The association between lymphocyte-to-monocyte ratio and all-cause mortality in obese hypertensive patients with diabetes and without diabetes: results from the cohort study of NHANES 2001-2018.

Objective: Obesity, hypertension and diabetes are high prevalent that are often associated with poor outcomes. They have become major global health concern. Little research has been done on the impact of lymphocyte-to-monocyte ratio (LMR) on outcomes in these patients. Thus, we aimed to explore the association between LMR and all-cause mortality in obese hypertensive patients with diabetes and without diabetes. Methods: The researchers analyzed data from the National Health and Nutrition Examination Survey (2001-2018), which included 4,706 participants. Kaplan-Meier analysis was employed to compare survival rate between different groups. Multivariate Cox proportional hazards regression models with trend tests and restricted cubic splines (RCS) analysis and were used to investigate the relationship between the LMR and all-cause mortality. Subgroup analysis was performed to assess whether there was an interaction between the variables. Results: The study included a total of 4706 participants with obese hypertension (48.78% male), of whom 960 cases (20.40%) died during follow-up (median follow-up of 90 months). Kaplan-Meier curves suggested a remarkable decrease in all-cause mortality with increasing LMR value in patients with diabetes and non-diabetes (P for log-rank test < 0.001). Moreover, multivariable Cox models demonstrated that the risk of mortality was considerably higher in the lowest quartile of the LMR and no linear trend was observed (P > 0.05). Furthermore, the RCS analysis indicated a non-linear decline in the risk of death as LMR values increased (P for nonlinearity < 0.001). Conclusions: Increased LMR is independently related with reduced all-cause mortality in patients with obese hypertension, regardless of whether they have combined diabetes.

AMPK-mediated autophagy pathway activation promotes ΔFosB degradation to improve levodopa-induced dyskinesia.

BACKGROUND: Parkinson's disease patients on chronic levodopa often suffer from motor complications, which tend to reduce their quality of life. Levodopa-induced dyskinesia (LID) is one of the most prevalent motor complications, often characterized by abnormal involuntary movements, and the pathogenesis of LID is still unclear but recent studies have suggested the involvement of autophagy. METHODS: The onset of LID was mimicked by chronic levodopa treatment in a unilateral 6-hydroxydopamine (6-OHDA) -lesion rat model. Overexpression of ΔFosB in HEK293 cells to mimic the state of ΔFosB accumulation. The modulation of the AMP-activated protein kinase (AMPK)-mediated autophagy pathway using by metformin, AICAR (an AMPK activator), Compound C (an AMPK inhibitor) and chloroquine (an autophagy pathway inhibitor). The severity of LID was assessed by axial, limb, and orofacial (ALO) abnormal involuntary movements (AIMs) score and in vivo electrophysiology. The activity of AMPK pathway as well as autophagy markers and FosB-ΔFosB levels were detected by western blotting. RT-qPCR was performed to detect the transcription level of FosB-ΔFosB. The mechanism of autophagy dysfunction was further explored by immunofluorescence and transmission electron microscopy. RESULTS: In vivo experiments demonstrated that chronic levodopa treatment reduced AMPK phosphorylation, impaired autophagosome-lysosomal fusion and caused FosB-ΔFosB accumulation in the striatum of PD rats. Long-term metformin intervention improved ALO AIMs scores as well as reduced the mean power of high gamma (hγ) oscillations and the proportion of striatal projection neurons unstable in response to dopamine for LID rats. Moreover, the intervention of metformin promoted AMPK phosphorylation, ameliorated the impairment of autophagosome-lysosomal fusion, thus, promoting FosB-ΔFosB degradation to attenuate its accumulation in the striatum of LID rats. However, the aforementioned roles of metformin were reversed by Compound C and chloroquine. The results of in vitro studies demonstrated the ability of metformin and AICAR to attenuate ΔFosB levels by promoting its degradation, while Compound C and chloroquine could block this effect. CONCLUSIONS: In conclusion, our results suggest that long-term metformin treatment could promote ΔFosB degradation and thus attenuate the development of LID through activating the AMPK-mediated autophagy pathway. Overall, our results support the AMPK-mediated autophagy pathway as a novel therapeutic target for LID and also indicate that metformin is a promising therapeutic candidate for LID.

Virus detection light diffraction fingerprints for biological applications.

The transmission of viral diseases is highly unstable and highly contagious. As the carrier of virus transmission, cell is an important factor to explore the mechanism of virus transmission and disease. However, there is still a lack of effective means to continuously monitor the process of viral infection in cells, and there is no rapid, high-throughput method to assess the status of viral infection. On the basis of the virus light diffraction fingerprint of cells, we applied the gray co-occurrence matrix, set the two parameters effectively to distinguish the virus status and infection time of cells, and visualized the virus infection process of cells in high throughput. We provide an efficient and nondestructive testing method for the selection of excellent livestock and poultry breeds at the cellular level. Meanwhile, our work provides detection methods for the recessive transmission of human-to-human, animal-to-animal, and zoonotic diseases and to inhibit and block their further development.

Design, synthesis and biological evaluation of bakuchiol derivatives as multi-target agents for the treatment of Alzheimer's disease.

The concept of multi-target-directed ligands offers fresh perspectives for the creation of brand-new Alzheimer's disease medications. To explore their potential as multi-targeted anti-Alzheimer's drugs, eighteen new bakuchiol derivatives were designed, synthesized, and evaluated. The structures of the new compounds were elucidated by IR, NMR, and HRMS. Eighteen compounds were assayed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in vitro using Ellman's method. It was shown that most of the compounds inhibited AChE and BuChE to varying degrees, but the inhibitory effect on AChE was relatively strong, with fourteen compounds showing inhibition of >50% at the concentration of 200 µM. Among them, compound 3g (IC50 = 32.07 ± 2.00 µM) and compound 3n (IC50 = 34.78 ± 0.34 µM) showed potent AChE inhibitory activities. Molecular docking studies and molecular dynamics simulation showed that compound 3g interacts with key amino acids at the catalytically active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and binds stably to acetylcholinesterase. On the other hand, compounds 3n and 3q significantly reduced the pro-inflammatory cytokines TNF-α and IL-6 released from LPS-induced RAW 264.7 macrophages. Compound 3n possessed both anti-acetylcholinesterase activity and anti-inflammatory properties. Therefore, an in-depth study of compound 3n is expected to be a multi-targeted anti-AD drug.

Soft-Hard Janus Nanoparticles Triggered Hierarchical Conductors with Large Stretchability, High Sensitivity, and Superior Mechanical Properties.

There is a long-standing conflict between the large stretchability and high sensitivity for strain sensors, a strategy of decoupling the mechanical/electrical module by constructing the hierarchical conductor has been developed in this study. The hierarchical conductor, consisting of a mechanically stretchable layer, a conductive network layer, and a strongly bonded interface, can be produced in a simple one-step process with the aid of soft-hard Janus nanoparticles (JNPs). The introduction of JNPs in the stretchable layer can evenly distribute stress and dissipate energy due to forming the rigid-flexible homogeneous networks. Specifically, JNPs can drive graphene nanosheets (GNS) to fold or curl, creating the unique JNPs-GNS building block that can further construct the conductive network. Due to its excellent deformability to hinder crack propagation, the flexible conductive network could be stretched continuously and the local conductive pathways could be reconstructed. Consequently, the hierarchical conductor could detect both subtle strain of 0-2% and large strain of up to 370%, with a gauge factor (GF) from 66.37 to 971.70, demonstrating outstanding stretchability and sensitivity. And it also owns large tensile strength (5.28 MPa) and high deformation stability. This hierarchical design will give graphene-based sensors a major boost in emerging applications.

Minimum Minutes Machine-Learning Microfluidic Microbe Monitoring Method (M7).

Frequent outbreaks of viral diseases have brought substantial negative impacts on society and the economy, and they are very difficult to detect, as the concentration of viral aerosols in the air is low and the composition is complex. The traditional detection method is manually collection and re-detection, being cumbersome and time-consuming. Here we propose a virus aerosol detection method based on microfluidic inertial separation and spectroscopic analysis technology to rapidly and accurately detect aerosol particles in the air. The microfluidic chip is designed based on the principles of inertial separation and laminar flow characteristics, resulting in an average separation efficiency of 95.99% for 2 µm particles. We build a microfluidic chip composite spectrometer detection platform to capture the spectral information on aerosol particles dynamically. By employing machine-learning techniques, we can accurately classify different types of aerosol particles. The entire experiment took less than 30 min as compared with hours by PCR detection. Furthermore, our model achieves an accuracy of 97.87% in identifying virus aerosols, which is comparable to the results obtained from PCR detection.

Thromboembolic prophylaxis in neurosurgical practice: a systematic review.

BACKGROUND: In neurosurgical patients, the risk of developing venous thromboembolism (VTE) is high due to the relatively long duration of surgical interventions, usually long immobilization time after surgery, and possible neurological deficits which can negatively influence mobility. In neurosurgical clinical practice, there is lack of consensus on optimal prophylaxis against VTE, mechanical or pharmacological. OBJECTIVE: To systematically review available literature on the incidence of VTE in neurosurgical interventions and to establish an optimum prevention strategy. METHODS: A literature search was performed in PubMed, Embase, Web of Science, Cochrane Library, and EmCare, based on a sensitive search string combination. Studies were selected by predefined selection criteria, and risk of bias was assessed by Newcastle-Ottawa Quality Assessment Scale and Cochrane risk of bias. RESULTS: Twenty-five studies were included, half of which had low risk of bias (21 case series, 3 comparative studies, 1 RCT). VTE was substantially higher if the evaluation was done by duplex ultrasound (DUS), or another systematic screening method, in comparison to clinical evaluation (clin). Without prophylaxis DVT, incidence varied from 4 (clin) to 10% (DUS), studies providing low molecular weight heparin (LMWH) reported an incidence of 2 (clin) to 31% (DUS), providing LMWH and compression stockings (CS) reported an incidence of 6.4% (clin) to 29.8% (DUS), and providing LMWH and intermittent pneumatic compression devices (IPC) reported an incidence of 3 (clin) to 22.3% (DUS). Due to a lack of data, VTE incidence could not meaningfully be compared between patients with intracranial and spine surgery. The reported incidence of pulmonary embolism (PE) was 0 to 7.9%. CONCLUSION: Low molecular weight heparin, compression stockings, and intermittent pneumatic compression devices were all evaluated to give reduction in VTE, but data were too widely varying to establish an optimum prevention strategy. Systematic screening for DVT reveals much higher incidence percentages in comparison to screening solely on clinical grounds and is recommended in follow-up of neurosurgical procedures with an increased risk for DVT development in order to prevent occurrence of PE.

Real-Time Video Super-Resolution with Spatio-Temporal Modeling and Redundancy-Aware Inference.

Video super-resolution aims to generate high-resolution frames from low-resolution counterparts. It can be regarded as a specialized application of image super-resolution, serving various purposes, such as video display and surveillance. This paper proposes a novel method for real-time video super-resolution. It effectively exploits spatial information by utilizing the capabilities of an image super-resolution model and leverages the temporal information inherent in videos. Specifically, the method incorporates a pre-trained image super-resolution network as its foundational framework, allowing it to leverage existing expertise for super-resolution. A fast temporal information aggregation module is presented to further aggregate temporal cues across frames. By using deformable convolution to align features of neighboring frames, this module takes advantage of inter-frame dependency. In addition, it employs a hierarchical fast spatial offset feature extraction and a channel attention-based temporal fusion. A redundancy-aware inference algorithm is developed to reduce computational redundancy by reusing intermediate features, achieving real-time inferring speed. Extensive experiments on several benchmarks demonstrate that the proposed method can reconstruct satisfactory results with strong quantitative performance and visual qualities. The real-time inferring ability makes it suitable for real-world deployment.

Activation of mGlu2/3 receptors in the striatum alleviates L-DOPA-induced dyskinesia and inhibits abnormal postsynaptic molecular expression.

Group II metabotropic glutamate receptors (mGlu2/3 receptors) have been regarded as promising candidates for the treatment of L-DOPA-induced dyskinesia (LID); however, confirmation is still lacking. As the hub of the basal ganglia circuit, the striatum plays a critical role in action control. Supersensitive responsiveness of glutamatergic corticostriatal input may be the key mechanism for the development of LID. In this study, we first examined the potency of LY354740 (12 mg/kg, i.p.) in modulating glutamate and dopamine release in lesioned striatum of stable LID rats. Then, we injected LY354740 (20nmoL or 40nmoL in 4 µL of sterile 0.9 % saline) directly into the lesioned striatum to verify its ability to reduce or attenuate L-DOPA-induced abnormal involuntary movements. In experiment conducted in established LID rats, after continuous injection for 4 days, we found that LY354740 significantly reduced the expression of dyskinesia. In another experiment conducted in parkinsonism rat models, we found that LY354740 attenuated the development of LID with an inverted-U dose-response curve. The role of LY354740 in modulating striatal expressions of LID-related molecular changes was also assessed after these behavioral experiments. We found that LY354740 significantly inhibited abnormal expressions of p-Fyn/p-NMDA/p-ERK1/2/p-HistoneH3/ΔFosB, which is in line with its ability to alleviate abnormal involuntary movements in both LID expression and induction phase. Our study indicates that activation of striatal mGlu2/3 receptors can attenuate the development of dyskinesia in parkinsonism rats and provide some functional improvements in LID rats by inhibiting LID-related molecular changes.

Identification of metabolism-related subtypes and feature genes in Alzheimer's disease.

BACKGROUND: Owing to the heterogeneity of Alzheimer's disease (AD), its pathogenic mechanisms are yet to be fully elucidated. Evidence suggests an important role of metabolism in the pathophysiology of AD. Herein, we identified the metabolism-related AD subtypes and feature genes. METHODS: The AD datasets were obtained from the Gene Expression Omnibus database and the metabolism-relevant genes were downloaded from a previously published compilation. Consensus clustering was performed to identify the AD subclasses. The clinical characteristics, correlations with metabolic signatures, and immune infiltration of the AD subclasses were evaluated. Feature genes were screened using weighted correlation network analysis (WGCNA) and processed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Furthermore, three machine-learning algorithms were used to narrow down the selection of the feature genes. Finally, we identified the diagnostic value and expression of the feature genes using the AD dataset and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. RESULTS: Three AD subclasses were identified, namely Metabolism Correlated (MC) A (MCA), MCB, and MCC subclasses. MCA contained signatures associated with high AD progression and may represent a high-risk subclass compared with the other two subclasses. MCA exhibited a high expression of genes related to glycolysis, fructose, and galactose metabolism, whereas genes associated with the citrate cycle and pyruvate metabolism were downregulated and associated with high immune infiltration. Conversely, MCB was associated with citrate cycle genes and exhibited elevated expression of immune checkpoint genes. Using WGCNA, 101 metabolic genes were identified to exhibit the strongest association with poor AD progression. Finally, the application of machine-learning algorithms enabled us to successfully identify eight feature genes, which were employed to develop a nomogram model that could bring distinct clinical benefits for patients with AD. As indicated by the AD datasets and qRT-PCR analysis, these genes were intimately associated with AD progression. CONCLUSION: Metabolic dysfunction is associated with AD. Hypothetical molecular subclasses of AD based on metabolic genes may provide new insights for developing individualized therapy for AD. The feature genes highly correlated with AD progression included GFAP, CYB5R3, DARS, KIAA0513, EZR, KCNC1, COLEC12, and TST.

Phylotranscriptomic analyses reveal deep gene tree discordance in Camellia (Theaceae).

Gene tree discordance is a significant legacy of biological evolution. Multiple factors can result in incongruence among genes, such as introgression, incomplete lineage sorting (ILS), gene duplication or loss. Resolving the background of gene tree discordance is a critical way to uncover the process of species diversification. Camellia, the largest genus in Theaceae, has controversial taxonomy and systematics due in part to a complex evolutionary history. We used 60 transcriptomes of 55 species, which represented 15 sections of Camellia to investigate its phylogeny and the possible causes of gene tree discordance. We conducted gene tree discordance analysis based on 1,617 orthologous low-copy nuclear genes, primarily using coalescent species trees and polytomy tests to distinguish hard and soft conflict. A selective pressure analysis was also performed to assess the impact of selection on phylogenetic topology reconstruction. Our results detected different levels of gene tree discordance in the backbone of Camellia, and recovered rapid diversification as one of the possible causes of gene tree discordance. Furthermore, we confirmed that none of the currently proposed sections of Camellia was monophyletic. Comparisons among datasets partitioned under different selective pressure regimes showed that integrating all orthologous genes provided the best phylogenetic resolution of the species tree of Camellia. The findings of this study reveal rapid diversification as a major source of gene tree discordance in Camellia and will facilitate future investigation of reticulate relationships at the species level in this important plant genus.

RNF213 inhibits migration in lung adenocarcinoma cell.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, and lung adenocarcinoma (LUAD) accounts for up to 40% of NSCLC. Ring finger protein 213(RNF213) has been demonstrated to suppress several cancers, including glioblastoma and breast cancer. Nonetheless, the role of RNF213 in LUAD has not been investigated. The expression of RNF213 in LUAD tissues was analyzed by western blotting, The Cancer Genome Atlas, Genotype Tissue Expression Project, and Gene Expression Omnibus databases. Prognostic value analysis was performed through the Kaplan-Meier Plotter database. We determined the role of RNF213 in LUAD cells through cell counting kit­8 assay, migration, and invasion assay. The clinical roles of RNF213 were evaluated by immunohistochemical staining assay (IHC) and Kaplan-Meier survival analysis. RNF213 expression was reduced in LUAD, thus affecting the prognosis of LUAD. And RNF213 could suppress the migration and invasion of LUAD cells to prevent tumor development. the expression of RNF213 is positively correlated with the overall survival, providing a novel marker in the prognosis of LUAD patients.

Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial.

BACKGROUND: Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC. MATERIALS AND METHODS: A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate. RESULTS: The incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR. CONCLUSION: Triweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570.

Dual Effects: Intrastriatal Injection of α-syn N103/tau N368 Preformed Fibrils Promotes Endogenous α-synuclein Aggregates in the Proximal Colon.

BACKGROUND: Pathological changes in the brain can affect the gastrointestinal tract, whereas there is less evidence regarding the brain-gut axis. OBJECTIVE: To identify whether cerebral endogenous phosphorylated α-synuclein induces gastrointestinal dysfunction via the brain-gut axis, mediated by the vagus nerve. METHODS: α-syn N103/tau N368 preformed fibrils were injected into the dorsal lateral striatum of rodents, and the cerebral and colonic synucleinopathies and changes in the enteric nervous system were analyzed. Moreover, subdiaphragmatic vagotomy was conducted to confirm the role of the vagus nerve in brain-gut propagation. RESULTS: An anterograde propagation of phosphorylated α-synuclein from the brain to the proximal colon mainly via the vagus nerve was observed at one month. The accumulation of phosphorylated α-synuclein was detected in the proximal colon over time, accompanied by infiltration of macrophages and eosinophils in the mucosa and submucosa. Upon injection with lower doses of preformed fibrils, the accumulation of phosphorylated α-synuclein and dopaminergic neuron loss was reduced to levels consistent with control at six months, while the expression levels of GFAP, Iba-1, and IL-6 increased. Under high preformed fibrils dose conditions, fecal traits and gastrointestinal motility were significantly reduced at six months, and aggregations of phosphorylated α-synuclein and an increasing level of IL-1ß appeared. CONCLUSION: Induced endogenous α-synuclein can quickly propagate into the proximal colon mainly via the vagus nerve. Injections of low doses of preformed fibrils can elicit recovery of the enteric nervous system and degradation of α-synuclein aggregates whereas high doses cause accumulation of pathological α-synuclein, enteric inflammation, and prominent gastrointestinal dysfunction.

Tumor Microbiome in Nasopharyngeal Carcinoma and Its Association With Prognosis.

Introduction: Previous studies have reported a close relationship between cancer and microbes, particularly gut and tumor microbiota; however, the presence of tumor microbiome in nasopharyngeal carcinoma (NPC) and its role in the prognosis of NPC remain unclear. Methods: We collected 64 samples including tissues from 50 patients with NPC (NPC group) and 14 patients with chronic nasopharyngitis (control group) receiver operating characteristics and we applied 16S ribosome RNA gene sequencing of all samples to assess microbiome profiles and immunohistochemistry to detect tumor microbiome in NPC. Results: Patients in the control group harbored higher species diversity than those in the NPC group; however, the beta diversity was more distinct in the NPC group. In total, three genera with statistically significant differences between the two groups were identified. The area under the receiver operating characteristics (ROC) curve (AUC) was calculated using the relative abundance of these three significant genera, and a value of 0.842 was achieved. Furthermore, Turicibacter was confirmed as a potentially independent prognostic factor for NPC patients, and the progression-free survival (PFS) was markedly prolonged in patients with a low relative abundance of Turicibacter compared to patients with a high relative abundance of this genus (cutoff: 0.0046, hazard ratio: 5.10, 95% confidence interval: 2.04-12.77, p = 0.004). Conclusions: The present study provided strong evidence of a correlation between tumor microbiome and NPC; the tumor microbiome may be considered a biomarker for early NPC diagnosis. Turicibacter potentially served as a independently prognostic indicator for NPC patients.

Bayesian Analysis of Aberrant Response and Response Time Data.

In this article, a highly effective Bayesian sampling algorithm based on auxiliary variables is proposed to analyze aberrant response and response time data. The new algorithm not only avoids the calculation of multidimensional integrals by the marginal maximum likelihood method but also overcomes the dependence of the traditional Metropolis-Hastings algorithm on the tuning parameter in terms of acceptance probability. A simulation study shows that the new algorithm is accurate for parameter estimation under simulation conditions with different numbers of examinees, items, and speededness levels. Based on the sampling results, the powers of the two proposed Bayesian assessment criteria are tested in the simulation study. Finally, a detailed analysis of a high-state and large-scale computerized adaptive test dataset is carried out to illustrate the proposed methodology.

Efficient sorting for an orbital angular momentum multiplexing communication link based on a digital micromirror device and a diffuser.

Efficient sorting multiple orbital angular momentum (OAM) spatial modes is a significant step in OAM multiplexing communications. Recently, wavefront shaping (WS) techniques have been implemented to manipulate light scattering through a diffuser. We reported a novel scheme for sorting multiplexed OAM modes faster and more accurately, using the complex amplitude WS based on a digital micromirror device (DMD) through a diffuser to shape the full field (phase and amplitude) of the OAM modes. In this study, we simulate this complex sorter for demultiplexing multiple modes and make a performance comparison with the previous sorter using the phase-only WS. Our results showed that for arbitrary two multiplexed modes, the sorter could achieve a high detection probability of more than 0.99. As the number of the multiplexed modes increases, the detection probability decreases to ∼0.82 when sorting seven modes, which contrasts the ∼0.71 of the phase-only sorters. We also experimentally verified the feasibility, that for arbitrary two modes, the sorter could reach a high detection probability of more than 0.99, and the complex sorter is capable of higher detection probability than the phase-only sorter under the same conditions. Hence, we anticipate that this sorter may potentially be demultiplexing multiple OAM spatial modes efficiently and quickly.

Association of Chronic Respiratory Symptoms With Incident Cardiovascular Disease and All-Cause Mortality: Findings From the Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Respiratory and cardiovascular diseases (CVDs) frequently coexist; however, there is limited evidence on the relationship between chronic respiratory symptoms in young adulthood and late-onset CVD. RESEARCH QUESTION: Are chronic respiratory symptoms in young adulthood associated with CVD and all-cause mortality in later life? STUDY DESIGN AND METHODS: A total of 4,621 participants from the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort study aged 18 to 30 years were included. Chronic respiratory symptoms were identified through respiratory symptom questionnaires in two consecutive examinations. Incident CVD and all-cause mortality were adjudicated over 30-year follow-up. Multivariable Cox proportional hazards models were used to explore the association of chronic respiratory symptoms with incident CVD and all-cause mortality. RESULTS: During a median follow-up of 30.9 years, 284 CVD events (6.15%) and 378 deaths (8.18%) occurred. Following multivariable adjustment for demographic characteristics, cardiovascular risk factors, smoking, and lung function, the hazard ratios (95% CIs) for CVD events were 1.51 (1.18-1.93) for any respiratory symptom, 1.57 (1.18-2.09) for cough or phlegm, 1.31 (1.01-1.68) for wheeze, 1.73 (1.25-2.41) for shortness of breath, and 1.32 (1.01-1.71) for chest illnesses. Similar findings were also observed in all-cause mortality. Comparing zero vs three to four respiratory symptoms, the hazard ratios (95% CIs) were 1.97 (1.34-2.91) for CVD and 1.75 (1.23-2.47) for all-cause mortality. Similar results were observed in various sensitivity analyses. INTERPRETATION: Chronic respiratory symptoms in young adulthood are associated with an increased risk of CVD and all-cause mortality in midlife independent of established cardiovascular risk factors, smoking, and lung function. Identifying chronic respiratory symptoms in young adulthood may help provide prognostic information regarding future cardiovascular health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT00005130; URL: https://www. CLINICALTRIALS: gov.

Computerised tomography features of giant cell tumour of the knee are associated with local recurrence after extended curettage.

BACKGROUND: Extended curettage has increasingly become the preferred treatment for giant cell tumour of bone (GCTB), but the high recurrence rate after curettage poses a major challenge for orthopaedic surgeons. Computed tomography (CT) is valuable in the evaluation of GCTB. Our aim was to identify specific features of GCTB around the knee in pre-operative CT images that might have prognostic value for local recurrence. METHODS: We retrospectively analyzed data from 124 patients with primary GCTB around the knee who underwent extended curettage from 2010 through 2019. We collected demographic, clinical, and therapeutic data along with several CT-derived tumour characteristics. CT-derived tumor characteristics included tumour size, the distance between the tumour edge and articular surface (DTA), and destruction of posterior cortical bone (DPC). Akaike information criterion (AIC) was used to select which variables to enter into multivariate logistic regression models and to determine significant factors affecting recurrence. RESULTS: The total recurrence rate was 21.0% (26/124), and the average follow-up time was 69.5 ± 31.2 months (24-127 months). Age, DTA (< 2 mm), and DPC were significantly related to recurrence, as determined by multivariate logistic regression. The C-index of the final model was 0.79 (95% CI: 0.71 to 0.88), representing a good model for predicting recurrence. CONCLUSION: Identifying certain features of GCTB around the knee on CT has prognostic value for patients treated with extended curettage. A three-factor model predicts tumour recurrence well after extended curettage.

A Novel and Highly Effective Bayesian Sampling Algorithm Based on the Auxiliary Variables to Estimate the Testlet Effect Models.

In this paper, a new two-parameter logistic testlet response theory model for dichotomous items is proposed by introducing testlet discrimination parameters to model the local dependence among items within a common testlet. In addition, a highly effective Bayesian sampling algorithm based on auxiliary variables is proposed to estimate the testlet effect models. The new algorithm not only avoids the Metropolis-Hastings algorithm boring adjustment the turning parameters to achieve an appropriate acceptance probability, but also overcomes the dependence of the Gibbs sampling algorithm on the conjugate prior distribution. Compared with the traditional Bayesian estimation methods, the advantages of the new algorithm are analyzed from the various types of prior distributions. Based on the Markov chain Monte Carlo (MCMC) output, two Bayesian model assessment methods are investigated concerning the goodness of fit between models. Finally, three simulation studies and an empirical example analysis are given to further illustrate the advantages of the new testlet effect model and Bayesian sampling algorithm.