Time-dependent Analysis Research Articles

Large Deformation Dynamic Characteristics of Cracked Laminated Panel and Improvement of Stiffness Using Shape Memory Alloy Fiber

Abstract This study explores the investigation of the nonlinear dynamic responses or time-dependent deflection analysis of a laminated composite shell panel integrated with a shape memory alloy (SMA), considering both undamaged and damaged set-ups. The primary focus of this research is to examine the impact of SMA incorporation on the structural behavior of the parent configuration, aimed at enhancing its structural stiffness. To ensure the validity of the proposed model, sensitivity analyses and numerical validations are presented. The mathematical framework employed in this study employs the higher-order shear deformation theory (HSDT), which offers enhanced accuracy in capturing the intricate behaviors of these shell panels. The dynamic responses are obtained using the Newmark average acceleration method. Numerical simulations are carried out using a dedicated MATLAB code developed in-house, allowing amplified correctness in outcomes and widespread analysis. The study thoroughly assesses a range of geometric parameters and those relevant to SMA for both intact and impaired shell panels. The outcomes of the investigation reveal affirmative findings, underscoring notable improvements in structural strength and enhanced nonlinear dynamic responses through the introduction of SMA reinforcement into the composite shell panel.

Association of body composition indices with cardiovascular outcomes: a nationwide cohort study

BackgroundPrevious studies regarding BMI (kg/m2) and associated cardiovascular outcomes yield inconsistent results. ObjectivesWe aimed to investigate the association between body composition and cardiovascular outcomes according to BMI categories in the Korean general population. MethodsA total of 2,604,401 participants were enrolled in this nationwide cohort study using the National Health Insurance Service-Health Checkup data set. Predicted lean BMI (pLBMI), body fat mass index (pBFMI), and appendicular skeletal muscle mass index (pASMMI) were calculated using validated anthropometric prediction equations. A multivariable time-dependent Cox regression analysis was conducted to assess the association with cardiovascular outcomes. The results were presented with adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), considering BMI categories (BMI < 18.5, BMI 18.5–24.9, BMI 25–29.9, and BMI ≥ 30). ResultsHigher pLBMI and pASMMI were correlated with a reduced risk of composite cardiovascular outcomes. For pLBMI, HR was 0.910 (95% CI: 0.908, 0.913, P < 0.001) for males and 0.905 (95% CI: 0.899, 0.910, P < 0.001) for females. For pASMMI, HR was 0.825 (95% CI: 0.820, 0.829, P < 0.001) for males and 0.788 (95% CI: 0.777, 0.800, P < 0.001) for females. Conversely, a higher pBFMI was associated with an increased risk, with HR of 1.082 (95% CI: 1.071, 1.093, P < 0.001) for males and 1.181 (95% CI: 1.170, 1.192, P < 0.001) for females. Subgroup analysis based on BMI categories revealed no significant risk association for pBFMI in the BMI < 18.5 group. In the group with BMI ≥ 30, neither pLBMI nor pASMMI demonstrated a significant risk association. ConclusionsOur results highlight the value of pLBMI, pBFMI, and pASMMI as variables for assessing risk of composite cardiovascular outcomes. The significance of indicators may vary depending on BMI categories.

Deciphering disulfidptosis: Uncovering a lncRNA-based signature for prognostic assessment, personalized immunotherapy, and therapeutic agent selection in lung adenocarcinoma patients

BackgroundDisulfidptosis, a recently identified type of regulated cell death, plays critical roles in various biological processes of cancer; however, whether they can impact the prognosis of lung adenocarcinoma (LUAD) remains to be fully elucidated. We aimed to adopt this concept to develop and validate a lncRNA signature for LUAD prognostic prediction. MethodsFor this study, the TCGA-LUAD dataset was used as the training cohort, and multiple datasets from the GEO database were pooled as the validation cohort. Disulfidptosis regulated genes were obtained from published studies, and various statistical methods, including Kaplan-Meier (KM), Cox, and LASSO, were used to train our gene signature DISULncSig. We utilized KM analysis, COX analysis, receiver operating characteristic analysis, time-dependent AUC analysis, principal component analysis, nomogram predictor analysis, and functional assays in our validation process. We also compared DISULncSig with previous studies. We performed analyses to evaluate DISULncSig's immunotherapeutic ability, focusing on eight immune algorithms, TMB, and TIDE. Additionally, we investigated potential drugs that could be effective in treating patients with high-risk scores. Additionally qRT-PCR examined the expression patterns of DISULncSig lncRNAs, and the ability of DISULncSig in pan-cancer was also assessed. ResultsDISULncSig containing twelve lncRNAs was trained and showed strong predictive ability in the validation cohort. Compared with previous similar studies, DISULncSig had more prognostic ability advantages. DISULncSig was closely related to the immune status of LUAD, and its tight relationship with checkpoints KIR2DL3, IL10, IL2, CD40LG, SELP, BTLA, and CD28 may be the key to its potential immunotherapeutic ability. For the high DISULncSig score population, we found ten drug candidates, among which epothilone-b may have the most potential. The pan-cancer analysis found that DISULncSig was a risk factor in multiple cancers. Additionally, we discovered that some of the DISULncSig lncRNAs could play crucial roles in specific cancer types. ConclusionThe current study established a powerful prognostic DISULncSig signature for LUAD that was also valid for most pan-cancers. This signature could serve as a potential target for immunotherapy and might help the more efficient application of drugs to specific populations.

Time-dependent rheological analysis of self-consolidating concrete mixtures considering various mixing temperatures

This study aims to investigate the effect of the temperature of the self-consolidating concrete (SCC) mixture during casting on fresh and hardened properties for two types of SCC. Also, the rheological properties of the mixtures were assessed at specific time intervals (0, 20 and 40 min after mixing) to determine their sensitivity to changes in mixtures’ properties and temperature over time. For this purpose, two categories of SCC were prepared: Powder type and Viscosity-Agent type. Silica fume, metakaolin (MK) and slag were utilised as substitutes for cement in these samples. The mixtures were tested at low and high temperatures of 5 °C and 34 °C, respectively, with an average temperature of 21 °C. Results indicated that as the mixture temperature decreased, the yield stress decreased by 30% and the plastic viscosity increased by 25% on average. Conversely, as the temperature increased, the yield stress increased by 20% and the plastic viscosity decreased by 40% on average. Moreover, increasing the mixture temperature resulted in a 10% increase in the 7-d compressive strength but a 15% decrease in the 28-d compressive strength of the specimens. Additionally, increasing the rest time after mixing increased the yield stress, while the plastic viscosity remained relatively stable with occasional increases.

MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial–mesenchymal transition in lung adenocarcinoma

PurposeTo explore the effect of microtubule-associated protein 4 (MAP4) on lung adenocarcinoma cells in vitro and evaluate its prognostic value. Radioresistance, indicated by reduced efficiency of radiotherapy, is a key factor in treatment failure in lung adenocarcinoma (LADC). This study aims to explore the primary mechanism underlying the relationship between MAP4 and radiation resistance in lung adenocarcinoma.MethodsWe analysed the expression of MAP4 in lung adenocarcinoma by real-time quantitative polymerase chain reaction (RT‒qPCR), immunohistochemistry (IHC) and bioinformatics online databases, evaluated the prognostic value of MAP4 in lung adenocarcinoma and studied its relationship with clinicopathological parameters. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis identified independent prognostic factors associated with lung adenocarcinoma that were used to construct a nomogram, internal validation was performed. We then evaluated the accuracy and clinical validity of the model using a receiver operating characteristic (ROC) curve, time-dependent C-index analysis, a calibration curve, and decision curve analysis (DCA). Scratch assays and transwell assays were used to explore the effect of MAP4 on the migration and invasion of lung adenocarcinoma cells. Bioinformatics analysis, RT‒qPCR, Cell Counting Kit-8 (CCK-8) assays and Western blot experiments were used to study the relationship between MAP4, epithelial–mesenchymal transition (EMT) and radiation resistance in lung adenocarcinoma.ResultsMAP4 expression in lung adenocarcinoma tissues was significantly higher than that in adjacent normal lung tissues. High expression of MAP4 is associated with poorer overall survival (OS) in patients with lung adenocarcinoma. Univariate Cox regression analysis showed that pT stage, pN stage, TNM stage and MAP4 expression level were significantly associated with poorer OS in LADC patients. Multivariate Cox regression analysis and LASSO regression analysis showed that only the pT stage and MAP4 expression level were associated with LADC prognosis. The nomogram constructed based on the pT stage and MAP4 expression showed good predictive accuracy. ROC curves, corrected C-index values, calibration curves, and DCA results showed that the nomogram performed well in both the training and validation cohorts and had strong clinical applicability. The results of in vitro experiments showed that the downregulation of MAP4 significantly affected the migration and invasion of lung adenocarcinoma cells. MAP4 was strongly correlated with EMT-related markers. Further studies suggested that the downregulation of MAP4 can affect the viability of lung adenocarcinoma cells after irradiation and participate in the radiation resistance of lung adenocarcinoma cells by affecting EMT.ConclusionMAP4 is highly expressed in lung adenocarcinoma; it may affect prognosis by promoting the migration and invasion of cancer cells. We developed a nomogram including clinical factors and MAP4 expression that can be used for prognosis prediction in patients with lung adenocarcinoma. MAP4 participates in radiation resistance in lung adenocarcinoma by regulating the radiation-induced EMT process. MAP4 may serve as a biomarker for lung adenocarcinoma prognosis evaluation and as a new target for improving radiosensitivity.

Characteristics and standards of severe sagittal imbalance in adult patients with spinal deformities: a retrospective analysis

ObjectiveTo analyze the characteristics of “severe” dynamic sagittal imbalance (DSI) in patients with adult spinal deformity (ASD) and establish criteria for them.MethodsWe retrospectively analyzed 102 patients with ASD presenting four cardinal signs of lumbar degenerative kyphosis. All patients underwent deformity corrective surgery and were divided into three groups according to the diagnostic criteria based on the Oswestry disability index and dynamic features (△Timewalk: time until C7 sagittal vertical axis [C7SVA] reaches ≥ 20 cm after the start of walking) of sagittal imbalance. The paravertebral back muscles were analyzed and compared using T2-weighted axial imaging. We performed a statistically time-dependent spinopelvic sagittal parameter analysis of full standing lateral lumbar radiographs. Lumbar flexibility was analyzed using dynamic lateral lumbar radiography.ResultsThe patients were classified into the mild (△Timewalk ≥ 180 s, 35 patients), moderate (180 s > △Timewalk ≥ 30 s, 38 patients), and severe (△Timewalk < 30 s, 29 patients) groups. The back muscles in the severe group exhibited a significantly higher signal intensity (533.4 ± 237.5, p < 0.05) and larger area of fat infiltration (35.2 ± 5.4, p < 0.05) than those in the mild (223.8 ± 67.6/22.9 ± 11.9) and moderate groups (294.4 ± 214.7/21.6 ± 10.6). The analysis of lumbar flexibility revealed significantly lower values in the severe group (5.8° ± 2.5°, p < 0.05) than in the mild and moderate groups (14.2° ± 12.4° and 11.4° ± 8.7°, respectively). The severe group had significantly lower lumbar lordosis (LL, 25.1° ± 22.7°, p < 0.05) and Pelvic incidence-LL mismatch (PI-LL, 81.5° ± 26.6°, p < 0.001) than those of the mild (8.2° ± 16.3°/58.7° ± 18.8°) and moderate (14.3° ± 28.6°/66.8° ± 13.4°) groups. On receiver operating characteristic curve analysis, PI-LL was statistically significant, with an area under the curve of 0.810 (95% confidence interval) when the baseline was set at 75.3°. The severe group had more postoperative complications than the other groups.ConclusionsOur results suggest the following criteria for severe DSI: C7SVA > 20 cm within 30 s of walking or standing, a rigid lumbar curve < 10° on dynamic lateral radiographs, and a PI-LL mismatch > 75.3°.Level of evidence3.

Nightshift work and irregular menstrual cycle: 8-year follow-up cohort study.

Irregular menstruation is a major health problem among women, although its association with nightshift work remains controversial. To study the association between nightshift work and irregular menstrual cycle among female workers and investigate any differences according to sleep quality, working hours or obesity. This study included female workers who underwent health examinations from 2012 to 2019. Nightshift work, working hours, sleep quality and menstrual cycles were assessed using self-administered questionnaires. Irregular menstrual cycle was defined as self-reported irregular or ≥36 days. Adjusted odds ratios and 95% confidence intervals (CIs) were calculated by multivariable logistic regression; adjusted hazard ratios (95% CIs) for incident irregular menstrual cycle were calculated by Cox proportional hazard models with time-dependent analysis. The study participants were 87 147 in the cross-sectional study and 41 516 in the longitudinal study. After adjusting for all covariates in the cross-sectional analyses, the odds ratio for prevalent irregular menstrual cycle among female nightshift workers versus the reference was 1.26 (95% CI 1.2-1.33). In the cohort study, the adjusted hazard ratio for incident irregular menstrual cycle among nightshift workers was 1.95 (95% CI 1.61-2.35) in the period after 6 years. No significant differences were observed among subgroups stratified by sleep quality, working hours or obesity. Nightshift work is associated with an increased risk of both prevalent and incident irregular menstrual cycle in female workers without significant interactions by sleep quality, working hours or obesity.

Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Impact of pulmonary complications following esophagectomy on long-term survival: multivariate meta-analysis and restricted mean survival time assessment.

Pulmonary complications (PC) are common after esophagectomy and their impact on long-term survival is not defined yet. The present study aimed to assess the effect of postoperative PCs on long-term survival after esophagectomy for cancer. Systematic review of the literature through February 1, 2023, was performed. The included studies evaluated the effect of PC on long-term survival. Primary outcome was long-term overall survival (OS). Cancer-specific survival (CSS) and disease-free survival (DFS) were secondary outcomes. Restricted mean survival time difference (RMSTD), hazard ratio (HR), and 95% confidence intervals (CI) were used as pooled effect size measures. Eleven studies were included (3423 patients). Overall, 674 (19.7%) patients developed PC. The RMSTD analysis shows that at 60-month follow-up, patients not experiencing PC live an average of 8.5 (95% CI 6.2-10.8; p < 0.001) months longer compared with those with PC. Similarly, patients not experiencing postoperative PC seem to have significantly longer CSS (8months; 95% CI 3.7-12.3; p < 0.001) and DFS (5.4months; 95% CI 1.6-9.1; p = 0.005). The time-dependent HRs analysis shows a reduced mortality hazard in patients without PC at 12 (HR 0.6, 95% CI 0.51-0.69), 24 (HR 0.64, 95% CI 0.55-0.73), 36 (HR 0.67, 95% CI 0.55-0.79), and 60months (HR 0.69, 95% CI 0.51-0.89). This study suggests a moderate clinical impact of PC on long-term OS, CSS, and DFS after esophagectomy. Patients not experiencing PC seem to have a significantly reduced mortality hazard up to 5years of follow-up.

Time-dependent hormesis transfer from five high-frequency personal care product components to mixtures

There is potential for personal care products (PCPs) components and mixtures to induce hormesis. How hormesis is related to time and transmitted from components to mixtures are not clear. In this paper, we conducted determination of components in 16 PCP products and then ran frequent itemset mining on the component data. Five high-frequency components (HFCs), betaine (BET), 1,3-butanediol (BUT), ethylenediaminetetraacetic acid disodium salt (EDTA), glycerol (GLO), and phenoxyethanol (POE), and 14 mixtures were identified. For each mixture system, one mixture ray with the actual mixture ratios in the products was selected. Time-dependent microplate toxicity analysis was used to test the luminescence inhibition toxicity of five HFCs and 14 mixture rays to Vibrio qinghaiensis sp.-Q67 at 12 concentration gradients and eight exposure times. It is showed that BET, EDTA, POE, and 13 mixture rays containing at least one J-type component showed time-dependent hormesis. Characteristic parameters used to describe hormesis revealed that the absolute value of the maximum stimulatory effect (|Emin|) generally increased with time. Notably, mixtures composed of POE and S-type components showed greater |Emin| than POE alone at the same time. Importantly, the maximum stimulatory effective concentration, NOEC/the zero effective concentration point, and EC50 remained relatively stable. Nine hormesis transmission phenomena were observed in different mixture rays. While all mixtures primarily exhibited additive action, varying degrees of synergism and antagonism were noted in binary mixtures, with no strong synergism or antagonism observed in ternary and quaternary mixtures. These findings offer valuable insights for the screening of HFCs and their mixtures, as well as the study of hormesis transmission in personal care products.

Pentacene to Octacene: The Limit of Fourfold TIPS-Ethynylation

Soluble acenes beyond hexacene are rare. Their sensitivity complicates isolation, purification and application in devices. To increase the stability of acenes, functionalization with trialkylsilylethynyl substituents prevents [4 + 4] dimerization and oxidation. At the same time, such acenes are soluble and processible. Here we present the modular synthesis of fourfold tri-iso-propylsilylethynyl-ethynylated pentacenes to octacenes and investigate their optical and redox properties, frontier orbital positions (CV, density functional theory calculations) as well as their stability in solution (UV/vis, NMR spectroscopy). We also investigated their magnetic properties as a function of acene length. Pentacene, hexacene and heptacene are sufficiently stable to serve as semiconductors in thin-film transistors – the octacene rapidly decays to its butterfly dimer evidence by time-dependent NMR spectroscopy and crystal structure analysis.

Effects of Pre-Transplant CONUT and Post-Transplant MRD on Prognosis of Patients with Multiple Myeloma after Auto-HSCT

To explore the effects of pre-transplant controlling nutritional status (CONUT) and post-transplant minimal residual disease (MRD) on prognosis of patients with multiple myeloma (MM) after autologous hematopoietic stem cell transplantation (auto-HSCT). The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The patients were divided into Low-CONUT group (n=62) and High-CONUT group (n=17) according to whether the CONUT score was less than 5. The differences in clinical features, hematopoietic reconstruction, adverse reactions, efficacy and survival between the two groups were compared. In addition, the prognostic risk factors were analyzed and verified by time-dependent ROC curve. The proportions of male patients and bone marrow plasma cells>30% at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group (both P <0.05). While, there were no significant differences in hematopoietic reconstruction and adverse reactions (>grade 2) between the two groups. The complete response (CR) rate and CR+very good partial response (VGPR) rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group (both P <0.05). After 3 months of transplantation, the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group (P <0.01), but CR rate did not(P >0.05). The overall survival (OS) and progression-free survival (PFS) in Low-CONUT group were both superior to those in High-CONUT group (both P <0.05). Low CONUT score (0-4) before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS (both P <0.05), while the International Myeloma Working Group (IMWG) high-risk at initial diagnosis and lactate dehydrogenase (LDH) level>250 U/L before transplantation were only risk factors for PFS (both P <0.05). Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1- and 2-year OS and PFS, and the combined prediction was more effective. The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.

Yet Another Sunshine Mystery: Unexpected Asymmetry in GeV Emission from the Solar Disk

The Sun is one of the most luminous γ-ray sources in the sky and continues to challenge our understanding of its high-energy emission mechanisms. This study provides an in-depth investigation of the solar disk γ-ray emission, using data from the Fermi Large Area Telescope spanning 2008 August to 2022 January. We focus on γ-ray events with energies exceeding 5 GeV, originating from 0.°5 angular aperture centered on the Sun, and implement stringent time cuts to minimize potential sample contaminants. We use a helioprojection method to resolve the γ-ray events relative to the solar rotation axes and combine statistical tests to investigate the distribution of events over the solar disk. We found that integrating observations over large time windows may overlook relevant asymmetrical features, which we reveal in this work through a refined time-dependent morphological analysis. We describe significant anisotropic trends and confirm compelling evidence of energy-dependent asymmetry in the solar disk γ-ray emission. Intriguingly, the asymmetric signature coincides with the Sun’s polar field flip during the cycle 24 solar maximum, around 2014 June. Our findings suggest that the Sun’s magnetic configuration plays a significant role in shaping the resulting γ-ray signature, highlighting a potential link between the observed anisotropies, solar cycle, and the solar magnetic fields. These insights pose substantial challenges to established emission models, prompting fresh perspectives on high-energy solar astrophysics.

Performance of a tumor-informed molecular residual disease (MRD) assay in resected bladder cancer with mixed or pure variant histology: Analysis of a real-world multicenter cohort.

649 Background: Circulating tumor DNA (ctDNA)-based MRD assays can detect clinically occult disease with high sensitivity and specificity in patients with solid tumors. Previous trials that evaluated MRD testing in bladder cancer, such as ABACUS and IMVigor010, enrolled patients with a predominant urothelial carcinoma component. Given the known histological and molecular heterogeneity in urothelial carcinoma, we examined the prognostic value of a tumor-informed MRD assay in bladder cancer patients with mixed or pure variant histologies (M/VH). Methods: This retrospective study analyzed the results of post-cystectomy longitudinal ctDNA testing from a multi-institutional database of patients with urothelial carcinoma (n=205). A personalized, tumor-informed assay (Signatera, Natera, Inc.) was used for the detection and quantification of ctDNA. Patients with M/VH and at least 3 months of postoperative follow-up data on relevant demographic, clinical, pathologic, and NGS variables were eligible for inclusion. Time-dependent Cox regression analyses were performed for disease-free survival (DFS) based on ctDNA during the MRD window (&lt;12 weeks from surgery, N=29) and surveillance window (&gt;12 weeks post-surgery or post-AT, N=29). Multivariable regression was performed to adjust hazards for clinicopathologic factors predicting DFS. Results: Of the 205 patients, 46 (74% male, median age: 69 years) met the inclusion criteria for analysis. Whole exome sequencing of tumor tissue revealed that TP53 (45.7%), ARID1A (32.6%), and KDM6A (30.4%) were the top three genes with somatic mutations. Twenty-seven (59%) patients received neoadjuvant therapy, 37% of whom (10/27) also received adjuvant therapy. ctDNA-positivity during the MRD window and during surveillance was strongly associated with poor DFS (MRD window: HR=4.93, 95%CI: 1.77-20.77, p=0.03; surveillance: HR=28.3, 95% CI: 3.52-3660, p&lt;0.001). None of the serially ctDNA-negative patients (N=25) recurred, whereas 58.9% (10/17) of patients who were ctDNA-positive anytime post-surgery recurred at a median follow-up of 9 months from the date of surgery, range: 3.1-36.4 months). When adjusted for all other risk factors, ctDNA-positivity anytime post-surgery was the only significant predictor of recurrence (HR=55.26, 95%CI: 5.3-7648, p&lt;0.00001). Conclusions: Personalized, tumor-informed ctDNA testing can identify patients with mixed or variant histology bladder cancer who are at high risk of recurrence. Further studies are warranted to evaluate the potential benefit of ctDNA-guided adjuvant therapy in this patient population.

Flow cytometry-based measurable residual disease (MRD) analysis identifies AML patients who may benefit from allogeneic hematopoietic stem cell transplantation.

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRDpos) post-induction. MRDpos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRDneg patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRDpos patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRDpos intermediate-risk AML patients.

Mapping the spatiotemporal variability in global storm surge water levels using satellite radar altimetry

Multi-mission satellite altimetry data have been used to study the spatial and temporal variability in global storm surge water levels. This was done by means of a time-dependent extreme value analysis applied to the monthly maximum detided water levels. To account for the limited temporal resolution of the satellite data, the data were first stacked on a 5∘×5∘\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\varvec{5}^{\\varvec{\\circ }} \ imes \\varvec{5}^{\\varvec{\\circ }}$$\\end{document} grid. Moreover, additional scaling was applied to the extreme value analysis for which the scaling factors were determined by means of a resampling method using reanalysis data. In addition to the conventional analysis using data from tide gauges, this study provides an insight in the ocean-wide storm surge properties. Nonetheless, where possible, results were compared to similar information derived from tide gauge data. Except for secular changes, the satellite-derived results are comparable to the information derived from tide gauges (correlation >0.5\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$> \\varvec{0.5}$$\\end{document}), although the tide gauges show more local variability. Where limited correlation was observed for the secular change, it was suggested that the satellites may not be able to fully capture the temporal variability in the short-lived, tropical storms, as opposed to extra-tropical storms.

Development and validation of a combined cuproptosis and immunogenic cell death prognostic model for diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide with a high degree of heterogeneity. Cuproptosis and immunogenic cell death (ICD) have been considered to be vital for tumor progression. However, current understanding of cuproptosis and immunogenic cell death in DLBCL is still very limited. We aim to explore a prognostic model combining cuproptosis and immunogenic cell death in DLBCL. Pearson's correlation analysis was utilized to acquire lncRNAs associated with cuproptosis and immunogenic cell death. Prognostic biomarker identification and model construction involved the use of univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression. We assessed the predictive capability of the risk model by conducting Kaplan-Meier analysis and time-dependent ROC analysis. The analysis and comparison of immune infiltration and drug sensitivity were conducted in this study. Moreover, RT-qPCR was employed to validate the expression of lncRNAs associated with cuproptosis and immunogenic cell death in DLBCL cell lines. We identified 4 prognosis-related lncRNAs (ANKRD10-IT1, HOXB-AS1, LINC00520 and LINC01165) that were correlated with cuproptosis and immunogenic cell death. The model was verified to have a good and independent predictive ability in the prognostic prediction of DLBCL patients. Moreover, significant difference was observed in immune infiltration and drug sensitivity between high- and low-risk groups. Our discoveries could enhance the comprehension of the role of cuproptosis and ICD in DLBCL, potentially offering novel viewpoints and knowledge for personalized and precise treatment of DLBCL individuals.

Differences in the response of Chlorella pyrenoidosa to three antidepressants and their mixtures in different light-dark start cycles.

The use of antidepressants is increasing along with the continuing spike in the prevalence of depression worldwide. As a result, more and more antidepressants are entering the water and probably does harm to the aquatic organisms and even human health. Therefore, three antidepressants, including fluoxetine (FLU), citalopram (CIT), and aspirin (APC), were selected to investigate the toxic risks of antidepressants and their mixtures to a freshwater green alga Chlorella pyrenoidosa (C. pyrenoidosa). Due light is critical for the growth of green algae, six different light-dark cycle experiments were constructed to investigate the differences in toxicity and interaction responses of C. pyrenoidosa to antidepressants and their ternary mixture designed by the uniform design ray method. The toxic effects of individual antidepressants and their mixtures on C. pyrenoidosa were systematically investigated by the time-dependent microplate toxicity analysis (t-MTA) method. Toxicity interactions (synergism or antagonism) within mixtures were analyzed by the concentration addition (CA) and the deviation from the CA model (dCA) models. The results showed that the toxicities of the three antidepressants were different, and the order was FLU > APC > CIT. Light-dark cycles obviously affect the toxicity of three antidepressants and their combined toxicity interaction. Toxicity of the three antidepressants increases with the duration of light but decreases with the duration of darkness. The ternary antidepressant mixture exhibits antagonism, and the longer the initial lighting is, the stronger the antagonism. The antagonism of the ternary mixture is also affected by exposure time and mixture components' pi as well as exposure concentration.

AST to ALT ratio as a prospective risk predictor for liver cirrhosis in patients with chronic HBV infection.

Serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR) is one of the most frequent indicators to discriminate fibrosis and cirrhosis. However, the results remained controversial. The aim of this study was to evaluate the predictive effect of AAR on hepatitis B virus (HBV)-related cirrhosis development. A retrospective cohort study was conducted based on 1754 chronic HBV-infected patients. Clinical variables at their initial visit and follow-up data were collected. Cox proportional hazards model was constructed to evaluate the predictive value of AAR on cirrhosis risk, and its discrimination accuracy was determined by receiver operating characteristic (ROC). The time-dependent effect was assessed by a Fine and Gray competing risk model. Compared to patients with lower AAR, those with elevated AAR level had higher risk of cirrhosis development by adjusting for host characteristics (dichotomized analyses: hazard ratio = 2.77, P = 8.25 × 10 -4 ; tertile analyses: hazard ratio = 2.95, P = 1.61 × 10 -3 ), with an increasing risk trend ( Ptrend = 4.56 × 10 -4 ). The effect remained prominent when ALT or AST was abnormal, while no significant risk was observed when AST and ALT were simultaneously normal. Time-dependent effect analysis demonstrated a persistently higher risk, with the average hazard ratio equivalent to 1.92. AAR level could improve the discrimination efficacy of host variables with area under the curve increased from 0.684 to 0.711 ( P = 0.039 ). Higher AAR was significantly associated with increased risk of HBV-related cirrhosis, and might be a potential predictor of cirrhosis development.

Time-dependent reliability analysis of structural systems based on parallel active learning Kriging model

Time-dependent reliability analysis quantifies the failures of structural systems due to time-dependent uncertainties, such as material degradation and dynamic loads. The active learning Kriging model methods are widely used in structural reliability analysis to replace extensive time-consuming finite element simulations. However, they can only update one training sample and one failure mode per iteration, which limits their application to time-dependent, parallel computing, and multiple failure modes problems. In this study, we propose a new parallel active learning Kriging model for time-dependent reliability analysis, which can update multiple training samples and multiple failure modes per iteration. It includes the following strategies: (1) a novel parallel learning function is proposed, which combines the correlation function and U learning function to allow for the selection of multiple training samples per iteration; (2) an adaptive adjustment strategy for the number of parallel samples is proposed, which takes into account the prediction probability of parallel samples; (3) the proposed parallel learning function is integrated into time-dependent reliability analysis with multiple failure modes, enabling simultaneous updates of multiple training samples and failure modes, thus greatly reducing the number of iterations and computational time; and (4) a new stopping criterion is proposed to improve the efficiency of the estimation of failure probability. The proposed method can be applied to series or parallel time-dependent structural systems with multiple failure modes. We demonstrate the effectiveness of the proposed method through three examples, and the proposed method can achieve a balance between the computational time and function calls while maintaining a high level of accuracy in the estimation of time-dependent failure probability.