DMA-HPCNet: Dual Multi-Level Attention Hybrid Pyramid Convolution Neural Network for Alzheimer's Disease Classification.

Computer-aided diagnosis (CAD) plays a crucial role in the clinical application of Alzheimer's disease (AD). In particular, convolutional neural network (CNN)-based methods are highly sensitive to subtle changes caused by brain atrophy in medical images (e.g., magnetic resonance imaging, MRI). Due to computational resource constraints, most CAD methods focus on quantitative features in specific regions, neglecting the holistic nature of the images, which poses a challenge for a comprehensive understanding of pathological changes in AD. To address this issue, we propose a lightweight dual multi-level hybrid pyramid convolutional neural network (DMA-HPCNet) to aid clinical diagnosis of AD. Specifically, we introduced ResNet as the backbone network and modularly extended the hybrid pyramid convolution (HPC) block and the dual multi-level attention (DMA) module. Among them, the HPC block is designed to enhance the acquisition of information at different scales, and the DMA module is proposed to sequentially extract different local and global representations from the channel and spatial domains. Our proposed DMA-HPCNet method was evaluated on baseline MRI slices of 443 subjects from the ADNI dataset. Experimental results show that our proposed DMA-HPCNet model performs efficiently in AD-related classification tasks with low computational cost.

The Causal Relationship between Plasma Myeloperoxidase Levels and Respiratory Tract Infections: A Bidirectional Mendelian Randomization Study.

Background: Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause-effect relation between plasma MPO levels and RTIs. Materials and Methods: Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. Results: We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011-1.274; P=0.032) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006-1.739; P=0.045). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072-1.251; P < 0.001; LRTI (ICU): OR = 1.216; 95% CI = 1.020-1.450; P=0.030). There was no evidence of a causal effect of URTI and LRTI (ICU) on plasma MPO concentration in the reverse analysis (P > 0.050). The sensitivity analysis revealed no violations of MR presumptions. Conclusions: Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels.

A causal relationship between educational attainment and risk of infectious diseases: A Mendelian randomisation study.

Background: Previous observational studies have investigated the association between educational attainment and sepsis, pneumonia, and urinary tract infections (UTIs). However, their findings have been susceptible to reverse causality and confounding factors. Furthermore, no study has examined the effect of educational level on the risk of infections of the skin and subcutaneous tissue (SSTIs). Thus, we aimed to evaluate the causal relationships between educational level and the risk of four infectious diseases using Mendelian randomisation (MR) techniques. Methods: We used univariable MR analysis to investigate the causal associations between educational attainment (years of schooling (n = 766 345) and holding college or university degree (n = 334 070)) and four infectious diseases (sepsis (n = 486 484), pneumonia (n = 486 484), UTIs (n = 463 010), and SSTIs (n = 218 792)). We included genetic instrumental variables with a genome-wide significance (P < 5 × 10-8) in the study. We used inverse variance-weighted estimation in the primary analysis and explored the stability of the results using multivariable MR analysis after adjusting for smoking, alcohol consumption, and body mass index. Results: Genetically predicted years of schooling were associated with a reduced risk of sepsis (odds ratio (OR) = 0.763; 95% confidence interval (CI) = 0.668-0.870, P = 5.525 × 10-5), pneumonia (OR = 0.637; 95% CI = 0.577-0.702, P = 1.875 × 10-19), UTIs (OR = 0.995; 95% CI = 0.993-0.997, P = 1.229 × 10-5), and SSTIs (OR = 0.696; 95% CI = 0.605-0.801, P = 4.034 × 10-7). We observed consistent results for the correlation between qualifications and infectious diseases. These findings remained stable in the multivariable MR analyses. Conclusions: Our findings suggest that increased educational attainment may be causally associated with a decreased risk of sepsis, pneumonia, UTIs, and SSTIs.

Advancing High-Throughput MS-Based Protein Quantification: A Case Study on Quantifying 10 Major Food Allergens by LC-MS/MS Using a One-Sample Multipoint External Calibration Curve.

The LC-MS-based method has emerged as the preferred approach for quantifying food allergens. However, the preparation of a traditional calibration curve (MSCC) is labor-intensive and error-prone. Here, a sensitive and robust LC-MS/MS method for quantifying 10 major food allergens was developed and validated, where the one-sample multipoint external calibration curve (OSCC) was employed instead of MSCC. By employing the multiple isotopologue reaction monitoring (MIRM) technique with only one spiked level in the blank, OSCC can be effectively established. Results demonstrate that the proposed method exhibits excellent performance in selectivity, sensitivity, accuracy, and precision, comparable to that of the traditional MSCC. Additionally, this strategy allows for isotope sample dilution by monitoring the less abundant MIRM channel. Moreover, the developed method was successfully applied to investigate the contamination of 10 food allergens in commercial food products. With its high throughput and robustness, the MIRM-OSCC-LC-MS/MS methodology has many potential applications, especially in the MS-based protein quantification analysis.

Icaritin activates p53 and inhibits aerobic glycolysis in liver cancer cells.

Metabolic reprogramming enables cancer cells to generate energy mainly through aerobic glycolysis, which is achieved by increasing the expression levels of glycolysis-related enzymes. Therefore, the development of drugs targeting aerobic glycolysis could be an effective strategy for cancer treatment. Icaritin (ICT) is an active ingredient from the Chinese herbal plant Epimedium with several biological activities, but its anti-cancer mechanism remains inconclusive. Using normal hepatocytes and hepatoma cells, our results showed that ICT suppressed cell proliferation and clonal formation and decreased glucose consumption and lactate production in liver cancer cells. In consistent, the mRNA and protein levels of several aerobic glycolysis-related genes were decreased upon ICT treatment. Furthermore, our results demonstrated that the expression levels of the aerobic glycolysis-related proteins were correlated with the p53 status in hepatoma cells. Using PFT-α or siRNA-p53, our results confirmed that ICT regulated aerobic glycolysis in a p53-dependent manner. In addition, ICT was found to stabilize p53 at the post-translational level which might be mediated by inhibiting MDM2 expression and affecting its interaction with p53. Finally, our results demonstrated that ICT increased the levels of ROS that activated p53 via the p38 MAPK pathway. In conclusion, ICT increased intracellular ROS levels in liver cancer cells, which promoted the stabilization and activation of p53, inhibiting the expression of aerobic glycolysis-related genes and glycolysis, and ultimately leading to the suppression of liver cancer development.

The oral-brain axis: can periodontal pathogens trigger the onset and progression of Alzheimer's disease?

Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by a progressive cognitive decline. Sporadic AD, accounting for more than 95% of cases, may arise due to the influence of environmental factors. It was reported that periodontitis, a common oral ailment, shares several risk factors with AD, including advanced age, smoking, diabetes, and hypertension, among others. Periodontitis is an inflammatory disease triggered by dysbiosis of oral microorganisms, whereas Alzheimer's disease is characterized by neuroinflammation. Many studies have indicated that chronic inflammation can instigate brain AD-related pathologies, including amyloid-ß plaques, Tau protein hyperphosphorylation, neuroinflammation, and neurodegeneration. The potential involvement of periodontal pathogens and/or their virulence factors in the onset and progression of AD by the oral-brain axis has garnered significant attention among researchers with ongoing investigations. This review has updated the periodontal pathogens potentially associated with AD, elucidating their impact on the central nervous system, immune response, and related pathological processes in the brain to provide valuable insights for future research on the oral-brain axis.

Possible pharmacological targets and mechanisms of sivelestat in protecting acute lung injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening syndrome induced by various diseases, including COVID-19. In the progression of ALI/ARDS, activated neutrophils play a central role by releasing various inflammatory mediators, including elastase. Sivelestat is a selective and competitive inhibitor of neutrophil elastase. Although its protective effects on attenuating ALI/ARDS have been confirmed in several models of lung injury, clinical trials have presented inconsistent results on its therapeutic efficacy. Therefore, in this report, we used a network pharmacology approach coupled with animal experimental validation to unravel the concrete therapeutic targets and biological mechanisms of sivelestat in treating ALI/ARDS. In bioinformatic analyses, we found 118 targets of sivelestat against ALI/ARDS, and identified six hub genes essential for sivelestat treatment of ALI/ARDS, namely ERBB2, GRB2, PTK2, PTPN11, ESR1, and CCND1. We also found that sivelestat targeted several genes expressed in human lung microvascular endothelial cells after lipopolysaccharide (LPS) treatment at 4 h (ICAM-1, PTGS2, RND1, BCL2A1, TNF, CA2, and ADORA2A), 8 h (ICAM-1, PTGS2, RND1, BCL2A1, MMP1, BDKRB1 and SLC40A1), and 24 h (ICAM-1). Further animal experiments showed that sivelestat was able to attenuate LPS-induced ALI by inhibiting the overexpression of ICAM-1, VCAM-1, and PTGS2 and increasing the phosphorylation of PTK2. Taken together, the bioinformatic findings and experimentative data indicate that the therapeutic effects of sivelestat against ALI/ARDS mainly focus on the early stage of ALI/ARDS by pharmacological modulation of inflammatory reaction, vascular endothelial injury, and cell apoptosis-related molecules.

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models.

BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.

Theoretical Investigation on the Metamaterials Based on the Magnetic Template-Assisted Self-Assembly of Magnetic-Plasmonic Nanoparticles for Adjustable Photonic Responses.

The assembly of artificial nano- or microstructured materials with tunable functionalities and structures, mimicking nature's complexity, holds great potential for numerous novel applications. Despite remarkable progress in synthesizing colloidal molecules with diverse functionalities, most current methods, such as the capillarity-assisted particle assembly method, the ionic assembly method based on ionic interactions, or the field-directed assembly strategy based on dipole-dipole interactions, are confined to focusing on achieving symmetrical molecules. But there have been few examples of fabricating asymmetrical colloidal molecules that could exhibit unprecedented optical properties. Here, we introduce a microfluidic and magnetic template-assisted self-assembly protocol that relies mainly on the magnetic dipole-dipole interactions between magnetized magnetic-plasmonic nanoparticles and the mechanical constraints resulting from the specially designed traps. This novel strategy not only requires no specific chemistry but also enables magnetophoretic control of magnetic-plasmonic nanoparticles during the assembly process. Moreover, the assembled asymmetrical colloidal molecules also exhibit interesting hybridized plasmon modes and produce exotic optical properties due to the strong coupling of the individual nanoparticle. The ability to fabricate asymmetrical colloidal molecules based on the bottom-up method opens up a new direction for the fabrication of novel microscale structures for biosensing, patterning, and delivery applications.

Metal-organic framework materials promote neural differentiation of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) is accompanied by loss of Zn2+, which is an important cause of glutamate excitotoxicity and death of local neurons as well as transplanted stem cells. Dental pulp stem cells (DPSCs) have the potential for neural differentiation and play an immunomodulatory role in the microenvironment, making them an ideal cell source for the repair of central nerve injury, including SCI. The zeolitic imidazolate framework 8 (ZIF-8) is usually used as a drug and gene delivery carrier, which can release Zn2+ sustainedly in acidic environment. However, the roles of ZIF-8 on neural differentiation of DPSCs and the effect of combined treatment on SCI have not been explored. ZIF-8-introduced DPSCs were loaded into gelatin methacryloyl (GelMA) hydrogel and in situ injected into the injured site of SCI rats. Under the effect of ZIF-8, axon number and axon length of DPSCs-differentiated neuro-like cells were significantly increased. In addition, ZIF-8 protected transplanted DPSCs from apoptosis in the damaged microenvironment. ZIF-8 promotes neural differentiation and angiogenesis of DPSCs by activating the Mitogen-activated protein kinase (MAPK) signaling pathway, which is a promising transport nanomaterial for nerve repair.

Preparation of Gd-doped AuNBP@mSiO2 nanocomposites for the MR imaging, drug delivery and chemo-photothermal synergistic killing of breast cancer cells.

Under near-infrared (NIR) light, gold nanobipyramids (AuNBPs) exhibit a high photothermal conversion rate and photothermal stability, making them ideal mediators for photothermal therapy (PTT). In this study, highly purified AuNBPs are prepared, followed by coating their surfaces with mesoporous silica (mSiO2). The obtained AuNBP@mSiO2 nanocomplex exhibits an ellipsoidal shape with a relatively large specific surface, pore diameter and pore volume. To achieve MRI guided chemo-photothermal therapy of breast cancer cells, the nanocomplex is further coupled with the MRI contrast agent Gd-DTTA and the chemotherapeutic drug doxorubicin (DOX). The results indicated that under NIR light irradiation, AuNBPs exhibited promising PTT effects, while the cumulative release rate of DOX was significantly enhanced to 81.40%. Moreover, the chemo-photothermal therapy approach effectively eradicated 4T1 breast cancer cells. This work successfully confirms that chemo-photothermal synergistic therapy is an effective tumor treatment strategy and demonstrates the potential application of AuNBP@mSiO2 as a nano-drug delivery platform. Additionally, it introduces new ideas for the integrated study of breast cancer diagnosis and treatment.

Activation persulfate for efficient tetrabromobisphenol A degradation via carbon-based materials: Synergistic mechanism of doped N and Fe.

In this study, a novel carbon-based material (Fe-N-PGWBC) utilizing the garden waste, melamine and FeSO4 as the precursor was successfully synthesized, efficiently activating peroxydisulfate (PDS) to degrade tetrabromobisphenol A (TBBPA). Under typical conditions (Fe-N-PGWBC dose of 100 mg·L-1, PDS of 0.2 mM and TBBPA of 10 mg·L-1), Fe-N-PGWBC/PDS system could achieve over 99% TBBPA removal (including adsorption and degradation) within 60 min, and the corresponding rate constant ks was 0.0724 min-1, which was almost 40.2 times higher than that of the pristine biochar. The extraction experiments implied that the excellent adsorption performance of Fe-N-PGWBC did not hinder the degradation of TBBPA. Abundant active sites (rich oxygen-containing functional groups, Fe-O and Fe3C) of Fe-N-PGWBC could effectively promote PDS decomposition to produce reactive oxygen species. The probe-based kinetic modelling methods verified that approximately 87.6% TBBPA was degraded by SO4·-, 12.2% TBBPA was degraded by 1O2, and 0.2% TBBPA was degraded by ·OH. Furthermore, based on the calculation of density functional theory and identification of products, TBBPA was mainly involved in three transformation pathways including hydroxylation, debromination and ß-scission process. The study proposed a facile resource approach of garden waste and provided deeper understanding for the TBBPA degradation mechanisms in heterogeneous system.

Systematic investigation of the underlying mechanisms of GLP-1 receptor agonists to prevent myocardial infarction in patients with type 2 diabetes mellitus using network pharmacology.

Background: Several clinical trials have demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) reduce the incidence of non-fatal myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. In this study, we applied a network pharmacology method to investigate the mechanisms by which GLP-1RAs reduce MI occurrence in patients with T2DM. Methods: Targets of three GLP-1RAs (liraglutide, semaglutide, and albiglutide), T2DM, and MI were retrieved from online databases. The intersection process and associated targets retrieval were employed to obtain the related targets of GLP-1RAs against T2DM and MI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analyses were performed. The STRING database was used to obtain the protein-protein interaction (PPI) network, and Cytoscape was used to identify core targets, transcription factors, and modules. Results: A total of 198 targets were retrieved for the three drugs and 511 targets for T2DM with MI. Finally, 51 related targets, including 31 intersection targets and 20 associated targets, were predicted to interfere with the progression of T2DM and MI on using GLP-1RAs. The STRING database was used to establish a PPI network comprising 46 nodes and 175 edges. The PPI network was analyzed using Cytoscape, and seven core targets were screened: AGT, TGFB1, STAT3, TIMP1, MMP9, MMP1, and MMP2. The transcription factor MAFB regulates all seven core targets. The cluster analysis generated three modules. The GO analysis for 51 targets indicated that the terms were mainly enriched in the extracellular matrix, angiotensin, platelets, and endopeptidase. The results of KEGG analysis revealed that the 51 targets primarily participated in the renin-angiotensin system, complement and coagulation cascades, hypertrophic cardiomyopathy, and AGE-RAGE signaling pathway in diabetic complications. Conclusion: GLP-1RAs exert multi-dimensional effects on reducing the occurrence of MI in T2DM patients by interfering with targets, biological processes, and cellular signaling pathways related to atheromatous plaque, myocardial remodeling, and thrombosis.

Room-Temperature Magnetism in 2D MnGa4 -H Induced by Hydrogen Insertion.

2D room-temperature magnetic materials are of great importance in future spintronic devices while only very few are reported. Herein, a plasma-enhanced chemical vapor deposition approach is exploited to construct the 2D room-temperature magnetic MnGa4 -H single crystal with a thickness down to 2.2 nm. The employment of H2 plasma makes hydrogen atoms can be easily inserted into the MnGa4 lattice to modulate the atomic distance and charge state, thereby ferrimagnetism can be achieved without destroying the structural configuration. The as-obtained 2D MnGa4 -H crystal is high-quality, air-stable, and thermo-stable, demonstrating robust and stable room-temperature magnetism with a high Curie temperature above 620 K. This work enriches the 2D room-temperature magnetic family and opens up the possibility for the development of spintronic devices based on 2D magnetic alloys.

Identifying the key genes of Epstein-Barr virus-regulated tumour immune microenvironment of gastric carcinomas.

The Epstein-Barr virus (EBV) is involved in the carcinogenesis of gastric cancer (GC) upon infection of normal cell and induces a highly variable composition of the tumour microenvironment (TME). However, systematic bioinformatics analysis of key genes associated with EBV regulation of immune infiltration is still lacking. In the present study, the TCGA and GEO databases were recruited to analyse the association between EBV infection and the profile of immune infiltration in GC. The weighted gene co-expression analysis (WGCNA) was applied to shed light on the key gene modules associated with EBV-associated immune infiltration in GC. 204 GC tissues were used to analysed the expression of key hub genes by using the immunohistochemical method. Real-time PCR was used to evaluate the association between the expression of EBV latent/lytic genes and key immune infiltration genes. Our results suggested that EBV infection changed the TME of GC mainly regulates the TIICs. The top three hub genes of blue (GBP1, IRF1, and LAP3) and brown (BIN2, ITGAL, and LILRB1) modules as representative genes were associated with EBV infection and GC immune infiltration. Furthermore, EBV-encoded LMP1 expression is account for the overexpression of GBP1 and IRF1. EBV infection significantly changes the TME of GC, and the activation of key immune genes was more dependent on the invasiveness of the whole EBV virion instead of single EBV latent/lytic gene expression.

Association between body mass index change and mortality in critically ill patients: A retrospective observational study.

OBJECTIVE: Previous studies have emphasized the association between baseline body mass index (BMI) and mortality in patients during a stay in the intensive care unit (ICU). However, to our knowledge, few studies have focused on BMI change during an ICU stay. The aim of this study was to explore the prognostic value of BMI change during ICU hospitalization. METHODS: This was a multicenter, retrospective cohort study with data extracted from the eICU Collaborative Research Database. Logistic regression models were used to explore the relationship between BMI change and mortality in ICU patients. BMI change was calculated as follows: {[discharge ICU weight (kg) - admission ICU weight (kg)] / height (m)2]}. Interaction and subgroup analyses were conducted for patients grouped with baseline BMI on ICU admission (≥30 versus 25-29.9 versus <25 kg/m2), Acute Physiology and Chronic Health Evaluation (APACHE) IV score (<53 versus ≥53), and ICU length of stay (≥3 versus <3 d). RESULTS: Compared with those with weight loss (n = 17 134), patients with weight gain during ICU hospitalization (n = 17 436) were associated with higher hospital mortality (odds ratio [OR], 1.251; 95% confidence interval [CI], 1.155-1.356; P < 0.001) and ICU mortality (OR, 1.360; 95% CI, 1.227-1.506; P < 0.001) after multivariable adjustment. The associations remained robust in patients with different baseline BMI levels and were especially remarkable among those with higher APACHE IV score and the longer ICU stay. CONCLUSIONS: The present study exposed the potential hazard of increasing BMI for hospital and ICU mortalities during ICU hospitalization and indicating that patients in the ICU may benefit from a more balanced nutritional strategy.

Role of oral microbiome in oral oncogenesis, tumor progression, and metastasis.

Squamous cell carcinoma is the most common malignant tumor of the oral cavity and its adjacent sites, which endangers the physical and mental health of patients and has a complex etiology. Chronic infection is considered to be a risk factor in cancer development. Evidence suggests that periodontal pathogens, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, are associated with oral squamous cell carcinoma (OSCC). They can stimulate tumorigenesis by promoting epithelial cells proliferation while inhibiting apoptosis and regulating the inflammatory microenvironment. Candida albicans promotes OSCC progression and metastasis through multiple mechanisms. Moreover, oral human papillomavirus (HPV) can induce oropharyngeal squamous cell carcinoma (OPSCC). There is evidence that HPV16 can integrate with host cells' DNA and activate oncogenes. Additionally, oral dysbiosis and synergistic effects in the oral microbial communities can promote cancer development. In this review, we will discuss the biological characteristics of oral microbiome associated with OSCC and OPSCC and then highlight the mechanisms by which oral microbiome is involved in oral oncogenesis, tumor progression, and metastasis. These findings may have positive implications for early diagnosis and treatment of oral cancer.

Relationship of Admission Serum Anion Gap and Prognosis of Critically Ill Patients: A Large Multicenter Cohort Study.

Background: There were controversies over the relationship between Anion gap (AG) and mortality in critically ill patients. Therefore, a large multicenter cohort study was conducted to evaluate the association of AG and mortality in large-scale intensive care units (ICUs) patients. Methods: This retrospective cohort study included adult ICU patients enrolled from eICU Collaborative Research Database. According to initial serum AG upon ICU admission, patients were divided into three groups: AG < 8 mmol/L, 8 ≤ AG ≤ 16 mmol/L, and AG > 16 mmol/L. Logistic regression models were built to investigate the association between serum AG and ICU and hospital mortalities. Serum AG was added into Acute Physiology and Chronic Health Evaluation (APACHE) IV score and the model discrimination was assessed by the area under the curve (AUC) of receiver operating characteristic curves. The relationship between serum AG and mortalities in patients with different acid-base status and serum lactate were also evaluated. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People's Hospital. Results: A total of 8520 patients entered the final cohort. There are 42 patients with serum AG < 8 mmol/L, 3238 patients with 8 ≤ AG ≤ 16 mmol/L, and 5240 patients with AG > 16 mmol/L. Serum AG > 16 mmol/L is related with increased ICU mortality (odds ratio [OR], 1.530; 95% confidence interval [CI], 1.305-1.794) and hospital mortality (OR, 1.618; 95% CI, 1.415-1.849), compared with 8 ≤ AG ≤ 16 mmol/L. Adding Serum AG to APACHE IV score could statistically improve the prediction of ICU (0.770 [0.761-0.779] to 0.774 [0.765-0.783], P = 0.001) and hospital mortalities (0.756 [0.747-0.765] to 0.761 [0.751-0.770], P = 0.012). The associations between serum AG and mortalities remain robust in patients with different acid-base statuses and serum lactate. The findings are validated in the external cohort. Conclusions: Initial serum AG > 16 mmol/L after ICU admission is associated with increased mortality in critically ill patients.

Topological patterns of motor networks in Parkinson's disease with different sides of onset: A resting-state-informed structural connectome study.

Parkinson's disease (PD) has a characteristically unilateral pattern of symptoms at onset and in the early stages; this lateralization is considered a diagnostically important diagnosis feature. We aimed to compare the graph-theoretical properties of whole-brain networks generated by using resting-state functional MRI (rs-fMRI), diffusion tensor imaging (DTI), and the resting-state-informed structural connectome (rsSC) in patients with left-onset PD (LPD), right-onset PD (RPD), and healthy controls (HCs). We recruited 26 patients with PD (13 with LPD and 13 with RPD) as well as 13 age- and sex-matched HCs. Rs-fMRI and DTI were performed in all subjects. Graph-theoretical analysis was used to calculate the local and global efficiency of a whole-brain network generated by rs-fMRI, DTI, and rsSC. Two-sample t-tests and Pearson correlation analysis were conducted. Significantly decreased global and local efficiency were revealed specifically in LPD patients compared with HCs when the rsSC network was used; no significant intergroup difference was found by using rs-fMRI or DTI alone. For rsSC network analysis, multiple network metrics were found to be abnormal in LPD. The degree centrality of the left precuneus was significantly correlated with the Unified Parkinson's Disease Rating Scale (UPDRS) score and disease duration (p = 0.030, r = 0.599; p = 0.037, r = 0.582). The topological properties of motor-related brain networks can differentiate LPD and RPD. Nodal metrics may serve as important structural features for PD diagnosis and monitoring of disease progression. Collectively, these findings may provide neurobiological insights into the lateralization of PD onset.