CT-based quantification of intratumoral heterogeneity for predicting pathologic complete response to neoadjuvant immunochemotherapy in non-small cell lung cancer.

Objectives: To investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC) using quantification of intratumoral heterogeneity from pre-treatment CT image. Methods: This retrospective study included 178 patients with NSCLC who underwent NAIC at 4 different centers. The training set comprised 108 patients from center A, while the external validation set consisted of 70 patients from center B, center C, and center D. The traditional radiomics model was contrasted using radiomics features. The radiomics features of each pixel within the tumor region of interest (ROI) were extracted. The optimal division of tumor subregions was determined using the K-means unsupervised clustering method. The internal tumor heterogeneity habitat model was developed using the habitats features from each tumor sub-region. The LR algorithm was employed in this study to construct a machine learning prediction model. The diagnostic performance of the model was evaluated using criteria such as area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). Results: In the training cohort, the traditional radiomics model achieved an AUC of 0.778 [95% confidence interval (CI): 0.688-0.868], while the tumor internal heterogeneity habitat model achieved an AUC of 0.861 (95% CI: 0.789-0.932). The tumor internal heterogeneity habitat model exhibits a higher AUC value. It demonstrates an accuracy of 0.815, surpassing the accuracy of 0.685 achieved by traditional radiomics models. In the external validation cohort, the AUC values of the two models were 0.723 (CI: 0.591-0.855) and 0.781 (95% CI: 0.673-0.889), respectively. The habitat model continues to exhibit higher AUC values. In terms of accuracy evaluation, the tumor heterogeneity habitat model outperforms the traditional radiomics model, achieving a score of 0.743 compared to 0.686. Conclusion: The quantitative analysis of intratumoral heterogeneity using CT to predict pCR in NSCLC patients undergoing NAIC holds the potential to inform clinical decision-making for resectable NSCLC patients, prevent overtreatment, and enable personalized and precise cancer management.

Comparison of commercial atlas-based automatic segmentation software for prostate radiotherapy treatment planning.

This study aims to assess the accuracy of automatic atlas-based contours for various key anatomical structures in prostate radiotherapy treatment planning. The evaluated structures include the bladder, rectum, prostate, seminal vesicles, femoral heads and penile bulb. CT images from 20 patients who underwent intensity-modulated radiotherapy were randomly chosen to create an atlas library. Atlas contours of the seven anatomical structures were generated using four software packages: ABAS, Eclipse, MIM, and RayStation. These contours were then compared to manual delineations performed by oncologists, which served as the ground truth. Evaluation metrics such as dice similarity coefficient (DSC), mean distance to agreement (MDA), and volume ratio (VR) were calculated to assess the accuracy of the contours. Additionally, the time taken by each software to generate the atlas contour was recorded. The mean DSC values for the bladder exhibited strong agreement (>0.8) with manual delineations for all software except for Eclipse and RayStation. Similarly, the femoral heads showed significant similarity between the atlas contours and ground truth across all software, with mean DSC values exceeding 0.9 and MDA values close to zero. On the other hand, the penile bulb displayed only moderate agreement with the ground truth, with mean DSC values ranging from 0.5 to 0.7 for all software. A similar trend was observed in the prostate atlas contours, except for MIM, which achieved a mean DSC of over 0.8. For the rectum, both ABAS and MIM atlases demonstrated strong agreement with the ground truth, resulting in mean DSC values of more than 0.8. Overall, MIM and ABAS outperformed Eclipse and RayStation in both DSC and MDA. These results indicate that the atlas-based segmentation employed in this study produces acceptable contours for the anatomical structures of interest in prostate radiotherapy treatment planning.

An advanced nomogram model using deep learning radiomics and clinical data for predicting occult lymph node metastasis in lung adenocarcinoma.

PURPOSE: To evaluate the effectiveness of deep learning radiomics nomogram in distinguishing the occult lymph node metastasis (OLNM) status in clinical stage IA lung adenocarcinoma. METHODS: A cohort of 473 cases of lung adenocarcinomas from two hospitals was included, with 404 cases allocated to the training cohort and 69 cases to the testing cohort. Clinical characteristics and semantic features were collected, and radiomics features were extracted from the computed tomography (CT) images. Additionally, deep transfer learning (DTL) features were generated using RseNet50. Predictive models were developed using the logistic regression (LR) machine learning algorithm. Moreover, gene analysis was conducted on RNA sequencing data from 14 patients to explore the underlying biological basis of deep learning radiomics scores. RESULT: The training and testing cohorts achieved AUC values of 0.826 and 0.775 for the clinical model, 0.865 and 0.801 for the radiomics model, 0.927 and 0.885 for the DTL-radiomics model, and 0.928 and 0.898 for the nomogram model. The nomogram model demonstrated superiority over the clinical model. The decision curve analysis (DCA) revealed a net benefit in predicting OLNM for all models. The investigation into the biological basis of deep learning radiomics scores identified an association between high scores and pathways related to tumor proliferation and immune cell infiltration in the microenvironment. CONCLUSIONS: The nomogram model, incorporating clinical-semantic features, radiomics, and DTL features, exhibited promising performance in predicting OLNM. It has the potential to provide valuable information for non-invasive lymph node staging and individualized therapeutic approaches.

Association of remnant cholesterol with decreased kidney function or albuminuria: a population-based study in the U.S.

BACKGROUND: Dyslipidemia is frequently exhibited in individuals with chronic kidney disease (CKD). Remnant cholesterol (RC), an emerging novel lipid marker, plays an elusive role in CKD progression. This study sought to investigate the association of RC with decreased kidney function or albuminuria in the general population of U.S. METHOD: Data were retrieved from the continuous 2001 to 2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Individuals aged between 18 and 70 years were included. RC was divided into quartiles. Albuminuria was defined by albumin-to-creatinine ratio (ACR) ≥30 mg/g, while reduced kidney function was described as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2. Using a multivariable regression model, the association of RC with decreased eGFR or albuminuria was examined. The dose‒response relationship between RC and eGFR or ACR was also investigated using a restricted cubic spline (RCS) model. RESULTS: A total of 1551 (10.98%) participants with impaired renal function or albuminuria were identified. After multivariate adjustment, RC was not significantly associated with kidney function decline or albuminuria (odds ratio (OR) 1.24, 95% confidence interval (95% CI): 0.95, 1.61). However, a significantly inverse correlation was observed between RC and eGFR in a dose‒response manner (ß -2.12, 95% CI: -3.04, -1.21). This association remained consistent when stratifying data by gender, age, race, hypertension, diabetes and body mass index (BMI). CONCLUSION: A higher RC was significantly correlated with a lower eGFR in the general population. The role of RC in predicting kidney outcomes needed further investigation in prospective studies.

Development and Validation of a Deep Learning Radiomics Model to Predict High-Risk Pathologic Pulmonary Nodules Using Preoperative Computed Tomography.

RATIONALE AND OBJECTIVES: To accurately identify the high-risk pathological factors of pulmonary nodules, our study constructed a model combined with clinical features, radiomics features, and deep transfer learning features to predict high-risk pathological pulmonary nodules. MATERIALS AND METHODS: The study cohort consisted of 469 cases of lung adenocarcinoma patients, divided into a training cohort (n = 400) and an external validation cohort (n = 69). We obtained computed tomography (CT) semantic features and clinical characteristics, as well as extracted radiomics and deep transfer learning (DTL) features from the CT images. Selected features were used for constructing prediction models using the logistic regression (LR) algorithm. The performance of the models was evaluated through metrics including the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, calibration curve, and decision curve analysis. RESULTS: The clinical model achieved an AUC of 0.774 (95% CI: 0.728-0.821) in the training cohort and 0.762 (95% confidence interval [CI]: 0.650-0.873) in the external validation cohort. The radiomics model demonstrated an AUC of 0.847 (95% CI: 0.810-0.884) in the training cohort and 0.800 (95% CI: 0.693-0.907) in the external validation cohort. The radiomics-DTL (Rad-DTL) model showed an AUC of 0.871 (95% CI: 0.838-0.905) in the training cohort and 0.806 (95% CI: 0.698-0.914) in the external validation cohort. The proposed combined model yielded AUC values of 0.872 and 0.814 in the training and external validation cohorts, respectively. The combined model demonstrated superiority over both the clinical model and the Rad-DTL model. There were no statistically significant differences observed in the comparison between the combined model incorporating clinical features and the Rad-DTL model. Decision curve analysis (DCA) indicated that the models provided a net benefit in predicting high-risk pathologic pulmonary nodules. CONCLUSION: Rad-DTL signature is a potential biomarker for predicting high-risk pathologic pulmonary nodules using preoperative CT, determining the appropriate surgical strategy, and guiding the extent of resection.

Effects of hydroxy methionine zinc on growth performance, immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii).

This study aimed to evaluate the effects of varying zinc (Zn) levels on the growth performance, non-specific immune response, antioxidant capacity, and intestinal microbiota of red claw crayfish (Procambarus clarkii (P. clarkii)). Adopting hydroxy methionine zinc (Zn-MHA) as the Zn source, 180 healthy crayfish with an initial body mass of 6.50 ± 0.05 g were randomly divided into the following five groups: X1 (control group) and groups X2, X3, X4, and X5, which were fed the basal feed supplemented with Zn-MHA with 0, 15, 30, 60, and 90 mg kg-1, respectively. The results indicated that following the addition of various concentrations of Zn-MHA to the diet, the following was observed: Specific growth rate (SGR), weight gain rate (WGR), total protein (TP), total cholesterol (TC), the activities of alkaline phosphatase (AKP), phenoloxidase (PO), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT), the expression of CTL, GPX, and CuZn-SOD genes demonstrated a trend of rising and then declining-with a maximum value in group X4-which was significantly higher than that in group X1 (P < 0.05). Zn deposition in the intestine and hepatopancreas, the activity of GSH-PX, and the expression of GSH-PX were increased, exhibiting the highest value in group X5. The malonaldehyde (MDA) content was significantly reduced, with the lowest value in group X4, and the MDA content of the Zn-MHA addition groups were significantly lower than the control group (P < 0.05). In the analysis of the intestinal microbiota of P. clarkii, the number of operational taxonomic units in group X4 was the highest, and the richness and diversity indexes of groups X3 and X4 were significantly higher than those in group X1 (P < 0.05). Meanwhile, the dietary addition of Zn-MHA decreased and increased the relative abundance of Proteobacteria and Tenericutes, respectively. These findings indicate that supplementation of dietary Zn-MHA at an optimum dose of 60 mg kg-1 may effectively improve growth performance, immune response, antioxidant capacity, and intestinal microbiota richness and species diversity in crayfish.

Caffeic acid phenethyl ester suppresses EGFR/FAK/Akt signaling, migration, and tumor growth of prostate cancer cells.

BACKGROUND: Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa. PURPOSE: We examined if caffeic acid phenethyl ester (CAPE) simultaneously suppresses the EGFR and Akt signaling, migration and tumor growth in PCa cells. METHODS: Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells. Western blot, immunoprecipitation, and immunohistochemistry staining were performed to determine the effects of CAPE on EGFR and Akt signaling. RESULTS: CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells. CAPE treatment inhibited the EGF-induced migration of PCa cells. Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells. Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts. CONCLUSIONS: Our study suggested that CAPE can simultaneously suppress the EGFR and Akt signaling in PCa cells and is a potential therapeutic agent for advanced PCa.

A Radiomics Study: Classification of Breast Lesions by Textural Features from Mammography Images.

This study investigates the feasibility of using texture radiomics features extracted from mammography images to distinguish between benign and malignant breast lesions and to classify benign lesions into different categories and determine the best machine learning (ML) model to perform the tasks. Six hundred and twenty-two breast lesions from 200 retrospective patient data were segmented and analysed. Three hundred fifty radiomics features were extracted using the Standardized Environment for Radiomics Analysis (SERA) library, one of the radiomics implementations endorsed by the Image Biomarker Standardisation Initiative (IBSI). The radiomics features and selected patient characteristics were used to train selected machine learning models to classify the breast lesions. A fivefold cross-validation was used to evaluate the performance of the ML models and the top 10 most important features were identified. The random forest (RF) ensemble gave the highest accuracy (89.3%) and positive predictive value (66%) and likelihood ratio of 13.5 in categorising benign and malignant lesions. For the classification of benign lesions, the RF model again gave the highest likelihood ratio of 3.4 compared to the other models. Morphological and textural radiomics features were identified as the top 10 most important features from the random forest models. Patient age was also identified as one of the significant features in the RF model. We concluded that machine learning models trained against texture-based radiomics features and patient features give reasonable performance in differentiating benign versus malignant breast lesions. Our study also demonstrated that the radiomics-based machine learning models were able to emulate the visual assessment of mammography lesions, typically used by radiologists, leading to a better understanding of how the machine learning model arrive at their decision.

Review of Magnetic Resonance Imaging and Post-processing for the Brain Tumor-related Epilepsy Study.

20% of brain tumor patients present with seizures at the onset of diagnosis, while a further 25-40% develop epileptic seizures as the tumor progresses. Tumor-related epilepsy (TRE) is a condition in which the tumor causes recurring, unprovoked seizures. The occurrence of TRE differs between patients, along with the effectiveness of treatment methods. Therefore, determining the tumor properties that correlate with epilepsy can help guide TRE treatment. This article reviews the MRI sequences and image post-processing algorithms in the study of TRE. It focuses on epilepsy caused by glioma tumors because it is the most common type of malignant brain tumor and it has a high prevalence of epilepsy. In correlational TRE studies, conventional MRI sequences and diffusion-weighted MRI (DWI) are used to extract variables related to the tumor radiological characteristics, called imaging factors. Image post-processing is used to correlate the imaging factors with the incidence of epilepsy. The earlier studies of TRE used univariate and multivariate analysis to study the correlations between specific variables and incidence of epilepsy. Later, studies used voxel-based morphometry and voxel lesion-symptom mapping. Radiomics has been recently used to post-process the images for the study of TRE. This article will discuss the limitation of the existing imaging modalities and post-processing algorithms. It ends with some suggestions and challenges for future TRE studies.

Influence of different factors on registration error in a 1.5 T MR-guided linac.

Purpose. Accurate image registration is an important step in online image-guided adaptive radiotherapy. The aim of this study was to investigate the effects of different factors on registration accuracy in a magnetic resonance (MR)-guided adaptive radiotherapy workflow.Materials and Methods. A thorax motion phantom was used to obtain computed tomography (CT) simulations in 8 different motion modes and to generate 8 reference plans. Daily pretreatment online MR images were obtained at 5 different positions in each reference plan. Online MR and CT simulations were separately registered using bone structures and the gross tumor volume (GTV) as ROIs, and the image shift distance was recorded by the online treatment planning system. The difference between the shift distance and the real isocentric distance was the registration error. The registration error was analyzed, and the effects of the setup position, motion mode and ROI selection on the registration error were investigated by multivariate analysis of variance.Result. The minimum values of registration error (ΔX, ΔY, ΔZ) were -1.90 mm, -2.70 mm and -2.40 mm, respectively, and the maximum values were 1.70 mm, 4.30 mm and -0.90 mm. ΔY showed the maximum mean standard deviation of 1.25 mm, and ΔZshowed the minimum mean standard deviation of 0.27 mm. The standard deviation of the registration error is largest in the inferior/superior direction. The motion mode of the phantom and ROI selection were significantly correlated with ΔX, ΔY, and ΔZ(p< 0.05).Conclusion. The registration result with the spine as the selected ROI was better than that with the GTV as the ROI. In 1.5 T MR-linac clinical treatment, more attention should be given to patient movement repeatability and to controlling the intrafractional motion as much as possible. It is not recommended to make the GTV-PTV margin expansion less than 2 mm for MR-linac.

Volumetric modulated arc therapy for hippocampal-sparing prophylactic cranial irradiation: Planning comparison of Halcyon and C-arm accelerators.

Background: The purpose of the study was to evaluate the dosimetry of the Halcyon in prophylactic cranial irradiation (PCI) with volumetric modulated arc therapy (VMAT) and hippocampal-sparing for small cell lung cancer (SCLC). Methods: Five VMAT plans were designed on CT images of 15 patients diagnosed with SCLC and received PCI. Three plans with two full arcs were generated on the Trilogy and the TrueBeam accelerators, and flattening filter (FF) and flattening filter free (FFF) modes were used on TrueBeam. Two Halcyon plans with two and three full arcs were generated, referred to as H-2A and H-3A, respectively. The prescription dose was 25 Gy in 2.5-Gy fractions. The dose limit for hippocampus were D100 ≤ 9Gy and Dmax ≤ 16Gy. The Wilcoxon matched-paired signed-rank test was used to evaluate the significance of the observed differences between the five plans. Results: H-2A plans significantly increased the D2 of PTV, and H-3A plans showed comparable or even better target dosimetry (better conformity) compared to the three plans on C-arm accelerators. Compared to T and TB plans, the two Halcyon plans significantly reduced the D100 and mean doses of bilateral hippocampus, the mean doses of eyeballs, and the maximum doses of lenses. D100 of hippocampus was reduced in TrueBeam plans comparing to Trilogy plans. The FFF plans on TrueBeam also represented advantages in Dmean and D100 of hippocampas, Dmean and Dmax of eyeballs, and the Dmax of lenses compared to FF plans. Halcyon plans and TrueBeam plans with FFF mode increased the MUs compared to FF plans. Comparing to H-2A, the H-3A plans exhibited additional dosimetric advantages, including D2, CI and HI of PTV, as well as the maximum and mean doses of hippocampus and eyeballs, and the maximum doses of optic nerves and brainstem. The two Halcyon plans significantly reduced the delivery time and showed the higher gamma passing rate than the three plans of C-arm accelerators. Conclusions: Compared with the C-arm accelerators, the dose of hippocampus and the delivery times on Halcyon are relatively significantly reduced for hippocampal-sparing PCI. Three arcs are recommended for VMAT plans with the Halcyon in hippocampal-sparing PCI.

Functional Anterior Temporal Lobectomy for Temporal Lobe Epilepsy: A Novel, Alternative, and Less Invasive Therapy.

BACKGROUND: Anterior temporal lobectomy is the most effective treatment for intractable temporal lobe epilepsy (TLE). However, patients are reluctant to choose this surgery for fear of risks after large frontotemporal craniotomy, and epileptologists likewise have a cautious attitude because of surgical trauma. Functional anterior temporal lobectomy (FATL) is a minimally invasive surgery procedure for addressing the above concerns. OBJECTIVE: To report preliminary data on this procedure and its safety and efficacy for treating TLE. METHODS: This consecutive case series study was conducted between October 2020 and September 2021. Patients with TLE underwent FATL by minicraniotomy with a diameter of 3 cm. Surgery duration, postoperative complications, and seizure control are described herein. Seizure outcomes were classified using Engel classifications. RESULTS: A total of 25 patients undergoing FATL for TLE were enrolled. The median epilepsy duration was 8 years. The median surgery duration was 165 min. The median blood loss was 100 mL. The median postoperative hospital stay was 8 days. No deaths occurred after surgery. Only 1 patient presented with a cerebrospinal fluid disorder that was successfully treated using a ventriculoperitoneal shunt. At the last follow-up, 23 patients (92%) were seizure-free (Engel-Ia), 1 patient remained substantially improved (Engel-II), and 1 patient obtained worthwhile seizure reduction (Engel-III). CONCLUSION: Our pilot study suggests that FATL is a viable surgical therapy for TLE. This method has the advantages of minimal invasiveness and high seizure-free rate. A controlled trial is warranted to verify the efficacy and safety of FATL comparing with anterior temporal lobectomy.

Human Umbilical Cord MSC Delivered-Soluble TRAIL Inhibits the Proliferation and Promotes Apoptosis of B-ALL Cell In Vitro and In Vivo.

The TNF-related apoptosis-inducing ligand (TRAIL) could induce apoptosis of leukemic cells, while showed no cytotoxic effect on normal cells. One of the limitations for application of recombinant TRAIL (rhTRAIL) in leukemia treatment is that the serum half-life of this protein is short. Gene delivery is a good strategy to prolong the half-life of TRAIL. In this study, we genetically engineered umbilical cord-MSCs to continuously express and secrete soluble TRAIL (MSC-sTRAIL), to investigate the effects of MSC-sTRAIL on B-cell acute lymphocytic leukemia (B-ALL) cells. In vitro, MSC-sTRAIL significantly inhibited the proliferation of B-ALL cells by suppressing PI3K/AKT and MEK/ERK signaling pathways, and induced apoptosis of B-ALL cells via the caspase cascade-mediated pathway and mitochondrial-mediated pathway. In vivo, MSC-sTRAIL dramatically inhibited B-ALL cell growth. Meanwhile, B-ALL-induced splenic and renal injuries were significantly alleviated after MSC-sTRAIL treatment. Moreover, the serum levels of MSC-secreted sTRAIL were still high in MSC-sTRAIL treated mice, indicating an extended half-life of sTRAIL. Our study suggests that MSC delivered-TRAIL secretion is a potential therapeutic strategy for B-ALL treatment.

Feasibility and safety of pedicled autologous bronchial flap reconstruction airway instead of sleeve lobectomy in partial lung cancer surgery.

Background: A sleeve lobectomy is a routine operation in thoracic surgery. However, sleeve lobectomy is not only a complex operation, but also has the risk of anastomotic leakage and stenosis. We used bronchial flap to reconstruct the airway instead of sleeve lobectomy. The above disadvantages can be avoided because the bronchial flap reconstruction airway has no anastomosis. This technique has not previously been reported. This paper discusses the feasibility and safety of reconstructing the bronchus with the pedicle autogenous bronchus flap in lung cancer surgery. Methods: During the operation, when the tumor tissue had invaded ≤1/3 of the circumference of the lobar bronchus, the bronchus wall was removed at least 5 mm away from the tumor, but the contralateral healthy bronchus wall was preserved. The healthy bronchial wall was made into a "tongue-shaped" pedicled autogenous bronchial flap, approximately the size of the bronchial defect, and the flap was turned up or down to repair the root defect of the bronchus. The patients were examined every 3 months after surgery by chest computed tomography (CT) to observe the re-expansion of lung and reconstruction of the bronchus, and analyze the incidence of bronchus stenosis and local recurrence. Results: The lobar bronchus was successfully reconstructed with the pedicled autologous bronchial flap in 45 patients; 36 males and 9 females with an average age of 56.5 years. The diameters of the tumors ranged from 3-12 cm. The pathological examination results showed that the margin of bronchus was negative. There was no perioperative death or bronchopleural fistula. The bronchoscopy showed that the reconstructed bronchus healed well, and no atelectasis or bronchostenosis was found in the follow-up period. Conclusions: This is the first report on the application of the pedicled autogenous bronchial flap being used to reconstruct the airway instead of a sleeve lobectomy in lung cancer surgery. In the radical resection of lung cancer, the operation can simplify the operation process, and reduce the risk of anastomotic leakage or stenosis. The operation is safe and feasible, and should be more widely used.

Study on the feasibility of quality improvement for automatic plans based on rapid plan model.

Objective: To study whether an interactive improved internal feedback system with the model can be established, we compared the plans generated by two automatic planning models. Methods: Seventy cases of pelvic patients were selected. Intensity-modulated radiation therapy (IMRT) plans (P0) generated by the clinical model (M0) were imported into the Rapid plan model to establish a dose-volume histogram. The predicted model through automatic planning model in clinical, and the new rapid plan model (M1) was generated by training and structure matching settings. The 70 new IMRT plans (P1) were generated by M1, and the new rapid plan model (M2) was trained by P1. In this same method, 70 IMRT plans (P2) were generated by M2. Dosimetric differences between P1 and P2 were then compared and analyzed. Results: For the model parameters, R2 and X2 in P2 were higher than those in P1, and the CD values of the bladder, right femoral head, and rectum in P1 were higher than those of corresponding organs in P2. The studentized residual (SR) value of the bladder and SR and difference of estimate values of the left femoral head and right femoral head in P1 were lower than P2. In planning, (D2, D98, and HI) P1 were better than P2 (P < 0.01); the bladder V10 and left femoral head V40 in P2 were lower than in P1 by 0.08% and 0.15%, respectively (P < 0.05); others in P2 were higher than those in P1 (P < 0.05) except the bladder V20, Dmean, rectum V10, V20, V30, right femoral head V10, and V40; and the MUs of P2 was lower than that of P1 for 132.2 (P < 0.05). Conclusion: The stability of M2 is stronger than that of M1. Therefore, the interactive improved internal feedback system within the model of "plan-model-plan-model" is feasible and meaningful.

CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction.

Recent studies showed that Ceramide Kinase-Like Protein (CERKL)was expressed in the nerve cells and could regulate autophagy. Sirtuin-1 (SIRT1) is the regulator of the mitophagy, which can be stabilized by CERKL. Furthermore, the study also revealed that the SIRT1 induced mitophagy by activating PINK1/Parkin signaling. Therefore, we speculated that CERKL has potential to activate the SIRT1/PINK1/Parkin pathway to induce mitophagy. In this study, cerebral ischemia reperfusion mouse model was established. CERKL was overexpressed in those mice and human neuroblastoma cells. Tunel staining and flow cytometry were applied for the detection of cell apoptosis. The ratios of LC3Ⅱ to LC3Ⅰ and the expression of LC3Ⅱ in mitochondria were determined by gel electrophoresis. Overexpression of CERKL alleviated the cerebral ischemia reperfusion injury and damage to OGD/R human neuroblastoma cells. Overexpression of CERKL enhanced the expression of LC3 Ⅱ in mitochondria and induced occurrence of mitophagy. Overexpression of CERKL promoted the stability of SIRT1 and facilitated the expression of PINK1 and Parkin in those cells. Knockdown of PINK1 impeded the mitophagy and suppressed the expression of LC3 Ⅱ in mitochondria. It can be concluded that CERKL alleviated the ischemia reperfusion induced nervous system injury through inducing mitophagy in a SIRT1/PINK1/Parkin dependent pathway.

Overview of heavy metal pollution and health risk assessment of urban soils in Yangtze River Economic Belt, China.

Using national multi-purpose regional geochemical survey (NMPRGS) data, this overview systematically summarizes the pollution levels and health risks posed by 8 heavy metals (As, Cd, Pb, Zn, Hg, Cu, Cr and Ni) in urban soils of 86 cities above the prefecture level in Yangtze River Economic Belt (YREB). Meanwhile, the spatial distribution and main sources of heavy metal pollutants in urban soils of key cities are described in detail. On a regional scale, Hg and Cd contamination in urban soils of YREB is most prominent, and As, Cu, Pb and Zn contamination exists in several cities, while Cr and Ni contamination is almost not shown. The type of industrialization and the history of urbanization affect the soil heavy metal pollution in majority cities, and the influence of geological background on the content of heavy metals in urban soils cannot be ignored. Specifically, the urban pollution of Cd, As, Pb and Zn is mainly concentrated in Hunan and Hubei Provinces, which are highly developed in mining industry, especially in Zhuzhou, Chenzhou, Huangshi and Xiangtan cities, while the major soil Hg pollution occurs in Zhejiang and Jiangsu Provinces with rapid economic development, where Shaoxing, Ningbo, Suzhou and Wuxi are the key polluted cities. Heavy metals in the urban soils investigated generally posed low non-carcinogenic and carcinogenic risks to the adults. However, the non-carcinogenic risk to minors in some cities (e.g., Chenzhou and Huangshi) should be given cautious attention.

Factors affecting outcomes in patients with cardiac arrest who receive target temperature management: The multi-center TIMECARD registry.

BACKGROUND: Target temperature management (TTM) is a recommended therapy for patients after cardiac arrest (PCA). The TaIwan Network of Targeted Temperature ManagEment for CARDiac Arrest (TIMECARD) registry was established for PCA who receive TTM therapy in Taiwan. We aim to determine the variables that may affect neurologic outcomes in PCA who undergo TTM. METHODS: We retrieved demographic variables, resuscitation variables, and cerebral performance category (CPC) scale score at hospital discharge from the TIMECARD registry. The primary outcome was a favorable neurologic outcome, defined as a CPC scale of 1 or 2 at discharge. A total of 540 PCA treated between January 2014 and September 2019 were identified from the registry. Univariate and multivariate analyses were performed to identify significant variables. RESULTS: The mortality rate was 58.1% (314/540). Favorable neurologic outcomes were noted in 117 patients (21.7%). The factors significantly influencing the neurologic outcome (p < 0.05) were the presence of an initial shockable rhythm or pulseless electric activity, a witnessed cardiac-arrest event, bystander cardiopulmonary resuscitation, a smaller total dose of epinephrine, the diastolic blood pressure value at return of spontaneous circulation, a pre-arrest CPC score of 1, coronary angiography, new-onset seizure, and new-onset serious infection. Older patients and those with premorbid diabetes mellitus, chronic kidney disease, malignancy, obstructive lung disease, or cerebrovascular accident were more likely to have an unfavorable neurologic outcome. CONCLUSION: In the TIMECARD registry, some PCA baseline characteristics, cardiac arrest events, cardiopulmonary resuscitation characteristics, and post-arrest management characteristics were significantly associated with neurologic outcomes.

Dosimetry study of nasopharyngeal carcinoma based on Halcyon accelerator fixed-field intensity-modulated radiation therapy.

OBJECTIVE: Halcyon accelerator applies the flattening filter (FF)-free mode instead of the lead gate and FF treatment mode for traditional C-type accelerators. We aimed at comparing and analyzing the quality and delivery of nasopharyngeal carcinoma (NPC) plans between Halcyon and VitalBeam (VB) accelerators in fixed-field intensity-modulated radiation therapy (IMRT). METHODS: The IMRT plans for thirty patients with NPC who had received radiotherapy were optimized using the VB (Plan VB) and Halcyon (Plan H) accelerators. Quality assurance verification was then conducted. The dose coverage of the planning target volume (PTV) and organs at risk (OARs), monitor units (MUs), and delivery time were analyzed for each plan. RESULTS: All PTV and OAR indexes of Plan H and Plan VB met the clinical requirements. In the exposure dose of bilateral optic nerves between Plan H and Plan VB, no difference was found. The maximum dose of the lens, brainstem, spinal cord were 1.13 Gy, 1.36 Gy, 1.35 Gy, 2.82 Gy lower than the plan using VB , and the mean dose of the parotid glands were 3.82 Gy, 5.56 Gy lower than the plan using VB respectively, and an insignificant difference was found in the brainstem (P > 0.05). The MU for Plan H (22.92 ± 1.58 Gy) was higher than that for Plan VB (19.69 ± 4.52 Gy), and the difference was significant (P < 0.05). CONCLUSIONS: The treatment plans designed by Halcyon can meet clinical requirements with better protection for OARs and show advantages over VB in the dosimetry of NPC IMRT plans.

The Prognostic Value of Bone Morphogenetic Proteins and Their Receptors in Lung Adenocarcinoma.

BACKGROUND: Bone morphogenetic proteins (BMPs) regulate tumor progression via binding to their receptors (BMPRs). However, the expression and clinical significance of BMPs/BMPRs in lung adenocarcinoma remain unclear due to a lack of systematic studies. METHODS: This study screened differentially expressed BMPs/BMPRs (deBMPs/BMPRs) in a training dataset combining TCGA-LUAD and GTEx-LUNG and verified them in four GEO datasets. Their prognostic value was evaluated via univariate and multivariate Cox regression analyses. LASSO was performed to construct an initial risk model. Subsequently, after weighted gene co-expression network analysis (WGCNA), differential expression analysis, and univariate Cox regression analysis, hub genes co-expressed with differentially expressed BMPs/BMPRs were filtered out to improve the risk model and explore potential mechanisms. The improved risk model was re-established via LASSO combining hub genes with differentially expressed BMPs/BMPRs as the core. In the testing cohort including 93 lung adenocarcinoma patients, immunohistochemistry (IHC) was performed to verify BMP5 protein expression and its association with prognosis. RESULTS: BMP2, BMP5, BMP6, GDF10, and ACVRL1 were verified as downregulated in lung adenocarcinoma. Survival analysis identified BMP5 as an independent protective prognostic factor. We also found that BMP5 was significantly correlated with EGFR expression and mutations, suggesting that BMP5 may play a role in targeted therapy. The initial risk model containing only BMP5 showed a significant correlation (HR: 1.71, 95% CI: 1.28-2.28, p: 3e-04) but low prognostic accuracy (AUC of 1-year survival: 0.6, 3-year survival: 0.6, 5-year survival: 0.63). Seventy-nine hub genes co-expressed with BMP5 were identified, and their functions were enriched in cell migration and tumor metastasis. The re-established risk model showed greater prognostic correlation (HR: 2.58, 95% CI: 1.92-3.46, p: 0) and value (AUC of 1-year survival: 0.72, 3-year survival: 0.69, and 5-year survival: 0.68). IHC results revealed that BMP5 protein was also downregulated in lung adenocarcinoma and higher expression was markedly associated with better prognosis (HR: 0.44, 95% CI: 0.23-0.85, p: 0.0145). CONCLUSION: BMP5 is a potential crucial target for lung adenocarcinoma treatment based on significant differential expression and superior prognostic value.