Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Estimating parameters of the variable infiltration capacity model using ant colony optimization.

Because hydrological models are so important for addressing environmental problems, parameter calibration is a fundamental task for applying them. A broadly used method for obtaining model parameters for the past 20 years is the evolutionary algorithm. This approach can estimate a set of unknown model parameters by simulating the evolution process. The ant colony optimization (ACO) algorithm is a type of evolutionary algorithm that has shown a strong ability in tackling combinatorial problems and is suitable for hydrological model calibration. In this study, an ACO based on the grid partitioning strategy was applied to the parameter calibration of the variable infiltration capacity (VIC) model for the Upper Heihe River basin and Xitiaoxi River basin, China. The shuffled complex evolution (SCE-UA) algorithm was used to test the applicability of the ACO. The results show that ACO is capable of model calibration of the VIC model; the Nash-Sutcliffe coefficient of efficiency is 0.62 and 0.81 in calibration and 0.65 and 0.86 in validation for the Upper Heihe River basin and Xitiaoxi River basin respectively, which are similar to the SCE-UA results. Despite the encouraging results obtained thus far, further studies could still be performed on the parameter optimization of an ACO to enlarge its applicability to more distributed hydrological models.

Effects of long-term magnesium L-threonate supplementation on neuroinflammation, demyelination and blood-brain barrier integrity in mice with neuromyelitis optica spectrum disorder.

In clinical practice, we found cerebrospinal fluid magnesium concentration significantly lower in neuromyelitis optica spectrum disorder (NMOSD) patients compared to controls with non-autoimmune encephalitis neurological diseases. To investigate the effects and potential mechanisms of long-term magnesium supplementation on neuroinflammation, demyelination, and blood-brain barrier (BBB) integrity in NMOSD, we used two models: (1) NMOSD mouse model, which was induced by intraperitoneal injection of purified NMO-IgG to experimental autoimmune encephalomyelitis (EAE) mice, and (2) cultured human cerebral microvascular endothelial cells/D3 (hCMEC/D3). In the NMOSD mouse model, Magnesium L-threonate (MgT) pretreatment alleviated NMO-IgG-induced effects, including AQP4 loss, leukocyte infiltration, astrocyte and microglia activation, demyelination, decreased tight junction (TJ) protein expression, and neurological deficits. In vitro, MgT pretreatment ameliorated NMO-IgG induced damage to TJ protein expression in a (transient receptor potential melastatin 7) TRPM7-dependent manner. Magnesium supplementation shows potential protective effects against NMOSD, suggesting it may be a novel therapeutic approach for this condition. The beneficial effects appear to be mediated through preservation of blood-brain barrier integrity and reduction of neuroinflammation and demyelination.

Autoimmune astrocytopathy double negative for AQP4-IgG and GFAP-IgG: Retrospective research of clinical practice, biomarkers, and pathology.

OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.

Integrating transcriptome and metabolome to explore the growth-promoting mechanisms of GABA in blueberry plantlets.

Tissue culture technology is the main method for the commercial propagation of blueberry plants, but blueberry plantlets grow slowly and have long growth cycles under in vitro propagation, resulting in low propagation efficiency. In addition, the long culturing time can also result in reduced nutrient content in the culture medium, and the accumulation of toxic and harmful substances that can lead to weak growth for the plantlets or browning and vitrification, which ultimately can seriously reduce the quality of the plantlets. Gamma-aminobutyric acid (GABA) is a four-carbon non-protein amino acid that can improve plant resistance to various stresses and promote plant growth, but the effects of its application and mechanism in tissue culture are still unclear. In this study, the effects of GABA on the growth of in vitro blueberry plantlets were analyzed following the treatment of the plantlets with GABA. In addition, the GABA-treated plantlets were also subjected to a comparative transcriptomic and metabolomic analysis. The exogenous application of GABA significantly promoted growth and improved the quality of the blueberry plantlets. In total, 2,626 differentially expressed genes (DEGs) and 377 differentially accumulated metabolites (DAMs) were detected by comparison of the control and GABA-treated plantlets. Most of the DEGs and DAMs were involved in carbohydrate metabolism and biosynthesis of secondary metabolites. The comprehensive analysis results indicated that GABA may promote the growth of blueberry plantlets by promoting carbon metabolism and nitrogen assimilation, as well as increasing the accumulation of secondary metabolites such as flavonoids, steroids and terpenes.

Case Report: Extraocular muscles paralysis associated with GAD65 antibody: a case series study.

Objective: To explore the clinical manifestations of glutamic acid decarboxylase 65 (GAD65) antibody-positive patients with extraocular symptoms and the possible mechanism. Method: Assays for the presence of GAD65 antibodies were performed on patients' serum and cerebral spinal fluid (CSF). The brain and ocular structures involved in eye movement were assessed via magnetic resonance imaging (MRI). Tests such as electromyography (EMG), particularly repetitive nerve stimulation (RNS), and neostigmine tests were utilized for differential diagnosis. Additionally, the interaction of GAD65 antibodies with muscle tissue was confirmed using immunofluorescence techniques. Result: Each patient exhibited symptoms akin to extraocular myasthenia gravis (MG), with two individuals reporting diplopia and two experiencing ptosis. GAD65 antibodies were detected in either the serum or CSF, which were shown to bind with monkey cerebellum slides and mouse muscle slides. Neuroimaging of the brain and extraocular muscles via MRI showed no abnormalities, and all patients tested negative for the neostigmine test, RNS via EMG, and the presence of MG antibodies. However, thyroid-related antibodies were found to be abnormal in four of the patients. Conclusion: Our results showed that GAD65 antibodies are not only associated with encephalitis, cerebellum ataxia or stiff-person syndrome caused by the decrease of GABAergic transmission but also diplopia and ptosis. Therefore, we should pay more attention to extraocular muscle paralysis patients without pathogenic antibodies directed against the components of neuromuscular junctions.

Brain radial enhancement pattern in patients with negative glial fibrillary acidic protein-IgG: A cases series study.

BACKGROUND AND OBJECTIVES: Brain radial enhancement pattern on magnetic resonance imaging (MRI) has been identified as typical lesions in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, the authors encountered several patients without GFAP-IgG showing that such specific imaging. In the present study, we reported the clinical pictures of 5 GFAP-IgG-negative patients with GFAP-A specific imaging pattern. METHODS: Data was retrospectively obtained from June 2013 through April 2023, and five GFAP-IgG-negative patients with valid data were recruited. Clinical information was either obtained by the investigators or retrieved from the referring clinicians and included prodromal symptoms, neurologic manifestations, comorbidities, results of ancillary studies. RESULTS: Altogether five GFAP-IgG-negative patients with "meningoencephalitis/encephalitis" manifestations and brain radial perivascular enhancement were confirmed. One patient had peripheral lymphoma. Four patients had other autoimmune antibody in serum and/or cerebrospinal fluid, of which one patient had positive aquaporin IgG. Clinical features of the five patients included headache, fever, epilepsy and abnormal behavioral symptoms. MRI of patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP-A. CONCLUSION: GFAP-A-like disorders with radial perivascular enhancement could be found in GFAP-IgG-negative patients with or without neoplasm, which could provide new insight into the differential diagnosis of GFAP-A.

Serological biomarkers in autoimmune GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.

Characteristics and risk factors of lower urinary tract dysfunction in patients with Parkinson's disease: A systematic evaluation and meta-analysis.

To systematically evaluate the risk factors of lower urinary tract dysfunction in patients with Parkinson's disease(PD), and to provide theoretical basis for clinical medical staff to identify the risk factors of lower urinary tract dysfunction in patients with PD. From the establishment of the database to January 2021, PubMed, the Cochrane Library, EMBASE, Web of Science, other English database, were searched for literatures about the risk factors of lower urinary tract dysfunction in patients with Parkinson's disease. According to the inclusion and exclusion criteria, after browsing the title, abstract and full text, the high-quality literature in line with the inclusion criteria was selected, and the Newcastle-Ottawa Scale（NOS）document quality evaluation tool was used to evaluate the literature quality and extract the data. The included research results were analyzed by RevMan 5.3 software. A total of 8 studies were included for Meta analysis. The results showed that 7 of the 20 related risk factors were statistically significant, and the statistically significant risk factors were duration of disease [Mean Difference (MD)= 0.59, 95% Confidence Interval (CI) (0.04, 1.14), P < 0.005], age [MD = 2.01, 95%CI (-0.36, 3.34), P < 0.005], Hoehn-Yahr (H-Y) score >2 [Odds Ratio (OR) = 1.56, 95%CI (1.09, 2.23), P < 0.001], sleep disorder [OR = 1.79, 95%CI (1.36,2.35), P < 0.001], constipation [OR = 1.88, 95%CI (1.42,2.48), P < 0.001], unified Parkinson's disease rating scale (UPDRS III) [MD= 4.43, 95%CI (2.20, 6.66), P < 0.001], Mini-mental state examination (MMSE) [MD = -1.16, 95%CI (1.23, -1.09), P < 0.001]. Age, duration of disease, H-Y score >2, sleep disorder, constipation, higher UPDRS Ⅲ score and lower MMSE score were the risk factors of lower urinary tract dysfunction in patients with Parkinson's disease.

Mapping flood susceptibility in mountainous areas on a national scale in China.

Mountainous terrain covers nearly half of China and is susceptible to floods, which can lead to substantial losses of human life and property. Historical flooding records from government bulletins and newspapers, the only available information regarding floods that have occurred in some mountainous areas, are valuable for understanding flood disaster mechanisms in these regions. In this study, the flood susceptibility in mountainous regions in China was mapped based on historical flooding records from 1949 to 2000. A Random Forest (RF) model, which can handle large datasets through factor contribution analysis, was chosen to characterize the relationships between flooding occurrences and twelve geographic, meteorological, and hydrological explanatory factors. The results indicate that the RF model can effectively identify flood-prone areas and has advantages over artificial neural network (ANN) and support vector machine (SVM) methods. Among these explanatory factors, the geographic factors (elevation, longitude and drainage density) are the most important predictors of flooding in China's mountainous areas, whereas the hydrological factors (relative elevation and curve number) are the least important. Two independent datasets of historical flooding events from the Bulletin of Flood and Drought Disasters in China (2006-2014) alongside news reports and yearbooks (2008-2014) were collected and chosen to validate the capability of the RF model. The validation results confirm that the RF model can identify the flood susceptibility with satisfactory accuracy. This study proposes a preliminary flood susceptibility map of mountainous areas in China and provides a reference for predicting and mitigating potentially disastrous flooding events.