A novel score for early prediction of urinary tract infection risk in patients with acute ischemic stroke: a nomogram-based retrospective cohort study.

This study aimed to construct and externally validate a user-friendly nomogram-based scoring model for predicting the risk of urinary tract infections (UTIs) in patients with acute ischemic stroke (AIS). A retrospective real-world cohort study was conducted on 1748 consecutive hospitalized patients with AIS. Out of these patients, a total of 1132 participants were ultimately included in the final analysis, with 817 used for model construction and 315 utilized for external validation. Multivariate regression analysis was applied to develop the model. The discriminative capacity, calibration ability, and clinical effectiveness of the model were evaluated. The overall incidence of UTIs was 8.13% (92/1132), with Escherichia coli being the most prevalent causative pathogen in patients with AIS. After multivariable analysis, advanced age, female gender, National Institute of Health Stroke Scale (NIHSS) score ≥ 5, and use of urinary catheters were identified as independent risk factors for UTIs. A nomogram-based SUNA model was constructed using these four factors (Area under the receiver operating characteristic curve (AUC) = 0.810), which showed good discrimination (AUC = 0.788), calibration, and clinical utility in the external validation cohort. Based on four simple and readily available factors, we derived and externally validated a novel and user-friendly nomogram-based scoring model (SUNA score) to predict the risk of UTIs in patients with AIS. The model has a good predictive value and provides valuable information for timely intervention in patients with AIS to reduce the occurrence of UTIs.

Performance and preference of larval parasitoid, Microplitis pallidipes (Hymenoptera: Braconidae), on 2 Spodoptera pest species.

Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) and Spodoptera litura (Fabricius) are the main pests on corn (Poaceae: Gramineae). The performance of the larval wasp, Microplitis pallidipes Szépligeti (Hymenoptera: Braconidae), was reported on S. frugiperda and S. litura. In this study, we evaluated host selectivity, constructed an age-stage, 2-sex life table, and assessed the pest control potential of M. pallidipes against these 2 pests under laboratory conditions. In a 2-choice host preference experiment, M. pallidipes exhibited a stronger preference for S. frugiperda over S. litura and a distinct preference for second instars. We also investigated the parasitism of females that were either unfed or fed with 10% honey-water solution under different host densities and found that the highest parasitism rate was observed when M. pallidipes were fed with honey-water solution on the first day after mating and a presented female wasp:host ratio of 1:90. In a nonselective assay, M. pallidipes successfully completed a full generation on both hosts. However, the parasitoids exhibited higher fitness and population growth potential when reared on S. frugiperda, with a net reproductive rate (R0) of 24.24, an intrinsic rate of increase (r) of 0.20 per day, a finite rate of increase (λ) of 1.23 per day, and a mean generation time (T) of 15.69 days. This study elucidates the performance of M. pallidipes on 2 Spodoptera host species and offers insights into its biological control potential on lepidopteran pests.

Genome-wide identification, characterization and expression of C2H2 zinc finger gene family in Opisthopappus species under salt stress.

BACKGROUND: The C2H2 zinc finger protein family plays important roles in plants. However, precisely how C2H2s function in Opisthopappus (Opisthopappus taihangensis and Opisthopappus longilobus) remains unclear. RESULTS: In this study, a total of 69 OpC2H2 zinc finger protein genes were identified and clustered into five Groups. Seven tandem and ten fragment repeats were found in OpC2H2s, which underwent robust purifying selection. Of the identified motifs, motif 1 was present in all OpC2H2s and conserved at important binding sites. Most OpC2H2s possessed few introns and exons that could rapidly activate and react when faced with stress. The OpC2H2 promoter sequences mainly contained diverse regulatory elements, such as ARE, ABRE, and LTR. Under salt stress, two up-regulated OpC2H2s (OpC2H2-1 and OpC2H2-14) genes and one down-regulated OpC2H2 gene (OpC2H2-7) might serve as key transcription factors through the ABA and JA signaling pathways to regulate the growth and development of Opisthopappus species. CONCLUSION: The above results not only help to understand the function of C2H2 gene family but also drive progress in genetic improvement for the salt tolerance of Opisthopappus species.

Development and validation of a prediction model for hyperuricemia risk in hypertensive patients.

OBJECTIVE: This study aimed to create a predictive model for hyperuricemia (HUA) in patients diagnosed with hypertension and evaluate its predictive accuracy. METHODS: Employing a retrospective cohort design, this study investigated HUA incidence and clinical data among 228 patients with essential hypertension selected from the Department of Cardiology at a tertiary A-level hospital in Anhui Province, China, between January 2018 and June 2021. The patients were divided randomly into a training group (168 cases) and a validation group (60 cases) at a 7:3 ratio. The training group underwent univariate and multivariate logistic regression analyses to identify risk factors for HUA. Additionally, an R software-generated nomogram model estimated HUA risk in hypertensive patients. The validation group assessed the nomogram model's discriminatory power and calibration using receiver operating characteristic curve analysis and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: The study found a 29.39% prevalence of HUA among the 228 participants. Logistic regression analyses identified age, body mass index, and concomitant coronary heart disease as independent HUA risk factors (odds ratio [OR] > 1 and P < 0.05). Conversely, high-density lipoprotein cholesterol emerged as an independent protective factor against HUA in hypertensive patients (OR < 1 and P < 0.05). Using these factors, a nomogram model was constructed to assess HUA risk, with an AUC of 0.873 (95% confidence interval [CI]: 0.818-0.928) in the training group and 0.841 (95% CI: 0.735-0.946) in the validation group, indicating a strong discriminatory ability. The Hosmer-Lemeshow goodness-of-fit test showed no significant deviation between predicted and actual HUA frequency in both groups (χ2 = 5.980, 9.780, P = 0.649, 0.281), supporting the nomogram's reliability. CONCLUSION: The developed nomogram model, utilizing independent risk factors for HUA in hypertensive patients, exhibits strong discrimination and calibration. It holds promise as a valuable tool for cardiovascular professionals in clinical decision-making.

Development and validation of a nomogram model for predicting the risk of pre-hospital delay in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a severe cardiovascular disease caused by the blockage of coronary arteries that leads to ischemic necrosis of the myocardium. Timely medical contact is critical for successful AMI treatment, and delays increase the risk of death for patients. Pre-hospital delay time (PDT) is a significant challenge for reducing treatment times, as identifying high-risk patients with AMI remains difficult. This study aims to construct a risk prediction model to identify high-risk patients and develop targeted strategies for effective and prompt care, ultimately reducing PDT and improving treatment outcomes. AIM: To construct a nomogram model for forecasting pre-hospital delay (PHD) likelihood in patients with AMI and to assess the precision of the nomogram model in predicting PHD risk. METHODS: A retrospective cohort design was employed to investigate predictive factors for PHD in patients with AMI diagnosed between January 2022 and September 2022. The study included 252 patients, with 180 randomly assigned to the development group and the remaining 72 to the validation group in a 7:3 ratio. Independent risk factors influencing PHD were identified in the development group, leading to the establishment of a nomogram model for predicting PHD in patients with AMI. The model's predictive performance was evaluated using the receiver operating characteristic curve in both the development and validation groups. RESULTS: Independent risk factors for PHD in patients with AMI included living alone, hyperlipidemia, age, diabetes mellitus, and digestive system diseases (P < 0.05). A nomogram model incorporating these five predictors accurately predicted PHD occurrence. The receiver operating characteristic curve analysis indicated area under the receiver operating characteristic curve values of 0.787 (95% confidence interval: 0.716-0.858) and 0.770 (95% confidence interval: 0.660-0.879) in the development and validation groups, respectively, demonstrating the model's good discriminatory ability. The Hosmer-Lemeshow goodness-of-fit test revealed no statistically significant disparity between the anticipated and observed incidence of PHD in both development and validation cohorts (P > 0.05), indicating satisfactory model calibration. CONCLUSION: The nomogram model, developed with independent risk factors, accurately forecasts PHD likelihood in AMI individuals, enabling efficient identification of PHD risk in these patients.

Potential Response Patterns of Endogenous Hormones in Cliff Species Opisthopappus taihangensis and Opisthopappus longilobus under Salt Stress.

When plants are exposed to salt stress, endogenous hormones are essential for their responses through biosynthesis and signal transduction pathways. However, the roles of endogenous hormones in two cliff species (Opisthopappus taihangensis and Opisthopappus longilobus (Opisthopappus genus)) in the Taihang Mountains under salt stress have not been investigated to date. Following different time treatments under 500 mM salt concentrations, 239 differentially expressed gene (DEG)-related endogenous hormones were identified that exhibited four change trends, which in Profile 47 were upregulated in both species. The C-DEG genes of AUX, GA, JA, BR, ETH, and ABA endogenous hormones were significantly enriched in Opisthopappus taihangensis (O. taihangensis) and Opisthopappus longilobus (O. longilobus). During the responsive process, mainly AUX, GA, and JA biosynthesis and signal transduction were triggered in the two species. Subsequently, crosstalk further influenced BR, EHT, ABA, and MAPK signal transduction pathways to improve the salt resistance of the two species. Within the protein-protein interactions (PPI), seven proteins exhibited the highest interactions, which primarily involved two downregulated genes (SAUR and GA3ox) and eight upregulated genes (ACX, MFP2, JAZ, BRI1, BAK1, ETR, EIN2, and SNRK2) of the above pathways. The more upregulated expression of ZEP (in the ABA biosynthesis pathway), DELLA (in the GA signaling pathway), ABF (in the ABA signaling pathway), and ERF1 (in the ETH signaling pathway) in O. taihangensis revealed that it had a relatively higher salt resistance than O. longilobus. This revealed that the responsive patterns to salt stress between the two species had both similarities and differences. The results of this investigation shed light on the potential adaptive mechanisms of O. taihangensis and O. longilobus under cliff environments, while laying a foundation for the study of other cliff species in the Taihang Mountains.

Establishment and validation of a heart failure risk prediction model for elderly patients after coronary rotational atherectomy based on machine learning.

Objective: To develop and validate a heart failure risk prediction model for elderly patients after coronary rotational atherectomy based on machine learning methods. Methods: A retrospective cohort study was conducted to select 303 elderly patients with severe coronary calcification as the study subjects. According to the occurrence of postoperative heart failure, the study subjects were divided into the heart failure group (n = 53) and the non-heart failure group (n = 250). Retrospective collection of clinical data from the study subjects during hospitalization. After processing the missing values in the original data and addressing sample imbalance using Adaptive Synthetic Sampling (ADASYN) method, the final dataset consists of 502 samples: 250 negative samples (i.e., patients not suffering from heart failure) and 252 positive samples (i.e., patients with heart failure). According to a 7:3 ratio, the datasets of 502 patients were randomly divided into a training set (n = 351) and a validation set (n = 151). On the training set, logistic regression (LR), extreme gradient boosting (XGBoost), support vector machine (SVM), and lightweight gradient boosting machine (LightGBM) algorithms were used to construct heart failure risk prediction models; Evaluate model performance on the validation set by calculating the area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, F1-score, and prediction accuracy. Result: A total of 17.49% of 303 patients occured postoperative heart failure. The AUC of LR, XGBoost, SVM, and LightGBM models in the training set were 0.872, 1.000, 0.699, and 1.000, respectively. After 10 fold cross validation, the AUC was 0.863, 0.972, 0.696, and 0.963 in the training set, respectively. Among them, XGBoost had the highest AUC and better predictive performance, while SVM models had the worst performance. The XGBoost model also showed good predictive performance in the validation set (AUC = 0.972, 95% CI [0.951-0.994]). The Shapley additive explanation (SHAP) method suggested that the six characteristic variables of blood cholesterol, serum creatinine, fasting blood glucose, age, triglyceride and NT-proBNP were important positive factors for the occurrence of heart failure, and LVEF was important negative factors for the occurrence of heart failure. Conclusion: The seven characteristic variables of blood cholesterol, blood creatinine, fasting blood glucose, NT-proBNP, age, triglyceride and LVEF are all important factors affecting the occurrence of heart failure. The prediction model of heart failure risk for elderly patients after CRA based on the XGBoost algorithm is superior to SVM, LightGBM and the traditional LR model. This model could be used to assist clinical decision-making and improve the adverse outcomes of patients after CRA.

Responsive Alternative Splicing Events of Opisthopappus Species against Salt Stress.

Salt stress profoundly affects plant growth, prompting intricate molecular responses, such as alternative splicing (AS), for environmental adaptation. However, the response of AS events to salt stress in Opisthopappus (Opisthopappus taihangensis and Opisthopappus longilobus) remains unclear, which is a Taihang Mountain cliff-dwelling species. Using RNA-seq data, differentially expressed genes (DEGs) were identified under time and concentration gradients of salt stress. Two types of AS, skipped exon (SE) and mutually exclusive exons (MXE), were found. Differentially alternative splicing (DAS) genes in both species were significantly enriched in "protein phosphorylation", "starch and sucrose metabolism", and "plant hormone signal transduction" pathways. Meanwhile, distinct GO terms and KEGG pathways of DAS occurred between two species. Only a small subset of DAS genes overlapped with DEGs under salt stress. Although both species likely adopted protein phosphorylation to enhance salt stress tolerance, they exhibited distinct responses. The results indicated that the salt stress mechanisms of both Opisthopappus species exhibited similarities and differences in response to salt stress, which suggested that adaptive divergence might have occurred between them. This study initially provides a comprehensive description of salt responsive AS events in Opisthopappus and conveys some insights into the molecular mechanisms behind species tolerance on the Taihang Mountains.

MHC class II regulation of CD8+ T cell tolerance and implications in autoimmunity and cancer immunotherapy.

Major histocompatibility complex (MHC) class II-reactive CD8+ T cells are found in humans and animals, but little is known about their identity, development, and function. In this study, we discover a group of CD8+ T cells reactive to both MHC class I and II molecules in MHC class II-deficient mice. We clone their T cell receptors (TCRs) and analyze their development and function. In wild-type animals, thymocytes bearing those TCRs are purged by negative selection. In the absence of MHC class II, they develop into mature CD8+ T cells. When encountering MHC class II in the periphery, they undergo robust activation and proliferation, attack self-tissues, and cause lethal autoimmune diseases. In adoptive T cell therapy, those CD8+ T cells are able to efficiently control MHC class II-expressing tumors. This study opens the door to investigation of dual-reactive CD8+ T cells, their development and selection in the thymus, and the perils and promises when their normal development and selection are compromised.

A neutron beam monitor based on ceramic gas electron multiplier with high spatial resolution for low flux measurements.

Neutron scattering instruments play an important role in studying the inner structure of materials. A neutron beam monitor is a detector commonly used in a neutron scattering instrument. The detection efficiency for most neutron beam monitors is quite low (10-4-10-6). However, in some experiments with a low neutron flux, such as small angle neutron scattering (SANS) and inelastic neutron scattering experiments, a neutron beam monitor with a higher detection efficiency (∼1% for thermal neutrons) is required to reduce the duration of the experiment. To meet this requirement, a ceramic gas electron multiplier-based neutron beam monitor equipped with a 1 µm 10B4C neutron converter was developed in this study. Its performance was determined both experimentally and in simulations. The detection efficiency in the wavelength range of 1.8-5.5 Å was measured experimentally and was confirmed by the simulation results. An algorithm based on event selection and position reconstruction was developed to improve the spatial resolution to about 1 mm full-width-half-maximum. The wavelength spectrum was measured in beamline 20 (BL20) and agreed well with the results obtained using a commercial monitor. The maximum counting rate was 1.3 MHz. The non-uniformity over the whole 100 × 100 mm2 active area was determined to be 1.4%. Due to the excellent performance of this monitor, it has been used in several neutron instruments, such as the SANS and the High-Energy Direct-Geometry Inelastic Spectrometer instruments in the China spallation neutron source.

A qualitative analysis of stress experiences and coping strategies in adolescents with Crohn's disease.

BACKGROUND: In this study, we investigated the coping mechanisms and stress perceptions of adolescent patients with Crohn's disease. METHODS: Using semi-structured face-to-face interviews, we conducted an extensive qualitative study of the disease perceptions, stress experiences, and corresponding coping mechanisms in adolescent patients with Crohn's disease. We used Colaizzi content analysis to synthesize the themes. RESULTS: The two main themes in this study were inappropriate coping mechanisms and physical and psychological stress. The primary initiators of physical and psychological stress in adolescents with Crohn's disease were weak disease perception, symptom distress, negative emotions, lack of support, and multiple stressors. The decrease in self-management and self-control induced by the initiators led to changes in cognition, emotions, and attitudes, which subsequently led to poor coping behavior. CONCLUSION: Adolescents with Crohn's disease can better combat the condition by implementing appropriate coping strategies. Their mental health should be given attention, and a multidisciplinary team should be assembled to provide them with supportive care.

Involved-field irradiation or elective-nodal irradiation in neoadjuvant chemo-radiotherapy for locally-advanced esophageal cancer: comprehensive analysis for dosimetry, treatment-related complications, impact on lymphocyte, patterns of failure and survival.

Purpose: To compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Materials and methods: We retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups. Results: The median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p<0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p=0.004) and pericardial effusion (26.7% vs. 11.8%, p=0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively (p=0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN- patients, especially in the first year of follow-up (6.67% vs. 0.56%, p=0.003). Conclusion: The ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted.

Distinct selectivity inside self-assembled coordination cages.

Supramolecular containers have long been applied to regulate organic reactions with distinct selectivity, owing to their diverse functions such as the ability to pose a guest molecule(s) with a certain orientation and conformation. In this review, we try to illustrate how self-assembled coordination cages could achieve this goal. Two representative cage hosts, namely, self-assembled Pd(II)-ligand octahedral coordination cages ([Pd6L4]12+) and self-assembled Ga(III)-ligand tetrahedral coordination cages ([Ga4L6]12-) are selected as the pilot hosts that this mini review covers. Representative works in this area are presented here in brief.

Magnetron sputtering system for depositing boron carbide film use as neutron detection.

Boron carbide (B4C) films used as neutron conversion layers were investigated in this paper to replace the traditional 3He detectors due to their shortage. A magnetron sputtering system was developed for depositing large-size B4C films with the 1500 × 400 mm2 uniform-area. B4C films at the micron scale were deposited on aluminum (Al), float glass (SiO2), and silicon (Si) substrates with an inserting adhesion layer. The key characteristics, including surface morphology, thickness nonuniformity, purity, and neutron efficiency of B4C films, were characterized using atomic force microscopy, scanning electron microscopy, grazing incidence x-ray reflectivity, x-ray photoelectron spectroscopy, and neutron radiation metrology. The experimental results indicate that the deposition thickness nonuniformity across a 1500 × 400 mm2 area was better than ±3%. The stoichiometric ratio of boron atoms and carbon atoms (B/C) is 5.18, with 6 at. % O and 0.79 at. % N concentrations. The measured neutron detection efficiency of a 3 µm 10B4C film for 25 meV neutrons was 3.3 ± 0.3(sys)%, which is close to the simulated results (3.4%). The results show that the B4C neutron conversion layer is a promising substitute for 3He for neutron detection in the future.

Constructing a prognostic tool for predicting the risk of non-adherence to antiplatelet therapy in discharged patients with coronary heart disease: a retrospective cohort study.

Objective: To investigate the incidence and influencing factors affecting the non-adherence behavior of patients with coronary heart disease (CHD) to antiplatelet therapy after discharge and to construct a personalized predictive tool. Methods: In this retrospective cohort study, 289 patients with CHD who were admitted to the Department of Cardiology of The First Affiliated Hospital of the University of Science and Technology of China between June 2021 and September 2021 were enrolled. The clinical data of all patients were retrospectively collected from the hospital information system, and patients were followed up for 1 year after discharge to evaluate their adherence level to antiplatelet therapy, analyze their present situation and influencing factors for post-discharge adherence to antiplatelet therapy, and construct a nomogram model to predict the risk of non-adherence. Results: Based on the adherence level to antiplatelet therapy within 1 year after discharge, the patients were divided into the adherence (n = 216) and non-adherence (n = 73) groups. Univariate analysis revealed statistically significant differences between the two groups in terms of variable distribution, including age, education level, medical payment method, number of combined risk factors, percutaneous coronary intervention, duration of antiplatelet medication, types of drugs taken at discharge, and CHD type (P < 0.05). Furthermore, multivariate logistic regression analysis revealed that, except for the medical payment method, all the seven abovementioned variables were independent risk factors for non-adherence to antiplatelet therapy (P < 0.05). The areas under the receiver operating characteristic curve before and after the internal validation of the predictive tool based on the seven independent risk factors and the nomogram were 0.899 (95% confidence interval [CI]: 0.858-0.941) and 0.89 (95% CI: 0.847-0.933), respectively; this indicates that the tool has good discrimination ability. The calibration curve and Hosmer-Lemeshow goodness of fit test revealed that the tool exhibited good calibration and prediction consistency (χ2 = 5.17, P = 0.739). Conclusion: In this retrospective cohort study, we investigated the incidence and influencing factors affecting the non-adherence behavior of patients with CHD after discharge to antiplatelet therapy. For this, we constructed a personalized predictive tool based on seven independent risk factors affecting non-adherence behavior. The predictive tool exhibited good discrimination ability, calibration, and clinical applicability. Overall, our constructed tool is useful for predicting the risk of non-adherence behavior to antiplatelet therapy in discharged patients with CHD and can be used in personalized intervention strategies to improve patient outcomes.

FOXN4 affects myocardial ischemia-reperfusion injury through HIF-1α/MMP2-mediated ferroptosis of cardiomyocytes.

Myocardial ischemia-reperfusion injury (MIRI) is an important factor leading to myocardial injury and necrosis, and can induce ischemic heart disease. Forkhead box protein N4 (FOXN4) belongs to the gene family of Fork head domain (Fox) transcription factors and plays an important role in heart formation and function. However, whether FOXN4 is involved in MIRI progression is unknown. In this study, we investigated the clinicopathological significance and potential mechanisms of FOXN4 in MIRI. The expressions of FOXN4 and MMP2 were measured by quantitative reverse transcriptase polymerase chain reaction, apoptosis was detected by flow cytometry, and cell viability was detected by examining EdU incorporation into DNA. The signaling pathway related proteins FOXN4, MMP2, HIF-1α, apoptosis-related proteins Bcl-2 and Bax, and ferroptosis-related proteins TFR1 and IREB2 were detected by western blot, the levels of malondialdehyde (MDA), Fe2+, reactive oxygen species (ROS), and glutathione were detected by commercially available kits, and the cardiac histopathology after MIRI was evaluated by hematoxylin and eosin staining. We found that knockdown of FOXN4 alleviated oxidative stress, inhibited ROS production, and inhibited ferroptosis in MIR-injured tissues and cardiomyocytes. In addition, knockdown of FOXN4 inhibited myocardial injury, improved myocardial cell viability, restored myocardial function, and alleviated MIRI. We interrogated the mechanism and found that FOXN4 can enhance its binding to HIF-1α, up-regulate the expression of MMP2, and mediate ferroptosis to regulate the functional activity of cardiomyocytes to affect the progression of MIRI. This study provides new insights into the role of FOXN4 in MIRI progression and suggests that FOXN4 may represent a potential therapeutic target in MIRI progression by regulating the active function of cardiomyocytes through HIF-1α/MMP2-mediated ferroptosis.

Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naïve Stage IV PD-L1+ Non-Small Cell Lung Cancer Patients.

PURPOSE: Low-dose radiotherapy (LDRT) may enhance the synergistic antitumor effect of combined immunotherapy and stereotactic body radiotherapy (SBRT). The safety and efficacy of this novel triple-combination therapy were evaluated for the first time as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This prospective phase I study enrolled 29 patients and included a dose-escalation and dose-expansion phase. Patients received SBRT [30 Gray (Gy)/3f] to small lesions and LDRT (2 Gy/1f, 4 Gy/2f, or 10 Gy/5f) to a large lesion concurrently, followed by sintilimab (a programmed death-1 inhibitor). The primary endpoint was safety and tolerability; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: No dose-limiting toxicities were observed during the dose-escalation phase; 4 Gy/2f was the recommended LDRT dose. Median follow-up was 15.6 months. Treatment-related adverse events (TRAE) occurred in 96.6% (28/29) of patients [grade ≥ 3; 20.7% (6/29)]; 2 patients (6.9%) discontinued due to TRAEs. Seven patients experienced pneumonitis (grade 2, n = 6; grade 3, n = 1). Immune-related adverse events were noted in 58.6% (17/29) of patients. In patients with tumor assessment (n = 28), ORR and confirmed ORR were 60.7% and 57.1%, respectively. Median PFS was 8.6 months (95% confidence interval, 3.7-16.5), and median OS was not reached. Exploratory analyses suggested both expanded and newly emerging T-cell receptor clonotypes were associated with better PFS. CONCLUSIONS: The findings indicate that the novel SBRT + LDRT + sintilimab therapy is safe and promising in patients with programmed death ligand-1-positive, driver gene-negative primary metastatic NSCLC.

Pericardial irradiation dose may be strongly associated with grade 4 lymphopenia and affect prognosis in patients with locally advanced esophageal cancer receiving definitive concurrent chemoradiotherapy.

BACKGROUND: The immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA-EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis. METHODS AND MATERIALS: We identified 190 LA-EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte-related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally. RESULTS: Median follow-up time for all patients was 27.5 months. On MVA for OS, higher pericardial V30 (PV30 ) was linked to worse survival (HR: 1.013, 95% CI: 1.001-1.026, p = 0.039). The median OS stratified by PV30 > 55.3% and PV30 ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335-3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage-IVA (p = 0.017), platelet-to-lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843. CONCLUSION: Higher doses of pericardial radiation might affect LA-EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune-checkpoint inhibitor treatment.

A combined passivator of zeolite and calcium magnesium phosphate fertilizer: Passivation behavior and mechanism for Cd (II) in composting.

Passivation of heavy metals is one of the most efficient techniques to improve the quality of compost. Many studies confirmed the passivation effect of passivators (e.g., zeolite and calcium magnesium phosphate fertilizer) on cadmium (Cd), but passivators with single component could not effectively passivate Cd in the long-term operation of composting. In the present study, a combined passivator of zeolite and calcium magnesium phosphate fertilizer (ZCP) was used to explore its impacts of adding at different composting periods (heating period, thermophilic period, cooling period) on the Cd control, compost quality (e.g., temperature, moisture content and humification), microbial community structure as well as the compost available forms of Cd and addition strategy of ZCP. Results showed that Cd passivation rate could be increased by 35.70-47.92% under all treatments in comparison to the control treatment. By altering bacterial community structure, reducing Cd bioavailability and improving the chemical properties of the compost, the combined inorganic passivator could achieve high efficiency for Cd passivation. To sum up, the addition of ZCP at different composting periods has effects on the process and quality of composting, which could provide ideas for the optimization of the passivators addition strategy.

Optimal timing of hypofractionated stereotactic radiotherapy for epidermal growth factor receptor-mutated non-small-cell lung cancer patients with brain metastases.

BACKGROUND: For epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients with limited brain metastases (BMs), who eventually receive both tyrosine kinase inhibitors (TKIs) treatment and brain radiotherapy, the optimal timing of radiotherapy is not clear. The present retrospective analysis aimed to partly solve this problem. METHODS: In total 84 EGFR-mutated NSCLC patients with limited BMs, who received both TKI treatment and brain hypofractionated stereotactic radiotherapy (HSRT), were enrolled. Patients were divided into three groups based on whether the HSRT was administrated 2 weeks before or after the beginning of TKI treatment (upfront HSRT), when intracranial lesions stabilized after TKI treatment (consolidative HSRT), or when the intracranial disease progressed after TKI treatment (salvage HSRT). The clinical efficacy and toxicities were evaluated. RESULTS: The median intracranial progression-free survival (iPFS) and overall PFS calculated from the initiation of HSRT (iPFS1 and PFS1) of all patients were 17.5 and 13.1 months, respectively. The median iPFS and PFS calculated from the initiation of TKI treatment (iPFS2 and PFS2) of all patients were 24.1 and 18.4 months, respectively. Compared to consolidative and salvage HSRT, upfront HSRT improved iPFS1 (not reached vs. 17.5 months vs. 11.0 months, p < 0.001) and PFS1 (18.4 months vs. 9.1 months vs. 7.9 months, p < 0.001), and reduced the initial intracranial failure rate (12.5% vs. 48.1% vs. 56%, p < 0.001). However, there were no significant differences between the three groups for iPFS2, PFS2, and overall survival. Hepatic metastases and diagnosis-specific Graded Prognostic Assessment (ds-GPA) at 2-3 were poor prognostic factors. CONCLUSION: For patients who receive both TKI treatment and brain HSRT, the timing of HSRT does not seem to influence the eventual therapeutic effect. Further validation in prospective clinical studies is needed.