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Abstract Glioblastoma (GBM) is associated with a median survival rate of less than 15 months, necessitating innovative treatment approaches. This study investigates the safety and efficacy of the low-frequency magnetic field (LFMF) OM-100 instrument in GBM therapy. In vitro experiments utilized normal astrocyte and GBM cell lines, determining that OM-100 at 100 kHz for 72 h selectively targeted GBM cells without harming normal cells. Subsequent analyses revealed OM-100’s impact on cell viability, apoptosis, migration, invasion, reactive oxide species levels, and PD-L1 expression. In vivo studies on mice with U87-induced GBM demonstrated OM-100's synergy with anti-PD-1 therapy, leading to significant tumor volume reduction and increased apoptosis. Notably, OM-100 exhibited safety in healthy mice. Overall, OM-100 could enhance anti-PD-1 immunotherapy effectiveness probably by directly inhibiting tumor proliferation and migration as well as promoting PD-L1 expression, offering a promising therapeutic strategy for GBM treatment.

Abstract Modern human society is burdened with the pandemic of cardiovascular and metabolic diseases. Metrnl is a widely distributed secreted protein in the body, involved in regulating glucose and lipid metabolism and maintaining cardiovascular system homeostasis. In this review, we present the predictive and therapeutic roles of Metrnl in various cardiovascular and metabolic diseases, including atherosclerosis, ischemic heart disease, cardiac remodeling, heart failure, hypertension, chemotherapy-induced myocardial injury, diabetes mellitus, and obesity.

Abstract The early diagnosis of esophageal cancer (EC) is extremely challenging due to a lack of effective diagnostic methods. The study presented herein aims to assess whether serum volatile organic compounds (VOCs) could be utilised as emerging diagnostic biomarkers for EC. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in the serum samples of 55 patients with EC, with samples from 84 healthy controls (HCs) patients analysed as a comparison. All machine learning analyses were based on data from serum VOCs obtained by GC-IMS. A total of 33 substance peak heights were detected in all patient serum samples. The ROC analysis revealed that four machine learning models were effective in facilitating the diagnosis of EC. In addition, the random forests model for 5 VOCs had an AUC of 0.951, with sensitivities and specificities of 94.1 and 96.0%, respectively.

Abstract The evolution and mechanism of ground collapse caused by underground water pipeline leakage have become increasingly significant as more urban areas experience collapses. Based on the principle of similarity, and considering the engineering context of road collapses in Anqing City, Anhui Province, this study designed a 3 m × 2 m × 2 m rupture-collapse model test device. Digital Image Correlation (DIC) technology was employed to investigate the erosion process and collapse mechanisms caused by underground pipeline leakage. The results indicate that groundwater seepage provides the driving force for collapses, combined with the migration space provided by defects, collectively triggering the collapses. When groundwater seepage is minimal, the cohesive forces between soil particles maintain soil stability. As groundwater seepage increases, the soil particle framework is eroded, leading to soil structure destabilization and collapse initiation. The depth of collapse significantly influences stress evolution: stress evolution intensity beneath and above the collapse pit is positively correlated with the distance from the collapse pit bottom, but negatively correlated with the distance from the defect. The research provides insights for the early warning and management of ground collapse.

Abstract The utilization of drag-reducing polymers has long been hindered by their irritancy, corrosiveness, and toxicity across various domains. In this investigation, we explored sodium alginate, a natural drag reducer, for its efficacy in reducing drag and its resilience to shear in millimeter-scale pipelines. Initially, an experimental setup was devised to assess the drag reduction capabilities of sodium alginate at varying concentrations and flow rates using Response Surface Methodology (RSM). The relationship between drag reduction (DR), concentration (C), and flow rate (Q) was established by analyzing the experimental data. Subsequently, variance analysis was employed to validate the data accuracy, with a comparison between predicted and experimental DR values revealing an error margin within ± 20%. Analysis of cyclic shear testing of sodium alginate solution in tubes demonstrated its effectiveness as a shear flow drag reducer. Furthermore, results from laser particle size analysis indicated minimal molecular breakage of sodium alginate during cyclic shear.

Abstract To investigate the damage mechanisms in granite’s physical and mechanical properties after high-temperature water quenching, this study employed MTS815.04 for uniaxial compression tests on thermally treated specimens, with concurrent acoustic emission monitoring, and utilized nanoindentation for micromechanical analysis. The results show that with increasing temperature, granite's peak strength and elastic modulus decrease, with a sharp decline after 400–500 °C, corresponding to a significant increase in the internal damage, which can be detected by acoustic emission monitoring. Below 500 °C, macroscopic mechanical degradation is due to mineral thermophysical property differences, while above 500 °C, microcrack development is the main deterioration factor. The failure mode shifts from tensile to tensile-shear complex to shear failure, with transition points at 400 °C and 800 °C. The results of this study are of certain reference value for improving the efficiency of extracting thermal energy from dry-hot rocks and providing security guidance for the tunnel restoration process following fire damage.

Abstract Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25–0.5 μg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.

Study Design A retrospective cohort study. Purpose This study aimed to assess the reliability of quantitative computed tomography (QCT) in measuring bone mineral density (BMD) of instrumented vertebrae and investigate the effect of less paraspinal muscle damage on BMD changes after lumbar interbody fusion. Overview of Literature Patients always experience a decrease in vertebral BMD after lumbar interbody fusion. However, to the best of our knowledge, no study has analyzed the effect of paraspinal muscles on BMD changes. Methods This retrospective analysis included a total of 155 patients who underwent single-level lumbar fusion, with 81 patients in the traditional group and 74 patients in the Wiltse group (less paraspinal muscle damage). QCT was used to measure the volumetric BMD (vBMD), Hounsfield unit value, and cross-sectional area of the paraspinal muscles at the upper instrumented vertebrae (UIV), vertebrae one segment above the UIV (UIV+1), and the vertebrae one segment above the UIV+1 (UIV+2). Statistical analyses were performed. Results No significant differences in general data were observed between the two groups (p>0.05). Strong correlations were noted between the preoperative and 1-week postoperative vBMD of each segment (p0.05). Vertebral BMD loss was significantly higher in UIV+1 and UIV+2 in the traditional group than in the Wiltse group (−13.6%±19.1% vs. −4.2%±16.5%, −10.8%±20.3% vs. −0.9%±37.0%; p0.05). Conclusions QCT can reliably determine BMD in the instrumented spine after lumbar interbody fusion. With QCT, we found that reducing paraspinal muscle destruction through the Wiltse approach during surgery can help preserve the adjacent vertebral BMD; however, it does not help increase the BMD in the instrumented vertebrae.

Abstract Retinoblastoma is one of the most common ocular malignancies in children. Bmi-1, a member of the Polycomb group family of transcriptional repressors, is expressed in a variety of tumors. The purpose of our study was to explore the role of Bmi-1 in retinoblastoma. RT-qPCR and western blot were used for calculating the mRNA and protein levels of Bmi-1 and RKIP. MTT, Wound healing and Transwell assays were performed to measure the proliferation, migration and invasion in retinoblastoma cells. Cell apoptosis was detected by flow cytometry. The volume and mass of transplanted tumors were detected in nude mice. Bmi-1 was over expressed, and RKIP was low expressed in retinoblastoma cells. Bmi-1 promoted cell proliferation, migration and invasion and suppressed cell apoptosis of Y79 and SO-RB50 cells. Downregulation of Bmi-1 and overexpression of RKIP inhibited cell proliferation, migration and invasion, and increased cell apoptosis. The functions of Bmi-1 knockdown on retinoblastoma cells were blocked by RKIP knockdown, but promoted by RKIP. Down-regulated Bmi-1 inhibited xenograft tumor growth, and RKIP exacerbated this inhibitory effect. Bmi-1 served as a potential therapeutic target for improving the efficacy of clinical treatment in retinoblastoma. All the findings revealed the functions of Bmi-1/RKIP axis in retinoblastoma tumorigenesis.

Abstract Metallic structures produced with laser powder bed fusion (LPBF) additive manufacturing method (AM) frequently contain microscopic porosity defects, with typical approximate size distribution from one to 100 microns. Presence of such defects could lead to premature failure of the structure. In principle, structural integrity assessment of LPBF metals can be accomplished with nondestructive evaluation (NDE). Pulsed infrared thermography (PIT) is a non-contact, one-sided NDE method that allows for imaging of internal defects in arbitrary size and shape metallic structures using heat transfer. PIT imaging is performed using compact instrumentation consisting of a flash lamp for deposition of a heat pulse, and a fast frame infrared (IR) camera for measuring surface temperature transients. However, limitations of imaging resolution with PIT include blurring due to heat diffusion, sensitivity limit of the IR camera. We demonstrate enhancement of PIT imaging capability with unsupervised learning (UL), which enables PIT microscopy of subsurface defects in high strength corrosion resistant stainless steel 316 alloy. PIT images were processed with UL spatial–temporal separation-based clustering segmentation (STSCS) algorithm, refined by morphology image processing methods to enhance visibility of defects. The STSCS algorithm starts with wavelet decomposition to spatially de-noise thermograms, followed by UL principal component analysis (PCA), fine-tuning optimization, and neural learning-based independent component analysis (ICA) algorithms to temporally compress de-noised thermograms. The compressed thermograms were further processed with UL-based graph thresholding K-means clustering algorithm for defects segmentation. The STSCS algorithm also includes online learning feature for efficient re-training of the model with new data. For this study, metallic specimens with calibrated microscopic flat bottom hole defects, with diameters in the range from 203 to 76 µm, were produced using electro discharge machining (EDM) drilling. While the raw thermograms do not show any material defects, using STSCS algorithm to process PIT images reveals defects as small as 101 µm in diameter. To the best of our knowledge, this is the smallest reported size of a sub-surface defect in a metal imaged with PIT, which demonstrates the PIT capability of detecting defects in the size range relevant to quality control requirements of LPBF-printed high-strength metals.

Abstract Dilated cardiomyopathy (DCM) is a common cause of heart failure, thromboembolism, arrhythmias, and sudden cardiac death. The quality of life and long-term survival rates of patients with dilated DCM have greatly improved in recent decades. Nevertheless, the clinical prognosis for DCM patients remains unfavorable. The primary driving factors underlying the pathogenesis of DCM remain incompletely understood. The present study aimed to identify driving factors underlying the pathogenesis of DCM from the perspective of gene regulatory networks. Single-cell RNA sequencing data and bulk RNA data were obtained from the Gene Expression Omnibus (GEO) database. Differential gene analysis, single-cell genomics analysis, and functional enrichment analysis were conducted using R software. The construction of Gene Regulatory Networks was performed using Python. We used the pySCENIC method to analyze the single-cell data and identified 401 regulons. Through variance decomposition, we selected 19 regulons that showed significant responsiveness to DCM. Next, we employed the ssGSEA method to assess regulons in two bulk RNA datasets. Significant statistical differences were observed in 9 and 13 regulons in each dataset. By intersecting these differentiated regulons and identifying shared targets that appeared at least twice, we successfully pinpointed three differentially expressed targets across both datasets. In this study, we assessed and identified 19 gene regulatory networks that were responsive to the disease. Furthermore, we validated these networks using two bulk RNA datasets of DCM. The elucidation of dysregulated regulons and targets (CDKN1A, SAT1, ZFP36) enhances the molecular understanding of DCM, aiding in the development of tailored therapies for patients.

Abstract Background Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. Methods In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. Results Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. Conclusions The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. Trial registration All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).

Abstract Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs

Objectives. Considerable research has been focused on independent predictors of difficult laryngeal exposure (DLE) during suspension laryngoscopy. However, previous studies have yielded inconsistent results and conclusions. Consequently, we performed a meta-analysis of the existing literature with the aim of identifying significant parameters for a standardized preoperative DLE prediction system. Methods. We systematically retrieved articles from the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases up to October 2022. Data from eligible studies were extracted and analyzed using the R programming language. The effect measures included odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous variables and mean differences (MDs) with 95% CIs for continuous variables. Results. The search yielded 1,574 studies, of which 18 (involving a total of 2,263 patients) were included. Pooled analysis demonstrated that patients with DLE during microsurgery tended to be male (OR, 1.73; 95% CI, 1.16–2.57); were older (MD, 5.47 years, 95% CI, 2.44–8.51 years); had a higher body mass index (BMI; MD, 1.19 kg/m2; 95% CI, 0.33–2.05 kg/m2); had a greater neck circumference (MD, 2.50 cm; 95% CI, 1.56–3.44 cm); exhibited limited mouth opening (MD, −0.52 cm; 95% CI, −0.88 to −0.15 cm); had limited neck flexibility (MD, −10.05 cm; 95% CI, −14.10 to −6.00 cm); displayed various other anatomical characteristics; and had a high modified Mallampati index (MMI) or test score (OR, 3.37; 95% CI, 2.07–5.48). Conclusion. We conducted a comprehensive and systematic analysis of the factors relevant to DLE. Ultimately, we identified sex, age, BMI, neck circumference, MMI, inter-incisor gap, hyomental distance, thyromental distance, sternomental distance, and flexion-extension angle as factors highly correlated with DLE.

Abstract Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Abstract The preoperative distinguishment of lymph nodes (LN) with metastasis plays a pivotal role in guiding the surgical extension for gastric cancer (GC). We aim to identify the preparative risk factors for LN metastasis in GC patients. We retrospectively reviewed 424 patients who underwent radical GC resection in our medical center between Jan 2011 and Dec 2018. Multivariate logistic regression was employed to identify risk factors for LN metastasis, while multivariate COX regression was utilized to evaluate prognostic factors. The median overall survival of patients with or without LN metastases was 31 and 58 months, respectively. In multivariate analysis, lower albumin (OR = 0.512; P = 0.004) and prealbumin (OR = 0.367, P = 0.001) and higher CEA (OR = 3.178, P

Abstract This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p

Abstract The complete compound of gefitinib is effective in the treatment of lung adenocarcinoma. However, the effect on lung adenocarcinoma (LUAD) during its catabolism has not yet been elucidated. We carried out this study to examine the predictive value of gefitinib metabolism-related long noncoding RNAs (GMLncs) in LUAD patients. To filter GMLncs and create a prognostic model, we employed Pearson correlation, Lasso, univariate Cox, and multivariate Cox analysis. We combined risk scores and clinical features to create nomograms for better application in clinical settings. According to the constructed prognostic model, we performed GO/KEGG and GSEA enrichment analysis, tumor immune microenvironment analysis, immune evasion and immunotherapy analysis, somatic cell mutation analysis, drug sensitivity analysis, IMvigor210 immunotherapy validation, stem cell index analysis and real-time quantitative PCR (RT-qPCR) analysis. We built a predictive model with 9 GMLncs, which showed good predictive performance in validation and training sets. The calibration curve demonstrated excellent agreement between the expected and observed survival rates, for which the predictive performance was better than that of the nomogram without a risk score. The metabolism of gefitinib is related to the cytochrome P450 pathway and lipid metabolism pathway, and may be one of the causes of gefitinib resistance, according to analyses from the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Immunological evasion and immunotherapy analysis revealed that the likelihood of immune evasion increased with risk score. Tumor microenvironment analysis found most immune cells at higher concentrations in the low-risk group. Drug sensitivity analysis found 23 sensitive drugs. Twenty-one of these drugs exhibited heightened sensitivity in the high-risk group. RT-qPCR analysis validated the characteristics of 9 GMlncs. The predictive model and nomogram that we constructed have good application value in evaluating the prognosis of patients and guiding clinical treatment.

Abstract The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

Abstract This mediation analysis aimed to investigate the associations among areal bone mineral density, mobility-related brain atrophy, and specific gait patterns. A total of 595 participants from the Taizhou Imaging Study, who underwent both gait and bone mineral density measurements, were included in this cross-sectional analysis. We used a wearable gait tracking device to collect quantitative gait parameters and then summarized them into independent gait domains with factor analysis. Bone mineral density was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of brain regions related to mobility were computed using FreeSurfer. Lower bone mineral density was found to be associated with higher gait variability, especially at the site of the lumbar spine (β = 0.174, FDR = 0.001). Besides, higher gait variability was correlated with mobility-related brain atrophy, like the primary motor cortex (β = 0.147, FDR = 0.006), sensorimotor cortex (β = 0.153, FDR = 0.006), and entorhinal cortex (β = 0.106, FDR = 0.043). Bidirectional mediation analysis revealed that regional brain atrophy contributed to higher gait variability through the low lumbar spine bone mineral density (for the primary motor cortex, P = 0.018; for the sensorimotor cortex, P = 0.010) and the low lumbar spine bone mineral density contributed to higher gait variability through the primary motor and sensorimotor cortices (P = 0.026 and 0.010, respectively).

Abstract Background Becoming a first-level discipline in China means access to more educational resources. The development of medical humanities in China has been going on for more than 40 years, and some medical schools have set up master’s and doctoral programs in medical humanities. The demand for medical humanities-related knowledge in China is also growing after COVID-19. However, medical humanities is only a second-level discipline and receives limited resources to meet the needs of society. This study aims to establish a system of indicators that can assess whether the medical humanities has a first-level discipline and provide a basis for its upgrading to a first-level. Methods A Delphi technique was used, with the panel of expert expressing their views in a series of two questionnaires. A coefficient of variation of less than 0.2 indicates expert agreement. Result A total of 25 experts participated in this Delphi study. Consensus was reached on 11 first-grade indices and 48 s-grade indices. The authoritative coefficient(Cr) of the experts was 0.804, which indicates that the experts have a high level of reliability. Conclusion This study provides a reliable foundation for the evaluation of medical humanities maturity.

Abstract Background The treatment for colon adenocarcinoma (COAD) faces challenges in terms of immunotherapy effectiveness due to multiple factors. Because of the high tumor specificity and immunogenicity, neoantigen has been considered a pivotal target for cancer immunotherapy. Therefore, this study aims to identify and predict the potential tumor antigens of MUC somatic mutations (MUCmut) in COAD. Methods Three databases of TCGA, TIMER2.0, and cBioPortal were used for a detailed evaluation of the association between MUCmut and multi-factors like tumor mutation burden (TMB), microsatellite instability (MSI), prognosis, and the tumor microenvironment within the context of total 2242 COAD patients. Next, TSNAdb and the differential agretopicity index (DAI) were utilized to predict high-confidence neopeptides for MUCmut based on 531 COAD patients’ genomic information. DAI was calculated by subtraction of its predicted HLA binding affinity of the MUCmut peptide from the corresponding wild-type peptide. Results The top six mutation frequencies (14 to 2.9%) were from MUC16, MUC17, MUC5B, MUC2, MUC4 and MUC6. COAD patients with MUC16 and MUC4 mutations had longer DFS and PFS. However, patients with MUC13 and MUC20 mutations had shorter OS. Patients with the mutation of MUC16, MUC5B, MUC2, MUC4, and MUC6 exhibited higher TMB and MSI. Moreover, these mutations from the MUC family were associated with the infiltration of diverse lymphocyte cells and the expression of immune checkpoint genes. Through TSNAdb 1.0/NetMHCpan v2.8, 452 single nucleotide variants (SNVs) of MUCmut peptides were identified. Moreover, through TSNAdb2.0/NetMHCpan v4.0, 57 SNVs, 1 Q-frame shift (TS), and 157 short insertions/deletions (INDELs) of MUCmut were identified. Finally, 10 high-confidence neopeptides of MUCmut were predicted by DAI. Conclusions Together, our findings establish the immunogenicity and therapeutic potential of mutant MUC family-derived neoantigens. Through combining the tools of TSNAdb and DAI, a group of novel MUCmut neoantigens were identified as potential targets for immunotherapy.

Abstract. Background:. Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. Methods:. The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4+) T-cell counts, CD8+ T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results:. The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6–6.5 copies/reaction) with linearity over a 5-log10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8–16.6 copies/reaction) with linearity over a 3-log10-unit range. Total HIV DNA in CD4+ T cells was positively associated with integrated HIV DNA (r = 0.76, P

Abstract The micro-scale gas adsorption–desorption characteristics determine the macro-scale gas transport and production behavior. To reveal the three-dimensional stress state-induced gas adsorption–desorption characteristics in coal-bearing shale reservoirs from a micro-scale perspective, the coal-bearing shale samples from the Dongbaowei Coal Mine in the Shuangyashan Basin were chosen as the research subject. Isothermal adsorption–desorption experiments under three-dimensional stress state were conducted using the low field nuclear magnetic resonance (L-NMR) T 2 spectrum method to simulate the in-situ coal-bearing shale gas adsorption–desorption process. The average effective stress was used as the equivalent stress indicator for coal-bearing shale, and the integral of nuclear magnetic resonance T 2 spectrum amplitude was employed as the gas characterization indicator for coal-bearing shale. A quantitative analysis was performed to examine the relationship between gas adsorption in coal-bearing shale and the average effective stress. And a quantitative analysis was performed to examine the relationship between the macroscopic and microscopic gas quantities of coal-bearing shale. Experimental findings: (1) The adsorption–desorption process of coal-bearing shale gas follows the L-F function model and the D-A-d function model respectively with respect to the amount of gas and the average effective stress. (2) There is a logarithmic relationship between the macroscopic and microscopic gas quantities of coal-bearing shale during the adsorption–desorption process. This quantitatively characterizes the differences in the curves, which may be related to the elastic–plastic deformation, damage and fracture of the micropores in coal-bearing shale, as well as the hysteresis of gas desorption and the stress field of the gas occurrence state.

ABSTRACT Objective: To compare effectiveness of Dynesys and hybrid system in treating patients with multi-segmental lumbar degenerative disease (LDD). Methods: Patients involved in this retrospective study were divided into Dynesys (n = 22) and Hybrid (n = 13) groups. Clinical outcomes were evaluated using Oswestry Disability Index (ODI), and Visual Analogue Scale (VAS). Radiologic evaluations included X-ray, MRI, and CT. Furthermore, different complications were analyzed. Results: At the last follow-up, ODI and VAS of each group were improved (p < 0.05), and the range of motion (ROM) of operating segments decreased. However, Dynesys group preserved a larger extent of ROM at the final follow-up (p < 0.05). ROM of the upper adjacent segment was increased in both groups (p < 0.05), while the disc heights were decreased at the final follow-up (p < 0.05). Besides, Dynesys group had a more obvious decrease in the disc height of dynamic segments (p < 0.05). No significant difference existed in complications between both groups (p > 0. 05). Conclusion: In our study, similar satisfactory results were obtained in both groups. Both surgical procedures can be employed as effective treatments for middle-aged and physically active patients with multi-segmental LDD. Level of Evidence III; Retrospective Comparative Study.

Abstract How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno‐occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity‐based and pathological distortion‐independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single‐subject level. Thirty‐three machine‐learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature‐based model for long‐term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate “fingerprints” of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

Abstract Aim of this comparative cross-sectional study was to evaluate the effect of anterior teeth retraction and related hard and soft tissue change under physiologic anchorage control in patients with chief complain of protrusive teeth. 68 Class I or II orthodontic patients undergoing four-premolar extraction and requiring maximum or medium anchorage were included. Patients were treated with physiologic anchorage control technique (PASS group, n = 34, 18.6 ± 7.7 years, 10 male and 24 female) and self-ligation technique (Damon group, n = 34, 17.5 ± 5.4 years, 13 male and 21 female), respectively. TADs were used for anchorage reinforcement in Damon group. Pre- and post-treatment cephalograms were collected. Twenty-six skeletal, dental and soft tissue items were measured and analyzed using a blinded method. T test and paired rank-sum test were used for statistical analysis. The baseline characteristics were similar between groups (P > 0.05). After treatment, inter-group comparison showed statistically significant differences in the decrease of skeletal measurements ∠ANB (− 0.73 ± 1.05° in PASS group and − 0.25 ± 0.84° in the Damon group), Wits value (− 2.56 ± 2.29 mm in PASS group and − 0.47 ± 2.15 mm in Damon group) and soft tissue measurement UL-E (− 2.75 ± 1.36 mm in PASS group and − 2.03 ± 1.30 mm in Damon group) and the increase of FCA and Z angle, which was 2.03 ± 2.12°and 9.52 ± 4.78°in PASS group and 0.97 ± 2.12°and 6.96 ± 4.43°in Damon group, respectively (P

Abstract The problem of repeated epidemic fluctuations in the normalized prevention and control stage is revealed by data from January 20, 2020, to January 30, 2023. In order to improve the collaborative response of the public and government departments to public health emergencies and avoid repeated fluctuations of the epidemic, a tripartite evolutionary game model of the public, local government, and central government departments is constructed, focusing on the evolutionary paths and evolutionary stabilization strategies of the three subjects, and the influence of each element on the evolutionary results is simulated by numerical simulation in Matlab, and based on the inadequacy of the static reward and punishment mechanism, a dynamic Based on the shortcomings of static reward and punishment mechanism, dynamic reward and punishment mechanism is introduced to control the stability of the evolving system. The study shows that (1) with the increase of the initial willingness of the three parties, the rate of the public choosing the discretionary flow strategy slows down, and the collaborative prevention and control process can be accelerated. (2) The reward and punishment mechanism of central government departments has a positive incentive effect on the local government's strict prevention and control and the public's conscious isolation. Appropriately increasing rewards, formulating reasonable subsidy strategies, and increasing penalties for violations are conducive to the overall optimization of the system, and the punishment mechanism is most sensitive to the regulation of the public's discretionary mobility behavior. (3) Government departments' prevention and control costs can influence their enthusiasm for strict prevention and control and real-time supervision. Reducing the human resources cost, time cost, and financial cost of prevention and control is conducive to government departments performing their duties more responsibly. (4) The static punishment mechanism fails to make timely adjustments according to the strategy choice of each actor. It cannot control the stability of the evolving system. In contrast, the dynamic punishment mechanism considers the punishment parameters to link the casual isolation rate with the lenient prevention and control rate, which can effectively control the system's fluctuating instability and is the system's stability control strategy. Finally, combining theoretical and simulation analysis, management suggestions are made for controlling repeated fluctuations of the epidemic in practice, and the research limitations of this paper are explained.

Abstract In this article, an engineering problem of three co-rotating exciters with the circular distribution in a vibrating system is investigated. The dynamical model constructed by the motion differential equations is established. By introducing the small parameter averaged method in the dynamic equation, the synchronization and stability conditions of the electromechanical coupling dynamical model is derived. To illustrate the necessity of the controlling method, the self-synchronization of the vibrating system is firstly analyzed with the theory, numerical simulations and experiments. With the self-synchronization results, it is indicated that the ellipse trajectory which is needed in the industry can’t be realizefd by the self-synchronization motion of the vibrating system. And then, a fuzzy PID controlling method based on the master–slave controlling strategy is introduced in the vibrating system to realize the controlled synchronization. The Lyapunov stability criterion is given to certify the stability of the controlling system. Through some simulations and experiments, the effectiveness of controlled synchronization is illustrated in the discussion. Finally, the present work illuminates the feasibility and practicality for designing some new types of vibrating screens in the industry.

Abstract Background Disulfidptosis is a recently discovered form of programmed cell death that could impact cancer development. Nevertheless, the prognostic significance of disulfidptosis-related genes (DRGs) in lung adenocarcinoma (LUAD) requires further clarification. Methods This study systematically explores the genetic and transcriptional variability, prognostic relevance, and expression profiles of DRGs. Clusters related to disulfidptosis were identified through consensus clustering. We used single-sample gene set enrichment analysis and ESTIMATE to assess the tumor microenvironment (TME) in different subgroups. We conducted a functional analysis of differentially expressed genes between subgroups, which involved gene ontology, the Kyoto encyclopedia of genes and genomes, and gene set variation analysis, in order to elucidate their functional status. Prognostic risk models were developed using univariate Cox regression and the least absolute shrinkage and selection operator regression. Additionally, single-cell clustering and cell communication analysis were conducted to enhance the understanding of the importance of signature genes. Lastly, qRT-PCR was employed to validate the prognostic model. Results Two clearly defined DRG clusters were identified through a consensus-based, unsupervised clustering analysis. Observations were made concerning the correlation between changes in multilayer DRG and various clinical characteristics, prognosis, and the infiltration of TME cells. A well-executed risk assessment model, known as the DRG score, was developed to predict the prognosis of LUAD patients. A high DRG score indicates increased TME cell infiltration, a higher mutation burden, elevated TME scores, and a poorer prognosis. Additionally, the DRG score showed a significant correlation with the tumor mutation burden score and the tumor immune dysfunction and exclusion score. Subsequently, a nomogram was established for facilitating the clinical application of the DRG score, showing good predictive ability and calibration. Additionally, crucial DRGs were further validated by single-cell sequencing data. Finally, crucial DRGs were further validated by qRT-PCR and immunohistochemistry. Conclusion Our new DRG signature risk score can predict the immune landscape and prognosis of LUAD. It also serves as a reference for LUAD's immunotherapy and chemotherapy.

Abstract High altitude exposure increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Machine learning techniques have been used to develop cardiovascular disease prediction models, but no reports exist for high altitude induced myocardial ischemia. Our objective was to establish a machine learning-based MI prediction model and identify key risk factors. Using a prospective cohort study, a predictive model was developed and validated for high-altitude MI. We consolidated the health examination and self-reported electronic questionnaire data (collected between January and June 2022 in 920th Joint Logistic Support Force Hospital of china) of soldiers undergoing high-altitude training, along with the health examination and second self-reported electronic questionnaire data (collected between December 2022 and January 2023) subsequent to their completion on the plateau, into a unified dataset. Participants were subsequently allocated to either the training or test dataset in a 3:1 ratio using random assignment. A predictive model based on clinical features, physical examination, and laboratory results was designed using the training dataset, and the model's performance was evaluated using the area under the receiver operating characteristic curve score (AUC) in the test dataset. Using the training dataset (n = 2141), we developed a myocardial ischemia prediction model with high accuracy (AUC = 0.86) when validated on the test dataset (n = 714). The model was based on five laboratory results: Eosinophils percentage (Eos.Per), Globulin (G), Ca, Glucose (GLU), and Aspartate aminotransferase (AST). Our concise and accurate high-altitude myocardial ischemia incidence prediction model, based on five laboratory results, may be used to identify risks in advance and help individuals and groups prepare before entering high-altitude areas. Further external validation, including female and different age groups, is necessary.

Abstract The study of walkability is of great significance to the construction of healthy cities. In this paper, taking 1283 articles of walkability, which were included in Web of Science, as the research object. This paper adopts to analysis the research progress by using the method of scientometrics and knowledge networks analysis. Objectively and systematically analyze the research progress of walkability abroad from the aspects of publication overview, knowledge foundation, research direction and hot spots, etc. It is found that foreign researches on walkability mainly include three core directions: walkability and physical activity, walkability evaluation, walkability and urban design. Among them, walkability and physical activity orientation have been studied from various perspectives, such as various groups, various environmental types, different behavioral patterns and various chronic diseases. With the increasingly prominent urbanization problems and the rapid development of new technologies, multiple data, new methods and interdisciplinary cooperation will actively promote the vigorous development of walking suitability research.

Abstract This study aimed to reveal the soil reinforcement by shrub root systems after repeated stress from external forces, such as high winds and runoff, for extended periods in the wind-hydraulic compound erosion zone. Using the widely distributed Shandong mine area soil and water-conserving plant species, Caragana microphylla, Hippophae rhamnoides, and Artemisia ordosica, cyclic loading tests were conducted on taproots of the three plant species (1–5 mm diameter) via a TY8000 servo-type machine to investigate the taproots’ tensile properties response to repeated loading–unloading using simulated high wind pulling and runoff scouring. Our study revealed that the tensile force was positively correlated with the root diameter but the tensile strength was negatively correlated under monotonic and cyclic loading of the three plants’ taproots. However, after cyclic loading, the three plant species' taproots significantly enhanced the tensile force and strength more than monotonic loading (P

Abstract. Background:. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. Methods:. Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT+CD4+ and TIGIT+CD8+ T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. Results:. Compared to that in HCs, the frequency of TIGIT+ CD8+ T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT+CD8+ T cells also increased. A decrease in the ratio of both T naïve (TN) and central memory (TCM) cells among TIGIT+CD8+ T cells and an increase in the ratio of the effector memory (TEM) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT+CD8+ T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT+CD8+ T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT+CD8+ T cells in PLWH were significantly weaker than those of TIGIT-CD8+ T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT+CD8+ T cells and TIGIT-CD8+ T cells was insignificant at 4W and 12W, except at 0W. Conclusions:. TIGIT expression on CD8+ T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8+ T cells, thereby enhancing the effectiveness of vaccination.

Abstract. Background:. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals. Methods:. Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated. Results:. SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16+ NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16+ NK cells was significantly negatively correlated with the proportion of CD107a+ NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs. Conclusion:. s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.

Abstract In this study, we investigated the drag reduction property of a premixed slurry drag reducer in a millimeter-scale pipe. The aim of this study is to establish the correlation between Darcy friction factor and drag reducer concentration (C) and volume flow (Q). First, the experimental plan was designed by using the response surface method (RSM), and then the experimental data were processed to establish the quadratic correlation between the response variable and the description variable. After that, ANOVA analysis of variance was used to verify the accuracy of the experimental data and the correlation. Finally, the prediction model is extended to a larger concentration and volume flow range, and it is found that the accuracy between the predicted value of friction coefficient and the experimental value is ± 30%, thus verifying that the correlation is suitable for the small-scale fully turbulent region. Compared with traditional experimental design and correlation methods, the implementation of Response Surface Methodology (RSM) in this study not only reduces the experimental time but also yields a more robust correlation for predicting the friction coefficient.

Abstract Aspirin, as a widely used anti-inflammatory drug, has been shown to exert anti-cancer effects in a variety of cancers. PD-L1 is widely expressed in tumor cells and inhibits anti-tumor immunity. This study aims to clarify whether aspirin exerts its anti-hepatocellular carcinoma (HCC) effect by inhibiting PD-L1 expression. The rat model of HCC was established by drinking 0.01% diethylnitrosamine (DEN), and aspirin was given by gavage. The gross and blood biochemical indexes of rats were analyzed. CD4 and CD8 expression in liver tissues were investigated by immunohistochemistry. CCK8 assay was used to detect the inhibitory effect of aspirin on the proliferation of HCC cells. The regulatory effect of aspirin on PD-L1 expression was analyzed by western blot. As a result, the tumor number and liver weight ratio in the DEN + ASA group were lower than those in the DEN group (P = 0.006, P = 0.046). Compared with the DEN group, the expression of CD4 in the DEN + ASA group was significantly increased, while CD8 was decreased (all P

Abstract This paper introduces an advanced inventory replenishment optimization approach tailored for the Physical Internet (PI), addressing the dynamic and complex nature of this environment. We propose a hybrid Simulated Annealing–Genetic Algorithm (SA–GA), engineered to optimize the balance between exploration and exploitation, ensuring adaptability and efficiency in a variety of PI contexts. The study also presents an enriched mathematical model integrating dynamic demand, and multi-objective optimization. The SA–GA algorithm emerges as a novel contribution, characterized by its computational efficiency and adaptability, marking an advancement in PI inventory management. The incorporation of real-time data analytics in our dynamic inventory replenishment strategy enhances adaptability and responsiveness, while the robust mathematical model offers a versatile tool for both theoretical analysis and practical application. Collectively, these innovations help bridge existing gaps in PI inventory management and serve as a reference for other similar studies.

Abstract Background Medical humanities education is an important part of medical education. The purpose of this study was to determine the effectiveness of medical humanities in improving empathy among medical students and healthcare professionals. Methods PubMed, Embase, EBSCO-ERIC, Web of Science were searched systematically for studies in the English language. The last retrieval date is May 1, 2023. Best Evidence Medical Education (BEME) Global Rating Scale and Kirkpatrick-based results were used to evaluate the quality of literature. In this study, a meta-analysis of continuous data was conducted. Results The pooled results by single-arm test meta-analysis showed a benefit with medical humanities programs in empathy (SMD 1.33; 95% CI 0.69–1.96). For single-arm trials of medical humanities program interventions of less than 4 months, 4 months to 12 months, and more than one year, the standardized mean differences(SMD) between post-test and pre-test were 1.74 (P

Objectives: Lifelong learning facilitates active ageing, and intragenerational learning—the process by which older adults learn from their peers—is an effective means of achieving this goal. The present research aims to elucidate the mechanisms and differences between intergenerational and intragenerational learning models for older adults as evidenced by brain-to-brain synchrony. Methods: Fifty-six instructor-learner dyads completed a study comparing intergenerational and intragenerational learning models, as well as task difficulty. The study utilized a block puzzle task and functional near-infrared spectroscopy (fNIRS) for hyperscanning. Results: The instructor-learner dyads showed greater interpersonal neural synchrony (INS) and learning acquisition in the intragenerational learning model in the difficult task condition (t (54) = 3.49, p

Objective To explore the relationship between receptor heterogeneity and clinicopathological characteristics in 166 patients with invasive breast cancer during metastasis. Methods We conducted a retrospective analysis of 166 patients diagnosed with metastatic breast cancer through biopsy, who were admitted to our hospital from January 2018 to December 2022. Statistical analysis was employed to assess the heterogeneity of receptors in both primary and metastatic lesions, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67, as well as their association with clinicopathological features such as tumor size, lymph node metastasis, treatment regimen, and disease-free survival. Results The discordant expression rates of ER, PR, HER2, Ki-67 and Luminal classification between primary and metastatic lesions were 21.7%, 41.6%, 8.9%, 34.4% and 36.8%, respectively. There is a significant difference in disease-free survival between patients with consistent and inconsistent receptor status of primary and metastatic lesions, which is statistically significant. The median DFS for primary HER2(-) to metastatic HER2(+) was 84 months, which was relatively high. The Cox multivariate regression analysis revealed that the expression differences of ER, PR, HER2, and Ki67 were not influenced by endocrine therapy and chemotherapy. However, a statistically significant difference in HER2 expression was observed with targeted therapy. Tumor size was correlated with ER and Ki67 receptor status (P = 0.019, 0.016). Tumor size was not correlated with PR, and HER2 (P = 0.679, 0.440). Lymph node metastasis was not associated with changes in ER, PR, HER2, and Ki67. The discordant rates of ER, PR, HER2, and Ki-67 in patients with local recurrence were 22%, 23.7%, 5.1%, and 28.8% respectively, whereas those in patients with distant metastasis were 21.5%, 36.4%, 10.3%, and 31.8% respectively. Conclusions The expression levels of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer exhibit heterogeneity, which is closely associated with the prognosis and treatment outcomes of patients.

Key Clinical Message The etiology of primary pulmonary angiosarcoma is still unknown. Here we report a case of primary pulmonary angiosarcoma originated from a tuberculous scar and presented as aggressive deterioration with uncontrolled bleeding from capillaries with angiodysplasia.

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, and more effective prognostic markers are needed. Lactic acid has been proved to be an important metabolite involved in cancer development, metastasis, and the tumor microenvironment, affecting the prognosis of patients. The role of lactic acid metabolism regulators (LAMRs) in HCC is still unclear. In this study, we analyzed the status of LAMRs, a gene list containing lactate from Molecular Signatures database, in HCC and consensus clustering was performed based on these LAMRs. Cluster B showed higher infiltrations of immune cells, higher TME scores, and a poorer prognosis. We further constructed a risk score based on DEGs using LASSO and COX regression analysis between two clusters, which could effectively predict the prognosis of TCGA-LIHC patients. The GSE14520 cohort confirmed the result. We also examined the correlation of risk scores with clinical characteristics, genetic mutations, drug sensitivity, immune checkpoint inhibitors(ICIs), and immunotherapy. In conclusion, our findings will facilitate a further understanding of the role of partial lactate metabolism related genes in HCC and suggest a new risk score to predict prognosis.

Abstract Early diagnosis of esophageal cancer (EC) is extremely challenging. The study presented herein aimed to assess whether urinary volatile organic compounds (VOCs) may be emerging diagnostic biomarkers for EC. Urine samples were collected from EC patients and healthy controls (HCs). Gas chromatography-ion mobility spectrometry (GC-IMS) was next utilised for volatile organic compound detection and predictive models were constructed using machine learning algorithms. ROC curve analysis indicated that an 8-VOCs based machine learning model could aid the diagnosis of EC, with the Random Forests having a maximum AUC of 0.874 and sensitivities and specificities of 84.2% and 90.6%, respectively. Urine VOC analysis aids in the diagnosis of EC.

Abstract Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. Methods Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. Results After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI

Abstract With the increase of mining depth and intensity, coal and gas outburst dynamic disasters occur frequently. In order to deeply study the macroscopic fracture mechanism of coal body and evolution characteristics analysis of impact force, taking the outburst coal seam of Pingmei No. 11 Coal Mine and Sunjiawan coal seam of Hengda Coal Mine as the research objects, the simulation roadway test system of self-developed true triaxial coal and gas outburst is applied to carry out the simulation test of deep coal and gas outburst with buried depths of 1000 m, 1200 m, 1400 m and 1600 m. During the test, the overlying strata stress is simulated by axial compression, the surrounding rock stress is simulated by confining pressure, the gas pressure is simulated by pore pressure, the impact force and acoustic emission monitoring technology are introduced, and the coal seam gas pressure is simulated by mixture pressure of 45% CO2 and 55% N2. From the viewpoint of fracture mechanics, the crack propagation mechanism of coal in the outburst launching area is discussed, the evolution characteristics of impact force and gas pressure are analyzed, and the influence law between acoustic emission signal and impact force is revealed. From the viewpoint of energy conversion, the transformation character of gas internal energy to impact kinetic energy (gas pressure to impact force) are analyzed. The results show that the generation of I-type crack is a prerequisite for outburst catastrophe. With the crack propagation, I-type and II-type cracks intersect and penetrate, resulting in internal structural damage and skeleton instability of coal. Gas wrapped fragmentized coal body thrown, outburst occurs. There is obvious negative pressure in the roadway after outburst. The occurrence of negative pressure is greatly affected by the physical and mechanical properties of coal, ground stress and gas pressure. Impact kinetic energy is mainly provided by gas internal energy. Part of the gas pressure is converted into impact force. The strength and duration of the impact force are determined by the gas pressure. Under the condition of deep working conditions (high ground stress and low gas pressure), the propagation of impact force in the roadway is more hindered. Both impact force and acoustic emission signals can monitor the occurrence of outburst. The peak point of acoustic emission ringing count is earlier than the impact force. The acoustic emission signal can monitor the outburst hazard earlier. The impact force can more specifically reflect the coal fracture.

Background Chronic post-surgical pain (CPSP) is one of the important causes of poor postoperative outcomes, the activation of microglia in the spinal cord is closely related to the generation, transmission and maintenance of CPSP. Xenon (Xe), an anesthetic gas, has been reported to be able to significantly reduce intraoperative analgesia and postoperative pain sensation at low doses. However, the mechanism of the regulatory effect of xenon on activated microglia after CPSP remains unclear. Methods In this study, CPSP model rats were treated with 50% Xe inhalation for 1 h following skin/muscle incision and retraction (SMIR), once a day for 5 consecutive days, and then the painbehavioraltests (pain behavior indexes paw withdrawal mechanical threshold, PWMT and thermal withdrawal latency, TWL), microglial activation, oxidative stress-related indexes (malondialdehyde, MDA; superoxide dismutase, SOD; hydrogen peroxide, H2O2; and catalase, CAT), mitophagy and PINK1/Parkin pathway were examined. Results The present results showed that a single dose of Xe treatment in SMIR rat model could significantly improve PWMT and TWL in the short-term at a single treatment and long-term at multiple treatments. Xe treatment inhibited microglia activation and oxidative stress in the spinal dorsal horn of SMIR rats, as indicated by the decrease of Iba1 and MDA/H2O2 levels and the increase of SOD/CAT levels. Compared with the control group, Xe further increased the CPSP promoted Mito-Tracker (a mitochondrial marker) and LC3 (an autophagy marker) co-localization positive spots and PINK1/Parkin/ATG5/BECN1 (autophagy-related proteins) protein expression levels, and inhibited the Mito-SOX (a mitochondrial reactive oxygen species marker) positive signal, indicating that Xe promoted microglia mitophagy and inhibited oxidative stress in CPSP. Mechanistically, we verified that Xe promoted PINK1/Parkin signaling pathway activation. Conclusion Xe plays a role in ameliorating chronic post-surgical pain by regulating the PINK1/Parkin pathway mediated microglial mitophagy and provide new ideas and targets for the prevention and treatment of CPSP.

Summary: Background: SARS-CoV-2-neutralizing antibodies (nABs) showed great promise in the early phases of the COVID-19 pandemic. The emergence of resistant strains, however, quickly rendered the majority of clinically approved nABs ineffective. This underscored the imperative to develop nAB cocktails targeting non-overlapping epitopes. Methods: Undertaking a nAB discovery program, we employed a classical workflow, while integrating artificial intelligence (AI)-based prediction to select non-competing nABs very early in the pipeline. We identified and in vivo validated (in female Syrian hamsters) two highly potent nABs. Findings: Despite the promising results, in depth cryo-EM structural analysis demonstrated that the AI-based prediction employed with the intention to ensure non-overlapping epitopes was inaccurate. The two nABs in fact bound to the same receptor-binding epitope in a remarkably similar manner. Interpretation: Our findings indicate that, even in the Alphafold era, AI-based predictions of paratope-epitope interactions are rough and experimental validation of epitopes remains an essential cornerstone of a successful nAB lead selection. Funding: Full list of funders is provided at the end of the manuscript.