Remote neuronal activity drives glioma progression through SEMA4F.

The tumour microenvironment plays an essential role in malignancy, and neurons have emerged as a key component of the tumour microenvironment that promotes tumourigenesis across a host of cancers1,2. Recent studies on glioblastoma (GBM) highlight bidirectional signalling between tumours and neurons that propagates a vicious cycle of proliferation, synaptic integration and brain hyperactivity3-8; however, the identity of neuronal subtypes and tumour subpopulations driving this phenomenon is incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumours promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity-dependent infiltrating population present at the leading edge of mouse and human tumours that is enriched for axon guidance genes. High-throughput, in vivo screening of these genes identified SEMA4F as a key regulator of tumourigenesis and activity-dependent progression. Furthermore, SEMA4F promotes the activity-dependent infiltrating population and propagates bidirectional signalling with neurons by remodelling tumour-adjacent synapses towards brain network hyperactivity. Collectively our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, and also show new mechanisms of glioma progression that are regulated by neuronal activity.

High-dimensional mediation analysis for continuous outcome with confounders using overlap weighting method in observational epigenetic study.

BACKGROUND: Mediation analysis is a powerful tool to identify factors mediating the causal pathway of exposure to health outcomes. Mediation analysis has been extended to study a large number of potential mediators in high-dimensional data settings. The presence of confounding in observational studies is inevitable. Hence, it's an essential part of high-dimensional mediation analysis (HDMA) to adjust for the potential confounders. Although the propensity score (PS) related method such as propensity score regression adjustment (PSR) and inverse probability weighting (IPW) has been proposed to tackle this problem, the characteristics with extreme propensity score distribution of the PS-based method would result in the biased estimation. METHODS: In this article, we integrated the overlapping weighting (OW) technique into HDMA workflow and proposed a concise and powerful high-dimensional mediation analysis procedure consisting of OW confounding adjustment, sure independence screening (SIS), de-biased Lasso penalization, and joint-significance testing underlying the mixture null distribution. We compared the proposed method with the existing method consisting of PS-based confounding adjustment, SIS, minimax concave penalty (MCP) variable selection, and classical joint-significance testing. RESULTS: Simulation studies demonstrate the proposed procedure has the best performance in mediator selection and estimation. The proposed procedure yielded the highest true positive rate, acceptable false discovery proportion level, and lower mean square error. In the empirical study based on the GSE117859 dataset in the Gene Expression Omnibus database using the proposed method, we found that smoking history may lead to the estimated natural killer (NK) cell level reduction through the mediation effect of some methylation markers, mainly including methylation sites cg13917614 in CNP gene and cg16893868 in LILRA2 gene. CONCLUSIONS: The proposed method has higher power, sufficient false discovery rate control, and precise mediation effect estimation. Meanwhile, it is feasible to be implemented with the presence of confounders. Hence, our method is worth considering in HDMA studies.

Outlier detection in spatial error models using modified thresholding-based iterative procedure for outlier detection approach.

BACKGROUND: Outliers, data points that significantly deviate from the norm, can have a substantial impact on statistical inference and provide valuable insights in data analysis. Multiple methods have been developed for outlier detection, however, almost all available approaches fail to consider the spatial dependence and heterogeneity in spatial data. Spatial data has diverse formats and semantics, requiring specialized outlier detection methodology to handle these unique properties. For now, there is limited research exists on robust spatial outlier detection methods designed specifically under the spatial error model (SEM) structure. METHOD: We propose the Spatial-Θ-Iterative Procedure for Outlier Detection (Spatial-Θ-IPOD), which utilizes a mean-shift vector to identify outliers within the SEM. Our method enables an effective detection of spatial outliers while also providing robust coefficient estimates. To assess the performance of our approach, we conducted extensive simulations and applied it to a real-world empirical study using life expectancy data from multiple countries. RESULTS: Simulation results showed that the masking and JD (Joint Detection) indicators of our Spatial-Θ-IPOD method outperformed several commonly used methods, even in high-dimensional scenarios, demonstrating stable performance. Conversely, the Θ-IPOD method proved to be ineffective in detecting outliers when spatial correlation was present. Moreover, our model successfully provided reliable coefficient estimation alongside outlier detection. The proposed method consistently outperformed other models (both robust and non-robust) in most cases. In the empirical study, our proposed model successfully detected outliers and provided valuable insights in the modeling process. CONCLUSIONS: Our proposed Spatial-Θ-IPOD offers an effective solution for detecting spatial outliers for SEM while providing robust coefficient estimates. Notably, our approach showcases its relative superiority even in the presence of high leverage points. By successfully identifying outliers, our method enhances the overall understanding of the data and provides valuable insights for further analysis.

LncRNA ADAMTS9-AS2 regulates periodontal ligament cell migration under mechanical compression via ADAMTS9/fibronectin.

BACKGROUND: Periodontal ligament cells (PDLCs) are key mechanosensory cells involved in extracellular matrix (ECM) remodeling during orthodontic tooth movement (OTM). Mechanical force changes the ECM components, such as collagens and matrix metalloproteinases. However, the associations between the changes in ECM molecules and cellular dynamics during OTM remain largely uncharacterized. OBJECTIVES: To investigate the influence of mechanical force on the morphology and migration of PDLCs and explore the interaction between ECM remodeling and cellular dynamics, including the detailed mechanisms involved. METHODS: Human PDLCs (hPDLCs) were subjected to a static mechanical compression to mimic the compression state of OTM in vitro. A mouse OTM model was used to mimic the OTM procedure in vivo. The migration of hPDLCs was compared by wound healing and transwell migration assays. Moreover, expression levels of ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) and fibronectin (FN) in hPDLCs were determined via western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assays. Expression levels of ADAMTS9 and FN in mice were assessed via immunohistochemical staining. Additionally, the relative expression of long non-coding RNA (lncRNA) ADAMTS9-antisense RNA 2 (ADAMTS9-AS2) was assessed via quantitative real-time polymerase chain reaction. ADAMTS9-AS2 knockdown was performed to confirm its function in hPDLCs. RESULTS: Mechanical compression induced changes in the morphology of hPDLCs. It also promoted migration and simultaneous upregulation of FN and downregulation of ADAMTS9, a fibronectinase. The mouse OTM model showed the same expression patterns of the two proteins on the compression side of the periodontium of the moved teeth. RNA sequencing revealed that lncRNA ADAMTS9-AS2 expression was significantly upregulated in hPDLCs under mechanical compression. After knocking down ADAMTS9-AS2, hPDLCs migration was significantly inhibited. ADAMTS9 expression was increased as FN expression decreased compared to that in the control group. Moreover, knockdown of ADAMTS9-AS2 reduced the effect of mechanical compression on hPDLCs migration and reversed the expression change of ADAMTS9 and FN. RNA immunoprecipitation revealed direct binding between ADAMTS9-AS2 and ADAMTS9 protein. CONCLUSION: Our study suggests that mechanical compression induces the expression of ADAMTS9-AS2, which directly binds to ADAMTS9 and inhibits its function, leading to the promotion of downstream FN expression and ECM remodeling to facilitate hPDLCs migration and maintain the stability of the periodontium.

Effect of conformation of interfacial adsorbed chains on physical aging of polymer nanocomposites.

The dynamics of polymer nanocomposites varies depending on the physics and chemistry at the polymer-nanoparticle interface. The physical aging of the nanocomposites is accelerated or retarded based on interfacial interactions and the state of polymer adsorption at the interfaces. In this study, we investigated the aging kinetics of silica-polystyrene nanocomposites using differential scanning calorimetry, focusing on the effect of local conformations of chains adsorbed on the nanofiller surface. The results show that the temperature dependence of the aging rate follows a Vogel-Fulcher-Tammann relationship at high temperatures, whereas it exhibits an Arrhenius-like behavior below a characteristic temperature (Tc). Notably, at T < Tc, the aging rate decreases with increasing loop height of the chains adsorbed on the filler surface, but the activation energy remains unchanged. We proposed that the suppression of the aging rate at T < Tc is likely related to an increase in the length scale over which the slow interfacial dynamics can propagate due to the increased topological interactions between the chain loops of a larger size and the free chains in the matrix. The increased packing frustration occurring at the filler surface occupied by the larger loops might also contribute to the decreased aging rate.

Development and Validation of an Automated Classification System for Osteonecrosis of the Femoral Head Using Deep Learning Approach: A Multicenter Study.

BACKGROUND: Accurate classification can facilitate the selection of appropriate interventions to delay the progression of osteonecrosis of the femoral head (ONFH). This study aimed to perform the classification of ONFH through a deep learning approach. METHODS: We retrospectively sampled 1,806 midcoronal magnetic resonance images (MRIs) of 1,337 hips from 4 institutions. Of these, 1,472 midcoronal MRIs of 1,155 hips were divided into training, validation, and test datasets with a ratio of 7:1:2 to develop a convolutional neural network model (CNN). An additional 334 midcoronal MRIs of 182 hips were used to perform external validation. The predictive performance of the CNN and the review panel was also compared. RESULTS: A multiclass CNN model was successfully developed. In internal validation, the overall accuracy of the CNN for predicting the severity of ONFH based on the Japanese Investigation Committee classification was 87.8%. The macroaverage values of area under the curve (AUC), precision, recall, and F-value were 0.90, 84.8, 84.8, and 84.6%, respectively. In external validation, the overall accuracy of the CNN was 83.8%. The macroaverage values of area under the curve, precision, recall, and F-value were 0.87, 79.5, 80.5, and 79.9%, respectively. In a human-machine comparison study, the CNN outperformed or was comparable to that of the deputy chief orthopaedic surgeons. CONCLUSION: The CNN is feasible and robust for classifying ONFH and correctly locating the necrotic area. These findings suggest that classifying ONFH using deep learning with high accuracy and generalizability may aid in predicting femoral head collapse and clinical decision-making.

Intermediate Field Coupling of Single Epitaxial Quantum Dots to Plasmonic Waveguides.

Key requirements for quantum plasmonic nanocircuits are reliable single-photon sources, high coupling efficiency to the plasmonic structures, and low propagation losses. Self-assembled epitaxially grown GaAs quantum dots are close to ideal as stable, bright, and narrowband single-photon emitters. Likewise, wet-chemically grown monocrystalline silver nanowires are among the best plasmonic waveguides. However, large propagation losses of surface plasmons on the high-index GaAs substrate prevent their direct combination. Here, we show by experiment and simulation that the best overall performance of the quantum plasmonic nanocircuit based on these building blocks is achieved in the intermediate field regime with an additional spacer layer between the quantum dot and the plasmonic waveguide. High-resolution cathodoluminescence measurements allow a precise determination of the coupling distance and support a simple analytical model to explain the overall performance. The coupling efficiency is increased up to four times by standing wave interference near the end of the waveguide.

Ultra-Galactocation to Sialic Acid on Tumor Cells with A Penta-Functional Dendritic Probe for Enhanced Immune-Killing.

Glycans on tumor cell surface have significant impacts in the immune-killing process. Here an ultra-galactocation to sialic acid (Sia) strategy is designed to hugely introduce galactose (Gal) to Sia and on tumor cells in vivo by using a penta-functional dendritic probe (Den@5F), which efficiently enhances the immune-killing of tumor cells. The Den@5F contains five different kinds of functional groups, including Gal, Cy5, amino, phenylboronic acid (PBA) and 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butanoate (mNB), which can be conveniently prepared through a two-step reaction. After injecting into the tumor-bearing mouse, Den@5F can efficiently block Sia through the specific recognition between PBA and Sia on tumor cells and hugely introduce Gal through the subsequent photo-crosslinking between mNB and amino groups to multiply conjugate excessive Den@5Fs. The comprehensively blocked Sia can prevent the immune escape, and the hugely introduced Gal can promote the immune stimulation of the immune cells, which lead to an efficient enhancement of the immune-killing. The proposed strategy provides a significant and promising tool to promote the clinical immunotherapy of tumor.

22R- but not 22S-hydroxycholesterol is recruited for diosgenin biosynthesis.

Diosgenin is an important compound in the pharmaceutical industry and it is biosynthesized in several eudicot and monocot species, herein represented by fenugreek (a eudicot), and Dioscorea zingiberensis (a monocot). Formation of diosgenin can be achieved by the early C22,16-oxidations of cholesterol followed by a late C26-oxidation. This study reveals that, in both fenugreek and D. zingiberensis, the early C22,16-oxygenase(s) shows strict 22R-stereospecificity for hydroxylation of the substrates. Evidence against the recently proposed intermediacy of 16S,22S-dihydroxycholesterol in diosgenin biosynthesis was also found. Moreover, in contrast to the eudicot fenugreek, which utilizes a single multifunctional cytochrome P450 (TfCYP90B50) to perform the early C22,16-oxidations, the monocot D. zingiberensis has evolved two separate cytochrome P450 enzymes, with DzCYP90B71 being specific for the 22R-oxidation and DzCYP90G6 for the C16-oxidation. We suggest that the DzCYP90B71/DzCYP90G6 pair represent more broadly conserved catalysts for diosgenin biosynthesis in monocots.

Autophagy mediates cementoblast mineralization under compression through periostin/ß-catenin axis.

Repair of orthodontic external root resorption and periodontal tissue dysfunction induced by mechanical force remains a clinical challenge. Cementoblasts are vital in cementum mineralization, a process important for restoring damaged cementum. Despite autophagy plays a role in mineralization under various environmental stimuli, the underlying mechanism of autophagy in mediating cementoblast mineralization remains unclear. Here we verified that murine cementoblasts exhibit compromised mineralization under compressive force. Autophagy was indispensable for cementoblast mineralization, and autophagic activation markedly reversed cementoblast mineralization and prevented cementum damage in mice during tooth movement. Subsequently, messenger RNA sequencing analyses identified periostin (Postn) as a mediator of autophagy and mineralization in cementoblasts. Cementoblast mineralization was significantly inhibited following the knockdown of Postn. Furthermore, Postn silencing suppressed Wnt signaling by modulating the stability of ß-catenin. Together our results highlight the role of autophagy in cementoblast mineralization via Postn/ß-catenin signaling under compressive force and may provide a new strategy for the remineralization of cementum and regeneration of periodontal tissue.

CXCR4 expression is associated with proneural-to-mesenchymal transition in glioblastoma.

Glioblastoma (GBM) is the most common primary intracranial malignant tumor and consists of three molecular subtypes: proneural (PN), mesenchymal (MES) and classical (CL). Transition between PN to MES subtypes (PMT) is the glioma analog of the epithelial-mesenchymal transition (EMT) in carcinomas and is associated with resistance to therapy. CXCR4 signaling increases the expression of MES genes in glioma cell lines and promotes EMT in other cancers. RNA sequencing (RNAseq) data of PN GBMs in The Cancer Genome Atlas (TCGA) and secondary high-grade gliomas (HGGs) from an internal cohort were examined for correlation between CXCR4 expression and survival as well as expression of MES markers. Publicly available single-cell RNA sequencing (scRNAseq) data was analyzed for cell type specific CXCR4 expression. These results were validated in a genetic mouse model of PN GBM. Higher CXCR4 expression was associated with significantly reduced survival and increased expression of MES markers in TCGA and internal cohorts. CXCR4 was expressed in immune and tumor cells based on scRNAseq analysis. Higher CXCR4 expression within tumor cells on scRNAseq was associated with increased MES phenotype, suggesting a cell-autonomous effect. In a genetically engineered mouse model, tumors induced with CXCR4 exhibited a mesenchymal phenotype and shortened survival. These results suggest that CXCR4 signaling promotes PMT and shortens survival in GBM and highlights its inhibition as a potential therapeutic strategy.

Compressive force-induced LincRNA-p21 inhibits mineralization of cementoblasts by impeding autophagy.

The mineralization capability of cementoblasts is the foundation for repairing orthodontic treatment-induced root resorption. It is essential to investigate the regulatory mechanism of mineralization in cementoblasts under mechanical compression to improve orthodontic therapy. Autophagy has a protective role in maintaining cell homeostasis under environmental stress and was reported to be involved in the mineralization process. Long noncoding RNAs are important regulators of biological processes, but their functions in compressed cementoblasts during orthodontic tooth movement remain unclear. In this study, we showed that compressive force downregulated the expression of mineralization-related markers. LincRNA-p21 was strongly enhanced by compressive force. Overexpression of lincRNA-p21 downregulated the expression of mineralization-related markers, while knockdown of lincRNA-p21 reversed the compressive force-induced decrease in mineralization. Furthermore, we found that autophagy was impeded in compressed cementoblasts. Then, overexpression of lincRNA-p21 decreased autophagic activity, while knockdown of lincRNA-p21 reversed the autophagic process decreased by mechanical compression. However, the autophagy inhibitor 3-methyladenine abolished the lincRNA-p21 knockdown-promoted mineralization, and the autophagy activator rapamycin rescued the mineralization inhibited by lincRNA-p21 overexpression. Mechanistically, the direct binding between lincRNA-p21 and FoxO3 blocked the expression of autophagy-related genes. In a mouse orthodontic tooth movement model, knockdown of lincRNA-p21 rescued the impeded autophagic process in cementoblasts, enhanced cementogenesis, and alleviated orthodontic force-induced root resorption. Overall, compressive force-induced lincRNA-p21 inhibits the mineralization capability of cementoblasts by impeding the autophagic process.

GCH1 reduces LPS-induced alveolar macrophage polarization and inflammation by inhibition of ferroptosis.

OBJECTIVE: GTP cyclohydrolase 1(GCH1) was reported to protect against ferroptosis. However, it is not clear whether GCH1 reduced lipopolysaccharide (LPS)-induced macrophage polarization and inflammation by inhibition of ferroptosis. METHODS: Bioinformatics analysis was used to screen differential expression genes (DEGs) and obtain the different pathways and biological features. Lasso cox regression analysis with ferroptosis related DEGs was established to screen the most relevant genes for disease risk. LPS induced Raw264.7 macrophage polarization model and GCH1-specific siRNA oligos transfection were performed to confirm the function of GCH1. Immunofluorescence staining, western blot and quantitative real-time PCR were performed to detect the expression of iNOS, CD206, GCH1, IL6, SLC2A6, F4/80, IL1ß, TNFα, IL10, GPX4, ACSL4, AMPK and p-AMPK in macrophages. The levels of ROS, SOD, MDA and GSH were detected according to the instructions of the reagent kit, respectively. RESULTS: 542 DEGs were screened from GSE40885 microarray. GO and KEGG pathway enrichment analysis showed that the upregulated DEGs induced by LPS in alveolar macrophage were closely associated with inflammatory and immune responses, the downregulated DEGs were related to lipid metabolism, insulin resistance and AMPK signal pathway. Lasso cox regression analysis screened GCH1, IL6, and SLC2A6. Our experimental results showed that the expression of GCH1 and IL6 in the LPS group was higher than that in the control group, but there was no difference in the expression of SLC2A6. Bioinformatics analysis with GSE112720 observed that ferroptosis was enriched in GCHfl/fl + LPS group compared with GCHfl/flTie2cre + LPS group and GCHfl/fl + control group. Silence of GCH1 increased the levels of IL6, TNF-α and IL-1ß and decreased IL10 level. Silence of GCH1 increased iNOS level and decreased CD206 level. Moreover, silence of GCH1 raised ferroptosis induced by LPS in macrophages and suppressed the activity of AMPK pathway. CONCLUSIONS: GCH1 inhibited ferroptosis in LPS-stimulated macrophages, reduced macrophage toward to M1 polarization and inflammatory response.

Incidence and risk factors for febrile neutropenia of patients with diffuse large B-cell lymphoma receiving R-CHOP-21 in China.

OBJECTIVE: Febrile neutropenia (FN) is a serious complication of patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP-21. The prophylactic use of granulocyte colony-stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSFs for patients receiving chemotherapy with FN risk of 20% or 10 to 20% with defined risk factors. However, there are few studies on the incidence and risk factors of FN in patients with DLBCL receiving R-CHOP-21, especially in patients without primary G-CSF prophylaxis. METHODS: We conducted a retrospective analysis for the clinical data of 103 patients with DLBCL who underwent first R-CHOP-21 without primary G-CSF prophylaxis. The objective of the assessment was the incidence and risk factors of FN after the first chemotherapy cycle. RESULTS: After the first chemotherapy cycle, the incidence of FN was 20.4%. Multivariate analysis showed that age ≥ 65 years, bone marrow involvement, albumin < 35 g/L, and average relative dose intensity ≥ 80% were independent risk factors for FN. According to risk factors, we created a risk score system. The incidence of FN in the low-, intermediate- and high-risk groups was 5.6%, 17.2%, and 61.9%, respectively. CONCLUSION: Our data indicated that R-CHOP-21 itself is associated with a high-risk regiment for FN. We recommend that intermediate/high-risk patients should actively consider primary G-CSF prophylaxis to reduce the incidence of FN after chemotherapy.

Astaxanthin could regulate the gut-kidney axis to mitigate kidney injury in high-fat diet/streptozotocin-induced diabetic mice.

Accumulating evidences have shown the beneficial effects of astaxanthin (AST) supplementation on metabolic diseases prevention and treatment. The goal of present study was to reveal the favorable interactions among AST supplementation, gut microbiota, and kidneys in vivo, so as to attenuate kidney impairment in diabetic mice. Twenty C57BL/6J mice were assigned to a normal control group and a diabetic model group induced by a high-fat diet plus low-dose streptozotocin, and then the diabetic mice were fed with a high-fat diet without or with AST [0.01% (AST_a) or 0.02% (AST_b)] for 12 weeks. When compared to the diabetes kidney disease (DKD) group, AST supplementation delayed the renal pathological progression, reduced fasting blood glucose (AST_b: 1.53-fold, p<0.05), repressed levels of lipopolysaccharide (LPS; AST_a: 1.24-fold, p=0.008; AST_b: 1.43-fold, p<0.001) and TMAO (AST_a: 1.51-fold, p=0.001; AST_b: 1.40-fold, p=0.003), inhibited IL-6 (AST_a: 1.40-fold, p=0.004; AST_b: 1.57-fold, p=0.001) and reactive oxygen species (ROS; AST_a: 1.30-fold, p=0.004; AST_b: 1.53-fold, p<0.001), as well as regulated the Sirt1/PGC-1α/NFκB p65 signaling pathway. Moreover, the results of 16S rRNA gene-based Illumina deep sequencing in each group revealed that dietary AST supplementation also favorably modulated the gut microbiota compared with the DKD group, as evidenced by the inhibition of the harmful bacteria Clostridium_sensu_stricto_1, Romboutsia, and Coriobacteriaceae_UCG-002, and the enhancement of the probiotics such as Lachnospiraceae_NK4A136_group, Roseburia, and Ruminococcaceae. Taken together, dietary AST supplementation could protect kidneys against inflammation and oxidative stress by adjusting the gut-kidney axis in diabetic mice.

Effects of repetitive transcranial magnetic stimulation combined with music therapy in non-fluent aphasia after stroke: A randomised controlled study.

BACKGROUND: Although existing studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and music therapy have advantages in the treatment of non-fluent aphasia, the efficacy of the combination of these two methods remains to be investigated. AIMS: To investigate the clinical efficacy of low-frequency rTMS combined with music therapy on language function and depression in patients with non-fluent aphasia after stroke. METHODS & PROCEDURES: A single-blind parallel randomised controlled trial was conducted. Sixty patients (mean duration = 93.78 days) with non-fluent aphasia after stroke were randomly divided into a traditional therapy group (n = 20), a music therapy group (n = 20) and a combined therapy group (n = 20, 1 Hz). The language function and depression were evaluated before and 3 weeks after treatment with the Chinese version of the Western Aphasia Battery scale, Boston Diagnostic Aphasia Examination scale and Stroke Aphasic Depression Questionnaire Hospital Version scale. OUTCOMES & RESULTS: The combined therapy group was significantly better in all outcomes than the traditional therapy group and was significantly better in depression than the music therapy group. The music therapy group was significantly better in repetition and depression than the traditional therapy group. Language improvement was positively correlated with depression improvement. For adverse events, only two patients in the combined therapy group showed slight dizziness during rTMS treatment and their symptoms improved after rest. CONCLUSIONS & IMPLICATIONS: Our preliminary randomised controlled study indicates that low-frequency rTMS combined with music therapy is feasible and safe in improving language function and depression in non-fluent aphasia patients after stroke. WHAT THIS PAPER ADDS: What is already known on this subject Repetitive transcranial magnetic stimulation (rTMS) and music therapy respectively have advantages in the treatment of non-fluent aphasia after stroke, but whether the combination of the two methods is more effective is still unknown. What this paper adds to the existing knowledge This is one of the first randomised control trials to investigate whether the clinical efficacy of low-frequency rTMS combined music therapy for non-fluent aphasia is better. The findings show that low-frequency rTMS combined music therapy is superior to traditional therapy in spontaneous speech, auditory comprehension, repetition, naming, aphasia quotient, functional language level and depression, and superior to music therapy in depression, while music therapy is superior to traditional therapy in repetition and depression. What are the potential or actual clinical implications of this work? Low-frequency rTMS combined music therapy may be a better method for treatment of non-fluent aphasia.

Automatic detection of early osteonecrosis of the femoral head from various hip pathologies using deep convolutional neural network: a multi-centre study.

PURPOSE: The aim of this study was to develop a deep convolutional neural network (DCNN) for detecting early osteonecrosis of the femoral head (ONFH) from various hip pathologies and evaluate the feasibility of its application. METHODS: We retrospectively reviewed and annotated hip magnetic resonance imaging (MRI) of ONFH patients from four participated institutions and constructed a multi-centre dataset to develop the DCNN system. The diagnostic performance of the DCNN in the internal and external test datasets was calculated, including area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, and F1 score, and gradient-weighted class activation mapping (Grad-CAM) technique was used to visualize its decision-making process. In addition, a human-machine comparison trial was performed. RESULTS: Overall, 11,730 hip MRI segments from 794 participants were used to develop and optimize the DCNN system. The AUROC, accuracy, and precision of the DCNN in internal test dataset were 0.97 (95% CI, 0.93-1.00), 96.6% (95% CI: 93.0-100%), and 97.6% (95% CI: 94.6-100%), and in external test dataset, they were 0.95 (95% CI, 0.91- 0.99), 95.2% (95% CI, 91.1-99.4%), and 95.7% (95% CI, 91.7-99.7%). Compared with attending orthopaedic surgeons, the DCNN showed superior diagnostic performance. The Grad-CAM demonstrated that the DCNN placed focus on the necrotic region. CONCLUSION: Compared with clinician-led diagnoses, the developed DCNN system is more accurate in diagnosing early ONFH, avoiding empirical dependence and inter-reader variability. Our findings support the integration of deep learning systems into real clinical settings to assist orthopaedic surgeons in diagnosing early ONFH.

Dityrosine in food: A review of its occurrence, health effects, detection methods, and mitigation strategies.

Protein and amino acid oxidation in food products produce many new compounds, of which the reactive and toxic compound dityrosine, derived from oxidized tyrosine, is the most widely studied. The high reactivity of dityrosine enables this compound to induce oxidative stress and disrupt thyroid hormone function, contributing to the pathological processes of several diseases, such as obesity, diabetes, cognitive dysfunction, aging, and age-related diseases. From the perspective of food safety and human health, protein-oxidation products in food are the main concern of consumers, health management departments, and the food industry. This review highlights the latest research on the formation pathways, toxicity, detection methods, occurrence in food, and mitigation strategies for dityrosine. Furthermore, the control of dityrosine in family cooking and food-processing industry has been discussed. Food-derived dityrosine primarily originates from high-protein foods, such as meat and dairy products. Considering its toxicity, combining rapid high sensitivity dityrosine detection techniques with feasible control methods could be an effective strategy to ensure food safety and maintain human health. However, the current dityrosine detection and mitigation strategies exhibit some inherent characteristics and limitations. Therefore, developing technologies for rapid and effective dityrosine detection and control at the industrial level is necessary.

Design and fabrication of ridge waveguide-based nanobeam cavities for on-chip single-photon sources.

We report on the design of nanohole/nanobeam cavities in ridge waveguides for on-chip, quantum-dot-based single-photon generation. Our design overcomes limitations of a low-refractive-index-contrast material platform in terms of emitter-mode coupling efficiency and yields an outcoupling efficiency of 0.73 to the output ridge waveguide. Importantly, this high coupling efficiency is combined with broadband operation of 9 nm full-width half-maximum. We provide an explicit design procedure for identifying the optimum geometrical parameters according to the developed design. Besides, we fabricate and optically characterize a proof-of-concept waveguide structure. The results of the microphotoluminescence measurements provide evidence for cavity-enhanced spontaneous emission from the quantum dot, thus supporting the potential of our design for on-chip single-photon sources applications.

The effect of music therapy on language recovery in patients with aphasia after stroke: a systematic review and meta-analysis.

OBJECTIVE: The aim of this meta-analysis was to evaluate the evidence on the effectiveness of music therapy in the recovery of language function in post-stroke aphasia, compared with conventional therapy or no therapy. METHODS: We searched studies that explored the effect of music therapy on language function in post-stroke aphasia and published in PubMed, Embase, the Cochrane Library, Web of Science, CINAHL, ProQuest Digital Dissertations, and ClinicalTrials.gov from inception to March 2021. Six reviewers independently screened out eligible studies, extracted data, and evaluated the methodological quality. Results were pooled using mean difference (MD) with 95% confidence interval (CI). Heterogeneity was assessed by the chi-square test and I2 statistic. RESULTS: Six studies were included in this meta-analysis involving 115 patients. The methodological quality of these studies ranged from poor to excellent. There was significant mean difference in functional communication for post-stroke aphasia by 1.45 (95% CI: 0.24, 2.65; P = 0.02, from poor to excellent evidence), in repetition by 6.49 (95% CI: 0.97, 12.00; P = 0.02, from acceptable to excellent evidence), and in naming by 11.44 (95% CI: 1.63, 21.26; P = 0.02, from acceptable to excellent evidence). But there was no significant difference in comprehension for post-stroke aphasia by 7.21 (95% CI: - 10.88, 25.29; P = 0.43, from acceptable to excellent evidence). CONCLUSIONS: Music therapy can improve functional communication, repetition, and naming in patients with post-stroke aphasia, but did not significantly improve comprehension. TRIAL REGISTRATION: CRD42021251526.