Search

To determine the associations of intravoxel incoherent motion (IVIM) parameters with expression of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), and evaluate the performance of the combined model established based on IVIM and clinicopathological parameters in predicting PD-L1and PD-1 status of cervical cancer (CC) patients. Seventy-eight consecutive CC patients were enrolled prospectively and underwent magnetic resonance imaging (MRI) including IVIM. IVIM quantitative parameters were measured, compared, and correlated with PD-L1 and PD-1 expression. Independent factors related to PD-L1 and PD-1 positivity were identified and were used to establish the combined model. The combined model's diagnostic performance was evaluated using the receiver operating characteristic (ROC) analysis. The Shapley additive explanation (SHAP) algorithm was used to explain the contribution of each parameter in the combined model. The real diffusion coefficient (D) value was significantly lower in the PD-L1-positive group than in the PD-L1-negative group (0.64 ± 0.12 versus 0.72 ± 0.11, p= 0.021). The PD-1-positive and PD-1-negative groups showed similar trends (0.63 ± 0.13 versus 0.73 ± 0.09, p= 0.003). Parametrial invasion, lymph node status, pathological grade, FIGO (International Federation of Gynecology and Obstetrics) staging, and D values were independently associated with PD-L1 and PD-1expression. A combined model incorporating these parameters showed good discrimination with the sensitivity, specificity of 90.9%, 82.6% for PD-L1, and 93.5%, 72% for PD-1. According to the SHAP value, FIGO staging and pathological grade were the most influential features of the prediction model. IVIM parameters were found to correlate with PD-L1 and PD-1 expression. The combined model, incorporating parametrial invasion, lymph node status, pathological grade, FIGO staging, and D values, showed good discrimination in predicting PD-L1 and PD-1 status, providing the basis for CC immunotherapy. • D value is negatively correlated with PD-L1 and PD-1 expression. • The combined model has the best discrimination providing a basis for immunotherapy. • According to SHAP analysis, FIGO staging and pathological grade are major features. [ABSTRACT FROM AUTHOR]

This study investigated auto-ignition characteristics of ammonia-air and ammonia-hydrogen-air laminar and turbulent mixing layers by means of direct numerical simulations (DNS) under elevated pressure conditions. The results show that elevated pressure and hydrogen addition accelerate the auto-ignition process, reducing the auto-ignition delay time. Analysis of the heat release rate revealed that the first peak of the heat release rate corresponds to the increment of appearance in temperature (induction stage) and the second peak of the heat release rate corresponds to the steady maximum temperature regime (thermal runaway stage). The results found that both induction and thermal runaway stages are affected by turbulence for pure ammonia-air mixing layers, while only the thermal runaway stage is affected by turbulence for ammonia-hydrogen-air mixing layers. The auto-ignition occurs along the most reactive mixture fraction with lower scalar dissipation rate, being further reduced by elevated pressure and hydrogen addition. Three radicals (NH 2, OH, HNO) distinguish the entire auto-ignition process very well for all cases. • DNS study of auto-ignition in ammonia and ammonia-hydrogen combustion. • Elevated pressure and hydrogen addition accelerate the auto-ignition process. • Induction and thermal runaway stages are identified. • The radicals NH 2, OH, HNO distinguish the entire auto-ignition process. [ABSTRACT FROM AUTHOR]

The combustion characteristics of ammonia and ammonia-hydrogen fuel blends under spark-ignited turbulent premixed engine-relevant conditions were investigated by means of direct numerical simulation and detailed chemistry. Several test cases were investigated for an outwardly expanding turbulent premixed flame configuration covering pure ammonia and ammonia-hydrogen fuel blends with 10% and 15% hydrogen content by volume for different equivalence ratio values of 0.9, 1.0 and 1.1. The results showed that the fuel-lean flames exhibit strong wrinkled structures at flame front compared to stoichiometric and fuel-rich flames. The heat release rate plots indicate that adding hydrogen into ammonia improves the reactivity of the flame and enhances the combustion process. The scatter plots of heat release rate versus local curvature coloured by NO formation, show that high heat release rate values occur in the concave structures and low heat release rate values occur in the convex structure, which is consistent with NO distribution. The highest turbulent burning velocity values were found for the fuel-lean cases due to more wrinkled flame front with lower effective Lewis number compared to fuel-rich cases. The results show a bending effect for the ratio between turbulent to laminar burning velocities with respect to hydrogen addition at all equivalence ratios with 10% hydrogen addition into ammonia exhibiting a highest value for the burning velocity ratio. Two distinct flame structures (concave and convex) were analysed in terms of local equivalence ratio based on the elements of N and O as well as H and O. They revealed an opposite distribution of NO formation normal to the flame front within concave and convex structures. Elementary chemical reactions involved in NO formation have shown that hydrogen addition into ammonia influences the reactivity of certain specific chemical reactions. [Display omitted] • Study of premixed ammonia and ammonia-hydrogen combustion at elevated pressures. • Adding hydrogen into ammonia improves the reactivity of the flame. • 10% hydrogen addition by volume into ammonia provides better flame conditions. • NO formation is analysed. [ABSTRACT FROM AUTHOR]

The combustion characteristics of ammonia and ammonia-hydrogen fuel blends under spark-ignited turbulent premixed engine-relevant conditions were investigated by means of direct numerical simulation and detailed chemistry. Several test cases were investigated for an outwardly expanding turbulent premixed flame configuration covering pure ammonia and ammonia-hydrogen fuel blends with 10% and 15% hydrogen content by volume for different equivalence ratio values of 0.9, 1.0 and 1.1. The results showed that the fuel-lean flames exhibit strong wrinkled structures at flame front compared to stoichiometric and fuel-rich flames. The heat release rate plots indicate that adding hydrogen into ammonia improves the reactivity of the flame and enhances the combustion process. The scatter plots of heat release rate versus local curvature coloured by NO formation, show that high heat release rate values occur in the concave structures and low heat release rate values occur in the convex structure, which is consistent with NO distribution. The highest turbulent burning velocity values were found for the fuel-lean cases due to more wrinkled flame front with lower effective Lewis number compared to fuel-rich cases. The results show a bending effect for the ratio between turbulent to laminar burning velocities with respect to hydrogen addition at all equivalence ratios with 10% hydrogen addition into ammonia exhibiting a highest value for the burning velocity ratio. Two distinct flame structures (concave and convex) were analysed in terms of local equivalence ratio based on the elements of N and O as well as H and O. They revealed an opposite distribution of NO formation normal to the flame front within concave and convex structures. Elementary chemical reactions involved in NO formation have shown that hydrogen addition into ammonia influences the reactivity of certain specific chemical reactions. [Display omitted] • Study of premixed ammonia and ammonia-hydrogen combustion at elevated pressures. • Adding hydrogen into ammonia improves the reactivity of the flame. • 10% hydrogen addition by volume into ammonia provides better flame conditions. • NO formation is analysed. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of concomitant chemoradiotherapy with nab-paclitaxel and cisplatin in patients with locally advanced non-small cell lung cancer (NSCLC). This study (NCT04284215) is a prospective, phase II, randomized controlled study, and the patients are enrolled in a ratio of 1:1 in the study with patients treat-naïve locally advanced stage III non-small cell lung cancer.in comparison with paclitaxel plus cisplatin, the regimen of nab-paclitaxel plus cisplatin was use in the treatment of DT:69 Gy/46f.Nab-paclitaxel 40mg/m2/week (4-6 weeks in total) and cisplatin 75mg/m2 for 2 cycles. Control arm: paclitaxel 175mg/m2 d1, cisplatin 75mg/m2 for 2 cycles. The primary endpoints are ORR and treatment-induced toxicity of concurrent chemoradiotherapy, and the secondary endpoints are PFS and OS. A total of 68 patients (1:1) were randomized from March 3, 2019 to August 23, 2021.Sixty-five patients received concomitant chemoradiotherapy according to the study protocol, including 32 patients in the nab-paclitaxel group and 33 patients in the paclitaxel group. There was no significant difference in ORR between the two groups (84.4% vs. 73.7%, p = 0.411).There was no difference in median PFS between the two groups (14 months (95% CI 14.60-22.93) vs. 12 months (95% CI 13.15-22.74), P = 0.521).The incidence of grade III-IV leukopenia and neutropenia, fatigue, nausea, vomiting and other toxic and adverse reactions in the nab-paclitaxel group were significantly lower than those in the paclitaxel group (P<0.006, P<0.000, 0.016, 0.021, 0.019) Compared with paclitaxel plus cisplatin regimen, the combination of nab-paclitaxel plus cisplatin regimen has no significant difference in ORR and PFS, but significantly reduces the incidence of grade III-IV granulocytopenia and gastrointestinal reactions. [ABSTRACT FROM AUTHOR]

To investigate the magnetic resonance imaging (MRI) features and explore the value of MRI in the diagnosis of central nervous system leukaemia (CNSL). A retrospective study was performed in 68 patients with leukaemia who underwent cranial MRI between January 2020 and June 2022 at Institute of Hematology and Blood Diseases Hospital. A total of 33 patients fulfilled the requirements for inclusion. The findings showed that 87.9% patients exhibited neurological symptoms, and 23 patients showed abnormal MRI findings. No differences were observed between the MRI+ and MRI− groups in terms of age, sex, neurological symptoms, glucose in the cerebrospinal fluid (CSF), chloride in the CSF, abnormal cells detected using conventional cytology (CC), bone marrow status at the diagnosis of CNSL, signal intensity ratio, and mortality, except for protein concentration and the number of leukaemic cells detected using flow cytometry (FCM) in the CSF. Kaplan–Meier survival analysis in patients with leukaemia revealed no statistical differences in the median survival times between the MRI+ group and MRI− group. Cox regression analysis and multivariate analysis showed no significant difference in survival rate between the MRI+ and MRI− groups. Kappa consistency test shows weak diagnostic consistency between MRI and CC, and weak diagnostic inconsistency between MRI and FCM. MRI could serve as an important complementary tool to CC and FCM in the diagnosis of CNSL, especially in patients without leptomeningeal involvement. • CNSL of leptomeninges involved presented as hyperintensity on T2 FLAIR imaging. • MRI plays a key role in the diagnosis of CNSL with non-leptomeninges involved. • MRI complements the deficiency of CC and FCM in the diagnosis of CNSL. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences (ACEs) are linked to negative pregnancy outcomes. However, little is known about the prevalence of ACEs and their relationship to mental and health outcomes among pregnant Palestine refugee women. This was a cross-sectional study. Data were collected from 772 pregnant Palestine refugee women with a median (interquartile range) age of 27 (23, 32) years, attending five antenatal clinics in Jordan between February and June 2021. The modified 33-item ACE International Questionnaire was used to assess eight domains of ACEs: (1) marriage and family, (2) relationship with parents, (3) neglect, (4) household dysfunction/domestic violence, (5) abuse, (6) peer violence, (7) community violence, and (8) collective violence. Multivariate logistic regression was used to examine the association between ACEs and mental and health outcomes. The ethical approval was obtained from United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) Research Review Board in May 2020. Eighty-eight percent of women experienced at least one type of ACE, and 26% of women experienced ≥4 types of ACEs. Compared with women with 0–3 types of ACE exposure, those with ≥4 types of ACEs had 1.58 (95% confidence interval [CI] 1.10–2.28) times higher prevalence of obesity before pregnancy, 3.28 (95% CI 1.79–6.03) times higher prevalence of depression during pregnancy, and 2.01 (95% CI 1.39–2.91) times higher prevalence of ever been smoking cigarettes or hookah. Exposure to ACEs is prevalent among pregnant Palestine refugee women. Exposure to multiple types of ACEs was associated with obesity, mental health conditions, and smoking. [ABSTRACT FROM AUTHOR]

To quantitatively characterize tumor biomechanical rigidity via ventilation-induced tumor deformation (VITD) and assess its prognostic values. This study utilized 10-bin 4D-CT and PET scans for 16 lung cancer patients (7 squamous cell carcinoma (SCC) and 9 adenocarcinoma (AC)). First, tumor surface models were generated based on binary segmentation for 10 respiratory phases and regionally aligned using surface-based registration. The resultant shape descriptors () across respiration phases were assembled as an intra-subject VITD. Subsequently, tumor strain was approximate as the magnitude of the averaged shape changes (VITD mag) between end-of-exhale (EOE) and end-of-inhale (EOI) phases in the relevant regions - areas showing significant morphological correlations with the respective lung volume trajectory. Afterward, para-tumor stress (PTS) was approximated as the averaged displacements in the dilated para-tumor region, by deforming EOE to EOI 4D-CTs. Finally, VITD rigi was calculated as PTS over VITD mag. To assess the prognostic value of the VITD model, VITD mag and VITD rigi were correlated with PET-derived SUV max for AC and SCC tumors, respectively. On lung SCC tumors, VITD mag , the extent of maximal shape changes in respiration, was negatively associated with SUV max, indictive of elevated tumor metabolism (r= -0.88, p= 0.01). After controlling for PTS, an increase in the derived tumor rigidity (VITD rigi) was found to be significantly associated with increased SUV max , with r= 0.76 and p= 0.04. In contrast, on AC tumors, featuring surfactant overproduction and thus complex tissue composition, neither VITD mag nor VITD rigi presented a significant association with SUV max (p = 0.98 and 0.88). We introduced a novel noninvasive pipeline to characterize lung tumor rigidity based on VITD in 4D-CT. The derived VITD rigi in lung SCC significantly correlated with tumor metabolism, indicating tumor aggressiveness. The proposed VITD model provides new biomechanical evidence in lung SCC prognosis. For AC tumors with complex tissue composition, deeper radiographic profiling besides tumor deformation is needed to effectively characterize its biomechanical properties. [ABSTRACT FROM AUTHOR]

To enhance the prediction of mutation status of isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter, which are crucial for glioma prognostication and therapeutic decision-making, via sub-regional radiomics analysis based on multiparametric magnetic resonance imaging (MRI). A retrospective study was conducted on 401 participants with adult-type diffuse gliomas. Employing the K-means algorithm, tumours were clustered into two to four subregions. Sub-regional radiomics features were extracted and selected using the Mann–Whitney U -test, Pearson correlation analysis, and least absolute shrinkage and selection operator, forming the basis for predictive models. The performance of model combinations of different sub-regional features and classifiers (including logistic regression, support vector machines, K-nearest neighbour, light gradient boosting machine, and multilayer perceptron) was evaluated using an external test set. The models demonstrated high predictive performance, with area under the receiver operating characteristic curve (AUC) values ranging from 0.918 to 0.994 in the training set for IDH mutation prediction and from 0.758 to 0.939 for TERT promoter mutation prediction. In the external test sets, the two-cluster radiomics features and the logistic regression model yielded the highest prediction for IDH mutation, resulting in an AUC of 0.905. Additionally, the most effective predictive performance with an AUC of 0.803 was achieved using the four-cluster radiomics features and the support vector machine model, specifically for TERT promoter mutation prediction. The present study underscores the potential of sub-regional radiomics analysis in predicting IDH and TERT promoter mutations in glioma patients. These models have the capacity to refine preoperative glioma diagnosis and contribute to personalised therapeutic interventions for patients. • Sub-regional MRI radiomics predicts IDH and TERT mutations in gliomas. • Various model combinations of sub-regional features and classifiers were assessed. • LR and SVM outperformed in predicting IDH and TERT mutations, respectively. • Enhanced models support precision in glioma therapeutic decisions. [ABSTRACT FROM AUTHOR]

This study aimed to assess the shifting patterns of the mediastinum, including the target volume and the isocenter point during the postoperative radiotherapy (PORT) process of non-small cell lung cancer (NSCLC), and to observe the occurrence of radiation injury. Additionally, we investigated the significance of mid-term assessment during the implementation of the PORT process. We established coordinate axes based on bone anatomy and measured the mediastinum's three-dimensional direction and the shift of the isocenter point's shift in the PORT process. Statistical analysis was performed using Wilcoxon, Kruskal-Wallis, and the Chi-square test. P < 0.05 was considered statistically significant. In this study, the analysis of patients revealed that the shift of anterior and posterior mediastinum (X), left and right mediastinum (Y), upper and lower mediastinum (Z), anterior and posterior isocenter point (X i), and the left and right isocenter points (Y i) in the PORT process were 0.04–0.53, 0.00–0.84, 0.00–1.27, 0.01–0.86, and 0.00–0.66 cm, respectively. The shift distance of the mediastinum was Z > Y > X, and the shift distance of the isocenter point was X i > Y i. According to the ROC curve, the cut-off values were 0.263, 0.352, 0.405, 0.238, and 0.258, respectively, which were more significant than the cut-off values in 25 cases (25%), 30 cases (30%), 30 cases (30%), 17 cases (17%), and 15 cases (15%). In addition, there was a significant difference in the shift of the mediastinum and the isocenter point (all P = 0.00). Kruskal-Wallis test showed no statistically significant difference between mediastinal shift and resection site in X, Y, and Z directions (P = 0.355, P = 0.239, P = 0.256), surgical method (P = 0.241, P = 0.110, P = 0.064). There was no significant difference in the incidence of RE and RP in PORT patients (P > 0.05). No III–IV RP occurred. However, the incidence of ≥ grade III RE in the modified plan cases after M-S was significantly lower than in the original PORT patients, 0% and 7%, respectively (P = 0.000). In conclusion, this study provides evidence that mediastinal shift is a potential complication during the PORT process for patients with N2 stage or R1–2 resection following radical resection of NSCLC. This shift affects about 20–30% of patients, manifesting as actual radiation damage to normal tissue and reducing the local control rate. Therefore, mid-term repositioning of the PORT and revision of the target volume and radiation therapy plan can aid in maintaining QA and QC during the treatment of NSCLC patients and may result in improved patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To assess the safety and tolerability of neoadjuvant radiotherapy combined with toripalimab for locally advanced, resectable esophageal squamous cell cancer (ESCC).Materials/methods: A total of 22 patients with newly diagnosed locally advanced, resectable ESCC (clinical stage: T3-4N0M0/T1-4N+M0, according to the 8th AJCC stage system) were enrolled. Patients received neoadjuvant radiotherapy (NRT) with 41.4 Gy in 23 fractions by intensity modulated radiotherapy (IMRT) combined with 4 cycles (240mg, Q3W) of toripalimab. Surgery was performed within 7-8 weeks after completion of NRT. The primary endpoints are treatment-related adverse events (TRAEs). The second endpoints are pathological complete response (pCR) and objective response rate (ORR). ORR was evaluated after NRT according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.Results: A total of 22 patients were enrolled between October 2019 to December 2020. 17 patients were male and 5 patients were female. The median age was 60 years (range, 48 to 70 years). 9 patients were in stage II and 13 patients were in stage III. All patients finished NRT as planned, 3 (13.6%) patients discontinued toripalimab treatment, one for progressive disease after 3 cycles of toripalimab, one for treatment-related AEs after 2 cycles and one for patient wishes after 2 cycles. 2 (9.1%) patients achieved complete response, 13 (59.1%) patients achieved partial response of which 1 patient had liver metastasis after 4 cycles of toripalimab, 6 (27.3%) patients remained stable disease, and 1 (4.5%) patient had progression disease. ORR was 68.2% (15/22), and disease control rate (DCR) was 95.5% (21/22). As of Feb. 26, 2021, 14 (63.6%) patients had received radical surgery, among them 7 (50.0%) experienced pCR of primary tumor and lymph nodes, 8 (57.1%) presented primary tumor pCR, and 9 (64.3%) had a major pathological response (MPR), 2 (9.1%) patients did not undergo surgery for progressive disease (1 patient of left supraclavicular lymph node metastasis and 1 patient of liver metastasis), and the remaining 6 patients still awaits radical surgery as scheduled. 15 (68.2%) patients experienced TRAEs. The common TRAEs were mild (grade 1 or 2) including leukopenia (n = 9), radiation esophagitis (n = 8) and aspartate transaminase (AST) elevation (n = 5), pruritus (n = 2), alanine transaminase (ALT) elevation (n = 1) and pneumonitis (n = 1). Only 1 (4.5%) patient developed grade 3 myocarditis, grade 3 AST elevation and grade 3 ALT elevation 2 weeks after NRT, improved after treatment with methylprednisolone, and is currently waiting for radical surgery.Conclusion: The trial showed that NRT plus toripalimab demonstrated a manageable safety profile and encouraging therapeutic effect in patients with locally advanced, resectable ESCC, which warrants additional investigations in larger cohorts. The trial was registered in Chictr.org.cn ((Registration Number: ChiCTR1900022282). [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To evaluate the efficiency and safety of Nab-paclitaxel plus cisplatin and concomitant thoracic radiotherapy in locally advanced non-small-cell lung cancer.Materials/methods: A total of 68 cases locally advanced NSCLC patients were enrolled in this study, and 38 cases were enrolled so far (1:1 in the experimental group and the control group, 19 cases in each group, 1 case in each group did not complete the treatment, a total of 36 cases were available for statistical analysis). The control group received paclitaxel combined with cisplatin regimen chemotherapy (paclitaxel 175mg/m2 on day 1, cisplatin 75mg/m2 on day 2; every 3-4 weeks for 2 consecutive cycles. Experimental group: nab-paclitaxel weekly at a dose of 40mg/m2, Cisplatin 75mg/m2 and repeated every 3-4 weeks for 2 consecutive cycles. Both groups received concomitant aggressive radical three-dimensional thoracic radiotherapy with continuously accelerated hyperfractionation. The primary endpoint was ORR and safety (including treatment-induced bone marrow suppression, the toxicity of liver and kidney function, cardiotoxicity, radiation pneumonia, and other toxic side effects). Secondary endpoints were local progression-free survival rate, the local recurrence rate of the primary tumor, and the local control rate of the primary tumor.Results: 38 patients completed concomitant chemoradiotherapy. The effective rates ORR of experimental group and control group were 89.6% and 68.5%, respectively. The short-term efficacy was CR (0 cases 0%, 1 case 5.2%), PR (17 cases 89.6%, 12 cases 63.3%), SD (1 case 5.2%, 5 cases 26.3%), PD (1 case 5.2%, 1 case 5.2%) P = 0.001. Grade 3/4 leukopenia 2 (10.5%), 14 (73.7%), P = 0.001; grade 3/4 neutropenia 2 (10.5%), 14 (73.7%), P = 0.001; grade 3/4 anemia 1 (5.3%) and 2 (10.5%), P = 0.547; grade 3/4 thrombocytopenia 0(0%) and 2 (10.5%) of, P = 0.146. There were 11 (57.9%) and 6 (31.6%) of grade I radiation esophagitis, and 8 (42.1%) and 13 (68.4%) of grade II esophagitis respectively. No grade III-IV esophagitis was found.Conclusion: The ORR and short-term efficiency of nab-paclitaxel plus cisplatin concomitant radiotherapy are better than the control group, and the hematological toxicity is lower than the control group. [ABSTRACT FROM AUTHOR]

This study assessed the association between adverse childhood experiences (ACEs) and clustering of high-risk behaviors in a sample of high school students. This was a cross-sectional study. A sample of students who attended randomly selected classes in 99 high schools completed the 2019 Nevada Youth Risk Behavior Survey (N = 4959). The survey included six ACE measures: (1) physical abuse, (2) sexual abuse, (3) verbal abuse, (4) household physical abuse, (5) household mental illness, and (6) household substance abuse. Students were assigned a cumulative ACE score (range = 0–6). A count of high-risk behavior domains was created using multiple questions across the following domains: (1) violence behaviors, (2) suicidal indicators, (3) non-suicidal self-injury, (4) substance use, (5) high-risk sexual behaviors, (6) poor diet, (7) physical inactivity, and (8) high screen time (range = 0–8). The relationship between ACEs and the count of high-risk behavior domains was assessed using weighted negative binomial regression; incidence rate ratios (IRRs) were calculated adjusting for sociodemographic characteristics. More than 40% of the sampled students reported high-risk behaviors across two or more domains. There was a strong, graded relationship between cumulative ACE score and the count of high-risk behavior domains. Compared with students who experienced zero ACEs, there was an increase in the count of high-risk behavior domains among students who experienced one ACE (adjusted IRR [aIRR] = 1.22, 95% confidence interval [CI] = 1.12–1.33), two ACEs (aIRR = 1.57, 95% CI = 1.42–1.73), three ACEs (aIRR = 1.73, 95% CI = 1.54–1.94), four ACEs (aIRR = 2.07, 95% CI = 1.84–2.33), five ACEs (aIRR = 2.69, 95% CI = 2.34–3.10), and six ACEs (aIRR = 2.91, 95% CI = 2.34–3.62). Trauma-informed prevention efforts may be an efficient way to address multiple adolescent risk behaviors that cluster. [ABSTRACT FROM AUTHOR]

Environmental scientists frequently rely on time series of explanatory variables to explain their impact on an important response variable. However, sometimes, researchers are less interested in raw observations of an explanatory variable than in derived indices induced by episodes embedded in its time series. Often these episodes are intermittent, occur within a specific limited memory, persist for varying durations, at varying levels of intensity, and overlap important periods with respect to the response variable. We develop a generic, parametrised, family of weighted indices extracted from an environmental signal called IMPIT indices. To facilitate their construction and calibration, we develop a user-friendly app in Shiny R referred to as IMPIT − a. We construct examples of IMPIT indices extracted from the Southern Oscillation Index and sea surface temperature signals. We illustrate their applications to two fished species in Queensland waters (i.e., snapper and saucer scallop) and wheat yield in New South Wales. • We developed indices from an environmental signal containing intermittent episodes. • The indices carry episode intensity, memory, persistence, intermittence and timing. • We illustrated indices' effectiveness and applications in fisheries and agriculture. • We developed IMPIT − a , an app to expedite index construction and calibration. • We expect IMPIT indices to be a useful addition to exploratory data analysis toolbox. [ABSTRACT FROM AUTHOR]

Thermodynamic modelling is an effective approach to accelerate the development of novel materials such as V-based alloys. In the present work, the results of thermodynamic modelling of the ternary system V–Ti–B using the "CALculation of PHAse Diagrams" (CALPHAD) method are presented. The thermodynamic descriptions of the binary systems V–Ti, V–B, and Ti–B are based on available publications whereas thermodynamic parameters for the ternary system stem from the iterative approximation to the experimental investigations, which further serve for verifying the calculated phase diagram. Thus, eight different alloys in the compositional range of 10–40 at.% Ti and B were analyzed aiming at identifying the evolving phases. A set of thermodynamic parameters is proposed. The calculated isothermal phase diagram at 1673 K exhibits a high degree of agreement with the literature and experimental observations. In our further work, the thermodynamic data generated in this study will be useful to develop the quaternary V–Ti–Si–B system. [ABSTRACT FROM AUTHOR]

[Display omitted] • MD-ReaxFF and experiments were utilised to study the flame retardant(FR) mechanisms. • The pyrolysis hindrance offered by the FRs is elucidated by increasing C/H ratio. • FR chemistries such as dehydration, radical capture and charring were characterised. • Novel removal techniques were employed to predict char residue of HDPE and HDPE/FR. Localised flame-retardant (FR) chemistry of polymer composites is complex, versatile and microscopic depending on the combination of polymer matrix and various FR systems. Particularly, the pyrolysis behaviour of the polymers can be varied and reinforced by effective microscopic synergistic effects between coating compositions. However, these atomistic reactions can be difficult to be characterised via experimental approaches. In this study, experimental studies and reactive molecular dynamic (ReaxFF-MD) simulation techniques were utilised to identify the thermal degradation behaviour of flame retarded high-density polyethylene (HDPE), coated with phosphoric acid (PA) and pentaerythritol (PER). The simulations tracked the pyrolysis product distribution under different heating temperatures and elucidated the pyrolysis hindrance offered by the FR system. The atomistic reaction pathways of phosphorus-based FR mechanism were also characterised, including secondary reactions and intermediate species, such as P-O-C and P-O-P cross-linking between FRs and radical capturing effects. These reactions were found to be increasing the C/H ratios of pyrolysed hydrocarbons and the aromaticity of residues. After applying the periodic removal techniques, the simulations can even predict the residue weight percentage of the polymer and exhibit similar degradation behaviour to the experimental results. [ABSTRACT FROM AUTHOR]

To address the urgent environmental challenges of transportation related air pollution and energy shortage, hybrid electric vehicles (HEV) and battery electric vehicles (BEV) with potential for higher energy efficiency are gaining in popularity and gradually replacing those conventional vehicles. Extended range electric vehicle (EREV) is a subset of these new energy vehicles aiming to gain benefits of both HEVs and BEVs and provide a solution to reducing tailpipe emissions whilst providing satisfactory driving-range compared with tradition internal combustion engine (ICE) vehicle counterparts. This paper systematically introduces the current developments of EREV in terms of the powertrain structure, energy management and vehicle performance, while the two key focus areas of auxiliary power unit (APU) charging control and (hybrid) energy storage system ((H)ESS) power management. A case analysis on a typical EREV is presented to study the application potential. Comprehensive comparisons of popular APU control strategies and different energy storage dispositions are shared, several existing issues are also discussed in this paper. Furthermore, a general manufacturing cost analysis for different types of vehicles is presented, and the outlook of EREV for future research is presented. • A review and assessment of extended-range electric vehicle powertrain is done. • An evaluation of state-of-the-art energy management strategies is presented. • A case analysis on a typical EREV is conducted to study its thorough potential. • An investigation of general manufacturing cost for different hybrid vehicles is made. • Outlook and recommendations for extended-range electric vehicle is provided. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis has been reported as a common complication of severe COVID-19, especially in patients who have undergone ARDS or mechanical ventilation treatment. As innate lymphocytes, NK cells play important roles in antiviral immunity and inhibit the progression of organ fibrosis. The exploration of key NK populations will clarify their role in the progression of COVID-19 and provide crucial cues for the treatment of post-COVID pulmonary fibrosis. Single-cell transcriptome data from bronchoalveolar lavage fluid (BALF) of COVID-19 patients and healthy donors were analyzed on normalized expression matrices of all cells screened. After annotation according to the marker genes, NK cells were extracted for further clustering and subsequent analyses of gene expression profiling, gene set enrichment, and molecular interaction. Reduced-dimensional clustering showed that NK cells in BALF were divided into 10 subpopulations. Compared with healthy persons, NK cells in the lungs of COVID-19 patients showed higher activated features and up-regulation of IFN-related genes. However, the GZMs+PRF1+ subpopulation was only 30% of the total NK cells and highly expressed apoptotic genes of Bax and BCL2L11 in severe patients, which may lead to insufficiency and poor cytotoxicity. In severe patients, AREG+ subpopulation was enriched in the lungs and decreased the expression of TNFSF10, FasL, and CCR2, which indicated under-recruitment and impaired antifibrosis function. Our data showed that NK cells decreased in BALF of severe COVID-19 patients, especially the effector/cytotoxic NK subset very significantly decreased. The impaired activity of antifibrotic NK cells may be associated with collagen deposition and senescent cell accumulation in the lungs with severe SARS-COV-2 infection. Improving the antiviral function and antifibrosis ability may be valid measures to prevent severe COVID-19 and reduce fibrosis complications. [ABSTRACT FROM AUTHOR]

Nearly all glioblastoma multiforme (GBM) patients experience local recurrence despite aggressive therapies. The outcomes of patients with recurrence continue to be disappointing, emphasizing the importance of early and voxel-wise recurrence prediction for early treatment intervention. Emerging evidence has linked the tumorigenesis of recurrence to stem cell niches (SCN). For the first time, our group introduced a novel multidimensional support vector machine (SVM) method coupling with SCN proximity estimation to predict GBM recurrence on the voxel level. The current study aims to develop an L1-sparsity regularized attention fusion U-net (L1-AF U-net) to further distinguish the most salient and complementary features from multi-modal MR images, improving voxel-wise GBM recurrence prediction. With IRB approval, fifty patients with pre-and post-surgery MR scans were retrospectively solicited, including T1, T2, T1_CE, ADC, and FLAIR. Post-surgery MR scans included two months before the clinical diagnosis of GBM recurrence and the day of the radiologically confirmed recurrence. The recurrences were manually annotated on the contrast-enhanced T1 MR, which were deformably registered to the 2-month pre-recurrence MR scans. The processing pipeline included a sparse attention learning module with L1 norm regularization for multi-modal feature fusion and a U-net for voxel-wise GBM recurrence prediction. The L1 sparsity regularized attention network embedded in the U-net architecture learns the coherent and mutual-complementary features across five MR modalities while eliminating the inherent redundancy and noisy artifacts. The high-risk recurrence (HRR) proximity map was determined by the weighted sum of inverse distances from two possible origins of recurrence: SCN and tumor cavity. The U-net was trained given the discriminative feature fusion in HRR for voxel-wise GBM recurrence prediction On the 2-month pre-recurrence testing MRs, the U-net segmentation with sparse multi-modal attention fusion achieved a recall of 0.83±0.15, a precision of 0.75±0.12, and an F1-score of 0.79±0.14. As a comparison, our previous GBM recurrence prediction using proximity estimation coupled SVM (SVM PE) achieved a recall of 0.80±0.10, a precision of 0.69±0.14, and an F1-score of 0.74±0.10. A Student's t-test has also been performed to evaluate the significance of the proposed method over SVM PE. The P-values are 0.0013 (for recall), 4.97 × 10−10 (for precision) and 7.94 × 10−8 (for F1-score), respectively. We present an advanced U-net-based GBM recurrence prediction framework with sparse multi-modal MR fusion. This constrained attention fusion of the multi-modal MR images facilitated the U-net to learn more effective features from the multi-modal MR images and enhanced the prediction performance comparing to SVM method. [ABSTRACT FROM AUTHOR]

The microstructural and mechanical property changes induced by 6 MeV titanium ion irradiation are comparatively investigated between a refractory medium-entropy alloy VTaTi and elemental metal V. Compared with V, the aggregation of irradiation induced defect clusters in VTaTi is strongly suppressed, as evidenced by the much smaller defect size. Moreover, the loops in VTaTi are dominantly <100>-type, in contrast to those in elemental metal V being mainly 1/2<111>-type. Furthermore, nanoindentation tests show that the irradiation hardening in VTaTi is significantly weaker than V, further demonstrating its improved irradiation resistance. [Display omitted] [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI), an inevitable acute lung injury during lung transplantation (LTx), contributes to the development of severe complications and limits the success of LTx. Metformin exerts beneficial actions to alleviate acute lung injury induced by a diversity of factors. However, the effect of metformin on IRI has not yet been elucidated in LTx. In this study, we conducted an animal experiment to investigate the effects of metformin on IRI and explore the possible therapeutic mechanism. LTx was performed on five groups of rats: sham operation (SM), ischemia-reperfusion (IR), metformin-IR (MI), metformin-anisomycin (MAPK activator)-IR (MAI), metformin-phorbol 12-myristate 13-acetate (PMA, NETosis activator)-IR (MPI). In MI, MAI, and MPI groups, metformin (400 mg/kg) was administered by gavage 72h, 48h, 24h, and 30min before cold ischemia. Anisomycin (15 mg/kg) and PMA (3 ug/kg) were intraperitoneally injected 30min before cold ischemia in MAI and MPI groups, respectively. Each group (n = 5) received a cold ischemic time of 1.5h followed by LTx except the SM group (n = 5). After reperfusion for two hours, recipient rats were sacrificed for further examination of arterial blood gas analysis, histopathology examination, and lung wet-to-dry weight (W/D) ratio. Compared to the IR group, the MI group showed significantly better PaO 2 /FiO 2 ratio and SaO 2 , lower W/D ratio, perivascular cuff area/vessel area (P/V) ratio, lung injury score, and red blood cell (RBC) infiltration (all P < 0.05). After the administration of MAPK signaling pathway and NETosis activators, significant deterioration was found in the MAI group with higher lung injury score, RBC infiltration, and W/D ratio (all P < 0.05) and the MPI group with lower SaO 2 and higher lung injury score and P/V ratio (all P < 0.05) (Figure 1). Metformin attenuates IRI and may be attributed to inhibition of MAPK signaling pathway and NETosis in rat LTx. [ABSTRACT FROM AUTHOR]

To compare an auto-segmentation model for defining high-risk clinical target volumes (HR-CTVs) for tandem-and-ovoid (T&O) brachytherapy to intra- and inter-operator volumes. Pre-implant T2-weighted MRI and post-implant CT images for 65 (48 for training, 8 for validation, and 9 for testing) patients who underwent T&O brachytherapy for FIGO IB-IIIC cervical cancer were included. The post-implant CT was aligned to the MRI using rigid registration and HR-CTVs were manually contoured or reviewed by a fellowship trained radiation oncologist (FRO) on both the CT and MRI. A dual-path 3D asymmetric convolutional neural network (CNN) architecture was built to extract CT (entire CT volume) and MRI features (masked HR-CTV MR volume), and was optimized with an asymmetric weighting of 18:6 for CT:MRI. Voxel-based dice similarity coefficients (DSC V) were used to evaluate the model performance and cross-validation was performed to assess model stability. The study cohort was divided into a small (< 20 cc), medium (20-40 cc), and large (> 40 cc) tumor group based on the HR-CTV CT for further model evaluation. To determine intra-operator variability, 10 patients were randomly selected from each of the volume groups and contours from the first two fractions of treatment were reviewed. For inter-operator variability, four patients were randomly selected from each of the volume groups and were independently contoured by two additional radiation oncologists (RO1 and RO2). DSC V were analyzed between the intra-operator contours, inter-operator contours (RO1 vs FRO and RO2 vs FRO), and auto-segmentation contours (auto-segmentation vs FRO). The dual-path asymmetric auto-segmentation model yielded a favorable contouring result with a mean DSC V (auto-segmentation vs. FRO) of 0.76 ± 0.06. This result was numerically superior to inter-operator uncertainties for RO1 vs FRO (DSC inter =0.68 ± 0.11) and RO2 vs FRO (DSC inter =0.69 ± 0.07), as well as the mean intra-operator agreement of FRO (DSC intra =0.74 ± 0.07). However, the differences were statistically insignificant with p values of 0.14, 0.08, 0.72, respectively. DSC V of volumetric subgroups of small, medium, and large tumors are shown in Table 1. An asymmetric dual-path CNN model utilizing pre-implant MRI (masked by HR-CTV MR) and post-implant CT images was successfully developed for auto-segmentation of HR-CTV CT for tandem-and-ovoid brachytherapy patients with a similar DSC V compared to intra-operator and inter-operator contours. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The grade of meningioma has significant implications on the selection of treatment regimens ranging from observation to surgical resection with adjuvant radiation. For most patients, meningiomas are diagnosed radiologically and grade is not determined unless a surgical procedure is completed. We hypothesize that the use of a 3D convolutional neural network (CNN) architecture with two encoding paths will provide auto-classification of grade I and II meningioma using T1-contrast enhancing (T1-CE) and T2-Fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images.Materials/methods: Ninety-six consecutive treatment naïve patients with pre-operative T1-CE and T2-FLAIR MR images from 2010 to 2019 were evaluated. The patients underwent surgical resection resulting in a diagnosis of grade I or II meningioma. Histopathology was confirmed by a neuropathologist and neuropathology fellow based on current classification guidelines described in the 2016 World Health Organization (WHO) Bluebook. The delineation of meningiomas was completed on both T1-CE and T2-FLAIR MR with the inclusion of surrounding T2-FLAIR hyperintensity. A novel asymmetric 3D CNN architecture was constructed with two encoding paths based on T1-CE and T2-FLAIR MR. Each path used the same 3 × 3 × 3 kernel with different filters to weight the spatial features of each sequence separately. Final model performance was assessed by 10-fold cross-validation.Results: Of the 96 patients, 55 (57%) were pathologically classified as grade I and 41 (43%) as grade II meningiomas. Optimization of our model led to a filter weighting of 18:2 between the T1-CE and T2-FLAIR MR image paths with alternative weighting shown in Table 1. Eighty-six (90%) patients were classified correctly and 10 (10%) were misclassified based on their pre-operative MRs with a model sensitivity of 0.85 and specificity of 0.93. Among the misclassified, 4 were grade I, and 6 were grade II. The model was robust to tumor locations and sizes.Conclusion: A novel asymmetric CNN with two differently weighted encoding paths was developed for successful automated meningioma grade classification. Our model outperforms CNN using a single path for single or multimodal MR-based classification. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The role of radiotherapy, in addition to chemotherapy, has not been thoroughly determined in metastatic non-small cell lung cancer (mNSCLC). The purpose of the study was to investigate clinical characterization and treatment-related parameter of long-term survival in mNSCLC patients treated with concurrent chemotherapy with thoracic radiation therapy. In our previous study, the count of CD4-positive and CD8-positive T cells was associated with overall survival (OS). We speculated that baseline lung immune prognostic index (LIPI) based on pretreatment neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level may be associated with OS. Thus, the prognostic value of LIPI level was also evaluated in this study.Materials/methods: We retrospectively analyzed 243 eligible patients with mNSCLC who were treated with chemotherapy and concurrent radiation to the primary tumor in two prospective studies. These patients had received at least two chemotherapy cycles and a thoracic radiation dose of at least 40 Gy in 2-Gy fractions, and did not receive targeted therapy or immunotherapy during lifetime. According to previous publications, dNLR greater than 3 and LDH greater than upper limit of normal was developed, characterizing 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 factors). Prognostic factors for OS were identified by using univariate and multivariate analysis. Propensity-score matching (PSM) were performed to further adjust for confounding. OS≥ 18 months was defined as long-term survival (LTS).Results: According to LIPI, 141 patients were classified into good group, 83 patients in intermediate, and 19 patients in poor group. The number of patients was small in poor group. Thus, intermediate group and poor group were merged into the same risk group (intermediate-poor group). A total of 78 patients with long-term survival, 57 (40.4%) patients in good group, and 21 (20.6%) patients in intermediate-poor group. Univariate analysis showed that KPS score, T status, number of metastatic organs, brain metastasis, bone metastasis, radiation dose, and number of chemotherapy cycles, and LIPI were significant difference between LTS and non-LTS. Multivariate analysis showed that good LIPI and radiation dose (≥60 Gy) independently predicted long-term survival (P = 0.006, P = 0.012). After PSM, good LIPI remained to be correlated with long-term survival; the median survival time for good and intermediate-poor group were 13.7 months (95% CI, 11.37 - 16.02) and 11.0 months (95% CI, 9.52 - 12.48); the 1-, 2-, and 3-year OS rates were 59.8%, 21.2%, and 15.5% versus 41.5%, 10.2%, and 7.0% (χ2 = 5.603, P = 0.018).Conclusion: For mNSCLC patients treated with chemotherapy in combination with thoracic radiation, LTS patients had good LIPI and receiving higher radiation dose to primary tumor. LIPI might be useful for identifying a subgroup that may benefit from thoracic radiotherapy with concurrent chemotherapy. [ABSTRACT FROM AUTHOR]

Refractory high entropy alloys have gained increasing research attention on their irradiation response for the potential applications in nuclear engineering. Considering the metastable nature of their single-phase solid solution structures, the phase stability under irradiation, especially at elevated temperatures, should be a critical concern during the long-term service. In the present study, a typical refractory high entropy alloy with a single-phase body-centered cubic (BCC) structure, HfNbZrTi, is irradiated with 1.5 MeV He ions under 700 °C to various fluences from 5 × 1015 to 1 × 1017 cm−2. Significant irradiation-enhanced precipitation with Hf and Zr enrichment is observed. Although most extended precipitates with tens of nanometers in size are with a hexagonal close-packed (HCP) structure, different structures, including HCP, face-centered cubic (FCC), and the close-packed structures containing highly mixed stacking sequences, are observed in the small precipitates with a few nanometers in size formed at the early-stage precipitation process, suggesting various precipitation paths. By carefully examining the interfaces between the matrix and precipitates, the precipitation mechanism is discussed with similar but slightly different orientation relationships from the Burgers path. Such irradiation-enhanced precipitation process has a strong impact on the cavity formation in this alloy. The cavities are dominantly formed through the heterogeneous nucleation and growth mechanisms, accompanied by the precipitation process. The cavities with low densities but large sizes are observed to be highly clustered with the precipitates. These findings not only unveil the detailed precipitation behavior in a model refractory high entropy alloy under irradiation, but also highlight the critical role that the phase stability plays on the irradiation damage of this novel alloy system. [ABSTRACT FROM AUTHOR]

In order to investigate the compositional effects on helium bubble formation in the refractory concentrated solid-solution alloys with single-phase body-centered cubic structures, TiVNbTa and TiVTa alloys, as well as a conventional V-alloy are irradiated with 1.5 MeV He ions to the fluences of 2 × 1016 and 1 × 1017 ion/cm2 at 700 °C. Under the same irradiation fluence, the average sizes of helium bubbles in TiVNbTa and V-alloy are similar, but the bubbles in TiVTa are much larger. Moreover, while the bubbles in TiVNbTa and V-alloy are uniformly distributed at both fluences, bubble clusters are observed in the TiVTa sample irradiated to the higher fluence. Both faceted and spherical bubbles are observed in all the three alloys, but the edges of the faceted bubbles have different preferential orientations: mostly <110> in TiVTa, mostly <100> in V-alloy, and co-appearance in TiVNbTa. Radiation induced segregation becomes more significant with increasing irradiation fluence; V-enrichment as well as Ti-, Nb-, and Ta-depletion around He bubbles is observed in TiVNbTa under the high fluence irradiation, while the segregation in the other two alloys is much less considerable. [ABSTRACT FROM AUTHOR]

• The self-ion irradiation response of CoCrFeNi and (CoCrFeNi) 94 Ti 2 Al 4 alloys is investigated. • The loop size and unfaulting process are suppressed with nanoprecipitates. • High precipitate stability is observed in this high-entropy alloy under irradiation. • Unusual segregation at loops is observed of Ni elements in (CoCrFeNi) 94 Ti 2 Al 4. In order to investigate the impact of coherent nanoprecipitates on the irradiation-induced microstructural change in high-entropy alloys and the stability of nanoprecipitates under irradiation, the single-phase CoCrFeNi and the coherent nanoprecipitate-containing (CoCrFeNi) 94 Ti 2 Al 4 alloys were irradiated with 2.7 MeV Fe ions at 823 K. With the introduction of L1 2 coherent nanoprecipitates, the size of irradiation-induced dislocation loops is significantly reduced and the unfaulting of faulted loops is delayed. Unlike that both Ni and Co are segregated towards the loops in CoCrFeNi, the enrichment of Ni at loops is suppressed in (CoCrFeNi) 94 Ti 2 Al 4 with the co-existence of nanoprecipitates. Furthermore, although minor coarsening and dissolution of nanoprecipitates are observed after irradiation, the stability is enhanced compared with some conventional Ni-based alloys. [Display omitted] [ABSTRACT FROM AUTHOR]