Comparison of cardiac function and structure after left atrial appendage occlusion without versus with ablation in patients with non-valvular atrial fibrillation: a retrospective study.

The Aim of this study was to investigate the long-term impact of left atrial appendage occlusion (LAAO) on cardiac function and structure in patients with non-valvular atrial fibrillation (NVAF). 157 patients with NVAF who underwent LAAO or combined with ablation were included and divided into simple LAAO group or combined group. Long term impact of LAAO on cardiac function and structure were evaluated. Results showed that the procedures were performed successfully with 6.4% complications. During follow-up, there was a significant decrease of left atrial anteroposterior diameter (LAAD) at 6 months and a significant increase of left ventricular end-diastolic dimension (LVEDD) at 12 months after LAAO. A significant decrease in plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) was noted at 3 months, 6 months and 12 months after procedure. There was a significant decrease of LAAD, LVEDD, left ventricular end-systolic dimension (LVESD) and NT-proBNP levels in combined group at 3 months, 6 months and 12 months post- procedure, while an increase of left ventricular ejection fraction (LVEF). Meanwhile, no significant change of LAAD, LVEDD, LVESD, NT-proBNP and LVEF was seen in simple LAAO group at 3 months follow-up, but a decrease of NT-proBNP during 6 months and 12 months follow-up. Compared with simple LAAO group, combined group was associated with a significant increase of residual flow. In conclusion, LAAO has no significant effect on cardiac structure and function but can significantly reduce NT-proBNP. The improvement of cardiac structure and function in combined therapy comes from the result of ablation, not LAAO.

Synergistic Assistance of Ir Clusters and NiCo2O4 Nanosheets Interfaces in Direct O-O Coupling for High-Efficiency Alkaline Oxygen Evolution.

Adopting noble metals on non-noble metals is an effective strategy to balance the cost and activity of electrocatalysts. Herein, a thorough analysis of the synergistic OER is conducted at the heterogeneous interface formed by Ir clusters and NiCo2O4 based on DFT calculations. Specifically, the electrons spontaneously bring an eg occupancy of interfacial Ir close to unity after the absorbed O, providing more transferable electrons for the conversion of the absorbed O-intermediates. Besides, the diffuse distribution of electrons in the Ir 5d orbital fills the antibonding orbital after O is absorbed, avoiding the desorption difficulties caused by the stronger Ir-O bonds. The electrons transfer from Ir to Co atoms at the heterogeneous interface and fill the Co 3d band near the Fermi level, stimulating the interfacial Co to participate in the direct O-O coupling (DOOC) pathway. Experimentally, the ultrathin-modulated NiCo2O4 nanosheets are used to support Ir clusters (Ircluster-E-NiCo2O4) by the electrodeposition method. The as-synthesized Ircluster-E-NiCo2O4 catalyst achieves a current density of 10 mA cm-2 at an ultralow overpotential of 238 mV and works steadily for 100 h under a high current of 100 mA cm-2, benefiting from the efficient DOOC pathway during the OER.

NDC80/HEC1 promotes macrophage polarization and predicts glioma prognosis via single-cell RNA-seq and in vitro experiment.

INTRODUCTION: Glioma is the most frequent and lethal form of primary brain tumor. The molecular mechanism of oncogenesis and progression of glioma still remains unclear, rendering the therapeutic effect of conventional radiotherapy, chemotherapy, and surgical resection insufficient. In this study, we sought to explore the function of HEC1 (highly expressed in cancer 1) in glioma; a component of the NDC80 complex in glioma is crucial in the regulation of kinetochore. METHODS: Bulk RNA and scRNA-seq analyses were used to infer HEC1 function, and in vitro experiments validated its function. RESULTS: HEC1 overexpression was observed in glioma and was indicative of poor prognosis and malignant clinical features, which was confirmed in human glioma tissues. High HEC1 expression was correlated with more active cell cycle, DNA-associated activities, and the formation of immunosuppressive tumor microenvironment, including interaction with immune cells, and correlated strongly with infiltrating immune cells and enhanced expression of immune checkpoints. In vitro experiments and RNA-seq further confirmed the role of HEC1 in promoting cell proliferation, and the expression of DNA replication and repair pathways in glioma. Coculture assay confirmed that HEC1 promotes microglial migration and the transformation of M1 phenotype macrophage to M2 phenotype. CONCLUSION: Altogether, these findings demonstrate that HEC1 may be a potential prognostic marker and an immunotherapeutic target in glioma.

[Construction of a mouse model of type 2 diabetes induced by high fat diet alone and evaluation of pathological changes].

The purpose of the present study was to investigate the modeling time of type 2 diabetes mellitus (T2DM) mouse model induced by high fat diet (HFD) alone and the effects of HFD on the pathology and function of organs related to glucose and lipid metabolism. C57BL/6 mice were fed with normal diet (NC group) or HFD (HFD group). The time of successful T2DM modeling was evaluated by measuring body weight, fasting blood glucose and glucose tolerance at time points of 0, 4, 8, 12, 16 and 20 weeks. The functional and pathological changes of glucose and lipid metabolism related organs were evaluated by detecting insulin tolerance, plasma lipid levels, vascular function, as well as HE staining of pancreas and liver. The results showed that compared with the NC group, the HFD group had significantly increased body weight after 8 weeks of HFD. After 16 weeks of HFD, the HFD group exhibited impaired fasting glucose tolerance. After 20 weeks of HFD, the HFD group mice reached diabetic state, showing impaired glucose tolerance and insulin resistance, islet volume reduction and vacuolar degeneration; Large number of lipid droplets appeared in liver cells, and the level of AMPK phosphorylation in liver tissue was significantly increased in the HFD groups, compared with the NC group; There was endothelial dependent diastolic dysfunction in the thoracic aorta of the HFD group; Compared with the NC group, the HFD group mice showed a significant increase in urinary protein levels. These results suggest that T2DM mouse model can be successfully established by HFD induction alone for 20 weeks. The model is characterized by insulin resistance, fatty liver, hyperlipidemia, vascular dysfunction, renal dysfunction and pathological changes of islet and liver cells, which are similar to those of T2DM patients. Therefore it can be used as an ideal animal model for T2DM research.

[Three-dimensional finite element analysis of lumbar disc herniation under different body positions].

OBJECTIVE: To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation (LDH) by finite element analysis. METHODS: Lumbar CT image of a 48-year-old female patient with LDH (heighted 163 cm, weighted 53 kg) was collected. Mimics 20.0, Geomagic Studio, Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments. Compression techniques under horizontal position, 30° forward bending and 10° backward extension were simulated respectively. After applying the pressure, the effects of compression techniques under different positions on stress, strain and displacement of various tissues of intervertebral disc and nerve root were observed. RESULTS: L4, 5 segment finite element model was successfully established, and the model was validated. When compression manipulation was performed on the horizontal position, 30° flexion and 10° extension, the annular stress were 0.732, 5.929, 1.286 MPa, the nucleus pulposus stress were 0.190, 1.527, 0.295 MPa, and the annular strain were 0.097, 0.922 and 0.424, the strain sizes of nucleus pulposus were 0.153, 1.222 and 0.282, respectively. The overall displacement distance of intervertebral disc on Y direction were -3.707, -18.990, -4.171 mm, and displacement distance of nerve root on Y direction were +7.836, +5.341, +3.859 mm, respectively. The relative displacement distances of nerve root and intervertebral disc on Y direction were 11.543, 24.331 and 8.030 mm, respectively. CONCLUSION: Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend, by increasing the distance between herniated intervertebral disc and nerve root, to reduce symptoms of nerve compression, to achieve purpose of treatment for patients with LDH, in which the compression manipulation is more effective when the forward flexion is 30°.

Preoperative diffusion tensor imaging: Fiber-trajectory-distribution-based tractography to identify facial nerve in vestibular schwannoma.

PURPOSE: Tractography of the facial nerve based on diffusion MRI is instrumental before surgery for the resection of vestibular schwannoma, but no excellent methods usable for the suppression of motion and image noise have been proposed. The aim of this study was to effectively suppress noise and provide accurate facial nerve reconstruction by extend a fiber trajectory distribution function based on the fourth-order streamline differential equations. METHODS: Preoperative MRI from 33 patients with vestibular schwannoma who underwent surgical resection were utilized in this study. First, T1WI and T2WI were used to obtain mask images and regions of interest. Second, probabilistic tractography was employed to obtain the fibers representing the approximate facial nerve pathway, and these fibers were subsequently translated into orientation information for each voxel. Last, the voxel orientation information and the peaks of the fiber orientation distribution were combined to generate a fiber trajectory distribution function, which was used to parameterize the anatomical information. The parameters were determined by minimizing the cost between the trajectory of fibers and the estimated directions. RESULTS: Qualitative and visual analyses were used to compare facial nerve reconstruction with intraoperative recordings. Compared with other methods (SD_Stream, iFOD1, iFOD2, unscented Kalman filter, parallel transport tractography), the fiber-trajectory-distribution-based tractography provided the most accurate facial nerve reconstructions. CONCLUSION: The fiber-trajectory-distribution-based tractography can effectively suppress the effect of noise. It is a more valuable aid for surgeons before vestibular schwannoma resection, which may ultimately improve the postsurgical patient's outcome.

Exploring ethnic differences in the distribution of blood test results in healthy adult populations to inform earlier cancer detection: a systematic review.

BACKGROUND: In primary care, health professionals use blood tests to investigate nonspecific presentations to inform referral decisions. Reference ranges for the commonly used blood tests in western countries were developed in predominately White populations, and so may perform differently when applied to non-White populations. Knowledge of ethnic variation in blood test results in healthy/general populations could help address ethnic inequalities in cancer referral for diagnosis and outcomes. OBJECTIVE: This systematic review explored evidence of ethnic differences in the distribution of selected blood test results among healthy/general populations to inform future research aimed at addressing inequalities in cancer diagnosis. METHODS: We searched PubMed and EMBASE to identify studies reporting measures of haemoglobin, MCV, calcium, albumin, platelet count, and CRP in nondiseased adults from at least 2 different ethnic groups. Two reviewers independently screened studies, completed data extraction and quality assessment using an adapted Newcastle-Ottawa scale. Participants were stratified into White, Black, Asian, Mixed, and Other groups. Data were synthesised narratively and meta-analyses were conducted where possible. RESULTS: A total of 47 papers were included. Black men and women have lower average values of haemoglobin, MCV, and albumin, and higher average values of CRP relative to their White counterparts. Additionally, Black men have lower average haemoglobin than Asian men, whereas Asian women have lower average CRP values when compared with White women. CONCLUSIONS: There is evidence of ethnic differences in average values of haemoglobin, MCV, CRP, and albumin in healthy/general populations. Further research is needed to explore the reasons for these differences. Systematic review registration: CRD42021274580.

Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study.

Objective: To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death. Design: Prospective cohort study. Setting: UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years). Participants: 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study. Main outcome measures: Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Results: Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99). Conclusions: Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

Axl as a potential therapeutic target for adamantinomatous craniopharyngiomas: Based on single nucleus RNA-seq and spatial transcriptome profiling.

Craniopharyngiomas (CPs), particularly Adamantinomatous Craniopharyngiomas (ACPs), often exhibit a heightened risk of postoperative recurrence and severe complications of the endocrine and hypothalamic function. The primary objective of this study is to investigate potential novel targeted therapies within the microenvironment of ACP tumors. Cancer-Associated Fibroblasts (CAFs) were identified in the craniopharyngioma microenvironment, notably in regions characterized by cholesterol clefts, wet keratin, ghost cells, and fibrous stroma in ACPs. CAFs, alongside ghost cells, basaloid-like epithelium cells and calcifications, were found to secrete PROS1 and GAS6, which can activate AXL receptors on the surface of tumor epithelium cells, promoting immune suppression and tumor progression in ACPs. Additionally, the AXL inhibitor Bemcentinib effectively inhibited the proliferation organoids and enhanced the immunotherapeutic efficacy of Atezolizumab. Furthermore, neural crest-like cells were observed in the glial reactive tissue surrounding finger-like protrusions. Overall, our results revealed that the AXL might be a potentially effective therapeutic target for ACPs.

Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease. However, the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies. Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoetiology and suggest functional therapeutic and diagnostic options. Pyroptosis, ferroptosis, and necroptosis are the main subtypes of non-apoptotic regulated cell deaths (RCDs), each of which represents particular characteristics. Considering the complexity of the findings, the present study aimed to review these types of RCDs and their contribution to NAFLD progression, and subsequently discuss in detail the role of necroptosis in the pathoetiology, diagnosis, and treatment of the disease. The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer, hence it has potential in diagnostic and therapeutic approaches. Nevertheless, further studies are necessary.

Long-term exposure to ambient ozone and adult-onset asthma: A prospective cohort study.

BACKGROUND: The association between long-term exposure to ozone (O3) and adult-onset asthma (AOA) remains inconclusive, and analysis of causality is lacking. OBJECTIVES: To examine the causal association between long-term O3 exposure and AOA. METHODS: A prospective cohort study of 362,098 participants was conducted using the UK Biobank study. Incident cases of AOA were identified using health administrative data of the National Health Services. O3 exposure at participants' residential addresses was estimated by a spatio-temporal model. Instrumental variable (IV) modelling was used to analyze the causal association between O3 exposure and AOA, by incorporating wind speed and planetary boundary layer height as IVs into time-dependent Cox model. Negative control outcome (accidental injury) was also used to additionally evaluate unmeasured confounding. RESULTS: During a mean follow-up of 11.38 years, a total of 10,973 incident AOA cases were identified. A U-shaped concentration-response relationship was observed between O3 exposure and AOA in the traditional Cox models with HR of 0.916 (95% CI: 0.888, 0.945) for O3 at low levels (<38.17 ppb), and 1.204 (95% CI: 1.168, 1.242) for O3 at high levels (≥38.17 ppb). However, in the IV analysis we only found a statistically significant association between high-level O3 exposure and AOA risk, but not for low-level O3 exposure. No significant associations between O3 exposure and accidental injury were observed. CONCLUSION: Our findings suggest a potential causal relationship between long-term exposure to high-level ambient O3 and increased risks of AOA.

Unveiling the Potential of Two-Terminal Perovskite/Organic Tandem Solar Cells: Mechanisms, Status, and Challenges.

Perovskite/organic tandem solar cells (PO-TSCs) demonstrate exceptional suitability for emerging applications such as building-integrated photovoltaics, wearable devices, and greenhouse farming. By leveraging the distinctive attributes of perovskite and organic materials, which encompass expanded solar spectrum utilization, chemically benign solubility, and soft nature, PO-TSCs position themselves as ideal candidates for high-performance semi-transparent photovoltaics (ST-PVs). Despite these advantages, their development significantly lags behind other perovskite-based counterparts, such as perovskite/perovskite, perovskite/silicon, and perovskite/Cu(In, Ga)Se2. To address existing challenges and unlock the full potential of PO-TSCs, an exploration of the fundamental mechanisms governing tandem photovoltaic devices is embarked. Delving into critical aspects such as charge generation/separation, energy level alignment, and material choices becomes pivotal for optimizing PO-TSC performance. The investigation of monolithic two-terminal PO-TSCs offers insights into achievements and barriers, recognizing the competitive landscape with other TSC counterparts. Further scrutiny of perovskite absorbers and organic absorbers in TSCs reveals strategies aimed at enhancing stability and efficiency. The discussion extends to interconnection layers, elucidating their role in optimizing light transmission and balancing carrier recombination. In conclusion, a compelling outlook on the dynamic landscape of PO-TSCs is presented, highlighting the remarkable efficiency progression and signaling their potential to revolutionize solar energy harvesting technologies.

GLI1 polymorphisms influence remission rate and prognosis of young de novo acute myeloid leukemia patients treated with cytarabine-based chemotherapy.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. Cytarabine (Ara-C)-based chemotherapy is the primary treatment for AML, but currently known prognostic risk stratification factors cannot fully explain the individual differences in outcome of patients. In this article, we reported that patients with homozygous GLI1 rs2228224 mutation (AA genotype) had a significantly lower complete remission rate than those with GG wild type (54.17% vs.76.02%, OR = 1.993, 95% CI: 1.062-3.504, P = 0.031). GLI1 rs2229300 T allele carriers had remarkably shorter overall survival (513 vs. 645 days, P = 0.004) and disease-free survival (342 vs. 456 days, P = 0.033) than rs2229300 GG carriers. Rs2229300 G > T variation increased the transcriptional activity of GLI1. CCND1, CD44 and PROM1 were potential target genes differentially regulated by GLI1 rs2229300. Our results demonstrated for the first time that GLI1 polymorphisms influence chemosensitivity and prognosis of young de novo AML patients treated with Ara-C.

[Effects of Biochar on Growth and Pollutant Accumulation of Lettuce in Soil Co-contaminated with Tetracycline and Copper].

Through lettuce potting experiments, the effects of different types of biochar (apple branch, corn straw, and modified sorghum straw biochar with phosphoric acid modification) on lettuce growth under tetracycline (TC) and copper (Cu) co-pollution were investigated. The results showed that compared with those under CK, the addition of biochar treatment significantly increased the plant height, root length, shoot fresh weight, and root fresh weight of lettuce (P < 0.05). The addition of different biochars significantly increased the nitrate nitrogen, chlorophyll, and soluble protein content in lettuce physiological indicators to varying degrees, while also significantly decreasing the levels of malondialdehyde, proline content, and catalase activity. The effects of biochar on lettuce physiological indicators were consistent during both the seedling and mature stages. Compared with those in CK, the addition of biochar resulted in varying degrees of reduction in the TC and Cu contents of both the aboveground and underground parts of lettuce. The aboveground TC and Cu levels decreased by 2.49%-92.32% and 12.79%-36.47%, respectively. The underground TC and Cu levels decreased by 12.53%-55.64% and 22.41%-42.29%, respectively. Correlation analysis showed that nitrate nitrogen, chlorophyll, and soluble protein content of lettuce were negatively correlated with TC content, whereas malondialdehyde, proline content, and catalase activity were positively correlated with TC content. The resistance genes of lettuce were positively correlated with TC content (P < 0.05). In general, modified biochar was found to be more effective in improving lettuce growth quality and reducing pollutant accumulation compared to unmodified biochar, with modified sorghum straw biochar showing the best remediation effect.

Exploring the traditional Chinese diet and its association with health status-a systematic review.

CONTEXT: Increased adherence to a traditional Chinese diet (TCD) could reduce the increasing prevalence of noncommunicable diseases. Currently, there is no consistent definition of the TCD in the literature, and its associations with health outcomes have not yet been identified. OBJECTIVE: This systematic review aimed to assess the definition of the TCD, in the literature, and to evaluate whether the TCD, as described, is associated with health outcomes. DATA SOURCES: Fourteen databases were searched up to April 25, 2022. DATA EXTRACTION: Three reviewers (in pairs) independently screened and extracted data. A modified risk-of-bias tool was used to assess the quality of the studies assessing the TCD definition; the Newcastle-Ottawa Scale and the Cochrane Risk-of-Bias tool were used to assess the quality of the observational studies and randomized controlled trials assessing associations between the TCD and health outcomes. DATA ANALYSIS: Ninety-nine studies were identified that assessed the TCD definition. In at least 75% of the studies, rice and leafy vegetables were consistently reported as food groups that characterize the TCD; the most frequently cited food items were white rice, spinach, bokchoy, and cabbage. Fish and seafood, pork, and pork products were consistently reported in studies exclusively referring to the TCD consumed in southern China (n = 21 studies), whereas wheat and wheat products were commonly reported in studies focusing on northern China (n = 14 studies). Fifteen studies reported on the quantities of food groups that are characteristic of the TCD, but their findings were inconsistent. Of the 99 studies, 54 assessed associations with health outcomes. The TCD was overall inversely associated with obesity risk and weight gain, while relationships between the TCD and other health outcomes were inconsistent. CONCLUSION: Further studies are needed to determine the quantities of foods consumed in the TCD and to establish a consistent definition for further exploration of the TCD's potential role in preventing non-communicable diseases.

High Dietary Intake of Iron Might Be Harmful to Atrial Fibrillation and Modified by Genetic Diversity: A Prospective Cohort Study.

Some studies suggest an association between iron overload and cardiovascular diseases (CVDs). However, the relationship between dietary iron intake and atrial fibrillation (AF) remains uncertain, as does the role of genetic loci on this association. The study involved 179,565 participants from UK Biobank, tracking incident atrial fibrillation (AF) cases. Iron intake was categorized into low, moderate, and high groups based on dietary surveys conducted from 2009 to 2012. The Cox regression model was used to estimate the risk of AF in relation to iron intake, assessing the hazard ratio (HR) and 95% confidence interval (95% CI). It also examined the impact of 165 AF-related and 20 iron-related genetic variants on this association. Pathway enrichment analyses were performed using Metascape and FUMA. During a median follow-up period of 11.6 years, 6693 (3.97%) incident AF cases were recorded. A total of 35,874 (20.0%) participants had high iron intake. High iron intake was associated with increased risk of AF [HR: 1.13 (95% CI: 1.05, 1.22)] in a fully adjusted model. Importantly, there were 83 SNPs (11 iron-related SNPs) that could enhance the observed associations. These genes are mainly involved in cardiac development and cell signal transduction pathways. High dietary iron intake increases the risk of atrial fibrillation, especially when iron intake exceeds 16.95 mg. The association was particularly significant among the 83 SNPs associated with AF and iron, the individuals with these risk genes. Gene enrichment analysis revealed that these genes are significantly involved in cardiac development and cell signal transduction processes.

Causal association between long-term exposure to air pollution and incident Parkinson's disease.

Epidemiological evidence for long-term air pollution exposure and Parkinson's disease (PD) is controversial, and analysis of causality is limited. We identified 293,888 participants who were free of PD at baseline in the UK Biobank (2006-2010). Time-varying air pollution [fine particulate (PM2.5) and ozone (O3)] exposures were estimated using spatio-temporal models. Incident cases of PD were identified using validated algorithms. Four methods were used to investigate the associations between air pollution and PD, including (1) standard time-varying Cox proportional-hazard model; (2) Cox models weighted by generalized propensity score (GPS) and inverse-probability weights (IPW); (3) instrumental variable (IV) analysis; and (4) negative control outcome analysis. During a median of 11.6 years of follow-up, 1822 incident PD cases were identified. Based on standard Cox regression, the hazard ratios (95% confidence interval) for a 1 µg/m3 or ppb increase in PM2.5 and O3 were 1.23 (1.17, 1.30) and 1.02 (0.98, 1.05), respectively. Consistent results were found in models weighted by GPS and IPW, and in IV analysis. There were no significant associations between air pollution and negative control outcomes. This study provides evidence to support a causal association between PM2.5 exposure and PD. Mitigation of air pollution could be a protective measure against PD.

Research on spatial localization method of composite damage under strong noise.

In this paper, a damage spatial imaging approach based on novel signal extraction is suggested to reconstruct the Lamb wave response signal under strong noise and realize the spatial localization of damage. First, the Variable Mode Decomposition (VMD) parameters are optimized by the improved Grey Wolf optimization method (IGWO) to decompose the response signal. To rebuild the response signal, the correlation coefficient is used to choose the optimal modal component and the residual. To give the best wavelet function and transform level for adaptive denoising of the reconstructed signal without a reference signal, an enhanced Discrete Wavelet Transform (DWT) based on Shannon entropy is proposed. To achieve damage localization imaging, a damage spatial localization model is built utilizing a reconstruction algorithm for probabilistic inspection of damage (RAPID) approach and a convolutional neural network (CNN). The suggested method may successfully increase the signal-to-noise ratio (SNR) of the reconstructed response signal and lower the error of spatial localization under strong noise through experiments. The spatial localization of composite damage using Lamb wave under strong noise is expanded in this paper.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer.

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied. Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS. Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041). Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

An omicron-specific neutralizing antibody test predicts neutralizing activity against XBB 1.5.

Introduction: Understanding the immune status of an individual using neutralizing antibody testing is complicated by the continued evolution of the SARS-CoV-2 virus. Previous work showed that assays developed against the wildtype strain of SARS-CoV-2 were insufficient predictors of neutralization of omicron variants, thus we developed an omicron-specific flow cytometry-based neutralizing antibody test and performed experiments to assess how well it compared to an omicron-specific PRNT assay (gold standard) and whether it could predict neutralizing activity to more recent omicron subvariants such as XBB.1.5. Methods: Accuracy of a novel flow cytometry-based neutralizing antibody (FC-NAb) assay was determined by comparison with an omicron-specific PRNT assay. A series of samples were evaluated in both the omicron FC-NAb assay and a second test was designed to assess neutralization of XBB.1.5. Results: Good concordance between the omicron FC-NAb test and the omicron PRNT was demonstrated (AUC = 0.97, p <0.001; sensitivity = 94%, specificity = 100%, PPV = 100%, and NPV = 97%). A strong linear relationship between the omicron FC-NAb and neutralization of XBB1.5 was observed (r = 0.83, p<0.001). Additionally, the omicron FC-NAb test was a very strong predictor of positive XBB1.5 NAb activity (AUC = 0.96, p<0.001; sensitivity = 94%, specificity = 90%, positive predictive value = 90%, and negative predictive values = 94%). Discussion: Our data suggest that despite continued evolution of the SARS-CoV-2 spike protein, the omicron FC-NAb assay described here is a good predictor of XBB1.5 neutralizing activity, as evidenced by a strong correlation and good predictive performance characteristics.