD by providing more detailed information about the brain's condition and the processes involved in the disease.

Characterizing microstructural patterns within the cortico-striato-thalamo-cortical circuit in Parkinson's disease.

PURPOSE: Parkinson's disease (PD) involves pathological alterations that include cortical impairments at levels of region and network. However, its microstructural abnormalities remain to be further elucidated via an appropriate diffusion neuroimaging approach. This study aimed to comprehensively demonstrate the microstructural patterns of PD as mapped by diffusion kurtosis imaging (DKI). METHODS: The microstructure of grey matter in both the PD group and the matched healthy control group was quantified by a DKI metric (mean kurtosis). The intergroup difference and classification performance of global microstructural complexity were analyzed in a voxelwise manner and via a machine learning approach, respectively. The patterns of information flows were explored in terms of structural connectivity, network covariance and modular connectivity. RESULTS: Patients with PD exhibited global microstructural impairments that served as an efficient diagnostic indicator. Disrupted structural connections between the striatum and cortices as well as between the thalamus and cortices were widely distributed in the PD group. Aberrant covariance of the striatocortical circuitry and thalamocortical circuitry was observed in patients with PD, who also showed disrupted modular connectivity within the striatum and thalamus as well as across structures of the cortex, striatum and thalamus. CONCLUSION: These findings verified the potential clinical application of DKI for the exploration of microstructural patterns in PD, contributing complementary imaging features that offer a deeper insight into the neurodegenerative process.

Causal association of micronutrients and supplements with pressure ulcer: A Mendelian randomization study.

BACKGROUND: Pressure ulcer (PU) is known to be associated with abnormalities of micronutrient status. However, to date, it is not clear whether a causal relationship exists between circulating levels of micronutrients and their supplementations and PU. METHODS: A two-sample Mendelian randomization (MR) study was conducted using summary statistics from Genome-Wide Association Studies (GWAS). Genetic instrumental variables (IVs) for 13 micronutrients were identified from a GWAS of 67 582 participants, IVs for supplement zinc were acquired from 18 826 cases and 44 255 880 controls, and IVs for PU were obtained from 663 PUs and 207 482 controls. The MR analysis was conducted using the MR base platform. The main analysis method was inverse variance weighted (IVW) analysis, supplemented by MR Egger, Weighted median, Weighted mode, and Simple mode analyses. Heterogeneity was assessed using Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger. Pleiotropy was determined by the MR-Egger regression. Sensitivity analysis was conducted using the leave-one-out method, and publication bias was evaluated using funnel plots. RESULTS: Genetically predicted lower circulating zinc levels were found to be causally linked to the development of PU (OR = 0.758, 95%CI 0.583-0.987, P = 0.040). However, there was no significant evidence of a causal relationship between supplemental zinc intake and PU development (P > 0.05). Additionally, no causal association was observed between the other circulating micronutrients and the occurrence of PU. Furthermore, there was no indication of horizontal pleiotropy or heterogeneity among genetic variants (P > 0.05), and the robustness of the findings was confirmed through leave-one-out tests and funnel plots. CONCLUSIONS: Our findings indicate a potential causal association between circulating zinc levels and decreased risk of PU. However, zinc supplementation did not demonstrate a significant reduction in the risk of PU. Further research is warranted to elucidate the underlying mechanisms through which zinc influences the pathogenesis of PU and evaluate the efficacy of zinc supplementation in the prevention and management of PU.

Early detection of dopaminergic dysfunction and glymphatic system impairment in Parkinson's disease.

PURPOSE: This study aimed to assess the glymphatic function and its correlation with clinical characteristics and the loss of dopaminergic neurons in Parkinson's disease (PD) using hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI) combined with diffusion tensor image analysis along the perivascular space (DTI-ALPS), choroid plexus volume (CPV), and enlarged perivascular space (EPVS) volume. METHODS: Twenty-five PD patients and thirty matched healthy controls (HC) participated in the study. All participants underwent 18F-fluorodopa (18F-DOPA) PET-MRI scanning. The striatal standardized uptake value ratio (SUVR), DTI-ALPS index, CPV, and EPVS volume were calculated. Furthermore, we also analysed the relationship between the DTI-ALPS index, CPV, EPVS volume and striatal SUVR as well as clinical characteristics of PD patients. RESULTS: PD patients demonstrated significantly lower values in DTI-ALPS (t = 3.053, p = 0.004) and larger CPV (t = 2.743, p = 0.008) and EPVS volume (t = 2.807, p = 0.008) compared to HC. In PD group, the ALPS-index was negatively correlated with the Unified Parkinson's Disease Rating Scale III (UPDRS-III) scores (r = -0.730, p < 0.001), and positively correlated with the mean putaminal SUVR (r = 0.560, p = 0.007) and mean caudal SUVR (r = 0.459, p = 0.032). Moreover, the mean putaminal SUVR was negatively associated with the UPDRS-III scores (r = -0.544, p = 0.009). CONCLUSION: DTI-ALPS has the potential to uncover glymphatic dysfunction in patients with PD, with this dysfunction correlating strongly with the severity of disease, together with the mean putaminal and caudal SUVR. PET- MRI can serve as a potential multimodal imaging biomarker for early-stage PD.

Effect of maternal cigarette smoke exposure on COPD progression in offspring mice.

OBJECTIVE: To investigate the impact of maternal smoking on chronic obstructive pulmonary disease (COPD) progression in offspring. METHODS: Using female C57BL/6 J mice, a maternal cigarette smoke exposure (CSE) model was established. Mice were exposed to cigarette smoke for 2 hours/day, 7 days/week, with a minimum 4-hour interval between exposures. Experimental groups included control (Con), pregnancy exposure (AS), pre-pregnancy exposure (SA), and pre-pregnancy + pregnancy exposure (SS). Lung function tests (Penh, PAU, TVb, EF50, Tr) were conducted on male offspring at 7 weeks. Histopathology, electron microscopy, and protein level changes were examined. RESULTS: Lung function tests revealed significant impairments in Penh, PAU, TVb, EF50, and Tr in offspring across all exposure scenarios. Specifically, AS experienced significant lung function impairment and mitochondrial dysfunction in offspring, with noticeable pulmonary lesions and increased apoptosis. SA showed similar or even more severe lung function impairment and cellular apoptosis. SS exhibited the most pronounced effects, with the highest levels of lung dysfunction, mitochondrial damage, and apoptosis. Histopathological analysis showed pulmonary lesions in offspring exposed to maternal CSE. Flow cytometry revealed increased apoptosis and reduced mitochondrial membrane potential in offspring lung cells. Electron microscopy confirmed mitochondrial dysfunction. Upregulation of apoptotic proteins and downregulation of anti-apoptotic protein Bcl-2 were found in offspring lung tissue exposed to maternal CSE. CONCLUSION: Maternal smoking induces impaired lung function, pulmonary lesions, and mitochondrial dysfunction in offspring, regardless of exposure timing and duration. Additionally, it alters expression of apoptosis-related proteins in offspring lung tissue, potentially contributing to COPD susceptibility.

Topological disruption of low- and high-order functional networks in presbycusis.

Prior efforts have manifested that functional connectivity (FC) network disruptions are concerned with cognitive disorder in presbycusis. The present research was designed to investigate the topological reorganization and classification performance of low-order functional connectivity (LOFC) and high-order functional connectivity (HOFC) networks in patients with presbycusis. Resting-state functional magnetic resonance imaging (Rs-fMRI) data were obtained in 60 patients with presbycusis and 50 matched healthy control subjects (HCs). LOFC and HOFC networks were then constructed, and the topological metrics obtained from the constructed networks were compared to evaluate topological differences in global, nodal network metrics, modularity and rich-club organization between patients with presbycusis and HCs. The use of HOFC profiles boosted presbycusis classification accuracy, sensitivity and specificity compared to that using LOFC profiles. The brain networks in both patients with presbycusis and HCs exhibited small-world properties within the given threshold range, and striking differences between groups in topological metrics were discovered in the constructed networks (LOFC and HOFC). NBS analysis identified a subnetwork involving 26 nodes and 23 signally altered internodal connections in patients with presbycusis in comparison to HCs in HOFC networks. This study highlighted the topological differences between LOFC and HOFC networks in patients with presbycusis, suggesting that HOFC profiles may help to further identify brain network abnormalities in presbycusis.

Molecular subtype identification and prognosis stratification by a immunogenic cell death-related gene expression signature in colorectal cancer.

OBJECTIVES: This study intended to develop a new immunogenic cell death (ICD)-related prognostic signature for colorectal cancer (CRC) patients. RESEARCH DESIGN AND METHODS: The Non-Negative Matrix Factorization (NMF) algorithm was adopted to cluster tumor samples based on ICD gene expression to obtain ICD-related subtypes. Survival analysis and immune microenvironment analysis were conducted among different subtypes. Regression analysis was used to construct the model. Based on riskscore median, cancer patients were classified into high and low risk groups, and independent prognostic ability of the model was analyzed. The CIBERSORT algorithm was adopted to determine the immune infiltration level of both groups. RESULTS: We analyzed the differential genes between cluster 4 and cluster 1-3 and obtained 12 genes with the best prognostic features finally (NLGN1, SLC30A3, C3orf20, ADAD2, ATOH1, ATP6V1B1, KCNQ2, MUCL3, RGCC, CLEC17A, COL6A5, and INSL4). In addition, patients with lower risk had higher levels of infiltration of most immune cells, lower Tumor Immune Dysfunction and Exclusion (TIDE) level and higher immunophenscore (IPS) level than those with higher risk. CONCLUSIONS: This study constructed and validated the ICD feature signature predicting CRC prognosis and provide a reference criteria for guiding the prognosis and immunotherapy of CRC cancer patients.

Intracerebral hemodynamic abnormalities in patients with Parkinson's disease: Comparison between multi-delay arterial spin labelling and conventional single-delay arterial spin labelling.

PURPOSE: The purpose of this study was to analyze the intracerebral abnormalities of hemodynamics in patients with Parkinson's disease (PD) through arterial spin labelling (ASL) technique with multi-delay ASL (MDASL) and conventional single-delay ASL (SDASL) protocols and to verify the potential clinical application of these features for the diagnosis of PD. MATERIALS AND METHODS: Perfusion data of the brain obtained using MDASL and SDASL in patients with PD were compared to those obtained in healthy control (HC) subjects. Intergroup comparisons of z-scored cerebral blood flow (zCBF), arterial transit time (zATT) and cerebral blood volume (zCBV) were performed via voxel-based analysis. Performance of these perfusion metrics were estimated using area under the receiver operating characteristic curve (AUC) and compared using Delong test. RESULTS: A total of 47 patients with PD (29 men; 18 women; mean age, 69.0 ± 7.6 (standard deviation, [SD]) years; range: 50.0-84.0 years) and 50 HC subjects (28 men; 22 women; mean age, 70.1 ± 6.2 [SD] years; range: 50.0-93.0 years) were included. Relative to the uncorrected-zCBF map, the corrected-zCBF map further refined the distributed brain regions in the PD group versus the HC group, manifested as the extension of motor-related regions (PFWE < 0.001). Compared to the HC subjects, patients with PD had elevated zATT and zCBV in the right putamen, a shortened zATT in the superior frontal gyrus, and specific zCBV variations in the left precuneus and the right supplementary motor area (PFWE < 0.001). The corrected-zCBF (AUC, 0.90; 95% confidence interval [CI]: 0.84-0.96) showed better classification performance than uncorrected-zCBF (AUC, 0.84; 95% CI: 0.75-0.92) (P = 0.035). zCBV achieved an AUC of 0.89 (95% CI: 0.82-0.96) and zATT achieved an AUC of 0.66 (95% CI: 0.55-0.77). The integration model of hemodynamic features from MDASL provided improved performance (AUC, 0.97; 95% CI: 0.95-0.98) for the diagnosis of PD by comparison with each perfusion model (P < 0.001). CONCLUSION: ASL identifies impaired hemodynamics in patients with PD including regional abnormalities of CBF, CBV and ATT, which can better be mapped with MDASL compared to SDASL. These findings provide complementary depictions of perfusion abnormalities in patients with PD and highlight the clinical feasibility of MDASL.

Optimization of structural connectomes and scaled patterns of structural-functional decoupling in Parkinson's disease.

Parkinson's disease (PD) is manifested with disrupted topology of the structural connection network (SCN) and the functional connection network (FCN). However, the SCN and its interactions with the FCN remain to be further investigated. This multimodality study attempted to precisely characterize the SCN using diffusion kurtosis imaging (DKI) and further identify the neuropathological pattern of SCN-FCN decoupling, underscoring the neurodegeneration of PD. Diffusion-weighted imaging and resting-state functional imaging were available for network constructions among sixty-nine patients with PD and seventy demographically matched healthy control (HC) participants. The classification performance and topological prosperities of both the SCN and the FCN were analyzed, followed by quantification of the SCN-FCN couplings across scales. The SCN constructed by kurtosis metrics achieved optimal classification performance (area under the curve 0.89, accuracy 80.55 %, sensitivity 78.40 %, and specificity 80.65 %). Along with diverse alterations of structural and functional network topology, the PD group exhibited decoupling across scales including: reduced global coupling; increased nodal coupling within the sensorimotor network (SMN) and subcortical network (SN); higher intramodular coupling within the SMN and SN and lower intramodular coupling of the default mode network (DMN); decreased coupling between the modules of DMN-fronto-parietal network and DMN-visual network, but increased coupling between the SMN-SN module. Several associations between the coupling coefficient and topological properties of the SCN, as well as between network values and clinical scores, were observed. These findings validated the clinical implementation of DKI for structural network construction with better differentiation ability and characterized the SCN-FCN decoupling as supplementary insight into the pathological process underlying PD.

Drooling disrupts the brain functional connectivity network in Parkinson's disease.

AIMS: This study aimed to investigate the causal interaction between significant sensorimotor network (SMN) regions and other brain regions in Parkinson's disease patients with drooling (droolers). METHODS: Twenty-one droolers, 22 PD patients without drooling (non-droolers), and 22 matched healthy controls underwent 3T-MRI resting-state scans. We performed independent component analysis and Granger causality analysis to determine whether significant SMN regions help predict other brain areas. Pearson's correlation was computed between imaging characteristics and clinical characteristics. ROC curves were plotted to assess the diagnostic performance of effective connectivity (EC). RESULTS: Compared with non-droolers and healthy controls, droolers showed abnormal EC of the right caudate nucleus (CAU.R) and right postcentral gyrus to extensive brain regions. In droolers, increased EC from the CAU.R to the right middle temporal gyrus was positively correlated with MDS-UPDRS, MDS-UPDRS II, NMSS, and HAMD scores; increased EC from the right inferior parietal lobe to CAU.R was positively correlated with MDS-UPDRS score. ROC curve analysis showed that these abnormal ECs are of great significance in diagnosing drooling in PD. CONCLUSION: This study identified that PD patients with drooling have abnormal EC in the cortico-limbic-striatal-cerebellar and cortio-cortical networks, which could be potential biomarkers for drooling in PD.

Exosomal PD­L1 promotes the formation of an immunosuppressive microenvironment in gastric diffuse large B­cell lymphoma.

Gastric diffuse large B­cell lymphoma (GDLBCL) is a common disease with an increasing incidence. However, the regulatory effect of exosomal programmed death­ligand 1 (PD­L1) on the immune microenvironment in GDLBCL is unclear. In the present study, the protein expression levels of exosomal PD­L1 in the supernatants of cultured diffuse large B­cell lymphoma (DLBCL) cells and the plasma of patients with GDLBCL was assessed using immunoblotting. Exosomes derived from DLBCL cells were cocultured with T lymphocytes or injected into tumor xenograft mice by tail vein injection. The relationship between the protein expression level of exosomal PD­L1 in the plasma and the clinical characteristics and immune microenvironmental parameters of GDLBCL was evaluated using immunoblotting and immunohistochemistry. High levels of exosomal PD­L1 were found in the supernatants of cultured DLBCL cells. Exosomes with high levels of PD­L1 promoted growth of tumors formed by DLBCL cells in vivo and inhibited the proliferation of T lymphocytes. Notably, the protein expression level of PD­L1 in plasma exosomes derived from GDLBCL patients was significantly higher than that of healthy individuals. High levels of PD­L1 in plasma exosomes were significantly associated with international prognostic index score, pathological type and advanced Lugano stage, which might lead to the poor prognosis of GDLBCL. Moreover, a high level of PD­L1 in plasma exosomes was significantly associated with an immunosuppressive microenvironment in GDLBCL. Therefore, the results of the present study indicated that exosomal PD­L1 inhibited the proliferation of T lymphocytes and promoted the formation of an immunosuppressive microenvironment in GDLBCL. High expression of exosomal PD­L1 may suggest a poor prognosis of GDLBCL, and exosomal PD­L1 in plasma may be a new diagnostic indicator for GDLBCL.

Functional-structural large-scale brain networks are correlated with neurocognitive impairment in acute mild traumatic brain injury.

Background: This study was conducted to investigate topological changes in large-scale functional connectivity (FC) and structural connectivity (SC) networks in acute mild traumatic brain injury (mTBI) and determine their potential relevance to cognitive impairment. Methods: Seventy-one patients with acute mTBI (29 males, 42 females, mean age 43.54 years) from Nanjing First Hospital and 57 matched healthy controls (HC) (33 males, 24 females, mean age 46.16 years) from the local community were recruited in this prospective study. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were acquired within 14 days (mean 3.29 days) after the onset of mTBI. Then, large-scale FC and SC networks with 116 regions from the automated anatomical labeling (AAL) brain atlas were constructed. Graph theory analysis was used to analyze global and nodal metrics. Finally, correlations were assessed between topological properties and neurocognitive performances evaluated by the Montreal Cognitive Assessment (MoCA). Bonferroni correction was performed out for multiple comparisons in all involved analyses. Results: Compared with HC, acute mTBI patients had a higher normalized clustering coefficient (γ) for FC (Cohen's d=4.076), and higher γ and small worldness (σ) for SC (Cohen's d=0.390 and Cohen's d=0.395). The mTBI group showed aberrant nodal degree (Dc), nodal efficiency (Ne), and nodal local efficiency (Nloc) for FC and aberrant Dc, nodal betweenness (Bc), nodal clustering coefficient (NCp) and Ne for SC mainly in the frontal and temporal, cerebellum, and subcortical areas. Acute mTBI patients also had higher functional-structural coupling strength at both the group and individual levels (Cohen's d=0.415). These aberrant global and nodal topological properties at functional and structural levels were associated with attention, orientation, memory, and naming performances (all P<0.05). Conclusions: Our findings suggested that large-scale FC and SC network changes, higher correlation between FC and SC and cognitive impairment can be detected in the acute stage of mTBI. These network aberrances may be a compensatory mechanism for cognitive impairment in acute mTBI patients.

Topological disruption of high-order functional networks in cognitively preserved Parkinson's disease.

AIMS: This study aimed to characterize the topological alterations and classification performance of high-order functional connectivity (HOFC) networks in cognitively preserved patients with Parkinson's disease (PD), relative to low-order FC (LOFC) networks. METHODS: The topological metrics of the constructed networks (LOFC and HOFC) obtained from fifty-one cognitively normal patients with PD and 60 matched healthy control subjects were analyzed. The discriminative abilities were evaluated using machine learning approach. RESULTS: The HOFC networks in the PD group showed decreased segregation and integration. The normalized clustering coefficient and small-worldness in the HOFC networks were correlated to motor performance. The altered nodal centralities (distributed in the precuneus, putamen, lingual gyrus, supramarginal gyrus, motor area, postcentral gyrus and inferior occipital gyrus) and intermodular FC (frontoparietal and visual networks, sensorimotor and subcortical networks) were specific to HOFC networks. Several highly connected nodes (thalamus, paracentral lobule, calcarine fissure and precuneus) and improved classification performance were found based on HOFC profiles. CONCLUSION: This study identified disrupted topology of functional interactions at a high level with extensive alterations in topological properties and improved differentiation ability in patients with PD prior to clinical symptoms of cognitive impairment, providing complementary insights into complex neurodegeneration in PD.

Rich-club reorganization of functional brain networks in acute mild traumatic brain injury with cognitive impairment.

Background: Mild traumatic brain injury (mTBI) is typically characterized by temporally limited cognitive impairment and regarded as a brain connectome disorder. Recent findings have suggested that a higher level of organization named the "rich-club" may play a central role in enabling the integration of information and efficient communication across different systems of the brain. However, the alterations in rich-club organization and hub topology in mTBI and its relationship with cognitive impairment after mTBI have been scarcely elucidated. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 88 patients with mTBI and 85 matched healthy controls (HCs). Large-scale functional brain networks were established for each participant. Rich-club organizations and network properties were assessed and analyzed between groups. Finally, we analyzed the correlations between the cognitive performance and changes in rich-club organization and network properties. Results: Both mTBI and HCs groups showed significant rich-club organization. Meanwhile, the rich-club organization was aberrant, with enhanced functional connectivity (FC) among rich-club nodes and peripheral regions in acute mTBI. In addition, significant differences in partial global and local network topological property measures were found between mTBI patients and HCs (P<0.01). In patients with mTBI, changes in rich-club organization and network properties were found to be related to early cognitive impairment after mTBI (P<0.05). Conclusions: Our findings suggest that such patterns of disruption and reorganization will provide the basic functional architecture for cognitive function, which may subsequently be used as an earlier biomarker for cognitive impairment after mTBI.

Reorganized Brain Functional Network Topology in Presbycusis.

Purpose: Presbycusis is characterized by bilateral sensorineural hearing loss at high frequencies and is often accompanied by cognitive decline. This study aimed to identify the topological reorganization of brain functional network in presbycusis with/without cognitive decline by using graph theory analysis approaches based on resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Resting-state fMRI scans were obtained from 30 presbycusis patients with cognitive decline, 30 presbycusis patients without cognitive decline, and 50 age-, sex-, and education-matched healthy controls. Graph theory was applied to analyze the topological properties of brain functional networks including global and nodal metrics, modularity, and rich-club organization. Results: At the global level, the brain functional networks of all participants were found to possess small-world properties. Also, significant group differences in global network metrics were observed among the three groups such as clustering coefficient, characteristic path length, normalized characteristic path length, and small-worldness. At the nodal level, several nodes with abnormal betweenness centrality, degree centrality, nodal efficiency, and nodal local efficiency were detected in presbycusis patients with/without cognitive decline. Changes in intra-modular connections in frontal lobe module and inter-modular connections in prefrontal subcortical lobe module were found in presbycusis patients exposed to modularity analysis. Rich-club nodes were reorganized in presbycusis patients, while the connections among them had no significant group differences. Conclusion: Presbycusis patients exhibited topological reorganization of the whole-brain functional network, and presbycusis patients with cognitive decline showed more obvious changes in these topological properties than those without cognitive decline. Abnormal changes of these properties in presbycusis patients may compensate for cognitive impairment by mobilizing additional neural resources.

Cerebral Blood Flow and its Connectivity Deficits in Patients With Lung Cancer After Chemotherapy.

Purpose: This study was performed to investigate the regional cerebral blood flow (CBF) and CBF connectivity in the chemotherapy-induced cognitive impairment of patients with lung cancer by using arterial spin labeling. Methods: Pseudocontinuous arterial spin labeling perfusion magnetic resonance imaging and neuropsychological tests were performed for 21 patients with non-small cell lung cancer who had received chemotherapy CT (+) and 25 non-small cell lung cancer patients who need chemotherapy but did not yet received CT (-). The CT (+) group previously received platinum-based therapy for 3 months to 6 months (the time from their first chemotherapy to the MRI scan). Group comparisons were performed in the regional normalized CBF and CBF connectivity, and the relationship between the regional normalized CBF and cognitive impairment were detected. Results: The CT (+) group exhibited higher CBF in the left insula, right caudate, right superior occipital gyrus, left superior temporal gyrus (STG), and right middle frontal gyrus (MFG). MoCA scores as well as the memory scores were negatively correlated with the increased CBF in the right MFG (r = -0.492, p = 0.023; r = -0.497, p = 0.022). Alterations in the CBF connectivity were detected only in the CT (+) group between the following: right MFG and the right precentral gyrus; the right caudate and the right lingual gyrus; right caudate and right precuneus; left STG and the bilateral MFG; and the left STG and the right middle cingulum. Conclusion: These findings indicated that chemotherapy is associated with abnormalities in the CBF and connectivity alterations, which may contribute to the cognitive impairment in patients with lung cancer.

Early disturbance of dynamic synchronization and neurovascular coupling in cognitively normal Parkinson's disease.

Pathological process in Parkinson's disease (PD) is accompanied with functional and metabolic alterations. The time-varying properties of functional coherence and their coupling to regional perfusion are still rarely elucidated. To investigate early disruption of dynamic regional homogeneity (dReho) and neurovascular coupling in cognitively normal PD patients, dynamic neuronal synchronization and regional perfusion were measured using dReho and cerebral blood flow (CBF), respectively. Neurovascular coupling was assessed by CBF-ReHo correlation coefficient and CBF/ReHo ratio. Multivariate pattern analysis was conducted for the differentiating ability of each feature. Relative to healthy controls (HC) subjects, PD patients demonstrated increased dReho in middle temporal gyrus (MTG), rectus gyrus, middle occipital gyrus, and precuneus, whereas reduced dReho in putamen and supplementary motor area (SMA); while higher CBF/dReho ratio was located in putamen, SMA, paracentral lobule, and postcentral gyrus, whereas lower CBF/dReho ratio in superior temporal gyrus, MTG, precuneus, and angular gyrus (AG). Global and regional CBF-Reho decoupling were both observed in PD groups. The CBF/Reho ratio features achieved more powerful classification performance than other features. From the view of dynamic neural synchronization and neurovascular coupling, this study reinforced the insights into neural basis underlying PD and the potential role in the disease diagnosis and differentiation.

Xylariaopyrones E-I, five new α-pyrone derivatives from the endophytic fungus Xylariales sp. (HM-1).

Five new α-pyrones, xylariaopyrones E-I (1-5), along with three known analogues (6-8) were isolated from the cultivation broth of the endophytic fungus Xylariales sp. (HM-1). The structures of the new compounds including their absolute configurations were elucidated by comprehensive spectroscopic methods and quantum ECD calculations. Xylariaopyrone E (1) is the first example of α-pyrone derivative with a novel [3, 2, 0] bridge ring system via a ketal function group in the side chain. In bioactivity assays, xylariaopyrones E-G (1-3) showed moderate inhibiting activities against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa with MIC values from 25.4 to 64.5 µg/mL, whereras xylariaopyrone G (3) exhibited significant inhibition of monoamine oxidase B with an IC50 value of 15.6 µmol/L. Xylariaopyrone H (4) and the known compound 7 showed moderate toxicity against brine shrimp larvae with inhibition rates of 42.8% and 44.5%, respectively.

Aberrant Static and Dynamic Functional Network Connectivity in Acute Mild Traumatic Brain Injury with Cognitive Impairment.

PURPOSE: This study aimed to investigate differences in static and dynamic functional network connectivity (FNC) and explore their association with neurocognitive performance in acute mild traumatic brain injury (mTBI). METHODS: A total of 76 patients with acute mTBI and 70 age-matched and sex-matched healthy controls were enrolled (age 43.79 ± 10.22 years vs. 45.63 ± 9.49 years; male/female: 34/42 vs. 38/32; all p > 0.05) and underwent resting-state functional magnetic resonance imaging (fMRI) scan (repetition time/echo time = 2000/30 ms, 230 volumes). Independent component analysis was conducted to evaluate static and dynamic FNC patterns on the basis of nine resting-state networks, namely, auditory network (AUDN), dorsal attention network (dAN), ventral attention network (vAN), default mode network (DMN), left frontoparietal network (LFPN), right frontoparietal network (RFPN), somatomotor network (SMN), visual network (VN), and salience network (SN). Spearman's correlation among aberrances in FNC values, and Montreal cognitive assessment (MoCA) scores was further measured in mTBI. RESULTS: Compared with controls, patients with mTBI showed wide aberrances of static FNC, such as reduced FNC in DMN-vAN and VN-vAN pairs. The mTBI patients exhibited aberrant dynamic FNC in state 2, involving reduced FNC aberrance in the vAN with AUDN, VN with DMN and dAN, and SN with SMN and vAN. Reduced dFNC in the SN-vAN pair was negatively correlated with the MoCA score. CONCLUSION: Our findings suggest that aberrant static and dynamic FNC at the acute stage may contribute to cognitive symptoms, which not only may expand knowledge regarding FNC cognition relations from the static perspective but also from the dynamic perspective.

Topological features of limbic dysfunction in chronicity of tinnitus with intact hearing: New hypothesis for 'noise-cancellation' mechanism.

PURPOSE: The reorganization of the limbic regions extend to general cognitive network is believed to exist in the chronicity of tinnitus with particular 'hubs' contributing to a 'noise-cancellation' mechanism. To test this hypothesis, we investigated the topological brain network of tinnitus in different periods. METHODS: Resting-state functional magnetic resonance imaging were obtained from 32 patients with acute tinnitus, 41 patients with chronic tinnitus and 60 age- and gender- matched healthy controls (HC). The topological features of their brain networks were explored using graph theory analysis. RESULTS: Common small-world attributes were compared between the three groups, all showed a significantly increased values in Cp, Lp, λ (all p < 0.05). Significantly increased nodal centralities in the left superior frontal gyrus and the right precuneus, significantly decreased nodal centralities in the right inferior temporal gyrus were observed for acute tinnitus patients compared to HC. While for chronic tinnitus patients, there were significant increased nodal centralities in the left hippocampus, amygdala, and temporal pole, but decreased nodal centralities in the right inferior temporal gyrus. Additionally, significant higher nodal centralities were found in bilateral medial superior frontal gyrus for acute tinnitus patients compared to chronic tinnitus patients. Besides, alterations in rich-club organization were found in acute tinnitus patients and chronic tinnitus patients compared with HC, with increased functional connections among rich-club nodes and peripheral nodes in patients with tinnitus. CONCLUSIONS: Brain network topological properties altered across prefrontal-limbic-subcortical regions in tinnitus. The existed hubs in tinnitus might indicate an emotional and cognitive burden in 'noise-cancellation' mechanism.