Glucocerebrosidase L444P Mutation Confers Genetic Risk for Parkinson’s Disease in Central China

Background: Mutations of the glucocerebrosidase (GBA) gene have reportedly been associated with Parkinson disease (PD) in various ethnic populations such as Singaporean, Japanese, Formosan, Canadian, American, Portuguese, Greek, Brazilian, British, Italian, Ashkenazi Jewish, southern and southwestern Chinese. The purpose of this study is to determine in central China whether or not the reported GBA mutations remain associated with PD. Methods: In this project, we conducted a controlled study in a cohort of 208 central Chinese PD patients and 298 controls for three known GBA mutations (L444P, N370S and R120W). Results: Our data reveals a significantly higher frequency of L444P mutation in GBA gene of PD cases (3.4%) compared with the controls (0.3%) (P = 0.007, OR = 10.34, 95% CI = 1.26 - 84.71). Specifically, the frequency of L444P mutation was higher in the late onset PD (LOPD) cases compared with that in control subjects. The N370S and R120W mutations were detected in neither the PD group nor the control subjects. Conclusions: Our observations demonstrated that the GBA L444P mutation confers genetic risk for PD, especially LOPD, among the population in the central China area

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion

AIM: To assess the long-term outcomes of treating macular edema (ME) associated with central retinal vein occlusion (CRVO) with a regimen of “5+pro re nata (PRN)”. METHODS: This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO (non-iCRVO group, n=15) and ischemic CRVO (iCRVO group, n=12). The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab, followed by reinjections as needed or PRN. Retinal laser photocoagulation or intravitreal dexamethasone implants (DEX) were implemented in both groups when necessary. The best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT) were recorded at baseline, at 1, 2, 3, 4, 5, 6, and 12mo, and at the final visit. The efficacy rates of BCVA and CRT before and after treatment were calculated. The number of injections at each visit and the incidence of adverse events were also recorded. RESULTS: The patients, aged 59.4±15.1y, were followed up for 24.7±8.8mo (range: 15-42mo). After treatment, BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR (P=0.038) at the final visit in all patients. Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points, but there was no statistical significance (P=0.197 and 0.33, respectively). The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups (all P0.05). Laser treatment was applied to all eyes in the iCRVO group, while only 5 patients in the non-iCRVO group. Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch. DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group. CONCLUSION: The 5+PRN anti-vascular endothelial growth factor (VEGF) regimen is found to be safe and effective for both iCRVO and non-iCRVO, especially in the iCRVO group. The best regimen for such patients needs to be further investigated. Adjuvant laser therapy and DEX are necessary in some cases

MAPT rs242562 and GSK3B rs334558 are associated with Parkinson’s Disease in central China

Background: Microtubule-associated protein tau (MAPT) is a neuronal protein involved in the pathogenesis of several neurodegenerative diseases including Parkinson’s Disease (PD). Glycogen synthase kinase 3 beta (GSK3B) catalyzes phosphorylation in multiple sites of tau protein. However, whether or not there is any association between the GSK3B gene alteration, MAPT haplotype and PD remains unexplored in Chinese population, especially in central Chinese population. Results: Here, we aimed at studying the effect of MAPT rs242562 and GSK3B rs334558 on the risk of PD by performing a case-control association study in central China. Our data showed that all PD patients and controls were of MAPT H1/H1 diplotype in our study, thus confirming that the distribution of the MAPT H1 haplotype is common in China. GG genotype of MAPT rs242562 serves protection effect on PD risk in central Chinese population, while genotype of GSK3B rs334558 showed no difference between PD patients and controls. Conclusions: We conclude that the MAPT rs242562 is associated with PD in central China in the background of MAPT H1/H1 diplotype. The GG genotype of rs242562 displays protection against PD in subgroup with GSK3B rs334558 T carrier

Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma

Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES

Improved Breath Phase and Continuous Adventitious Sound Detection in Lung and Tracheal Sound Using Mixed Set Training and Domain Adaptation

Previously, we established a lung sound database, HF_Lung_V2 and proposed convolutional bidirectional gated recurrent unit (CNN-BiGRU) models with adequate ability for inhalation, exhalation, continuous adventitious sound (CAS), and discontinuous adventitious sound detection in the lung sound. In this study, we proceeded to build a tracheal sound database, HF_Tracheal_V1, containing 11107 of 15-second tracheal sound recordings, 23087 inhalation labels, 16728 exhalation labels, and 6874 CAS labels. The tracheal sound in HF_Tracheal_V1 and the lung sound in HF_Lung_V2 were either combined or used alone to train the CNN-BiGRU models for respective lung and tracheal sound analysis. Different training strategies were investigated and compared: (1) using full training (training from scratch) to train the lung sound models using lung sound alone and train the tracheal sound models using tracheal sound alone, (2) using a mixed set that contains both the lung and tracheal sound to train the models, and (3) using domain adaptation that finetuned the pre-trained lung sound models with the tracheal sound data and vice versa. Results showed that the models trained only by lung sound performed poorly in the tracheal sound analysis and vice versa. However, the mixed set training and domain adaptation can improve the performance of exhalation and CAS detection in the lung sound, and inhalation, exhalation, and CAS detection in the tracheal sound compared to positive controls (lung models trained only by lung sound and vice versa). Especially, a model derived from the mixed set training prevails in the situation of killing two birds with one stone.Comment: To be submitted, 31 pages, 6 figures, 5 table

Light-Soaking-Free Inverted Polymer Solar Cells with an Efficiency of 10.5% by Compositional and Surface Modifications to a Low-Temperature-Processed TiO2 Electron-Transport Layer.

Compositional modification and surface treatments of a TiO2 film prepared by a low-temperature route are carried out by a new promising method. Inverted polymer solar cells incorporating the post-treated TiO2 :TOPD electron-transport layer achieve the highest efficiency of 10.5%, and more importantly, eliminate the light-soaking problem that is commonly observed in metal-oxide-based inverted polymer solar cells

Quantum phase transition in magnetic nanographenes on a lead superconductor

Quantum spins, referred to the spin operator preserved by full SU(2) symmetry in the absence of the magnetic anistropy, have been proposed to host exotic interactions with superconductivity4. However, spin orbit coupling and crystal field splitting normally cause a significant magnetic anisotropy for d/f-shell spins on surfaces6,9, breaking SU(2) symmetry and fabricating the spins with Ising properties10. Recently, magnetic nanographenes have been proven to host intrinsic quantum magnetism due to their negligible spin orbital coupling and crystal field splitting. Here, we fabricate three atomically precise nanographenes with the same magnetic ground state of spin S=1/2 on Pb(111) through engineering sublattice imbalance in graphene honeycomb lattice. Scanning tunneling spectroscopy reveals the coexistence of magnetic bound states and Kondo screening in such hybridized system. Through engineering the magnetic exchange strength between the unpaired spin in nanographenes and cooper pairs, quantum phase transition from the singlet to the doublet state has been observed, in consistent with quantum models of spins on superconductors. Our work demonstrates delocalized graphene magnetism host highly tunable magnetic bound states with cooper pairs, which can be further developed to study the Majorana bound states and other rich quantum physics of low-dimensional quantum spins on superconductors.Comment: 13 pages, 4figure

Postoperative ecchymoma of eyelid after botulinum toxin injection for hemifacial spasm: a case report

Hemifacial spasm (HFS) is a rare movement disorder characterized by involuntary muscle contractions on one side of the face. Compared to the high therapeutic effect, adverse effects of botulinum toxin treatment for HFS occurred rarely. However, managing HFS patients who are also taking antithrombotic drugs poses a challenge. Here, we present a case of postoperative ecchymoma of the eyelid following a botulinum toxin injection in a patient receiving daily vinpocetine and aspirin antiplatelet therapy. This case highlights the importance of considering the potential risks and formulating a treatment plan that maximizes benefit while minimizing complications in HFS patients undergoing botulinum toxin injections and taking antithrombotic medications. To the best of our knowledge, this is the first reported case of postoperative ecchymoma of the eyelid following a botulinum toxin injection. Further research and additional case reports are needed to better understand the management strategies for this patient population

Paraconsistent Reasoning for OWL 2

A four-valued description logic has been proposed to reason with description logic based inconsistent knowledge bases. This approach has a distinct advantage that it can be implemented by invoking classical reasoners to keep the same complexity as under the classical semantics. However, this approach has so far only been studied for the basid description logic ALC. In this paper, we further study how to extend the four-valued semantics to the more expressive description logic SROIQ which underlies the forthcoming revision of the Web Ontology Language, OWL 2, and also investigate how it fares when adapated to tractable description logics including EL++, DL-Lite, and Horn-DLs. We define the four-valued semantics along the same lines as for ALC and show that we can retain most of the desired properties