Unveiling the Cation Dependence in Alkaline Hydrogen Evolution by Differently-Charged Ruthenium/Molybdenum Sulfide Hybrids.

The sluggish kinetics of hydrogen evolution reaction (HER) via water reduction limits the efficiency of alkaline water electrolysis. The HER kinetics is not only intimately related to the catalyst surface structure but also relevant to the cation identity of the electrolyte. The cation dependence also relies on the surface electronic structure and applied potential, but this interrelated effect and its underlying mechanism awaits elucidation. Herein, differently-charged molybdenum sulfide (MoSx) cluster supports ([Mo3S13]2- and [Mo3S7]4+) are utilized to hybridize with the identical metallic Ru centers. The specific electrostatic interaction between MoSx clusters and Ru precursors induces different Ru valences of the hybrids, with a higher valence state for Ru/Mo3S13 endowing a higher activity. The Ru/Mo3S13 and Ru/Mo3S7 exhibited drastically-different cation dependence, in which the charged support determines the local accumulation of cations and resulting water structures. The more negatively-charged Mo3S13 support induces the facile accumulation of cations, especially for less-hydrated K+ cations. The water activation capability by Ru valences and cation accumulation from the support effect in-together determine the cation-dependent alkaline HER activity. This work not only enriches the understanding about the cation-dependent HER mechanism but also shines a light on the rational optimization strategy of electrode/electrolyte interfaces.

Dexmedetomidine: a real-world safety analysis based on FDA adverse event reporting system database.

Objective: Using the FDA adverse event reporting system (FAERS) database to analyze the safety profile of Dexmedetomidine and provide guidance for clinical application. Methods: Data from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were collected. Reporting odds ratio (ROR), the proportional reporting ratio (PRR), and the Bayesian confidence propagation neural network (BCPNN) were employed to detect and assess adverse events associated with Dexmedetomidine. Results: A total of 1910 reports of Dexmedetomidine as the primary suspect drug were obtained. After screening, 892 preferred terms were obtained, including 52 new preferred terms not mentioned in the drug insert. The common adverse events of Dexmedetomidine include bradycardia, cardiac arrest, hypotension, diabetes insipidus, arteriospasm coronary and agitation. Notably, cardiac disorders exhibited the highest number of reports and the highest signal intensity in the system organ class. Among the new preferred terms, those with high signal intensity include transcranial electrical motor evoked potential monitoring abnormal, acute motor axonal neuropathy, trigemino-cardiac reflex, glossoptosis, floppy iris syndrome, phaeochromocytoma crisis, postresuscitation encephalopathy and diabetes insipidus. Conclusion: This study mined and evaluated adverse events associated with Dexmedetomidine and also identified new adverse events. This could help alert clinicians to new adverse events not mentioned in the drug inserts, reducing the risk of drug.

Surgical resection and neoadjuvant therapy in patients with gastric cancer and ovarian metastasis: A real-world study.

BACKGROUND: Regarding when to treat gastric cancer and ovarian metastasis (GCOM) and whether to have metastatic resection surgery, there is presently debate on a global scale. The purpose of this research is to examine, in real-world patients with GCOM, the survival rates and efficacy of metastatic vs non-metastasized resection. AIM: To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM. METHODS: This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People's Hospital from June 2009 to July 2023. The diagnosis of all patients was confirmed by pathology. The primary study endpoints included overall survival (OS), ovarian survival, OS after surgery (OSAS), disease-free survival (DFS), differences in efficacy. RESULTS: This study had 41 patients in total. The surgical group (n = 27) exhibited significantly longer median OS (mOS) and median overall months (mOM) compared to the nonoperative group (n = 14) (mOS: 23.0 vs 6.9 months, P = 0.015; mOM: 18.3 vs 3.8 months, P = 0.001). However, there were no significant differences observed in mOS, mOM, median OSAS (mOSAS), and median DFS (mDFS) between patients in the surgical resection plus neoadjuvant therapy group (n = 11) and those who surgical resection without neoadjuvant therapy group (n = 16) (mOS: 26.1 months vs 21.8 months, P = 0.189; mOM: 19.8 vs 15.2 months, P = 0.424; mOSAS: 13.9 vs 8.7 months, P = 0.661, mDFS: 5.1 vs 8.2 months, P = 0.589). CONCLUSION: Compared to the non-surgical group, the surgical group's survival duration and efficacy are noticeably longer. The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.

Hypertension and iron deficiency anemia: Exploring genetic associations and causal inference.

BACKGROUND AND AIM: Observational studies have suggested a potential association between hypertension and Iron deficiency anemia (IDA). However, it is unclear whether there is a genetic and causal link between hypertension and IDA. METHODS AND RESULTS: Genome-Wide Association Studies (GWAS) data for hypertension were sourced from the UK Biobank and FinnGen. Genetic variants data for IDA were extracted from FinnGen and the IEU Open GWAS project, all derived from European populations. The genetic association between hypertension and IDA was assessed using Linkage Disequilibrium Score Regression (LDSC), with MR employed to determine causality. Inverse variance weighted (IVW) as a major analytical method for MR. Sensitivity and heterogeneity analyses were conducted to ensure result reliability. Furthermore, validation analysis was performed to further strengthen the robustness of the findings. A genetic association between hypertension and IDA was observed (rg = 0.121, P = 0.002). Our findings suggest that hypertension increases the risk of developing IDA (OR = 2.493,P = 0.038), and IDA maybe serve as a risk factor for hypertension (OR = 1.006,P < 0.001). Validation analysis yielded consistent results. Importantly, our findings demonstrated no heterogeneity or horizontal pleiotropy. CONCLUSION: Additional insights into the connection between hypertension and IDA were gained. Regular testing of iron ions and anemia-related markers in hypertensive patients is crucial for early identification of IDA. Furthermore, it is imperative to closely monitor the blood pressure of patients with IDA to promptly identify and diagnose hypertension. The implementation of these integrated health strategies is vital for global efforts to tackle the dual challenges of hypertension and IDA.

Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma.

Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

Scalable Layer-Controlled Oxidation of Bi2O2Se for Self-Rectifying Memristor Arrays With sub-pA Sneak Currents.

Smart memristors with innovative properties are crucial for the advancement of next-generation information storage and bioinspired neuromorphic computing. However, the presence of significant sneak currents in large-scale memristor arrays results in operational errors and heat accumulation, hindering their practical utility. This study successfully synthesizes a quasi-free-standing Bi2O2Se single-crystalline film and achieves layer-controlled oxidation by developing large-scale UV-assisted intercalative oxidation, resulting ß-Bi2SeO5/Bi2O2Se heterostructures. The resulting ß-Bi2SeO5/Bi2O2Se memristor demonstrates remarkable self-rectifying resistive switching performance (over 105 for ON/OFF and rectification ratios, as well as nonlinearity) in both nanoscale (through conductive atomic force microscopy) and microscale (through memristor array) regimes. Furthermore, the potential for scalable production of self-rectifying ß-Bi2SeO5/Bi2O2Se memristor, achieving sub-pA sneak currents to minimize cross-talk effects in high-density memristor arrays is demonstrated. The memristors also exhibit ultrafast resistive switching (sub-100 ns) and low power consumption (1.2 pJ) as characterized by pulse-mode testing. The findings suggest a synergetic effect of interfacial Schottky barriers and oxygen vacancy migration as the self-rectifying switching mechanism, elucidated through controllable ß-Bi2SeO5 thickness modulation and theoretical ab initio calculations.

Dissolution Manufacturing Strategy for the Facile Synthesis of Nanoporous Metallic Glass Multifunctional Catalyst.

The quest for heightened energy efficiency is inextricably linked to advancements in energy storage and conversion technologies, wherein multifunctional catalysts play a pivotal role by mitigating the slow kinetics endemic to many catalytic reactions. The intricate synthesis and bespoke design of such catalysts, however, present notable challenges. Addressing this, the present study capitalizes on a novel dissolution manufacturing strategy to engineer self-supporting, nanoporous multifunctional electrocatalysts, circumventing the prevalent issue of customizing catalytic functionalities upon demand. This innovative approach grants the flexibility to finely tune the incorporation of active species and metalloid binders, culminating in the creation of a self-supporting nanoporous metal glass electrocatalyst doped with RuO2 (NPMG@RuO2) with outstanding performance in alkaline media. The catalyst showcases superior electrocatalytic activity, achieving low overpotentials of 41.50 mV for the Hydrogen Evolution Reaction and 226.0 mV for Oxygen Evolution Reaction alongside sustained stability over 620 hours.These achievements are attributed to the distinct nanoporous architecture that ensures a high density of catalytic sites and mechanical strength, bolstered by the synergistic interplay between RuO2 and Pt-based metallic glass. The findings provide a versatile template for the development of nanoporous multifunctional catalysts, signifying a leap forward in the realm of energy conversion technologies.

Demethylzeylasteral ameliorates podocyte damage in murine lupus by inhibiting inflammation and enhancing autophagy.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan and tissue involvement. Lupus nephritis (LN), an inflammatory condition of the kidneys associated with SLE, represents a significant cause of morbidity and mortality in SLE patients. Current immunosuppressive therapies for LN have limited efficacy and can lead to significant side effects. Demethylzeylasteral (DML) has shown promise in the treatment of LN, but its precise mechanism of action remains unclear. PURPOSE: To assess the therapeutic effects and potential molecular mechanisms of DML in LN METHODS: The study evaluated the renal protective effects of DML in MRL/lpr mice through assessments of immune complex levels, renal function, and pathological changes. Network pharmacology and transcriptomics approaches were used to elucidate the underlying mechanisms. Molecular docking, biacore assay, monoclonal antibody blocking experiments, and in vitro studies were conducted to verify the mechanisms of action. RESULTS: DML treatment reduced levels of anti-Sm and anti-dsDNA IgG antibodies, as well as serum creatinine and blood urea nitrogen levels. DML also mitigated glomerular damage and fibrosis. Mechanistically, DML alleviated podocyte damage by suppressing inflammation and enhancing autophagy through inhibition of the IL-17A/JAK2-STAT3 pathways. Additionally, DML exhibited high binding affinity with IL17A, JAK2, and STAT3. CONCLUSION: These findings provide strong evidence for the beneficial effects of DML in LN, suggesting its potential as a novel therapeutic strategy for improving renal function in autoimmune kidney diseases.

AlphaFold2-guided engineering of split-GFP technology enables labeling of endogenous tubulins across species while preserving function.

Dynamic properties are essential for microtubule (MT) physiology. Current techniques for in vivo imaging of MTs present intrinsic limitations in elucidating the isotype-specific nuances of tubulins, which contribute to their versatile functions. Harnessing the power of the AlphaFold2 pipeline, we engineered a strategy for the minimally invasive fluorescence labeling of endogenous tubulin isotypes or those harboring missense mutations. We demonstrated that a specifically designed 16-amino acid linker, coupled with sfGFP11 from the split-sfGFP system and integration into the H1-S2 loop of tubulin, facilitated tubulin labeling without compromising MT dynamics, embryonic development, or ciliogenesis in Caenorhabditis elegans. Extending this technique to human cells and murine oocytes, we visualized MTs with the minimal background fluorescence and a pathogenic tubulin isoform with fidelity. The utility of our approach across biological contexts and species set an additional paradigm for studying tubulin dynamics and functional specificity, with implications for understanding tubulin-related diseases known as tubulinopathies.

Natural Derivatives of Selective HDAC8 Inhibitors with Potent in Vivo Antitumor Efficacy against Breast Cancer.

HDAC8 is a therapeutic target with great promise for breast cancer. Here, we reported a novel compound corallorazine D from Nocardiopsis sp. XZB108, selectively inhibited HDAC8 (IC50 = 0.90 ± 0.014 µM), suggesting that it may be a promising nonhydroxamate HDAC8 inhibitor. Upon additional modifications of corallorazine D, a candidate compound 5k, demonstrated remarkable inhibitory potency against HDAC8 (IC50 = 0.12 ± 0.01 nM), 89-fold superior to PCI-34051. The selectivity of 5k was at least 439-fold, superior to corallorazine D, confirming the efficacy of our modifications. In an orthotopic mouse model of breast cancer, 5k displayed nearly 4-fold superior antitumor activity than SAHA. Furthermore, 5k triggered antitumor immunity by activating T cells. Treatment with 5k significantly increased the proportion of M1 macrophages and decreased the proportion of M2 macrophages (M1/M2 ratio = 2.67 ± 0.25). 5k represents a promising compound for further investigation as a potential treatment for breast cancer.

Efficacy and safety of rectal chloral hydrate for pediatric procedural sedation: A systematic review and meta-analysis.

BACKGROUND: To evaluate the efficacy and safety of rectal chloral hydrate (CH) in pediatric procedural sedation. METHODS: Seven electronic databases and 3 clinical trials registry platforms were searched, and the deadline was August 2022. Randomized controlled trials evaluating the efficacy and safety of rectal CH in pediatric procedural sedation were included by 2 reviewers. The extracted outcomes included the success rate of sedation, sedation latency, sedation duration, and adverse events. The Cochrane risk of bias tool was used to assess the risk of bias. The outcomes were analyzed using Review Manager 5.3 software. RESULTS: Forty-four randomized controlled trials with 8007 children were included in the meta-analysis. The success rate of sedation in the rectal CH group was significantly higher than that in the placebo group (risk ratio [RR], 2.60 [95% confidence interval [CI], 1.74-3.89]; P < .01; RR, 1.24 [95% CI, 1.01-1.54]; P = .04), oral CH group (RR, 1.12 [95% CI, 1.09-1.14]; I2 = 36%; P < .001; number needed to treat [NNT] = 10), diazepam group (RR, 1.21 [95% CI, 1.10-1.33]; I2 = 0%; P < .001; NNT = 6), phenobarbital group (RR, 1.24 [95% CI, 1.13-1.35]; I2 = 12%; P < .001; NNT = 6), and ketamine group (RR, 1.39 [95% CI, 1.20-1.60]; I2 = 20%; P < .001; NNT = 5). There was no significant difference in the success rate of sedation between the rectal CH group and the midazolam group (RR, 0.98 [95% CI, 0.86-1.11]; I2 = 51%; P > .05). The sedation latency was significantly shorter in rectal CH group than that in the oral CH group (mean difference [MD], -6.36 [95% CI, -7.04 to -5.68]; I2 = 49%; P < .001) and the phenobarbital group (MD, -7.64 [95% CI, -9.12 to -6.16]; P < .00001). The sedation duration in the rectal CH group was significantly longer than in the oral CH group (MD, 6.43 [95% CI, 4.39-8.47]; I2 = 0%; P < .001). The overall incidence of adverse events was significantly lower with rectal CH than with oral CH (RR, 0.21 [95% CI, 0.16-0.29]; I2 = 45%; P < .001) and ketamine (RR, 0.26 [95% CI, 0.12-0.60]; I2 = 0%; P = .001). There was no significant difference in the overall incidence of adverse events with rectal CH compared with intramuscular midazolam (RR, 0.55 [95% CI, 0.23-1.28]; P = .17) and intranasal midazolam (RR, 3.00 [95% CI, 0.66-13.69]; P = .16). CONCLUSION: The available evidence suggests that rectal CH cloud be an effective and safe sedative agent for pediatric procedural sedation.

Specialized metabolites of the endophyte Annulohypoxylon areolatum hosted by Aconitum carmichaelii.

Seven previously undescribed compounds, including one amino acid hybrid sesquiterpene areolatol A (1), two unusual natural sesquiterpenoid skeleton areolatones A-B (2-3) and four benzo[j]fluoranthene areolaranes A-D (4-7) were characterized from Annulohypoxylon areolatum. The structures of the compounds were determined by extensive spectroscopic analysis, X-ray diffraction analysis, and ECD and NMR computational. Notably, areolatol A (1) was the first reported sesquiterpene featuring a 5/7/3-ring system and hybridized with two molecular amino acids. In addition, areolaranes A-D (4-7) were identified as possible chemophenetic markers.

Phosphofructokinase-1 in Cancer: A Promising Target for Diagnosis and Therapy.

Tumor cells have distorted enzymatic houses, which change the metabolic state from oxidative phosphorylation to glycolysis with high lactate levels in a hypoxic environment. Redrafting the metabolic profile is an emerging hallmark of cancer. Glycolytic enzyme amplification occurs in about 70% of all malignancies. Current studies have found that PFK-1 overexpression is linked to cell migration, proliferation, and Overall Survival (OS) rate in various human cancer cell lines. This review intended to uncover the bona fide therapeutic target for cancer therapy and elucidate the role of PFK-1 in cancer. Furthermore, this review has outlined the listed pharmacological and genetic inhibitors of PFK-1. Following this review, future studies on PFK-1 should emphasize the molecular pathways implicated in PFK-1 overexpression in cancer development. The terms "PFK-1", "PFKP-1", "PFKL-1", "PFKM-1", "PFKM-1 and cancer", "PFKP-1 and cancer", "PFKL-1 and cancer", and "inhibitors of PFK-1" were used to retrieve the information from a variety of databases, including PubMed, Scopus, Google Scholar, and ScienceDirect. In a variety of malignancies, inhibiting the expression of PFK-1 isoforms has been reported to be the most effective therapeutic method. Overexpression of PFK-1 isoforms induces the Warburg effect, cell proliferation, and carcinogenesis by downregulating apoptotic proteins, such as active caspase-3, caspase-9, and caspase-8. YY1, synoviolin, Sh-RNA-507, SNAI, miR-520a/b/e, miR-128, and ß-miR-6517 are some of the putative genetic inhibitors against PFK-1 that have been used to manage the development of malignancies. Pharmacological inhibitors, such as penfluridol, synoviolin/HRD1, quercetin, ginsenoside 20(S)-Rg3, triptolide, worenine, acetylsalicylic acid, and salicylic acid, can regulate the advancement of malignancies by inhibiting PFK-1. Thus, PFK-1 is a promising molecular biomarker for cancer treatment. A prospective investigation can validate the unbiased approaches for discovering brandnew PFK-1 inhibitors for cancer treatment.

Experimental quantum Byzantine agreement on a three-user quantum network with integrated photonics.

Quantum communication networks are crucial for both secure communication and cryptographic networked tasks. Building quantum communication networks in a scalable and cost-effective way is essential for their widespread adoption. Here, we establish a complete polarization entanglement-based fully connected network, which features an ultrabright integrated Bragg reflection waveguide quantum source, managed by an untrusted service provider, and a streamlined polarization analysis module, which requires only one single-photon detector for each user. We perform a continuously working quantum entanglement distribution and create correlated bit strings between users. Within the framework of one-time universal hashing, we provide the experimental implementation of source-independent quantum digital signatures using imperfect keys circumventing the necessity for private amplification. We further beat the 1/3 fault tolerance bound in the Byzantine agreement, achieving unconditional security without relying on sophisticated techniques. Our results offer an affordable and practical route for addressing consensus challenges within the emerging quantum network landscape.

Nutritional Indices Predict All Cause Mortality in Patients with Multi-/Rifampicin-Drug Resistant Tuberculosis.

Background: Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) with high mortality remains a public health crisis and health security threat. This study aimed to explore the predictive value of nutritional indices for all-cause mortality (ACM) in MDR/RR-TB patients. Methods: We retrospectively recruited MDR/RR-TB patients between January 2015 and December 2021, randomly assigning them to training and validation cohorts. Patients were divided into high nutritional risk groups (HNRGs) and low nutritional risk groups (LNRGs) based on the optimal cut-off value obtained from receiver operating characteristic (ROC) analyses of the hemoglobin-albumin-lymphocyte-platelet (HALP) score, prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score. In the training cohort, Kaplan-Meier survival curves and Log rank tests were used to compare overall survival (OS) between the groups. Cox risk proportion regression analyses were used to explore the risk factors of ACM in patients with MDR/RR-TB. The predictive performance of ACM was assessed using area under the curve (AUC), sensitivity and specificity of ROC analyses. Results: A total of 524 MDR/RR-TB patients, with 255 in the training cohort and 269 in the validation cohort, were included. Survival analyses in the training cohort revealed significantly lower OS in the HNRGs compared to the LNRGs. After adjusting for covariates, multivariate analysis identified low HALP score, low PNI and high CONUT score were independent risk factors for ACM in MDR/RR-TB patients. ROC analyses demonstrated good predictive performance for ACM with AUCs of 0.765, 0.783, 0.807, and 0.811 for HALP score, PNI, CONUT score, and their combination, respectively. Similar results were observed in the validation set. Conclusion: HALP score, PNI, and CONUT scores could effectively predict ACM in patients with MDR/RR-TB. Hence, routine screening for malnutrition should be given more attention in clinical practice to identify MDR/RR-TB patients at higher risk of mortality and provide them with nutritional support to reduce mortality.

The metabolic clock of ketamine abuse in rats by a machine learning model.

Ketamine has recently become an anesthetic drug used in human and veterinary clinical medicine for illicit abuse worldwide, but the detection of illicit abuse and inference of time intervals following ketamine abuse are challenging issues in forensic toxicological investigations. Here, we developed methods to estimate time intervals since ketamine use is based on significant metabolite changes in rat serum over time after a single intraperitoneal injection of ketamine, and global metabolomics was quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Thirty-five rats were treated with saline (control) or ketamine at 3 doses (30, 60, and 90 mg/kg), and the serum was collected at 21 time points (0 h to 29 d). Time-dependent rather than dose-dependent features were observed. Thirty-nine potential biomarkers were identified, including ketamine and its metabolites, lipids, serotonin and other molecules, which were used for building a random forest model to estimate time intervals up to 29 days after ketamine treatment. The accuracy of the model was 85.37% in the cross-validation set and 58.33% in the validation set. This study provides further understanding of the time-dependent changes in metabolites induced by ketamine abuse.

Peritumoral edema enhances MRI-based deep learning radiomic model for axillary lymph node metastasis burden prediction in breast cancer.

To investigate whether peritumoral edema (PE) could enhance deep learning radiomic (DLR) model in predicting axillary lymph node metastasis (ALNM) burden in breast cancer. Invasive breast cancer patients with preoperative MRI were retrospectively enrolled and categorized into low (< 2 lymph nodes involved (LNs+)) and high (≥ 2 LNs+) burden groups based on surgical pathology. PE was evaluated on T2WI, and intra- and peri-tumoral radiomic features were extracted from MRI-visible tumors in DCE-MRI. Deep learning models were developed for LN burden prediction in the training cohort and validated in an independent cohort. The incremental value of PE was evaluated through receiver operating characteristic (ROC) analysis, confirming the improvement in the area under the curve (AUC) using the Delong test. This was complemented by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) metrics. The deep learning combined model, incorporating PE with selected radiomic features, demonstrated significantly higher AUC values compared to the MRI model and the DLR model in the training cohort (n = 177) (AUC: 0.953 vs. 0.849 and 0.867, p < 0.05) and the validation cohort (n = 111) (AUC: 0.963 vs. 0.883 and 0.882, p < 0.05). The complementary analysis demonstrated that PE significantly enhances the prediction performance of the DLR model (Categorical NRI: 0.551, p < 0.001; IDI = 0.343, p < 0.001). These findings were confirmed in the validation cohort (Categorical NRI: 0.539, p < 0.001; IDI = 0.387, p < 0.001). PE improved preoperative ALNM burden prediction of DLR model, facilitating personalized axillary management in breast cancer patients.

Development and Validation of a Comprehensive Analysis of the Competing Endogenous circRNA/miRNA/mRNA Network for the Identification of Immune-Related Targets in Esophageal Squamous Cell Carcinoma.

Immunotherapy for esophageal squamous cell carcinoma (ESCC) exhibits notable variability in efficacy. Concurrently, recent research emphasizes circRNAs' impact on the ESCC tumor microenvironment. To further explore the relationship, we leveraged circRNA, microRNA, and mRNA sequence datasets to construct a comprehensive immune-related circRNA-microRNA-mRNA network, revealing competing endogenous RNA (ceRNA) roles in ESCC. The network comprises 16 circular RNAs, 13 microRNAs, and 1,560 mRNAs. Weighted gene co-expression analysis identified immune-related modules, notably cancer-associated fibroblast (CAF) and myeloid-derived suppressor cell modules, correlating significantly with immune and stemness scores. Among them, the CAF module plays a crucial role in extracellular matrix function and effectively discriminates ESCC patients. Four hub collagen family genes within CAF correlated robustly with CAF, macrophage infiltration, and T-cell exclusion. In-house sequencing and RT-qPCR validated their elevated expression. We also identified CAF module-targeting drugs as potential ESCC treatments. In summary, we established an immune-related circRNA-miRNA-mRNA network that not only illuminates ceRNA functionality but also highlights circRNAs' involvement in the CAF through collagen gene targeting. These findings hold promise to predict ESCC immune landscapes and therapy responses, ultimately aiding in more personalized and effective clinical decision-making.

A Machine Learning Method for Differentiation Crohn's Disease and Intestinal Tuberculosis.

Background: Whether machine learning (ML) can assist in the diagnosis of Crohn's disease (CD) and intestinal tuberculosis (ITB) remains to be explored. Methods: We collected clinical data from 241 patients, and 51 parameters were included. Six ML methods were tested, including logistic regression, decision tree, k-nearest neighbor, multinomial NB, multilayer perceptron, and XGBoost. SHAP and LIME were subsequently introduced as interpretability methods. The ML model was tested in a real-world clinical practice and compared with a multidisciplinary team (MDT) meeting. Results: XGBoost displays the best performance among the six ML models. The diagnostic AUROC and the accuracy of XGBoost were 0.946 and 0.884, respectively. The top three clinical features affecting our ML model's result prediction were T-spot, pulmonary tuberculosis, and onset age. The ML model's accuracy, sensitivity, and specificity in clinical practice were 0.860, 0.833, and 0.871, respectively. The agreement rate and kappa coefficient of the ML and MDT methods were 90.7% and 0.780, respectively (P<0.001). Conclusion: We developed an ML model based on XGBoost. The ML model could provide effective and efficient differential diagnoses of ITB and CD with diagnostic bases. The ML model performs well in real-world clinical practice, and the agreement between the ML model and MDT is strong.