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Background and Purpose: Multiple system atrophy (MSA) is a progressive, adult‐onset neurodegenerative disorder clinically characterized by combinations of autonomic failure, parkinsonism, cerebellar ataxia and pyramidal signs. Although a few genetic factors have been reported to contribute to the disease, its mutational profiles have not been systemically studied. Methods: To address the genetic profiles of clinically diagnosed MSA patients, exome sequencing and triplet repeat detection was conducted in 205 MSA patients, including one familial case. The pathogenicity of variants was determined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. Results: In the familial patient, a novel heterozygous COQ2 pathogenic variant (p.Ala351Thr) was identified in the MSA pedigree. In the sporadic patients, 29 pathogenic variants were revealed in 21 genes, and the PARK7 p.Ala104Thr variant was significantly associated with MSA (p = 0.0018). Moreover, burden tests demonstrated that the pathogenic variants were enriched in cerebellar ataxia‐related genes in patients. Furthermore, repeat expansion analyses revealed that two patients carried the pathogenic CAG repeat expansion in the CACNA1A gene (SCA6), one patient carried the (ACAGG)exp/(ACAGG)exp expansion in RFC1 and one carried the GAA‐pure expansion in FGF14 gene. Conclusion: In conclusion, a novel COQ2 pathogenic variant was identified in a familial MSA patient, and repeat expansions in CACNA1A, RFC1 and FGF14 gene were detected in four sporadic patients. Moreover, a PARK7 variant and the burden of pathogenic variants in cerebellar ataxia‐related genes were associated with MSA. [ABSTRACT FROM AUTHOR]

Autosomal recessive spinocerebellar ataxias (SCARs) are a heterogeneous group of neurodegenerative disorders. VPS13D gene is currently the only gene associated with autosomal recessive spinocerebellar ataxia type 4 (SCAR4), also known as VPS13D dyskinesia. SCAR4 is a rare inherited disease, with only 34 reported cases reported worldwide. In this study, we reported three independent SCAR4 cases with adolescent onsets caused by five novel variants of the VPS13D gene. Each patient carried one frameshift and one missense variant: Patient 1 with c.10474del and c.9734C > A (p.Leu3492Tyrfs*43 and p.Thr3245Asn), Patient 2 with c.6094_6107delGTTCTCTTGATCCC and c.9734C > A (p.Val2032Argfs*7 and p.Thr3245Asn), and Patient 3 with c.11954_11963del and c.9833 T > G (p.Phe3985Serfs*10 and p.Ile3278Ser). Two of the three patients shared nystagmus with an identical variant c.9734C > A. Magnetic resonance imaging indicated thoracic spinal atrophy in all three patients and corpus callosum atrophy in one patient, along with other typical manifestations of white matter degradation, cerebral atrophy, and cerebellar atrophy. These findings expanded the genetic, clinical, and neuroimaging spectrum of SCAR4, and provided new insights into the genetic counseling, molecular mechanisms, and differential diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Background: Accurate diagnosis of Parkinson's disease (PD) is challenging due to its diverse manifestations. Machine learning (ML) algorithms can improve diagnostic precision, but their generalizability across medical centers in China is underexplored. Objective: To assess the accuracy of an ML algorithm for PD diagnosis, trained and tested on data from different medical centers in China. Methods: A total of 1656 participants were included, with 1028 from Beijing (training set) and 628 from Fuzhou (external validation set). Models were trained using the least absolute shrinkage and selection operator–logistic regression (LASSO-LR), decision tree (DT), random forest (RF), eXtreme gradient boosting (XGboost), support vector machine (SVM), and k-nearest neighbor (KNN) techniques. Hyperparameters were optimized using five-fold cross-validation and grid search techniques. Model performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, accuracy, sensitivity (recall), specificity, precision, and F1 score. Variable importance was assessed for all models. Results: SVM demonstrated the best differentiation between healthy controls (HCs) and PD patients (AUC: 0.928, 95% CI: 0.908–0.947; accuracy: 0.844, 95% CI: 0.814–0.871; sensitivity: 0.826, 95% CI: 0.786–0.866; specificity: 0.861, 95% CI: 0.820–0.898; precision: 0.849, 95% CI: 0.807–0.891; F1 score: 0.837, 95% CI: 0.803–0.868) in the validation set. Constipation, olfactory decline, and daytime somnolence significantly influenced predictability. Conclusion: We identified multiple pivotal variables and SVM as a precise and clinician-friendly ML algorithm for prediction of PD in Chinese patients. [ABSTRACT FROM AUTHOR]

Background: Epilepsy (EP) is a common neurological disease in which 70–80% are thought to have a genetic cause. In patients with epilepsy, neurodevelopmental delay (NDD) was prevalent. Next generation of sequencing has been widely used in diagnosing EP/NDD. However, the diagnostic yield remains to be 40%–50%. Many reanalysis pipelines and software have been developed for automated reanalysis and decision making for the diseases. Nevertheless, it is a highly challenging task for smaller genetic centers or a routine pediatric practice. To address the clinical and genetic "diagnostic odyssey," we organized a Multidisciplinary Molecular Consultation (MMC) team for molecular consultation for 202 children with EP/NDD patients referred by lower level hospitals. Methods: All the patients had undergone an aligned and sequential consultations and discussions by a "triple reanalysis" procedure by clinical, genetic specialists, and researchers. Results: Among the 202 cases for MMC, we totally identified 47 cases (23%) harboring causative variants in 24 genes and 15 chromosomal regions after the MMC. In the 15 cases with positive CNVs, 3 cases harbor the deletions or duplications in 16p11.2, and 2 cases for 1p36. The bioinformatical reanalysis revealed 47 positive cases, in which 12 (26%) were reported to be negative, VUS or incorrectly positive in pre‐MMC reports. Additionally, among 87 cases with negative cases, 4 (5%) were reported to be positive in pre‐MMC reports. Conclusion: We established a workflow allowing for a "one‐stop" collaborative assessments by experts of multiple fields and helps for correct the diagnosis of cases with falsenegative and −positive and VUS genetic reports and may have significant influences for intervention, prevention and genetic counseling of pediatric epilepsy and neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Hartnup disease cases were rare, and the genotype–phenotype correlation was not fully understood. Here we reported two unrelated young men diagnosed as Hartnup disease, who carried novel compound heterozygote mutations in the SLC6A19 gene and presented with new phenotypes. Other than intermittent encephalopathy and photosensitive rashes, they displayed symptoms and signs of spastic paraplegia and severe peripheral nerve damages. Magnetic resonance imaging showed mild bilateral cerebellar atrophy and thinning of the thoracic spinal cord. Electromyogram detected mixed sensorimotor polyneuropathy in lower limbs. Sural nerve biopsy and pathological study indicated the moderately reduced neural fibers in the periphery nerves. Urinary amino acid analysis showed increased levels of multiple neutral amino acids. Moreover, muscle strengths in the lower limbs and the walking ability have been improved in both cases (MRC 3/5 to 4/5 in Patient 1; walking distance elongated from 50 to 100 m in Patient 2) after the treatment with oral nicotinic acid and intravenous injection of multiple amino acids. Exome sequencing revealed and confirmed the existence of the novel compound heterozygous SLC6A19 mutations: c.533G>A (p.Arg178Gln) and c.1379‐1G>C mutations in patient1, and c.1433delG (p.Gly478AlafsTer44) and c.811G>A (p.Ala271Thr) in patient 2. Taken together, these findings expanded the clinical, neuroimaging, pathology, and genetic spectrum of Hartnup disease. However, the co‐existence of HSP and peripheral neuropathy was only inferred based on clinical observations, and pathological and molecular studies are needed to further dissect the underlying mechanisms. [ABSTRACT FROM AUTHOR]

The article presents a study on the genetic analysis of seven infectious bronchitis viruses (IBVs) isolated in Shanxi province, China, in which the results showed that N protein genes of the five isolates were comprised of 1,230 nucleotides and the remaining two were composed of 1,227 nucleotides.

The article reports on the isolating and identifying the biological properties of several strains of infectious bronchitis virus (IBV) from chicken. Isolation was achieved by systematic identification of the propagation of Newcastle disease virus, the pathological role of virus in chicken embryo and specific pathogen-free chicken, hemagglutination activity, physicochemical and reverse transcription polymerase chain reaction (RT-PCR). Results show five strains of IBV.

Objective: To review the diagnosis of chronic wound biofilms and discuss current treatment approaches., Data Sources: Articles included in this review were obtained from the following databases: Wanfang, China National Knowledge Infrastructure, PubMed, and the Web of Science. We focused on research published before August 2019 with keywords including chronic wound, biofilm, bacterial biofilms, and chronic wound infection., Study Selection: Relevant articles were selected by carefully reading the titles and abstracts. Further, different diagnosis and clinical treatment methods for chronic wound biofilm were compared and summarized from the selected published articles., Results: Recent guidelines on medical biofilms stated that approaches such as the use of scanning electron microscopy and confocal laser scanning microscopy are the most reliable types of diagnostic techniques. Further, therapeutic strategies include debridement, negative pressure wound therapy, ultrasound, antibiotic, silver-containing dressing, hyperbaric oxygen therapy, and others., Conclusion: This review provides the identification and management of biofilms, and it can be used as a tool by clinicians for a better understanding of biofilms and translating research to develop best clinical practices.

In the present paper, the structural, morphological and optical properties of PbI2 thick films prepared by close-spaced sublimation technique were investigated. It was found that the thickness of PbI2 films decreased from 1 000 μm to 220 μm with the increase in the sublimation source temperature. X-ray diffraction (XRD) pattern shows that the thick films are polycrystalline hexagonal structure with preferred growth orientation of (002) plane, and their grain size, dislocation density and growth stress are closely related to the source temperature. Images of scanning electron microscopy (SEM) reveal the accumulation of hexagonal plate-like particles which constitute the samples, and the particles with a diameter of 248 μm and a thickness of 32.7 μm, exhibit clearly layered structure. By spectrum fitting using Gauss function, the Raman spectra show a shift of about 147, 169, 217 and 210 cm(-1) respectively, the first three peaks correspond to the longitudinal optical vibrations (LO) mode in 4H-PbI2 crystal, while the last peak originate from a vibration pattern associated with SnO2 in substrate. Raman peak of 147 cm(-1) changes significantly with the increases in source temperature, and a dramatic decrease in peak intensity with broadening peak width occurred when the source temperature increased up to 225 degrees C or more. Under 340 nm excitation at room temperature, several weak photoluminescence peaks of PbI2 samples which associated with defects and exciton recombination near 2.25, 2.57 and 2.64 eV were observed. Given a comprehensive consideration of structural and spectral characterization results, PbI2 thick films with a thickness of about 659 μm deposited at a source temperature of 200 degrees C achieves the best crystalline quality.

Objective: To observe the effect of electroacupuncture (EA) preconditioning on cerebral ischemia and the role of cerebral neuroglobin (NgB) in EA-induced brain protection in focal cerebral ischemia and reperfusion injury (CI/RI) rats., Methods: Male SD rats were randomly assigned to sham control, CI/RI 6 h, CI/RI 24 h and CI/RI 72 h groups (n = 6) for observing changes of NgB at different time-points. Additional SD rats were randomly assigned to sham, model, and EA preconditioning (EA-PC) groups (n = 16) for observing changes of cerebral NgB positive cell counts in the ischemic penumbra region 24 h after reperfusion. EA pre-conditioning was applied to "Baihui" (GV 20) for 30 min, once daily for 5 days before CI/RI. CI/RI model was established by occlusion of the right middle cerebral artery and reperfusion for 6 h, 24 h and 72 h respectively. The neurological behavior scores (NBS) of all the rats were evaluated according to Garcia's methods. The cerebral infarct volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The number of cerebral NgB positive cells was detected by immunofluorescent staining., Results: No infarct loci were found in the sham group. The cerebral infarction volume percentage was significantly higher in the model group than in the EA-PC group (P < 0.01), while the NBS was significantly lower in the model group than in the EA-PC group (P < 0.01). The number of cerebral NgB positive cells in the ischemic penumbra was up-regulated 6 h after CI/RI injury, peaked at 24 h and continued at 72 h. Compared with the sham group, the number of cerebral NgB positive cells of the model group was increased significantly, whereas that of the EA-PC group up-regulated further obviously in comparison with the model group (P < 0.01)., Conclusion: EA pretreatment has a significant neuroprotective effect on cerebral ischemia-reperfusion, which is closely related to its effect in up-regulating NgB protein expression.