Colletotrichum fructicola co-opts cytotoxic ribonucleases that antagonize host competitive microorganisms to promote infection.

Phytopathogens secrete numerous molecules into the environment to establish a microbial niche and facilitate host infection. The phytopathogenic fungus Colletotrichum fructicola, which causes pear anthracnose, can colonize different plant tissues like leaves and fruits, which are occupied by a diversity of microbes. We speculate that this fungus produces antimicrobial effectors to outcompete host-associated competitive microorganisms. Herein, we identified two secreted ribonucleases, CfRibo1 and CfRibo2, from the C. fructicola secretome. The two ribonucleases both possess ribonuclease activity and showed cytotoxicity in Nicotianan benthamiana without triggering immunity in an enzymatic activity-dependent manner. CfRibo1 and CfRibo2 recombinant proteins exhibited toxicity against Escherichia coli, Saccharomyces cerevisiae, and, importantly, the phyllosphere microorganisms isolated from the pear host. Among these isolated microbial strains, Bacillus altitudinis is a pathogenic bacterium causing pear soft rot. Strikingly, CfRibo1 and CfRibo2 were found to directly antagonize B. altitudinis to facilitate C. fructicola infection. More importantly, CfRibo1 and CfRibo2 functioned as essential virulence factors of C. fructicola in the presence of host-associated microorganisms. Further analysis revealed these two ribonucleases are widely distributed in fungi and are undergoing purifying selection. Our results provide the first evidence of antimicrobial effectors in Colletotrichum fungi and extend the functional diversity of fungal ribonucleases in plant-pest-environment interactions. IMPORTANCE: Colletotrichum fructicola is emerging as a devastating pathogenic fungus causing anthracnose in various crops in agriculture, and understanding how this fungus establishes successful infection is of great significance for anthracnose disease management. Fungi are known to produce secreted effectors as weapons to promote virulence. Considerable progress has been made in elucidating how effectors manipulate plant immunity; however, their importance in modulating environmental microbes is frequently neglected. The present study identified two secreted ribonucleases, CfRibo1 and CfRibo2, as antimicrobial effectors of C. fructicola. These two proteins both possess toxicity to pear phyllosphere microorganisms, and they efficiently antagonize competitive microbes to facilitate the infection of pear hosts. This study represents the first evidence of antimicrobial effectors in Colletotrichum fungi, and we consider that CfRibo1 and CfRibo2 could be targeted for anthracnose disease management in diverse crops in the future.

A multimodal approach integrating cognitive and motor demands into physical activity for optimal mental health: Methodological issues and future directions.

Physical activity is known for its positive effects on cognition and affect, with existing literature suggesting that these mental health benefits may be optimally experienced by incorporating cognitive and motor demands during physical activity (PA). However, the existing body of literature lacks a comprehensive guideline for designing the qualitative characteristics of a PA program. Accordingly, this narrative review aimed to (1) provide a working two-dimension model that operationally defines the cognitive and motor demands involved in PA and the rationale for systematically studying these qualitative aspects of PA, (2) identify methods to assess the cognitive and motor demands of PA and address associated methodological issues, and (3) offer potential future directions for research on the cognitive and motor aspects of PA in support of the development of PA programs designed to maximize PA-induced cognitive and affective benefits. We anticipate this article to inform the need for future research and development on this topic, aiming to create clear, evidence-based guidelines for designing innovative and effective PA interventions.

Electrophysiological differences in inhibitory control processing between collegiate level soccer players and non-athletes in the absence of performance differences.

Inhibitory control, the ability to manage conflicting responses and suppress inappropriate actions, is crucial for team sports athletes, including soccer players. While previous studies have shown that soccer players possess superior inhibitory control, the underlying mechanisms responsible for this advantage remain unclear. Thus, this research aimed to investigate the neural processes involved in conflict resolution and response inhibition, comparing collegiate level soccer players with non-athletes. Participants completed a novel go/no-go task that involved conflict resolution and response inhibition, while their electroencephalograms were recorded. Despite no significant difference in behavioral performance between the two groups, soccer players exhibited notable N2 and frontal midline theta modulations in response to conflict resolution and inhibition, which were comparatively weaker in non-athletes. Our findings suggest that expertise in team sports may enhance neural sensitivity to subtle yet significant information, even without a discernible behavioral advantage.

A multi-institutional meningioma MRI dataset for automated multi-sequence image segmentation.

Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

Extracellular perception of multiple novel core effectors from the broad host-range pear anthracnose pathogen Colletotrichum fructicola in the nonhost Nicotiana benthamiana.

Colletotrichum fructicola is emerging as a devastating pathogenic fungus causing anthracnose in a wide range of horticultural crops, particularly fruits. Exploitation of nonhost resistance (NHR) represents a robust strategy for plant disease management. Perception of core effectors from phytopathogens frequently leads to hypersensitive cell death and resistance in nonhost plants; however, such core effectors in C. fructicola and their signaling components in non-hosts remain elusive. Here, we found a virulent C. fructicola strain isolated from pear exhibits non-adaptation in the model plant Nicotiana benthamiana. Perception of secreted molecules from C. fructicola appears to be a dominant factor in NHR, and four novel core effectors-CfCE4, CfCE25, CfCE61, and CfCE66-detected by N. benthamiana were, accordingly, identified. These core effectors exhibit cell death-inducing activity in N. benthamiana and accumulate in the apoplast. With a series of CRISPR/Cas9-edited mutants or gene-silenced plants, we found the coreceptor BAK1 and helper NLRs including ADR1, NRG1, and NRCs mediate perceptions of these core effectors in N. benthamiana. Concurrently, multiple N. benthamiana genes encoding cell surface immune receptors and intracellular immune receptors were greatly induced by C. fructicola. This work represents the first characterization of the repertoire of C. fructicola core effectors responsible for NHR. Significantly, the novel core effectors and their signaling components unveiled in this study offered insights into a continuum of layered immunity during NHR and will be helpful for anthracnose disease management in diverse horticultural crops.

Impact of programmed cell death protein 1 inhibitor therapy on the survival of patients with advanced or recurrent uterine cancers: a meta-analysis.

Introduction: No prior meta-analysis has investigated the impact of programmed cell death protein 1 (PD-1) inhibitor therapy on survival outcomes in patients with advanced or recurrent uterine cancers (including both corpus and cervical cancers). Methods: A comprehensive search of PubMed and Embase databases was conducted, covering the past 10 years (up to August 2023) and encompassing all clinical research related to uterine cancer. Five randomized controlled trials and one cohort study met the inclusion criteria and were included in the meta-analysis. Data on patient demographics, clinical characteristics, treatment regimens, and survival outcomes were extracted. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as the relative risk of grade 3 or higher adverse events, were pooled using random-effects models. Results: Patients receiving PD-1 inhibitors had better OS (HR, 0.65, 95% CI, 0.59-0.72; P<.001) and PFS (HR, 0.59, 95% CI, 0.49-0.70; P<.001) than those receiving variable non-PD-1 inhibitor therapies among 3452 uterine cancer patients. The leave-one-out meta-analysis of the HR of OS showed no individual study impact on the estimation of the overall effect size. Subgroup analysis revealed better OS in the PD-1 inhibitors use than the controls in cervical cancer (HR, 0.68, 95% CI, 0.59-0.79), endometrial cancer (HR, 0.62, 95% CI, 0.54-0.72), and pembrolizumab use (HR, 0.66, 95% CI, 0.57-0.75) subgroups. Patients with advanced cervical cancer, who had CPS > 1, receiving PD-1 inhibitors have statistically significant benefits in OS compared to controls (HR, 0.65, 95% CI, 0.53-0.80). The pooled HR for overall survival was 0.71 (95% CI, 0.60-0.82; P<.001) in patients who received PD-1 inhibitors as compared to those who did not receive PD-1 inhibitors in proficient mismatch repair (MMR) endometrial cancer patients. However, in deficient MMR patients, the HR was 0.30 (95% CI, 0.13-0.70). The relative risk of grade 3 or higher adverse events was not higher in the PD-1 inhibitor group (relative risk, 1.12, 95% CI, 0.98-1.27). Conclusion: Survival was significantly better using PD-1 inhibitor therapy than variable non-PD-1 inhibitor chemotherapies among patients with advanced or recurrent uterine cancers.

Dose-Incorporated Deep Ensemble Learning for Improving Brain Metastasis Stereotactic Radiosurgery Outcome Prediction.

PURPOSE: To develop a novel deep ensemble learning model for accurate prediction of brain metastasis (BM) local control outcomes after stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A total of 114 brain metastases (BMs) from 82 patients were evaluated, including 26 BMs that developed biopsy-confirmed local failure post-SRS. The SRS spatial dose distribution (Dmap) of each BM was registered to the planning contrast-enhanced T1 (T1-CE) magnetic resonance imaging (MRI). Axial slices of the Dmap, T1-CE, and planning target volume (PTV) segmentation (PTVseg) intersecting the BM center were extracted within a fixed field of view determined by the 60% isodose volume in Dmap. A spherical projection was implemented to transform planar image content onto a spherical surface using multiple projection centers, and the resultant T1-CE/Dmap/PTVseg projections were stacked as a 3-channel variable. Four Visual Geometry Group (VGG-19) deep encoders were used in an ensemble design, with each submodel using a different spherical projection formula as input for BM outcome prediction. In each submodel, clinical features after positional encoding were fused with VGG-19 deep features to generate logit results. The ensemble's outcome was synthesized from the 4 submodel results via logistic regression. In total, 10 model versions with random validation sample assignments were trained to study model robustness. Performance was compared with (1) a single VGG-19 encoder, (2) an ensemble with a T1-CE MRI as the sole image input after projections, and (3) an ensemble with the same image input design without clinical feature inclusion. RESULTS: The ensemble model achieved an excellent area under the receiver operating characteristic curve (AUCROC: 0.89 ± 0.02) with high sensitivity (0.82 ± 0.05), specificity (0.84 ± 0.11), and accuracy (0.84 ± 0.08) results. This outperformed the MRI-only VGG-19 encoder (sensitivity: 0.35 ± 0.01, AUCROC: 0.64 ± 0.08), the MRI-only deep ensemble (sensitivity: 0.60 ± 0.09, AUCROC: 0.68 ± 0.06), and the 3-channel ensemble without clinical feature fusion (sensitivity: 0.78 ± 0.08, AUCROC: 0.84 ± 0.03). CONCLUSIONS: Facilitated by the spherical image projection method, a deep ensemble model incorporating Dmap and clinical variables demonstrated excellent performance in predicting BM post-SRS local failure. Our novel approach could improve other radiation therapy outcome models and warrants further evaluation.

Prognostic value of different discretization parameters in 18fluorodeoxyglucose positron emission tomography radiomics of oropharyngeal squamous cell carcinoma.

Purpose: We aim to interrogate the role of positron emission tomography (PET) image discretization parameters on the prognostic value of radiomic features in patients with oropharyngeal cancer. Approach: A prospective clinical trial (NCT01908504) enrolled patients with oropharyngeal squamous cell carcinoma (N=69; mixed HPV status) undergoing definitive radiotherapy and evaluated intra-treatment 18fluorodeoxyglucose PET as a potential imaging biomarker of early metabolic response. The primary tumor volume was manually segmented by a radiation oncologist on PET/CT images acquired two weeks into treatment (20 Gy). From this, 54 radiomic texture features were extracted. Two image discretization techniques-fixed bin number (FBN) and fixed bin size (FBS)-were considered to evaluate systematic changes in the bin number ({32, 64, 128, 256} gray levels) and bin size ({0.10, 0.15, 0.22, 0.25} bin-widths). For each discretization-specific radiomic feature space, an LASSO-regularized logistic regression model was independently trained to predict residual and/or recurrent disease. The model training was based on Monte Carlo cross-validation with a 20% testing hold-out, 50 permutations, and minor-class up-sampling to account for imbalanced outcomes data. Performance differences among the discretization-specific models were quantified via receiver operating characteristic curve analysis. A final parameter-optimized logistic regression model was developed by incorporating different settings parameterizations into the same model. Results: FBN outperformed FBS in predicting residual and/or recurrent disease. The four FBN models achieved AUC values of 0.63, 0.61, 0.65, and 0.62 for 32, 64, 128, and 256 gray levels, respectively. By contrast, the average AUC of the four FBS models was 0.53. The parameter-optimized model, comprising features joint entropy (FBN = 64) and information measure correlation 1 (FBN = 128), achieved an AUC of 0.70. Kaplan-Meier analyses identified these features to be associated with disease-free survival (p=0.0158 and p=0.0180, respectively; log-rank test). Conclusions: Our findings suggest that the prognostic value of individual radiomic features may depend on feature-specific discretization parameter settings.

Mindfulness induction and executive function after high-intensity interval training with and without mindful recovery intervals.

OBJECTIVES: Determine the effect of incorporating mindfulness-based activities into the recovery intervals of high-intensity interval training (HIIT) on mindfulness induction and subsequent executive function performance. DESIGNS: A within-subject crossover trial. METHODS: Forty adults participated in two experimental conditions, including a 30-min bout of HIIT involving mindfulness recovery intervals (Mindful) and a 30-min bout of HIIT without mindfulness recovery intervals (Non-mindful), on two separate days in counterbalanced order. Before and after each condition, participants completed the flanker task, switch-flanker task, and n-back task to measure inhibitory control, cognitive flexibility, and working memory, respectively. RESULTS: A higher level of mindfulness state was observed following the Mindful condition than the Non-mindful condition. Dispositional mindfulness was positively correlated with the level of the mindful state only during the Mindful condition but not the Non-mindful condition. The switch-flanker response accuracy was improved from the pretest to posttest during the Non-mindful condition but remained unchanged over time during the Mindful condition. Time-related improvements in the flanker and n-back task outcomes were observed for both the Mindful and Non-mindful conditions and did not differ between conditions. CONCLUSION: Although incorporating mindfulness-based activities during the recovery intervals of HIIT successfully led to greater state-related mindfulness, such a heightened mindful state did not correspond with additional modulation in inhibitory control and working memory performance while attenuating HIIT-related positive changes in task performance requiring cognitive flexibility.

Independent Monte Carlo dose calculation identifies single isocenter multi-target radiosurgery targets most likely to fail pre-treatment measurement.

PURPOSE: For individual targets of single isocenter multi-target (SIMT) Stereotactic radiosurgery (SRS), we assess dose difference between the treatment planning system (TPS) and independent Monte Carlo (MC), and demonstrate persistence into the pre-treatment Quality Assurance (QA) measurement. METHODS: Treatment plans from 31 SIMT SRS patients were recalculated in a series of scenarios designed to investigate sources of discrepancy between TPS and independent MC. Targets with > 5% discrepancy in DMean[Gy] after progressing through all scenarios were measured with SRS MapCHECK. A matched pair analysis was performed comparing SRS MapCHECK results for these targets with matched targets having similar characteristics (volume & distance from isocenter) but no such MC dose discrepancy. RESULTS: Of 217 targets analyzed, individual target mean dose (DMean[Gy]) fell outside a 5% threshold for 28 and 24 targets before and after removing tissue heterogeneity effects, respectively, while only 5 exceeded the threshold after removing effect of patient geometry (via calculation on StereoPHAN geometry). Significant factors affecting agreement between the TPS and MC included target distance from isocenter (0.83% decrease in DMean[Gy] per 2 cm), volume (0.15% increase per cc), and degree of plan modulation (0.37% increase per 0.01 increase in modulation complexity score). SRS MapCHECK measurement had better agreement with MC than with TPS (2%/1 mm / 10% threshold gamma pass rate (GPR) = 99.4 ± 1.9% vs. 93.1 ± 13.9%, respectively). In the matched pair analysis, targets exceeding 5% for MC versus TPS also had larger discrepancies between TPS and measurement with no GPR (2%/1 mm / 10% threshold) exceeding 90% (71.5% ± 16.1%); whereas GPR was high for matched targets with no such MC versus TPS difference (96.5% ± 3.3%, p = 0.01). CONCLUSIONS: Independent MC complements pre-treatment QA measurement for SIMT SRS by identifying problematic individual targets prior to pre-treatment measurement, thus enabling plan modifications earlier in the planning process and guiding selection of targets for pre-treatment QA measurement.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

BACKGROUND AND AIM: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. METHODS: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. RESULTS: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. CONCLUSION: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases.

Purpose: Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it is unknown whether ATM variants affect rates of radionecrosis (RN) and local intracranial progression (LIP) after stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials: Patients undergoing an initial course of SRS for non-small cell lung cancer (NSCLC) brain metastases at a single institution were retrospectively identified. Kaplan-Meier estimates were calculated and Cox proportional hazards testing was performed based on ATM variant status. Results: A total of 541 patients completed SRS for brain metastasis secondary to NSCLC, of whom 260 completed molecular profiling. Variants of ATM were identified in 36 cases (13.8%). Among patients who completed molecular profiling, RN incidence was 4.9% (95% CI, 1.6%-8.2%) at 6 months and 9.9% (95% CI, 4.8%-15.0%) at 12 months. Incidence of RN was not significantly increased among patients with ATM variants, with an RN incidence of 5.3% (95% CI, 0.0%-15.3%) at both 6 and 12 months (P = .46). For all patients who completed genomic profiling, LIP was 5.4% (95% CI, 2.4%-8.4%) at 6 months and 9.8% (5.5%-14.1%) at 12 months. A significant improvement in LIP was not detected among patients with ATM variants, with an LIP incidence of 3.1% (0.0%-9.1%) at both 6 and 12 months (P = .26). Although differences according to ATM variant type (pathologic variant or variant of unknown significance) did not reach significance, no patients with ATM pathologic variants experienced LIP. Conclusions: We did not detect significant associations between ATM variant status and RN or LIP after SRS for NSCLC brain metastases. The current data set allows estimation of patient cohort sizes needed to power future investigations to identify genetic variants that associate with significant differences in outcomes after SRS.

Radiomics on spatial-temporal manifolds via Fokker-Planck dynamics.

BACKGROUND: Delta radiomics is a high-throughput computational technique used to describe quantitative changes in serial, time-series imaging by considering the relative change in radiomic features of images extracted at two distinct time points. Recent work has demonstrated a lack of prognostic signal of radiomic features extracted using this technique. We hypothesize that this lack of signal is due to the fundamental assumptions made when extracting features via delta radiomics, and that other methods should be investigated. PURPOSE: The purpose of this work was to show a proof-of-concept of a new radiomics paradigm for sparse, time-series imaging data, where features are extracted from a spatial-temporal manifold modeling the time evolution between images, and to assess the prognostic value on patients with oropharyngeal cancer (OPC). METHODS: To accomplish this, we developed an algorithm to mathematically describe the relationship between two images acquired at time t = 0 $t = 0$ and t > 0 $t > 0$ . These images serve as boundary conditions of a partial differential equation describing the transition from one image to the other. To solve this equation, we propagate the position and momentum of each voxel according to Fokker-Planck dynamics (i.e., a technique common in statistical mechanics). This transformation is driven by an underlying potential force uniquely determined by the equilibrium image. The solution generates a spatial-temporal manifold (3 spatial dimensions + time) from which we define dynamic radiomic features. First, our approach was numerically verified by stochastically sampling dynamic Gaussian processes of monotonically decreasing noise. The transformation from high to low noise was compared between our Fokker-Planck estimation and simulated ground-truth. To demonstrate feasibility and clinical impact, we applied our approach to 18F-FDG-PET images to estimate early metabolic response of patients (n = 57) undergoing definitive (chemo)radiation for OPC. Images were acquired pre-treatment and 2-weeks intra-treatment (after 20 Gy). Dynamic radiomic features capturing changes in texture and morphology were then extracted. Patients were partitioned into two groups based on similar dynamic radiomic feature expression via k-means clustering and compared by Kaplan-Meier analyses with log-rank tests (p < 0.05). These results were compared to conventional delta radiomics to test the added value of our approach. RESULTS: Numerical results confirmed our technique can recover image noise characteristics given sparse input data as boundary conditions. Our technique was able to model tumor shrinkage and metabolic response. While no delta radiomics features proved prognostic, Kaplan-Meier analyses identified nine significant dynamic radiomic features. The most significant feature was Gray-Level-Size-Zone-Matrix gray-level variance (p = 0.011), which demonstrated prognostic improvement over its corresponding delta radiomic feature (p = 0.722). CONCLUSIONS: We developed, verified, and demonstrated the prognostic value of a novel, physics-based radiomics approach over conventional delta radiomics via data assimilation of quantitative imaging and differential equations.

Quantifying U-Net uncertainty in multi-parametric MRI-based glioma segmentation by spherical image projection.

BACKGROUND: Uncertainty quantification in deep learning is an important research topic. For medical image segmentation, the uncertainty measurements are usually reported as the likelihood that each pixel belongs to the predicted segmentation region. In potential clinical applications, the uncertainty result reflects the algorithm's robustness and supports the confidence and trust of the segmentation result when the ground-truth result is absent. For commonly studied deep learning models, novel methods for quantifying segmentation uncertainty are in demand. PURPOSE: To develop a U-Net segmentation uncertainty quantification method based on spherical image projection of multi-parametric MRI (MP-MRI) in glioma segmentation. METHODS: The projection of planar MRI data onto a spherical surface is equivalent to a nonlinear image transformation that retains global anatomical information. By incorporating this image transformation process in our proposed spherical projection-based U-Net (SPU-Net) segmentation model design, multiple independent segmentation predictions can be obtained from a single MRI. The final segmentation is the average of all available results, and the variation can be visualized as a pixel-wise uncertainty map. An uncertainty score was introduced to evaluate and compare the performance of uncertainty measurements. The proposed SPU-Net model was implemented on the basis of 369 glioma patients with MP-MRI scans (T1, T1-Ce, T2, and FLAIR). Three SPU-Net models were trained to segment enhancing tumor (ET), tumor core (TC), and whole tumor (WT), respectively. The SPU-Net model was compared with (1) the classic U-Net model with test-time augmentation (TTA) and (2) linear scaling-based U-Net (LSU-Net) segmentation models in terms of both segmentation accuracy (Dice coefficient, sensitivity, specificity, and accuracy) and segmentation uncertainty (uncertainty map and uncertainty score). RESULTS: The developed SPU-Net model successfully achieved low uncertainty for correct segmentation predictions (e.g., tumor interior or healthy tissue interior) and high uncertainty for incorrect results (e.g., tumor boundaries). This model could allow the identification of missed tumor targets or segmentation errors in U-Net. Quantitatively, the SPU-Net model achieved the highest uncertainty scores for three segmentation targets (ET/TC/WT): 0.826/0.848/0.936, compared to 0.784/0.643/0.872 using the U-Net with TTA and 0.743/0.702/0.876 with the LSU-Net (scaling factor = 2). The SPU-Net also achieved statistically significantly higher Dice coefficients, underscoring the improved segmentation accuracy. CONCLUSION: The SPU-Net model offers a powerful tool to quantify glioma segmentation uncertainty while improving segmentation accuracy. The proposed method can be generalized to other medical image-related deep-learning applications for uncertainty evaluation.

Enhanced ability of toluene oxidation by controlling inversion degree of spinel composed of only Co, Mn.

Exploring the single relationship between the inversion degree of spinel and its catalytic performance is a great challenge, but has important significance for further structural design and application. A series of CoMn inverse spinels were prepared and the general formula [Formula: see text] was deduced through X-ray diffraction refinement to find a decreased inversion degree x as calcination temperature rose. Catalytic oxidation of toluene showed that higher inversion degree (S-300 with x ≈ 0.95) can reach larger conversion rate (90 % at about 250 °C for 400 ppm toluene) with greater reaction stability (140 h). Density Functional Theory (DFT) calculations on density of states indicated its metallic nature, and found that the strength of O-p and Transition metal-d orbitals at Fermi energy is positively correlated to the inversion degree, meaning stronger electron migration ability. Along with the adsorption calculation analysis that lattice oxygen species are proved to work dominantly (S-300 with lowest adsorption energy but highest performance), this work uncovered a theoretical insight into inverse spinel oxide, to provide the possibility of elevated oxidation ability through structural control.

Long-Term Intracranial Outcomes With Combination Dual Immune-Checkpoint Blockade and Stereotactic Radiosurgery in Patients With Melanoma and Non-Small Cell Lung Cancer Brain Metastases.

PURPOSE: The intracranial benefit of offering dual immune-checkpoint inhibition (D-ICPI) with ipilimumab and nivolumab to patients with melanoma or non-small cell lung cancer (NSCLC) receiving stereotactic radiosurgery (SRS) for brain metastases (BMs) is unknown. We hypothesized that D-ICPI improves local control compared with SRS alone. METHODS AND MATERIALS: Patients with melanoma or NSCLC treated with SRS from 2014 to 2022 were evaluated. Patients were stratified by treatment with D-ICPI, single ICPI (S-ICPI), or SRS alone. Local recurrence, intracranial progression (IP), and overall survival were estimated using competing risk and Kaplan-Meier analyses. IP included both local and distant intracranial recurrence. RESULTS: Two hundred eighty-eight patients (44% melanoma, 56% NSCLC) with 1,704 BMs were included. Fifty-three percent of patients had symptomatic BMs. The median follow-up was 58.8 months. Twelve-month local control rates with D-ICPI, S-ICPI, and SRS alone were 94.73% (95% CI, 91.11%-96.90%), 91.74% (95% CI, 89.30%-93.64%), and 88.26% (95% CI, 84.07%-91.41%). On Kaplan-Meier analysis, only D-ICPI was significantly associated with reduced local recurrence (P = .0032). On multivariate Cox regression, D-ICPI (hazard ratio [HR], 0.4003; 95% CI, 0.1781-0.8728; P = .0239) and planning target volume (HR, 1.022; 95% CI, 1.004-1.035; P = .0059) correlated with local control. One hundred seventy-three (60%) patients developed IP. The 12-month cumulative incidence of IP was 41.27% (95% CI, 30.27%-51.92%), 51.86% (95% CI, 42.78%-60.19%), and 57.15% (95% CI, 44.98%-67.59%) after D-ICPI, S-ICPI, and SRS alone. On competing risk analysis, only D-ICPI was significantly associated with reduced IP (P = .0408). On multivariate Cox regression, D-ICPI (HR, 0.595; 95% CI, 0.373-0.951; P = .0300) and presentation with >10 BMs (HR, 2.492; 95% CI, 1.668-3.725; P < .0001) remained significantly correlated with IP. The median overall survival after D-ICPI, S-ICPI, and SRS alone was 26.1 (95% CI, 15.5-40.7), 21.5 (16.5-29.6), and 17.5 (11.3-23.8) months. S-ICPI, fractionation, and histology were not associated with clinical outcomes. There was no difference in hospitalizations or neurologic adverse events between cohorts. CONCLUSIONS: The addition of D-ICPI for patients with melanoma and NSCLC undergoing SRS is associated with improved local and intracranial control. This appears to be an effective strategy, including for patients with symptomatic or multiple BMs.

Lung Cancer Screening in Clinical Practice: A 5-Year Review of Frequency and Predictors of Lung Cancer in the Screened Population.

PURPOSE: The aims of this study were to evaluate (1) frequency, type, and lung cancer stage in a clinical lung cancer screening (LCS) population and (2) the association between patient characteristics and Lung CT Screening Reporting & Data System (Lung-RADS®) with lung cancer diagnosis. METHODS: This retrospective study enrolled individuals undergoing LCS between January 1, 2015, and June 30, 2020. Individuals' sociodemographic characteristics, Lung-RADS scores, pathology-proven lung cancers, and tumor characteristics were determined via electronic health record and the health system's tumor registry. Associations between the outcome of lung cancer diagnosis within 1 year after LCS and covariates of sociodemographic characteristics and Lung-RADS score were determined using logistic regression. RESULTS: Of 3,326 individuals undergoing 5,150 LCS examinations, 102 (3.1%) were diagnosed with lung cancer within 1 year of LCS; most of these cancers were screen detected (97 of 102 [95.1%]). Over the study period, there were 118 total LCS-detected cancers in 113 individuals (3.4%). Most LCS-detected cancers were adenocarcinomas (62 of 118 [52%]), 55.9% (65 of 118) were stage I, and 16.1% (19 of 118) were stage IV. The sensitivity, specificity, positive predictive value, and negative predictive value of Lung-RADS in diagnosing lung cancer within 1 year of LCS were 93.1%, 83.8%, 10.6%, and 99.8%, respectively. On multivariable analysis controlling for sociodemographic characteristics, only Lung-RADS score was associated with lung cancer (odds ratio for a one-unit increase in Lung-RADS score, 4.68; 95% confidence interval, 3.87-5.78). CONCLUSIONS: The frequency of LCS-detected lung cancer and stage IV cancers was higher than reported in the National Lung Screening Trial. Although Lung-RADS was a significant predictor of lung cancer, the positive predictive value of Lung-RADS is relatively low, implying opportunity for improved nodule classification.

Development of a multi-feature-combined model: proof-of-concept with application to local failure prediction of post-SBRT or surgery early-stage NSCLC patients.

Objective: To develop a Multi-Feature-Combined (MFC) model for proof-of-concept in predicting local failure (LR) in NSCLC patients after surgery or SBRT using pre-treatment CT images. This MFC model combines handcrafted radiomic features, deep radiomic features, and patient demographic information in an integrated machine learning workflow. Methods: The MFC model comprised three key steps. (1) Extraction of 92 handcrafted radiomic features from the GTV segmented on pre-treatment CT images. (2) Extraction of 512 deep radiomic features from pre-trained U-Net encoder. (3) The extracted handcrafted radiomic features, deep radiomic features, along with 4 patient demographic information (i.e., gender, age, tumor volume, and Charlson comorbidity index), were concatenated as a multi-dimensional input to the classifiers for LR prediction. Two NSCLC patient cohorts from our institution were investigated: (1) the surgery cohort includes 83 patients with segmentectomy or wedge resection (7 LR), and (2) the SBRT cohort includes 84 patients with lung SBRT (9 LR). The MFC model was developed and evaluated independently for both cohorts, and was subsequently compared against the prediction models based on only handcrafted radiomic features (R models), patient demographic information (PI models), and deep learning modeling (DL models). ROC with AUC was adopted to evaluate model performance with leave-one-out cross-validation (LOOCV) and 100-fold Monte Carlo random validation (MCRV). The t-test was performed to identify the statistically significant differences. Results: In LOOCV, the AUC range (surgery/SBRT) of the MFC model was 0.858-0.895/0.868-0.913, which was higher than the three other models: 0.356-0.480/0.322-0.650 for PI models, 0.559-0.618/0.639-0.682 for R models, and 0.809/0.843 for DL models. In 100-fold MCRV, the MFC model again showed the highest AUC results (surgery/SBRT): 0.742-0.825/0.888-0.920, which were significantly higher than PI models: 0.464-0.564/0.538-0.628, R models: 0.557-0.652/0.551-0.732, and DL models: 0.702/0.791. Conclusion: We successfully developed an MFC model that combines feature information from multiple sources for proof-of-concept prediction of LR in patients with surgical and SBRT early-stage NSCLC. Initial results suggested that incorporating pre-treatment patient information from multiple sources improves the ability to predict the risk of local failure.