Bushen Antai recipe ameliorates immune microenvironment and maternal-fetal vascularization in STAT3-deficient abortion-prone mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Spontaneous abortion (SA) is an intricate disorder affecting women of reproductive age. Previous studies have confirmed the indispensable role of signal transducer and activator of transcription (STAT) 3 in normal pregnancy. Bushen Antai recipe (BAR) is a satisfactory formula commonly used in practice, based on the rationale of traditional Chinese medicine (TCM) for SA. AIM OF THE STUDY: The current study explores the potential therapeutic effects and mechanistic insights of BAR in STAT3-deficient abortion-prone mice. MATERIALS AND METHODS: A STAT3-deficient abortion-prone mouse model was developed using intraperitoneal injection of stattic from embryo day (ED) 5.5 to ED9.5 among pregnant females (C57BL/6). We separately administered BAR1 (5.7 g/kg), BAR2 (11.4 g/kg), progesterone (P4), or distilled water at 10 ml/kg/day from ED0.5 until ED10.5. The embryo resorption rate and placenta-uterus structure were observed on ED10.5. The systemic immune status was examined by analyzing the frequency of immunosuppressive myeloid-derived suppressor cells (MDSCs), the ratio of two macrophage (M) subtypes, and the protein expression of associated molecules. Morphological observation, immunohistochemistry, and western blotting were used to evaluate the vascularization conditions at the maternal-fetal interface. RESULTS: BAR1, BAR2, or P4 treatment exerted remarkable effects in alleviating embryo resorption rate and disordered placental-uterus structure in STAT3-deficient abortion-prone mice. Western blotting indicated the deficiency of phosphorylated STAT3 and two prime target molecules, PR and HIF-1α, at the maternal-fetal interface under STAT3 inhibition. Simultaneously, BAR2 treatment significantly upregulated their expression levels. The systemic immune environment was disrupted, indicated by the reduced serum cytokine concentrations, MDSCs frequency, M2/M1 ratio, and the expression of immunomodulatory factors. Nonetheless, BAR2 or P4 treatment revived the immune tolerance for semi-allogenic embryos by enhancing the immune cells and factors. Besides, the western blot and immunohistochemistry results revealed that BAR2 or P4 treatment upregulated VEGFA/FGF2 and activated ERK/AKT phosphorylation. Therefore, BAR2 or P4 facilitated vascularization at the maternal-fetal interface in STAT3-deficient abortion-prone mice. CONCLUSIONS: BAR sustained pregnancy by reviving the systemic immune environment and promoting angiogenesis at the maternal-fetal interface in STAT3-deficient abortion-prone mice.

Modified Simiaowan prevents and treats gouty arthritis via the Nrf2/NLRP3 inflammasome signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Simiaowan (MSM) is a six-herb formula that has been shown to be effective in gouty arthritis (GA) has been proven, but its regulatory mechanism has not been fully elucidated. AIM OF THE STUDY: To investigate the therapeutic effects and mechanism of MSM on gouty arthritis. MATERIALS AND METHODS: Mouse J774A.1 macrophages were induced with Lipopolysaccharide (LPS) and then stimulated with Adenosine 5'-triphosphate (ATP) or Nigericin (Nig.) in presence or absence of MSM. Expression of key indicators of pro-inflammatory cytokines and the NLRP3 inflammasome signaling pathway were investigated by western blot, ELISA and qRT-PCR. Fluorescence staining and flow cytometry were performed to detect intracellular reactive oxygen species (ROS) production. Another study, the anti-inflammatory and antioxidant activities of MSM were evaluated in rats with monosodium urate (MSU) -induced gouty arthritis using ELISA, hematoxylin-eosin staining (HE) staining, immunohistochemistry, and oxidative stress kits to measure relevant inflammatory markers and oxidative stress-related biomarkers. RESULTS: ELISA and qRT-PCR results demonstrated that MSM effectively reduced the secretion and the mRNA expression levels of pro-inflammatory cytokines. Western blot results indicated that MSM can suppress the expression of NLRP3, an inflamasomes-related protein. In addition, MSM regulated the transition from M1 to M2 macrophages and upregulated the protein expression of Nrf2 and HO-1. The flow cytometry results and the fluorescence staining result were consistent with hypothesis that a large amount of ROS could be effectively cleared by MSM. However, the anti-inflammatory effect of MSM was attenuated after the use of ML385. In vivo experiments demonstrated that joint swelling was significantly attenuated and knee neutrophil infiltration was alleviated in rats given MSM. SOD and GSH-px levels were elevated significantly, while COX-2 and MDA levels decreased. The immunohistochemical results suggested that MSM could effectively inhibit the activation of the NLRP3 inflammasome and the regulation of macrophage polarization in rat synovial tissue, and remarkably enhance the expression of Nrf2 and HO-1. CONCLUSION: MSM has potent anti-inflammatory and antioxidant effects on MSU-induced gouty arthritis. MSM alleviates GA through Nrf2/HO-1/ROS/NLRP3 signaling pathway.

Exploring carbon content variation in microplastics sequestrated from seawater to sediment in the Haima cold seep area.

In the decades since plastic has become widely used, deep-sea areas, specifically cold seeps, have developed into plastic sinks. Cold seeps contain clean energy natural gas hydrates and act as a barrier reducing methane migration to the upper water column. However, the impacts of microplastics (MPs) on the carbon content in the cold seep remain unclear. In this study, we explored spatial changes in the MPs' carbon content (MPC) selecting the Haima cold seep (HCS) as the study area. The main conclusions are as follows: (1) For active seepage areas, the mass abundance of the MPs increases with the methane seepage strength in all water columns and sediment of strong seepage areas. It decreases with the seepage strength in the sediment cores in other areas. (2)The MPC is positively correlated with the depth of the water column in the non-seepage area, while it is negatively correlated in the sediment core. (3) The surface roughness of the MPs was greater in the middle of the water column and the sediment core at ROV1. In the high-pressure and oligotrophic cold seep, the amount and method of microbial utilization of carbon from the MPs deserve greater attention.

Thrombin induces ferroptosis in triple-negative breast cancer through the cPLA2α/ACSL4 signaling pathway.

Ferroptosis is a recently identified form of regulated cell death that plays a crucial role in tumor suppression. In this study, we found that F2 (the gene encoding thrombin) was strongly upregulated in breast cancer (BRCA, TCGA Study Abbreviations) compared with normal samples and that lower F2 levels were associated with poorer prognosis in breast cancer patients. Thrombin induces ferroptosis in triple-negative breast cancer (TNBC) cells by activation of cytosolic phospholipase A2α (cPLA2α) activity to increase the release of arachidonic acid (AA). TNBC in all breast cancer subtypes exhibited the highest levels of PLA2G4A (the gene encoding cPLA2α) and Acsl4, and inhibition of cPLA2α and its downstream enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) reversed thrombin toxicity. In a mouse xenograft model of TNBC, thrombin treatment suppressed breast cancer growth which can be inhibited by ferroptosis inhibitor Liproxstatin-1 (Lip-1). Our study underscores the potential of the thrombin-ACSL4 axis as a promising therapeutic target for the treatment of TNBC.

The impact of virtual clinical simulation on nursing students' palliative care knowledge, ability, and attitudes: A mixed methods study.

BACKGROUND: Palliative care is fraught with numerous challenges when it comes to conducting practical teaching as it involves caring for people facing the complexities of end-of-life and death. Insufficient clinical practice hinders nursing students from mastering knowledge, attitude and ability of hospice care. Virtual clinical simulation has demonstrated its effectiveness as a valuable educational tool in nursing. However, there is a dearth of evidence supporting its utilization in the context of palliative care practice education. OBJECTIVE: To develop a virtual clinical simulation education system and assess its impact on enhancing nursing students' knowledge, ability, and attitudes toward palliative care. DESIGN: A single-group pretest-posttest design and focus group interviews were employed. SETTING: The study was conducted at a medical university in southwest China. PARTICIPANTS: A total of 76 third-year nursing students participated. METHODS: Participants underwent a 1-hour learning session using the virtual clinical simulation education system. Pre-test and post-test evaluations were conducted to assess the participants' knowledge, ability, and attitudes toward palliative care. Survey questionnaire was administered to gauge the students' acceptance and perception of virtual clinical simulation. Focus group interviews were integrated to gain insight into students' subjective perceptions and feedback on the virtual clinical simulation. RESULTS: There were notable enhancements in the students' overall scores of palliative care knowledge, ability, and attitudes after the learning session. Students positively evaluated the usefulness and usability of virtual clinical simulation. Students' feedback regarding virtual clinical simulation can be categorized into four themes: the value of virtual clinical simulation education system, its role as a complement to clinical practice teaching, the enjoyment and accessibility of learning, and the technological challenges encountered. CONCLUSION: Virtual clinical simulation is an effective learning tool in palliative care practice education, which has the potential to enhance students' knowledge, ability, and attitudes toward palliative care.

Preliminary study on the short-term changes of pulmonary perfusion after a single balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Little is known about immediate responses of blood perfusion to the balloon pulmonary angioplasty (BPA) procedure. OBJECTIVES: To investigate the changes in pulmonary perfusion of balloon-dilated vessels and untreated vessels with before, immediately after a single BPA and at follow-up. DESIGN: Retrospective single-center cohort study. METHODS: Patients who had chronic thromboembolic pulmonary hypertension (CTEPH) and completed the pulmonary perfusion single photon emission computed tomography (SPECT) imaging before, immediately after BPA and at follow-up were included. We evaluated the perfusion defects of both-lung, BPA target (balloon dilated) and non-target (untreated) vessel segments according to Begic 3-point scale in each lung segment. RESULTS: Forty patients (40 BPA procedures) were included and were given next BPA after 89 (62-125) days. The hemodynamic parameters including mPAP, PVR, and RAP were significantly improved after a single BPA. Visual scoring results of pulmonary perfusion imaging in 40 BPAs showed the perfusion defect scores of target vessels reduced from 5.6 ± 2.6 to 4.2 ± 2.2 (p < 0.001) immediately after BPA, and then further diminished to 3.1 ± 1.9 (p < 0.001) at follow-up. While in the non-target vessels, the post-BPA perfusion defect scores did not change significantly (13.4 ± 4.7 versus 12.8 ± 4.6, p = 0.182), but tended to decrease at follow-up (12.2 ± 4.2). However, there were 17 BPAs of which the post-BPA perfusion defect scores of non-target vessels increased significantly (p < 0.001), but decreased at follow-up. CONCLUSION: In addition to improving the blood perfusion of target vessels, BPA also has a certain effect on the perfusion of some non-target vessels.

Targeting Diverse Wounds and Scars: Recent Innovative Bio-design of Microneedle Patch for Comprehensive Management.

Wounds and the subsequent formation of scars constitute a unified and complex phased process. Effective treatment is crucial; however, the diverse therapeutic approaches for different wounds and scars, as well as varying treatment needs at different stages, present significant challenges in selecting appropriate interventions. Microneedle patch (MNP), as a novel minimally invasive transdermal drug delivery system, has the potential for integrated and programmed treatment of various diseases and has shown promising applications in different types of wounds and scars. In this comprehensive review, the latest applications and biotechnological innovations of MNPs in these fields are thoroughly explored, summarizing their powerful abilities to accelerate healing, inhibit scar formation, and manage related symptoms. Moreover, potential applications in various scenarios are discussed. Additionally, the side effects, manufacturing processes, and material selection to explore the clinical translational potential are investigated. This groundwork can provide a theoretical basis and serve as a catalyst for future innovations in the pursuit of favorable therapeutic options for skin tissue regeneration.

Effect of optical fiber end face scratches on laser-induced damage threshold.

The scratches on the fiber end face can enhance the local electrical field, which lowers the damage threshold. The damage mechanism of a high-energy laser is investigated. The effect of scratches on the electric field is simulated by the finite difference time domain (FDTD) solution. The results show that the depth of the scratch has a greater ability to influence the electric field than the width, and multiple scratches have a stronger modulation than a single scratch. In calculation, the damage threshold of the scratch-free end face is 0.456J/c m 2 when the incident light electric field intensity is 50M V/c m, compared to 0.345J/c m 2 in the presence of the scratch on the end face.

Cryptotanshinone suppresses ovarian cancer via simultaneous inhibition of glycolysis and oxidative phosphorylation.

Ovarian cancer is one of the most lethal cancers in female reproductive system due to heterogeneity and lack of effective treatment. Targeting aerobic glycolysis, a predominant energy metabolism of cancer cells has been recognized a novel strategy to overcome cancer cell growth. However, the capability of cancer cells to undergo metabolic reprogramming guarantees their survival even when glycolysis is inhibited. Here in this study, we have shown that Cryptotanshinone (CT), a lipid-soluble bioactive anticancer molecule of Salvia miltiorrhiza, inhibits both glycolysis and oxidative phosphorylation (OXPHOS) in ovarian cancer cells leading to growth suppression and apoptosis induction. Our mechanistic study revealed that CT decreased glucose uptake and lactate production, and inhibited the kinase activity of LDHA and HK2. The molecular docking study showed that CT could directly bind with GLUT1, LDHA, HK2, PKM2 and complex-1. The immunoblotting data showed that CT decreased the expression of aberrantly activated glycolytic proteins includingGLUT1, LDHA, HK2, and PKM2. Besides, we found that CT inhibited mitochondrial ComplexⅠ activity, decreased the ratio of NAD+/NADH, and suppressed the generation of ATP and induced activation of AMPK, which controls energy-reducing processes. These in vitro findings were further validated using xenograft model. The findings of in vivo studies were in line with in vitro studies. Taken together, CT effectively suppressed glycolysis and OXPHOS, inhibited growth and induced apoptosis in ovarian cancer cells both in vitro and in vivo study models.

Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight.

BACKGROUND: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. METHODS: Bile samples from 20 patients (10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by further bioinformatic analysis. RESULTS: Among the differentially-expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially-expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor (PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APOA-I and APOA-II, were confirmed using enzyme-linked immunosorbent assay. CONCLUSIONS: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

Long-Term Exposure to Low-Level PM2.5 and Mortality: Investigation of Heterogeneity by Harmonizing Analyses in Large Cohort Studies in Canada, United States, and Europe.

BACKGROUND: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) exposure with large heterogeneity in the magnitude of reported associations and the shape of concentration-response functions (CRFs). We aimed to evaluate the impact of key study design factors (including confounders, applied exposure model, population age, and outcome definition) on PM2.5 effect estimates by harmonizing analyses on three previously published large studies in Canada [Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE), 1991-2016], the United States (Medicare, 2000-2016), and Europe [Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), 2000-2016] as much as possible. METHODS: We harmonized the study populations to individuals 65+ years of age, applied the same satellite-derived PM2.5 exposure estimates, and selected the same sets of potential confounders and the same outcome. We evaluated whether differences in previously published effect estimates across cohorts were reduced after harmonization among these factors. Additional analyses were conducted to assess the influence of key design features on estimated risks, including adjusted covariates and exposure assessment method. A combined CRF was assessed with meta-analysis based on the extended shape-constrained health impact function (eSCHIF). RESULTS: More than 81 million participants were included, contributing 692 million person-years of follow-up. Hazard ratios and 95% confidence intervals (CIs) for all-cause mortality associated with a 5-µg/m3 increase in PM2.5 were 1.039 (1.032, 1.046) in MAPLE, 1.025 (1.021, 1.029) in Medicare, and 1.041 (1.014, 1.069) in ELAPSE. Applying a harmonized analytical approach marginally reduced difference in the observed associations across the three studies. Magnitude of the association was affected by the adjusted covariates, exposure assessment methodology, age of the population, and marginally by outcome definition. Shape of the CRFs differed across cohorts but generally showed associations down to the lowest observed PM2.5 levels. A common CRF suggested a monotonically increased risk down to the lowest exposure level. https://doi.org/10.1289/EHP12141.

Performance of the MeltPro TB assay as initial test for diagnosis of pulmonary tuberculosis with drug-resistance detection.

BACKGROUND: The MeltPro TB assay (MeltPro) is a molecular rapid diagnostic test designed for detecting resistance to antituberculosis drugs. However, the performance of MeltPro as an initial diagnostic test for simultaneously detecting the presence of Mycobacterium tuberculosis (MTB) and drug resistance has not been evaluated. This study aims to assess the performance of MeltPro as initial diagnostic test for simultaneous detection of MTB and drug resistance in clinical samples from patients with presumptive pulmonary tuberculosis (PTB). METHODS: A retrospective analysis was conducted on 1283 patients with presumptive PTB from two clinical centers, out of which 875 were diagnosed with PTB. The diagnostic accuracy of MeltPro, Xpert MTB/RIF (Xpert), and MGIT 960 for PTB detection was evaluated. Rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and fluoroquinolone (FQ) resistance were detected using MeltPro, with Xpert and/or the broth microdilution plate method (MYCOTB) results as references. RESULTS: For the diagnosis of PTB, MeltPro showed a sensitivity of 69.0%, which was similar to Xpert (72.7%; P > 0.05) and higher than MGIT (58.1%; P < 0.001). The specificity of MeltPro was 97.1%, similar to Xpert (98.0%; P > 0.05). In smear-negative patients, MeltPro's sensitivity was 50.9%, similar to Xpert (56.5%; P > 0.05), and higher than MGIT (33.1%; P < 0.001). Based on Xpert and/or MYCOTB results, MeltPro exhibited a sensitivity and specificity of 98.3% and 99.2%, respectively, for detecting RIF resistance. Based on MYCOTB results, MeltPro's sensitivity for detecting resistance to INH, EMB, STR, and FQ was 96.4%, 89.1%, 97.5%, and 90.3%, respectively, with specificities of 96.0%, 96.0%, 95.2%, and 99.4%, respectively. CONCLUSION: The MeltPro TB assay could potentially be an effective alternative as the initial test for rapid diagnosis of PTB with drug-resistance detection in clinical practice.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of Leukoaraiosis in a South Chinese Han Population: A Case-Control Study.

Leukoaraiosis (LA) appears as white matter hyperintensities on T2-weighted brain magnetic resonance imaging scans. Age and hypertension are considered the primary risk factors for LA, but its pathogenesis remains uncertain. This study aims to investigate the correlation between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and LA. A total of 140 patients with LA and 136 neuroimaging alteration-free controls were recruited in a case-control study. ACE I/D polymorphism was determined using the polymerase chain reaction method. The allele and genotype distributions of the ACE I/D polymorphism were significantly different between subjects with and without LA. Significant difference was observed in the genotypic distribution between LA patients and controls for recessive and additive models. A statistically significant association remained apparent after adjusting for potential risk factors (D/D vs. I/D + I/I: adjusted OR 3.251, 95% CI 1.185-8.918; D/D vs. I/I: adjusted OR 3.277, 95% CI 1.187-9.047). Our results indicate that the D/D genotype and D allele are important risk factors for LA. Future studies with larger populations are needed to validate our results.

Reduced miR-513a-5p expression in COPD may regulate airway mucous cell hyperplasia through TFR1-dependent signaling.

Airway mucous cell metaplasia and mucous hypersecretion is one of the key characteristic pathophysiological status of chronic obstructive pulmonary disease (COPD). micro(mi)RNAs are acknowledged as non-encoding RNA molecules playing important roles in gene expression regulation. In this study, we searched the Gene Expression Omnibus (GEO) database for the differentially expressed miRNAs between COPD and non-COPD controls with bioinformatics analysis. Finally, we focused on miR-513a-5p and investigated the potential mechanism by which miR-513a-5p regulates airway mucous hypersecretion and goblet cell metaplasia. A dual-luciferase reporter assay was then showing that miR-513a-5p targeted the 3'-UTR of TFR1 and inhibited its expression in vitro. In vivo transfection demonstrated that TFR1 downregulation partially blocked MUC5AC hypersecretion and goblet cell hyperplasia in COPD model rats. In vitro study, CSE increased the intracellular expression and secretion of MUC5AC by BEAS-2B branchial epithelial cells in the BEAS-2B cell and THP-1 cell coculture system. Coculture with either miR-513a-5p mimic-pretreated or TFR1-deficient THP-1 cells attenuated intracellular MUC5AC expression in BEAS-2B cells exposed to CSE. ELISA demonstrated that transfection of TFR1 siRNA or pretreatment with miR-513a-5p mimic reduced the secretion of inflammatory factors that are responsible for airway goblet cell hyperplasia, such as IL-1ß, IL-13, and IL-17, by THP-1 cells after CSE stimulation. Our findings supported that miR-513a-5p/TFR1 signaling axis might activate macrophages as well as promote airway inflammation and airway mucous cell hyperplasia in COPD.

Analysis of microbiota reveals the underlying mechanism of PHF11 in the development of Enterococcus-regulated endometriotic cysts.

Endometriosis (EMS) is a prevalent disease and the etiologies has not uniform. Microbiota is associated with human diseases. To delve into the relationship between EMS and microbiota, Ectopic (EM) and eutopic (EU) endometrial tissues, pharyngeal swabs, and stools were collected from EMS patients. The microbiota composition of EM and EU partially overlapped, with similar taxon numbers and diversity, but the richness levels were significantly different. A comparison of intestinal microbes in healthy individuals (FN) and EMS patients (FE) revealed that the richness of Enterococcus, Pseudomonas, Haemophilus, and Neisseria was enhanced in FE. In addition, Enterococcus-induced mice (EFA) presented with a higher degree of lesion infiltration and a wider distribution of lesions. Proteomic analysis revealed the expression of plant homeodomain finger 11 (PHF11) was notably downregulated in EFA. And the downregulated expression of PHF11 was accompanied by the upregulated expression of interleukin 8 (IL-8). Our findings suggest a potential regulatory mechanism for PHF11 in EMS development.

Interpretable Machine Learning Model to Predict Bone Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fracture Based on SHapley Additive exPlanations.

STUDY DESIGN: Retrospective study. OBJECTIVES: Our objective is to create comprehensible machine learning (ML) models that can forecast bone cement leakage in percutaneous vertebral augmentation (PVA) for individuals with osteoporotic vertebral compression fracture (OVCF) while also identifying the associated risk factors. METHODS: We incorporated data from patients (n = 425) which underwent PVA. To predict cement leakage, we devised six models based on a variety of parameters. Evaluate and juxtapose the predictive performances relied on measures of discrimination, calibration, and clinical utility. SHapley Additive exPlanations (SHAP) methodology was used to interpret model and evaluate the risk factors associated with cement leakage. RESULTS: The occurrence rate of cement leakage was established at 50.4%. A binary logistic regression analysis identified cortical disruption (OR 6.880, 95% CI 4.209-11.246), the basivertebral foramen sign (OR 2.142, 95% CI 1.303-3.521), the fracture type (OR 1.683, 95% CI 1.083-2.617), and the volume of bone cement (OR 1.198, 95% CI 1.070-1.341) as independent predictors of cement leakage. The XGBoost model outperformed all others in predicting cement leakage in the testing set, with AUC of .8819, accuracy of .8025, recall score of .7872, F1 score of .8315, and a precision score of .881. Several important factors related to cement leakage were drawn based on the analysis of SHAP values and their clinical significance. CONCLUSION: The ML based predictive model demonstrated significant accuracy in forecasting bone cement leakage for patients with OVCF undergoing PVA. When combined with SHAP, ML facilitated a personalized prediction and offered a visual interpretation of feature importance.

Development and Validation of a Machine Learning-Based Model Using CT Radiomics for Predicting Immune Checkpoint Inhibitor-related Pneumonitis in Patients With NSCLC Receiving Anti-PD1 Immunotherapy: A Multicenter Retrospective CaseControl Study.

RATIONALE AND OBJECTIVES: This study aimed to develop and evaluate a radiomics-based model combined with clinical and qualitative radiological (semantic feature [SF]) features to predict immune checkpoint inhibitor-related pneumonitis (CIP) in patients with non-small cell lung cancer (NSCLC) treated with programmed cell death protein 1 inhibitors. MATERIALS AND METHODS: This was a multicenter retrospective casecontrol study conducted from January 1, 2018, to December 31, 2022, at three centers. Patients with NSCLC treated with anti-PD1 were enrolled and randomly divided into two groups (7:3): training (n = 95) and validation (n = 39). Logistic regression (LR) and support vector machine (SVM) algorithms were used to transform features into the models. RESULTS: The study comprised 134 participants from three independent centers (male, 114/134, 85%; mean [±standard deviation] age, 63.92 [±7.9] years). The radiomics score (RS) models built based on the LR and SVM algorithms could accurately predict CIP (area under the receiver operating characteristics curve [AUC], 0.860 [0.780, 0.939] and 0.861 [0.781, 0.941], respectively). The AUCs for the RS-clinic-SF combined model were 0.903 (0.839, 0.967) and 0.826 (0.688, 0.964) in the training and validation cohorts, respectively. Decision curve analysis showed that the combined models achieved high clinical net benefit across the majority of the range of reasonable threshold probabilities. CONCLUSION: This study demonstrated that the combined model constructed by the identified features of RS, clinical features, and SF has the potential to precisely predict CIP. The RS-clinic-SF combined model has the potential to be used more widely as a practical tool for the noninvasive prediction of CIP to support individualized treatment planning.

Cobalt-catalyzed aminoalkylative carbonylation of alkenes toward direct synthesis of γ-amino acid derivatives and peptides.

γ-Amino acids and peptides analogues are common constituents of building blocks for numerous biologically active molecules, pharmaceuticals, and natural products. In particular, γ-amino acids are providing with better metabolic stability than α-amino acids. Herein we report a multicomponent carbonylation technology that combines readily available amides, alkenes, and the feedstock gas carbon monoxide to build architecturally complex and functionally diverse γ-amino acid derivatives in a single step by the implementation of radical relay catalysis. This transformation can also be used as a late-stage functionalization strategy to deliver complex, advanced γ-amino acid products for pharmaceutical and other areas.