Chinese Verbal Fluency Deficiency in Temporal Lobe Epilepsy with and without Hippocampal Sclerosis: A Multiscale Study.

To test a Chinese character version of the phonemic verbal fluency task in patients with temporal lobe epilepsy (TLE) and assess the verbal fluency deficiency pattern in TLE with and without hippocampal sclerosis, a cross-sectional study was conducted including 30 patients with TLE and hippocampal sclerosis (TLE-HS), 28 patients with TLE and without hippocampal sclerosis (TLE-NHS), and 29 demographically matched healthy controls (HC). Both sexes were enrolled. Participants finished a Chinese character verbal fluency (VFC) task during functional MRI. The activation/deactivation maps, functional connectivity, degree centrality, and community features of the left frontal and temporal regions were compared. A neural network classification model was applied to differentiate TLE-HS and TLE-NHS using functional statistics. The VFC scores were correlated with semantic fluency in HC while correlated with phonemic fluency in TLE-NHS. Activation and deactivation deficiency was observed in TLE-HS and TLE-NHS (p < 0.001, k ≥ 10). Functional connectivity, degree centrality, and community features of anterior inferior temporal gyri were impaired in TLE-HS and retained or even enhanced in TLE-NHS (p < 0.05, FDR-corrected). The functional connectivity was correlated with phonemic fluency (p < 0.05, FDR-corrected). The neural network classification reached an area under the curve of 0.90 in diagnosing hippocampal sclerosis. The VFC task is a Chinese phonemic verbal fluency task suitable for clinical application in TLE. During the VFC task, functional connectivity of phonemic circuits was impaired in TLE-HS and was enhanced in TLE-NHS, representing a compensative phonemic searching strategy applied by patients with TLE-NHS.

Gliosarcoma: a clinical and radiological analysis of 48 cases.

OBJECTIVES: To retrospectively review the radiological and clinicopathological features of gliosarcoma (GSM) and differentiate it from glioblastoma multiforme (GBM). METHODS: The clinicopathological data and imaging findings (including VASARI analysis) of 48 surgically and pathologically confirmed GSM patients (group 1) were reviewed in detail, and were compared with that of other glioblastoma (GBM) cases in our hospital (group 2). RESULTS: There were 28 men and 20 women GSM patients with a median age of 52.5 years (range, 24-80 years) in this study. Haemorrhage (n = 21), a salt-and-pepper sign on T2-weighted images (n = 36), unevenly thickened wall (n = 36) even appearing as a paliform pattern (n = 32), an intra-tumoural large feeding artery (n = 32) and an eccentric cystic portion (ECP) (n = 19) were more commonly observed in the GSM group than in GBM patients. Based on our experience, GSM can be divided into four subtypes according to magnetic resonance imaging (MRI) features. When compared to GBM (group 2), there were more patients designated with type III lesions (having very unevenly thickened walls) and IV (solid) lesions among the GSM cases (group 1). On univariate prognostic analysis, adjuvant therapy (radiotherapy, chemotherapy, and radiochemotherapy) and existence of an eccentric cyst region were prognostic factors. However, Cox's regression model showed only adjuvant therapy as a prognostic factor for GSM. CONCLUSIONS: When compared to GBM, certain imaging features are more likely to occur in GSM, which may help raise the possibility of this disease. All GSM patients are recommended to receive adjuvant therapy to achieve a better prognosis with radiotherapy, chemotherapy or radiochemotherapy all as options. KEY POINTS: • Diagnosis of gliosarcoma can be suggested preoperatively by imaging. • Gliosarcoma can be divided into four subtypes based on MRI. • Paliform pattern and ECP tend to present in gliosarcoma more than GBM. • The cystic subtype of gliosarcoma may predict a more dismal prognosis. • All gliosarcoma patients should receive adjuvant therapy to achieve better prognosis.

[Clinical and image features for 12 cases of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy].

OBJECTIVE: To analyze the clinical and image features for 12 patients of cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL).
 Methods: A total of 12 CADASIL patients were collected in Xiangya Hospital of Central South University from January 2013 to December 2018. The clinical manifestation, risk factors, MRI imaging data and NOTCH3 mutations were analyzed retrospectively.
 Results: The mean age of 12 patients was (47.25±9.49) years. The clinical manifestation was most common in cognitive impairment (75%) and stroke events (58.3%), and 2 cases showed cerebral hemorrhage. Migraine was only seen in 25% patients. All MRI showed white matter hyperintensity (WMH), lacune and enlarged perivascular space (PVS). WMH mainly occurred in the frontal parietal lobe (100%), temporal lobe (83.3%), external capsule (66.7%), occipital lobe (41.6%), callosum 41.6% and the temporal pole (33.3%), while lacune mainly appeared in frontal lobe (91.6%), parietal lobe(83.3%), temporal lobe(66.7%), basal ganglia (66.7%), brain stem (41.6%), occipital lobe (33.3%), cerebellum (8.3%). Enlarged PVS located in the basal ganglia (100%), partly under the cortex (45.4%). WMH of the patient with intracerebral hemorrhage was mild (Fezakas score 1-2), which was not found in external capsule. 16.7% of the patients had intracranial arterial stenosis. In 12 patients, 8 different Notch3 mutations were detected. The c1013G>c p.(Cys338Ser) located in exon 6, which was a new pathogenic mutation of CADASIL.
 Conclusion: The patients with cerebral hemorrhage have mild WMH and specific genotype, indicating that the clinical characteristics of CADASIL with cerebral hemorrhage may be related to image features and genotype.

Serum Krebs von den Lungen-6 as a potential biomarker for distinguishing combined pulmonary fibrosis and emphysema from chronic obstructive pulmonary disease: A retrospective study.

Background: The presence of fibrotic interstitial lung disease (ILD) is relatively common in patients with emphysema. This has been designated combined pulmonary fibrosis and emphysema (CPFE). CPFE had worse prognosis than emphysema alone. Krebs von den Lungen-6 (KL-6) levels as a biomarker of alveolar type 2 epithelial cell injury, which is widely used to identify the presence of ILD, whether it can differentiate CPFE from COPD remains unknown. Methods: 259 patients from Xiangya Hospital with diagnosis of COPD, with or without ILD, and who had KL-6 tests were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. Results: Among 259 patients, 52 patients were diagnosed with CPFE. The mean age was 67.39 ± 8.14 yeas. CPFE patients had higher ratio of rheumatic diseases (21.2 % vs 7.2 %, P = 0.003). CPFE patients exhibited higher values of FEV1 (1.97 vs 1.57, P = 0.002) and FEV1/FVC ratio (69.46 vs 57.64, P < 0.001) compared to COPD patients. CPFE patients had higher eosinophil counts, percentage of eosinophils, lactate dehydrogenase, total bilirubin levels and lower platelet counts. Serum KL-6 levels were higher in CPFE group compared to COPD group (574.95 vs 339.30 U/mL, P < 0.001). Multiple logistic regression showed that KL-6 level was an independent predictive factor for the presence of ILD among COPD patients. The AUC of serum KL-6 levels to differentiate CPFE was 0.711, with 95 % CI being 0.635 to 0.787. The cutoff point of KL-6 level was 550.95 U/mL with 57.7 % sensitivity and 79.7 % specificity for the discrimination of CPFE from COPD. Conclusion: CPFE patients show higher KL-6 levels compared to isolated COPD, suggesting the potential of KL-6 as a practical screening tool for interstitial lung disease, specifically CPFE. A KL-6 threshold of 550.95 U/mL in COPD patients may indicate a high need for high-resolution chest computed tomography to detect fibrosis.

Intramuscular ziprasidone versus haloperidol for managing agitation in Chinese patients with schizophrenia.

Intramuscular (IM) antipsychotics are preferred for efficient control of agitation symptoms. Previous studies have demonstrated that IM ziprasidone is efficacious and safe for treatment of agitation in schizophrenia. However, clinicians now recognize that racial differences may contribute to altered therapeutic response and tolerability. This study compared the efficacy and tolerability of IM ziprasidone versus IM haloperidol for the management of agitation in Chinese subjects with schizophrenia. Subjects with acute schizophrenia were randomized to either ziprasidone (n = 189, 10 to 20 mg as required up to a maximum of 40 mg/d) or haloperidol (n = 187, 5 mg every 4 to 8 hours to a maximum of 20 mg/d) for 3 days. Psychiatric assessments and adverse events were assessed at baseline, 2, 4, 24, 48, and 72 hours. In the ziprasidone group, 2.1% of subjects discontinued versus 3.7% in the haloperidol group. The least squares mean change (SE) from baseline to 72 hours in Brief Psychiatry Rating Scale total score was -17.32 (0.7) for ziprasidone (n = 167) and -18.44 (0.7) for haloperidol (n = 152), with a 95% confidence interval treatment difference of -0.7 to 2.9. Fewer subjects experienced adverse events after ziprasidone (n = 54, 28.6%) than haloperidol (n = 116, 62.0%), with a notably higher incidence of extrapyramidal symptoms in the haloperidol group (n = 69, 36.9%) compared to the ziprasidone group (n = 4, 2.1%). For controlling agitation in schizophrenia in this Chinese study, ziprasidone had a favorable tolerability profile and comparable efficacy and safety compared to haloperidol.

Serum Krebs von den Lungen-6 is associated with in-Hospital mortality of patients with severe Community-Acquired Pneumonia: A retrospective cohort study.

BACKGROUND: Currently, no ideal biomarker can accurately stratify the risk of patients with severe community-acquired pneumonia (SCAP). This study aimed to evaluate the role of serum Krebs von den Lungen-6 (sKL-6) in predicting in-hospital mortality in adults with SCAP. METHODS: In this retrospective cohort study, 249 severe pneumonia adult patients were recruited between 6 May 2021 to 30 April 2023 in Xiangya Hospital of Central South University. The sKL-6 level within 48 h of admission was measured, and the primary outcome assessed was in-hospital mortality. Multivariable logistic regression analysis was performed to calculate adjusted odds ratios (OR) with 95% confidence intervals (CI). Survival curves were plotted and subgroup analyses were conducted, stratified by relevant covariates. RESULTS: A total of 249 patients were included in the study,with 124 patients having normal sKL-6 levels, and 125 patients having abnormal sKL-6 levels. The overall in-hospital mortality rate was 28.9% (72 out of 249 patients). Univariate and multivariate logistic regression analysis revealed that the patients with abnormal sKL-6 levels had a higher risk of in-hospital mortality compared to those with normal sKL-6 levels, both in the total SCAP patient population (OR: 5.38, 95%CI: 2.41-12.01, P < 0.001) and the non-COVID-19 SCAP patients subgroup (OR: 8.12, 95%CI: 3.16-20.84, P < 0.001). Subgroup and interaction analyses confirmed the stability of the relationship between sKL-6 levels and in-hospital mortality(P for interaction > 0.05). Kaplan-Meier survival curves showed that patients with abnormal sKL-6 levels had a higher in-hospital mortality rate than those with normal sKL-6 levels (P < 0.05). However, the results of restricted cubic spline plots(RCS) analysis demonstrated a nonlinear association between sKL-6 levels (as a continuous variable) and in-hospital mortality in patients with SCAP. Similar results were observed in non-COVID-19 SCAP patients. Furthermore, the receiver operating characteristic curve (ROC) analysis revealed that sKL-6 had superior predictive performance compared to existing biomarkers (e.g., APACHE-II, SOFA, BUN/Cr, PCT, and D-dimer) for in-hospital mortality in non-COVID-19 SCAP patients. CONCLUSION: sKL-6 is a practical and useful biomarker for predicting in-hospital mortality in patients with SCAP.

KL-6 levels in the connective tissue disease population: typical values and potential confounders-a retrospective, real-world study.

Background: Krebs von den Lungen 6 (KL-6) is a potential biomarker for determining the severity of interstitial lung disease (ILD) in patients with connective tissue disease (CTD). Whether KL-6 levels can be affected by potential confounders such as underlying CTD patterns, patient-associated demographics, and comorbidities needs further investigation. Methods: From the database created by Xiangya Hospital, 524 patients with CTD, with or without ILD, were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers, autoimmune antibodies, and the KL-6 level at admission. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. The percent of predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and computed tomography (CT) scans were used to determine the severity of ILD. Results: Univariate linear regression analysis showed that BMI, lung cancer, TB, lung infections, underlying CTD type, white blood cell (WBC) counts, neutrophil (Neu) counts, and hemoglobin (Hb) were related to KL-6 levels. Multiple linear regression confirmed that Hb and lung infections could affect KL-6 levels independently; the ß were 9.64 and 315.93, and the P values were 0.015 and 0.039, respectively. CTD-ILD patients had higher levels of KL-6 (864.9 vs 463.9, P < 0.001) than those without ILD. KL-6 levels were closely correlated to the severity of ILD assessed both by CT and DLCO%. Additionally, we found that KL-6 level was an independent predictive factor for the presence of ILD and further constructed a decision tree model to rapidly determine the risk of developing ILD among CTD patients. Conclusion: KL-6 is a potential biomarker for gauging the incidence and severity of ILD in CTD patients. To use this typical value of KL-6, however, doctors should take Hb and the presence of lung infections into account.

Shared functional network abnormality in patients with temporal lobe epilepsy and their siblings.

AIM: Temporal lobe epilepsy is a neurological network disease in which genetics played a greater role than previously appreciated. This study aimed to explore shared functional network abnormalities in patients with sporadic temporal lobe epilepsy and their unaffected siblings. METHODS: Fifty-eight patients with sporadic temporal lobe epilepsy, 13 unaffected siblings, and 30 healthy controls participated in this cross-sectional study. We examined the task-based whole-brain functional network topology and the effective functional connectivity between networks identified by group-independent component analysis. RESULTS: We observed increased global efficiency, decreased clustering coefficiency, and decreased small-worldness in patients and siblings (p < 0.05, false discovery rate-corrected). The effective network connectivity from the ventral attention network to the limbic system was impaired (p < 0.001, false discovery rate-corrected). These features had higher prevalence in unaffected siblings than in normal population and was not correlated with disease burden. In addition, topological abnormalities had a high intraclass correlation between patients and their siblings. CONCLUSION: Patients with temporal lobe epilepsy and their unaffected siblings showed shared topological functional disturbance and the effective functional network connectivity impairment. These abnormalities may contribute to the pathogenesis that promotes the susceptibility of seizures and language decline in temporal lobe epilepsy.

Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a mouse model of temporal lobe epilepsy.

Recurrent excitatory circuits and abnormal recurrent excitatory inputs are essential in epileptogenesis. Studies in temporal lobe epilepsy have shown that mossy fiber sprouting, which represents synaptic reorganization, renders the formation of abnormal recurrent excitatory circuits and inputs. The mammalian target of rapamycin (mTOR) pathway has recently been proved important in mossy fiber sprouting. In the present study, rapamycin, a mTOR inhibiter, was injected into the mouse of temporal lobe epilepsy. Electrophysiological and histological properties of the hippocampus were investigated by whole cell patch clamp, extracellular recording and Timm staining. Following the development of epilepsy, frequency of spontaneous excitatory postsynaptic currents (EPSCs) and amplitude of antidromically evoked EPSCs in granule cells were remarkably increased, as well as the epileptiform activity and mossy fiber sprouting were detected, which indicated the formation of abnormal recurrent excitatory circuits. By the use of rapamycin, frequency of spontaneous EPSCs, amplitude of antidromically evoked EPSCs, the epileptiform activity and mossy fiber sprouting were all remarkably suppressed. Our findings suggested an anti-epileptogenic role of rapamycin by suppressing the recurrent excitatory circuits of dentate gyrus.

Sphingomonas endophytica sp. nov., isolated from Artemisia annua L.

A novel bacterium (strain YIM 65583(T)) belonging to the genus Sphingomonas was isolated from surface-sterilized tissue of Artemisia annua L., which was collected from Yunnan province, south-west China. Its morphology, physiology and biochemical features were consistent with those of members of the genus Sphingomonas. Analysis of the 16S rRNA gene sequence of strain YIM 65583(T) further confirmed that it should be classified as a member of the genus Sphingomonas and was most closely related to Sphingomonas phyllosphaerae FA2(T) (99.7%) and Sphingomonas yunnanensis YIM 003(T) (98.3%). The isolate was Gram-negative and formed yellow-pigmented colonies on ISP 2 medium. It grew optimally at pH 6.0-8.0, at 20-37 °C and in the presence of 0-1% (w/v) NaCl. The major respiratory lipoquinone was ubiquinone-10; C(18:1)ω7c, anteiso-C(16:1), C(14:0)-2OH, C(17:1)ω6c, C(16:0) and C(15:0) were the major fatty acids. Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and sphingoglycolipid. The G+C content of the genomic DNA was 63.3 mol%. The DNA-DNA relatedness values of the isolate YIM 65583(T) with S. phyllosphaerae FA2(T) and S. yunnanensis YIM 003(T) were 43.1% and 37.9%, respectively. Based on these features, it is concluded that the strain represents a novel species of the genus Sphingomonas, for which the name Sphingomonas endophytica sp. nov. is proposed, with YIM 65583(T) (=CCTCC AA 209035(T)=JCM 17394(T)) as the type strain.

Tuning self-assembly of amphiphilic sodium alginate-decorated selenium nanoparticle surfactants for antioxidant Pickering emulsion.

Delivering effectively zero-valent selenium nanoparticles (SeNPs) and develop its functions in more fields is still a challenge. Herein, a novel template for the preparation and stabilization of SeNP-based surfactants was developed, amphiphilic sodium alginate (APSA), which can self-assemble into micelles in an aqueous solution. Primarily, physicochemical properties of SeNPs stabilized by APSA with different molecular weights were compared and the interaction mechanism of APSA/SeNPs was investigated. Moreover, a functional Pickering emulsion (PE) was presented using the SeNP-based surfactants. Results showed that high molecular weight-stabilized SeNPs had small particle size (54.72 nm) and great stability due to the hydrogen bonding between Se atoms and APSA. The "soft" particle-decorated SeNPs with interface activity formed a dense interfacial layer on the oil-water interface, which exhibited excellent antioxidant properties. The contents of lipid hydrogen peroxide (LH) and malondialdehyde (MDA) were significantly reduced by 88.7% and 63.4%. Overall, SeNPs stabilized by APSA have great application potential as an emulsifier and antioxidant in industrial field.

Fabricating Network-Link Acetamiprid-Loading Micelles Based on Dopamine-Functionalized Alginate and Alkyl Polyglucoside To Enhance Folia Deposition and Retention.

The development of an eco-friendly nanopesticide formulation can alleviate the problems of low pesticide utilization and environmental pollution. However, the development of green nanopesticide carriers with ideal physical properties and specific bioavailability is still a challenging task at present. In this study, we propose a novel binary additive pesticide carrier system that is a functional polysaccharide-based polymer/surfactant (Alg-DA/APG) to improve the deposition and retention of pesticide droplets. The self-assembled micelle morphology of Alg-DA/APG and its effect on the apparent viscosity were investigated by transmission electron microscopy (TEM) and a Discovery HR-2 rotational rheometer. Surface tension was carried out to investigate the surface activity and critical micelle concentration (CMC) of Alg-DA/APG. The drop impacting experiments exhibited superior antisplash performance of Alg-DA/APG. Furthermore, a binary additive was used as the carrier material and loaded acetamiprid to prepare nanopesticide formulation Ace@Alg-DA/APG. The encapsulation efficiency (EE) and acetamiprid release behavior from Ace@Alg-DA/APG were also studied. Moreover, the dynamic contact angle (DCA) and retention experiment showed that the DCA and wetting radius at 600 s were, respectively, 6.8 ± 2.39° and 4.044 ± 0.0662 mm for the Ace@0.05 wt % Alg-DA/0.05 wt % APG on the banana foliage surface, and its retention rates on foliage surface were up to 74.80% after washing. The novel binary additive as a nanopesticide carrier has the potential to alleviate the problems of low pesticide utilization and environmental pollution in the future.

Depletion stabilization of emulsions based on bacterial cellulose/carboxymethyl chitosan complexes.

The regulation of the magnitude of the depletion effect is necessary for accurately predicting and explaining the emulsion stabilization mechanism. Herein, the bacterial cellulose/carboxymethyl chitosan (BC/CCS) complexes with tunable assembled behaviors were prepared and designed via electrostatic interaction. Specially, the emulsions stabilized by BC/CCS complexes exhibited excellent stability as compared with that stabilized by BC polymers alone. At pH 9.6, BC/CCS complexes in the continuous phase induced long-range depletion-stabilization effect to stabilize emulsions. Additionally, the magnitude of depletion effect of BC/CCS complexes could be improved by increasing BC concentration, and effectively stabilized emulsions. Furthermore, with the decrease to pH 7.0, the interfacial adsorption layers at the oil-water interface prevented oil droplets from agglomerating, but did not show better emulsion stability. These results clarified that the magnitude of the depletion effect could be controlled by altering BC-based complexes particles, which would be useful for the applications of emulsions in numerous fields.

Age of onset correlates with clinical characteristics and prognostic outcomes in neuromyelitis optica spectrum disorder.

Objective: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease preferentially affects the optic nerve and the spinal cord. The first attack usually occurs in the third or fourth decade, though patients with disease onset in the fifties or later are not uncommon. This study aimed to investigate the clinical characteristics and prognosis in patients with different age of onset and to explore the correlations between age of onset and clinical characteristics and prognostic outcomes. Method: We retrospectively reviewed the medical records of 298 NMOSD patients diagnosed according to the 2015 updated version of diagnostic criteria. Patients were divided into early-onset NMOSD (EO-NMOSD) (<50 years at disease onset) and late-onset NMOSD (LO-NMOSD) (≥50 years at disease onset) based on the age of disease onset. LO-NMOSD patients were divided into two subgroups: relative-late-onset NMOSD (RLO-NMOSD) (50~70 years at disease onset) and very-late-onset NMOSD (≥70 years at disease onset). Clinical characteristics, laboratory findings, neuroimaging features, and prognostic outcomes were investigated. Results: Compared to EO-NMOSD patients, patients with LO-NMOSD showed more frequent transverse myelitis (TM) (58.20% vs. 36.00%, p = 0.007) while less frequent optic neuritis (ON) (23.10% vs. 34.80%, p = 0.031) and brainstem/cerebral attacks (7.50% vs. 18.30%, p = 0.006) as the first attack. Patients with LO-NMOSD showed less frequent relapses, higher Expanded Disability Status Scale (EDSS) score at the last follow-up, fewer NMOSD-typical brain lesions, and longer segments of spinal cord lesions. Patients with older onset age showed a higher proportion of increased protein levels in cerebrospinal fluid during the acute phase of attacks. Age at disease onset positively correlated with length of spinal cord lesions at first attack and at last follow-up, negatively correlated with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up), irrespective of AQP4-IgG serostatus. Patients with older age at disease onset progressed to severe motor disability sooner, and age of onset positively correlated with EDSS score at the last follow-up, irrespective of AQP4-IgG serostatus. Conclusion: Age of disease onset affects clinical characteristics and prognosis outcomes of patients with NMOSD.

Novel PRRT2 gene variants identified in paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy in Chinese families.

The present study was performed to investigate the clinical manifestations and pathogenic variants in three large families with autosomal dominant paroxysmal kinesigenic dyskinesia (PKD) and/or benign familial infantile epilepsy (BFIE) in China. Detailed clinical data and family history were collected. Genomic DNA was isolated from the peripheral blood samples of all available members. The genetic diagnosis was made by whole-exome sequencing on the three probands and the candidate variants were verified by PCR-Sanger sequencing. The pathogenicity of variants was predicted by bioinformatics analyses and classified according to the American College of Medical Genetics criteria. A total of three causative heterozygous variants were identified in the proline-rich transmembrane protein 2 (PRRT2) gene by DNA sequencing: A novel c.324_334del(p.Val109Argfs*21) deletion variant in Family A, as well as the previously known c.510_513del(p.Ser172Argfs*3) deletion variant in Family B and c.649dupC(p.Arg217Profs*8) duplication variant in Family C. The three variants of PRRT2 co-segregated with the phenotype and genotype in the family members. The present results deepen the current understanding of PKD/BFIE and extend the genotypic-phenotypic spectrum of PKD/BFIE.

Preoperative Magnetic Resonance Imaging Radiomics for Predicting Early Recurrence of Glioblastoma.

PURPOSE: Early recurrence of glioblastoma after standard treatment makes patient care challenging. This study aimed to assess preoperative magnetic resonance imaging (MRI) radiomics for predicting early recurrence of glioblastoma. PATIENTS AND METHODS: A total of 122 patients (training cohort: n = 86; validation cohort: n = 36) with pathologically confirmed glioblastoma were included in this retrospective study. Preoperative brain MRI images were analyzed for both radiomics and the Visually Accessible Rembrandt Image (VASARI) features of glioblastoma. Models incorporating MRI radiomics, the VASARI parameters, and clinical variables were developed and presented in a nomogram. Performance was assessed based on calibration, discrimination, and clinical usefulness. RESULTS: The nomogram consisting of the radiomic signatures, the VASARI parameters, and blood urea nitrogen (BUN) values showed good discrimination between the patients with early recurrence and those with later recurrence, with an area under the curve of 0.85 (95% CI, 0.77-0.94) in the training cohort and 0.84 [95% CI, 0.71-0.97] in the validation cohort. Decision curve analysis demonstrated favorable clinical application of the nomogram. CONCLUSION: This study showed the potential usefulness of preoperative brain MRI radiomics in predicting the early recurrence of glioblastoma, which should be helpful in personalized management of glioblastoma.

NOTCH3 Variants and Genotype-Phenotype Features in Chinese CADASIL Patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations in the NOTCH3 gene. Archetypal disease-causing mutations are cysteine-affecting variants within the 34 epidermal growth factor-like repeat (EGFr) region of the Notch3 extracellular subunit. Cysteine-sparing variants and variants outside the EGFr coding region associated with CADASIL phenotype have been reported. However, the linkage between untypical variants and CADASIL is unclear. In this study, we investigated the spectrum of NOTCH3 variants in a cohort of 38 probands from unrelated families diagnosed as CADASIL. All coding exons of the NOTCH3 gene were analyzed, and clinical data were retrospectively studied. We identified 23 different NOTCH3 variants including 14 cysteine-affecting pathogenic variants, five cysteine-sparing pathogenic variants, two reported cysteine-sparing variants of unknown significance (VUS), and two novel VUS outside EGFr region. In retrospective studies of clinical data, we found that patients carrying cysteine-sparing pathogenic variants showed later symptom onset (51.36 ± 7.06 vs. 44.96 ± 8.82, p = 0.023) and milder temporal lobe involvement (1.50 ± 1.74 vs. 3.11 ± 2.32, p = 0.027) than patients carrying cysteine-affecting pathogenic variants. Our findings suggested that untypical variants comprise a significant part of NOTCH3 variants and may be associated with a distinctive phenotype.