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Deep learning-based cross-attention fusion of multimodal MRI for survival prediction and risk stratification in IDH-wildtype glioblastoma: a multicenter study.

BACKGROUND: Glioblastoma (GBM) exhibits profound molecular and spatial heterogeneity, complicating prognostic evaluations. While multiparametric MRI provides crucial multidimensional biological information, conventional end-to-end deep learning integration strategies, such as early or late fusion, often fail to capture complex nonlinear cross-modal interactions. We aimed to systematically evaluate a cross-attention fusion (CAF) architecture for GBM survival prediction and quantify its incremental prognostic value relative to existing clinical tools. METHODS: In this multicenter retrospective study, 386 adults with IDH-wildtype, WHO grade 4 GBM were assembled from an institutional cohort (n = 226), the Chinese Glioma Genome Atlas (CGGA, n = 62), and The Cancer Genome Atlas (TCGA, n = 98). Using a unified 3D ResNet-18 backbone, we compared single-modality models, early fusion, late fusion, and CAF on preoperative T1-weighted, contrast-enhanced T1-weighted (T1CE), and T2-weighted MRI, and integrated the resulting deep learning risk score with routine clinical variables through multivariable Cox regression. Performance was assessed using Harrell's C-index, time-dependent AUC, and decision curve analysis. RESULTS: CAF showed numerically higher, more consistent C-index trends than early fusion, late fusion, and single-modality models (pooled C-index 0.629, 95% CI 0.594-0.664), although pairwise differences in time-dependent AUC were not statistically significant. Integrating clinical variables raised the pooled C-index to 0.691 (95% CI 0.660-0.721) in the treatment-era model, with comparable performance across the three cohorts (Local 0.688; CGGA 0.716; TCGA 0.689); a pre-treatment configuration excluding adjuvant therapy yielded a pooled C-index of 0.642. Under leave-one-cohort-out external validation, the combined model retained significant risk stratification in all held-out cohorts (C-index 0.63-0.71; all log-rank P&#xa0;<&#xa0;0.01), albeit with attenuated discrimination. The deep learning risk score remained independent after multivariable adjustment (HR 1.41 per SD, 95% CI 1.26-1.57; P&#xa0;<&#xa0;0.001). Kaplan-Meier analysis confirmed significant high- versus low-risk separation in all cohorts, and decision curve analysis showed greater net benefit than clinical-only and deep-learning-only models. CONCLUSION: The CAF-derived risk score offers prognostic information complementary to routine clinical variables, representing a promising noninvasive tool for individualized risk stratification when molecular profiling is incomplete or unavailable; these findings warrant prospective external validation before clinical use.

cross-attention fusion↗

Improved odds ratio estimation by post hoc stratification of case-control data.

We propose a logistic regression analysis of unmatched or frequency matched case-control studies with conditional maximum likelihood estimation through post hoc stratification. In this model fewer parameters have to be estimated. With a simulation study we show that parameter estimates have smaller variance and are less biased. Also, the residual confounding effect was quantified. A more refined post hoc stratification reduces computing time, but to the cost of a larger bias and a loss in efficiency. The model was also applied to data of unmatched case-control studies on laryngeal cancer, oesophageal cancer and lung cancer.

Case-Control Studies↗

Effects of stratification in a fluidized bed bioreactor during treatment of metalworking wastewater

During wastewater treatment, biofilm-coated sand particles stratified in a fluidized bed bioreactor (FBB); particles coated by thicker biofilm segregated toward the top of the bed. Stratification was so well developed that at least two co-existing regions of significantly different mean biofilm thickness were visually distinct within the operating FBB. The observed stratification is attributed to differences in forces of drag, buoyancy, shear, and collisional impact, as well as differences of collision rate within the different regions. Particles with thick biofilm (thickness >100 μm) near the top of the bed consumed substrate at significantly lower rates per unit biomass than particles with thin biofilm (10-20 μm) near the bottom of the bed, thereby suggesting that substrate mass-transfer resistance through biofilm may limit biodegradation rates in the upper portion of the FBB. Large agglomerates of biomass floc and sand, which formed at the top of the fluidized bed, and sand particles with thick biofilm were susceptible to washout from the FBB, causing operational and treatment instability. Radial injection of supplemental liquid feed near the top of the bed increased shear and mixing, thereby preventing formation and washout of agglomerates and thickly coated sand particles. Supplemental liquid injection caused the mean specific biomass loading on the sand to increase and also increased the total biomass inventory in the FBB. Rates of biodegradation in the FBB appeared to be limited by penetration of substrates into the biofilm and absorption of oxygen from air into the wastewater. Copyright 1999 John Wiley & Sons, Inc.

Journal Article↗

Stratification based on language-related endophenotypes in autism: attempt to replicate reported linkage.

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non-parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples.

Autistic Disorder↗

Testing for association in the presence of population stratification: a simulation study comparing the S-TDT, STRAT and the GC.

A novel approach for association testing in the presence of population stratification has been introduced by Pritchard et al. (2000a) and Pritchard et al. (2000b). The structured association approach is a two-tiered procedure that first estimates the population structure and then tests the null hypothesis H0: 'no association within subpopulations' in the second step. A power comparison of the stratified test for association (STRAT) (Pritchard et al., 2000b) and the Transmission-Disequilibrium-Test (TDT) (Spielman and Ewens, 1993a) in a simulation framework showed superiority of STRAT if allele frequencies or associations between allele and disease differ strongly in subpopulations. In more homogeneous situations, the TDT had greater power than STRAT. However, the TDT, based on family trios,that uses population controls, needs 50% more genotyping compared to STRAT. The Sib-Transmission-Disequilibrium-Test (S-TDT) needs the same amount of genotyping since it relays in its minimal configuration on pairs of siblings. This raises the question how the S-TDT (Spielman and Ewens, 1998a) performs compared to the population based methods STRAT and Genomic Controls (GC). In this paper, we present a simulation study accounting for two different models of population stratification in different settings of allele frequencies and under different risk models. The results showed that under a discrete as well as under an admixed population model, STRAT strongly outperformed the S-TDT and the GC when different alleles were associated in different subpopulations. In contrast, the S-TDT had greater power than STRAT when the same allele was associated in both subpopulations. Here, the GC was sometimes even more powerful than the S-TDT, depending on the population model and the allele frequency differences. A general recommendation for the use of one of the tests can therefore not be given.

Algorithms↗

Redox-stratification controlled biofilm (ReSCoBi) for completely autotrophic nitrogen removal: the effect of co- versus counter-diffusion on reactor performance.

A multi-population biofilm model for completely autotrophic nitrogen removal was developed and implemented in the simulation program AQUASIM to corroborate the concept of a redox-stratification controlled biofilm (ReSCoBi). The model considers both counter- and co-diffusion biofilm geometries. In the counter-diffusion biofilm, oxygen is supplied through a gas-permeable membrane that supports the biofilm while ammonia (NH(4)(+)) is supplied from the bulk liquid. On the contrary, in the co-diffusion biofilm, both oxygen and NH(4)(+) are supplied from the bulk liquid. Results of the model revealed a clear stratification of microbial activities in both of the biofilms, the resulting chemical profiles, and the obvious effect of the relative surface loadings of oxygen and NH(4)(+) (J(O(2))/J(NH(4)(+))) on the reactor performances. Steady-state biofilm thickness had a significant but different effect on T-N removal for co- and counter-diffusion biofilms: the removal efficiency in the counter-diffusion biofilm geometry was superior to that in the co-diffusion counterpart, within the range of 450-1,400 microm; however, the efficiency deteriorated with a further increase in biofilm thickness, probably because of diffusion limitation of NH(4)(+). Under conditions of oxygen excess (J(O(2))/J(NH(4)(+)) > 3.98), almost all NH(4)(+) was consumed by aerobic ammonia oxidation in the co-diffusion biofilm, leading to poor performance, while in the counter-diffusion biofilm, T-N removal efficiency was maintained because of the physical location of anaerobic ammonium oxidizers near the bulk liquid. These results clearly reveal that counter-diffusion biofilms have a wider application range for autotrophic T-N removal than co-diffusion biofilms.

Ammonia↗

Cardiac troponin I for risk stratification following percutaneous coronary artery intervention in acute coronary syndromes.

The cardiac troponins have been shown to provide prognostic information allowing risk stratification of patients with acute coronary syndromes (ACS). The benefit of early percutaneous coronary intervention (PCI) in this setting has been highlighted by the FRISC II study. We assessed the pattern of release of cardiac troponin I (cTnI) following PCI in patients with ACS and evaluated its prognostic value for major adverse cardiac events (MACE): death, Q-wave myocardial infarction (QWMI), and repeat revascularization at follow-up. cTnI was sampled at baseline and 6, 14, and 24 hr following PCI in 73 patients presenting with unstable and post-MI angina. Clinical follow-up was obtained in all 73 patients at a mean period of 43 +/- 19.9 weeks (range, 11-68 weeks). Patients were stratified into two groups according to whether cTnI remained unchanged or fell below baseline 24 hr post-PCI (group 1, n = 47) or increased above baseline 24 hr following PCI (group 2, n = 26). MACE occurred in 4 (8.5%) of patients in group 1 (QWMI = 1, CABG = 1, re-PCI = 2) and in 19 (73%) of patients in group 2 (death = 1, QWMI = 2, CABG = 2, re-PCI = 14; chi-square = 32.34, P < 0.0001). The positive predictive value of rising cTnI within 24 hr following PCI for MACE at follow-up was 0.73 and the negative predictive value was 0.92 (specificity = 83%, sensitivity = 86%; odds ratio = 29.18, 95% CI = 7.62-110.64, P < 0.0001). cTnI is an inexpensive and widely applicable tool that offers reliable prognostic information for the risk stratification of patients undergoing coronary revascularization in the setting of acute coronary syndromes and may identify a group of patients at particular risk of repeat PCI.

Aged↗

Improved risk stratification in unstable angina: identification of patients at low risk for in-hospital cardiac events by admission echocardiography.

BACKGROUND: Current protocols for risk stratification of patients with acute chest pain syndromes rely on clinical parameters and are oriented toward identification of patients at high risk for adverse cardiac events; however, this paradigm for risk stratification does not adequately address the observation that adverse cardiac events are relatively uncommon in this population. In an era of cost containment, consideration also should be given to identification of patients at low risk for adverse cardiac events, who may be safely discharged without expensive inpatient hospitalization. HYPOTHESIS: The purpose of this study was to develop echocardiographic predictors that identify unstable angina patients at low risk for adverse cardiac events and that discriminate between low- and high-risk patients. METHODS: The predictive accuracy of retrospectively determined echocardiographic predictors were compared in a population-based sample of 66 consecutive unstable angina patients undergoing echocardiography within 24 h of admission. RESULTS: Echocardiographic predictors of adverse events included wall motion score index > or = 0.2, ejection fraction < or = 40%, and mitral regurgitation severity > 2. One or more echocardiographic predictors of adverse events were present in 32 patients (48%). A composite echocardiographic predictor of adverse events was specific, had a high positive predictive value for the identification of high-risk patients, and discriminated between unstable angina patients at high and low risk for adverse cardiac events. CONCLUSION: Echocardiographic predictors of adverse events are specific and discriminate between unstable angina patients at high and low risk for adverse cardiac events.

Acute Disease↗

Clusters of life-threatening ventricular arrhythmias in patients with implanted cardioverter-defibrillators: prevalence, characteristics, and risk stratification.

BACKGROUND: Series of discharges from an implanted defibrillator (ICD) to terminate life-threatening ventricular tachyarrhythmias are one particular aspect of energy use and success of ICD therapy. Little is known about prevalence. characteristics, and risk stratification of so-called "cluster arrhythmias." HYPOTHESIS: The objective of this study was to examine the frequency of cluster arrhythmias, to characterize the temporal relationship precisely, and to assess the accompanying circumstances of their occurrence, whereby risk stratification was to be made if appropriate. METHODS: In all, 63 consecutive patients were followed prospectively over 727 +/- 684 days to determine the presence and characteristics of cluster arrhythmias (45,801 patient days). In 30 patients, 374 ICD episodes of ventricular tachyarrhythmias were analyzed for their temporal relationship. After a first successfully terminated ventricular tachyarrhythmia, further ICD discharges within 3 h were observed during 145 of 374 (39%) episodes; mean time interval between these arrhythmias was 25 +/- 32 min. RESULTS: Arrhythmia clusters occurred in 19 of 30 (63%) patients. In multivariate analysis, only underlying heart disease was predictive for accumulation of ventricular tachyarrhythmias. Cluster arrhythmias were more frequent among patients with ischemic heart disease than among those with nonischemic heart disease (40.0 vs. 29.2%, p < 0.05). Ejection fraction, age, gender, and other parameters were not predictive for occurrence of arrhythmia clusters. In 4 of 19 patients, accumulation of ICD discharges was predictive for new onset of myocardial ischemia elicited by exercise test. CONCLUSIONS: Cluster arrhythmias are most common in patients with ICDs with coronary heart disease and may indicate disease progression and increasing instability, for example, due to new onset of myocardial ischemia.

Adult↗

Gastrointestinal stromal tumors in Iceland, 1990-2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study.

Gastrointestinal stromal tumor (GIST) is a newly defined clinical and pathologic entity. This study examines the whole population-based incidence of GIST as well as pathologic risk stratification schemes. All patients diagnosed in Iceland with a gastrointestinal mesenchymal tumor over the years 1990-2003 were evaluated with an immunohistochemical panel including staining for c-kit. The age-adjusted incidence of GIST was calculated. Size, mitotic rate per 50 HPF and various other pathologic parameters were evaluated. Each tumor was categorized into 1 of 4 recently defined NIH risk stratification categories. Fifty-seven of the mesenchymal gastrointestinal tumors were positive for c-kit and therefore categorized as GIST. The annual incidence for the study period is 1.1 per 100,000. The median age of patients was 65.8 years and median tumor size was 4.6 cm. Only 2 of 35 gastric tumors fall into the NIH high-risk category while half of the nongastric tumors (11 of 22) fall into this high-risk category. Eight of the 57 tumors (14%) metastasized, 7 of which were nongastric. The positive predictive value for malignant behavior of the high-risk category is 46%. The negative predictive value of low- and very-low-risk NIH category is 100%. Pathologic predictors of malignant behavior are tumor size, mitotic rate, mucosal disruption, necrosis and high cellularity. Nongastric GISTs are clearly at much higher risk of a malignant behavior than gastric GISTs. This population-based GIST study estimates the incidence of GISTs at 1.1 per 100,000 and furthermore supports the NIH consensus categories for the prediction of malignant behavior of GISTs.

Age Factors↗

Epithelial stratification in the developing chick cornea.

The process of epithelial stratification was studied in the embryonic chick corneal eipthelium between 10 and 21 days of incubation. Information was collected on the DNA synthetic activity occurring in individual cell layers, on cell density changes in the basal layer, and on mitotic spindle orientation in each cell layer before, during, and upon the completion of alyer formation. Prior to the initiation of stratification, mitotic spindles are oriented parallel to the basement membrane interface. This orientation changes to predominantly vertically directed spindles as layer formation proceeds. Later, the majority of the spindles are horizontally aligned once more. This pattern was observed as each successive cell layer formed. The possible relationship between the spindle data and that obtained on DNA synthetic activity and cell density changes is discussed in terms of the role these factors might play in layer formation in the cornea, as well as in other stratified epithelia.

Animals↗

Risk stratification after radical prostatectomy in men with pathologically organ-confined prostate cancer using volume-weighted mean nuclear volume.

OBJECTIVE: We examined the impact of volume-weighted mean nuclear volume (MNV) on biochemical failure after radical prostatectomy (RP) in pathologically organ-confined prostate cancer (PC) and developed a prognostic factor-based stratification model for these patients. PATIENTS AND METHODS: We analyzed 141 patients with pathologically organ-confined PC treated solely with RP. Unbiased estimates of MNV were calculated from biopsy specimens based on a stereological method, and compared with other clinical and pathologic findings including patient age, pre-treatment PSA, biopsy and RP specimen Gleason score, pathologic stage, total cancer volume, index cancer volume, tumor differentiation, number of tumor foci, main tumor location, and surgical margin status, with regard to prediction of disease outcome after RP using Cox proportional hazard models. RESULTS: The median follow-up was 38.6 months (range 4--119 months). Twenty patients (14.2%) experienced biochemical failure. On multivariate analysis, MNV was demonstrated to be an independent prognostic factor, along with pre-treatment PSA and total cancer volume (P=0.0004, 0.0184, and 0.0285, respectively). All patients were stratified into three groups according to their prognostic scores developed on the basis of multivariate analysis, with statistically significant prognostic differences revealed for each of the between-group comparisons. CONCLUSION: The results demonstrated that estimates of MNV contribute most significantly to the prediction of biochemical control of pathologically organ-confined PC. The combination of MNV with other independent predictors such as pre-treatment PSA and total cancer volume provided a statistically verifiable basis for risk stratification, facilitating more accurate prediction of disease outcome.

Aged↗

A comparison of mixed-effects quantile stratification propensity adjustment strategies for longitudinal treatment effectiveness analyses of continuous outcomes.

The propensity adjustment is used to reduce bias in treatment effectiveness estimates from observational data. We show here that a mixed-effects implementation of the propensity adjustment can reduce bias in longitudinal studies of non-equivalent comparison groups. The strategy examined here involves two stages. Initially, a mixed-effects ordinal logistic regression model of propensity for treatment intensity includes variables that differentiate subjects who receive various doses of time-varying treatments. Second, a mixed-effects linear regression model compares the effectiveness of those ordinal doses on a continuous outcome over time. Here, a simulation study compares bias reduction that is achieved by implementing this propensity adjustment through various forms of stratification. The simulations demonstrate that bias decreased monotonically as the number of quantiles used for stratification increased from two to five. This was particularly pronounced with stronger effects of the confounding variables. The quartile and quintile strategies typically removed in excess of 80-90 per cent of the bias detected in unadjusted models; whereas a median-split approach removed from 20 to 45 per cent of bias. The approach is illustrated in an evaluation of the effectiveness of somatic treatments for major depression in a longitudinal, observational study of affective disorders.

Adult↗

Planning the size of survival time clinical trials with allowance for stratification.

Approximate allocation designs for comparing two survival distributions are considered and compared with the exact solution. The influence of incorporating covariates by stratification, accrual and follow-up duration on trial size and power is investigated. The Bernstein and Lagakos design is suited for exponential survival due to its generality and allowance for stratification while the Freedman design is convenient for distribution-free survival in view of its simplicity. With other specifications fixed, the saving in sample size becomes minimal as the accrual period or post-accrual follow-up time units expand above three. Required sample size also increases dramatically when the number of strata exceeds three.

Clinical Trials as Topic↗

Stratification and age-related differences in blubber fatty acids of the male harbour porpoise (Phocoena phocoena).

Fatty acid composition of blubber was determined at four body sites of 19 male harbour porpoises. A total of 65 fatty acids were quantified in each sample. The array of fatty acids contained in harbour porpoise blubber was similar to those found in other marine mammals. While chemical composition of total blubber was uniform over the body, with the exception of the caudal peduncle, vertical stratification was evident between the deep (inner) and superficial (outer) blubber layers. Fatty acids with chain lengths shorter than 18 carbons were present in significantly greater amounts in the outer blubber layer, while the longer-chain unsaturated fatty acids were more prevalent in the inner layer. This distribution suggests that the inner blubber layer is more active metabolically than the outer layer in terms of lipid deposition and mobilization. The degree of stratification between the two layers appears to increase with age, indicating a predictable turnover in the blubber layer of male porpoises. Harbour porpoise blubber contained high levels (2-27%) of isovaleric acid in the outer blubber layer, and these levels were positively correlated with age.

Adipose Tissue↗

Evaluation of renormalised entropy for risk stratification using heart rate variability data.

Standard time and frequency parameters of heart rate variability (HRV) describe only linear and periodic behaviour, whereas more complex relationships cannot be recognised. A method that may be capable of assessing more complex properties is the non-linear measure of 'renormalised entropy.' A new concept of the method, RE(AR), has been developed, based on a non-linear renormalisation of autoregressive spectral distributions. To test the hypothesis that renormalised entropy may improve the result of high-risk stratification after myocardial infarction, it is applied to a clinical pilot study (41 subjects) and to prospective data of the St George's Hospital post-infarction database (572 patients). The study shows that the new RE(AR) method is more reproducible and more stable in time than a previously introduced method (p<0.001). Moreover, the results of the study confirm the hypothesis that on average, the survivors have negative values of RE(AR) (-0.11+/-0.18), whereas the non-survivors have positive values (0.03+/-0.22, p<0.01). Further, the study shows that the combination of an HRV triangular index and RE(AR) leads to a better prediction of sudden arrhythmic death than standard measurements of HRV. In summary, the new RE(AR) method is an independent measure in HRV analysis that may be suitable for risk stratification in patients after myocardial infarction.

Electrocardiography↗

Risk stratification analysis of operative mortality in coronary artery bypass surgery.

OBJECTIVE: We assessed the operative mortality of coronary artery bypass grafting (CABG) surgery using risk stratification. METHODS: In 294 consecutive patients who underwent CABG with or without concomitant surgery from August 1994 to December 1999, we compared operative mortality calculated conventionally and by risk stratification. Scores for each patient were calculated using the Parsonnet additive model and stratified based on the probability of operative mortality. RESULTS: Overall crude hospital mortality was 4.8%-4.0% among patients younger than 80 years and 14% among those 80 years of age or older (p = 0.0692). Hospital mortality was 12% in urgent/emergency surgery, and 1.5% in elective surgery (p < 0.0002), and 4.5% in CABG alone and 7.4% in CABG with concomitant surgery (p = 0.3763), and 25% in patients receiving vein grafts only and 3.0% in those receiving at least 1 artery graft (p = 0.0003). Overall patient distribution was 32% good, 20% fair, 20% poor, 11% high-risk, and 16% extremely high-risk. Predicted mortality was 2.2% for patients who were a good risk, 6.7% for fair-risk, 12% for poor-risk, 16% for high-risk, and 25% for extremely high-risk patients. Actual operative mortality was 1.0% for good-risk, 0% for fair-risk, 3.4% for poor-risk, 6.3% for high-risk, and 18% for extremely high-risk patients, making actual mortality significantly lower than that predicted. CONCLUSION: Comparing predicted mortality and actual mortality enabled us to objectively calculate operative results and assess operative quality.

Age Factors↗

[Risk stratification in acute coronary syndrome].

BACKGROUND: The spectrum of symptoms of patients with active ischemic heart disease ranges from silent ischemia to acute myocardial infarction and the extent of myocardial damage from reversible myocardial injury to extensive necrosis. The term "acute coronary syndrome" comprises this continuum. In particular the evaluation of patients without ST-segment elevation is difficult, for clinical symptoms, ECG criteria and CK-MB measurements appear insufficient for appropriate risk stratification. TROPONIN MEASUREMENT: Serial measurements of either troponin T or I reliably detect minor myocardial damage in those patients, who are known to be at a higher risk for adverse cardiac events comparable to the risk of patients with acute myocardial infarction. Hence determination of troponins allow superior risk stratification contributing to early triage and therapeutic decision making. Without elevation of troponins the cardiac risk for death or myocardial infarction will not exceed 1%. CONCLUSION: Patients with elevated troponins should be early hospitalized and further evaluated in order to begin efficacious therapy as soon as possible. These patients represent a high-risk subgroup of patients clinically classified as unstable angina, who might benefit from potential antithrombotic treatment such as low-molecular weight heparin or glycoprotein IIb/IIIa antagonists without or with revascularization strategies.

Abciximab↗