ABSTRACT
BACKGROUND: Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. METHODS: We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan-Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. RESULTS: The TSR cutoff was identified to be - 6.6%. Median PFS and OS were longer in the group with a TSR < -6.6% than in the group with a TSR ≥ - 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < - 6.6% than when it was > - 6.6%. Brain metastasis-free survival was better in the group with a TSR < - 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS. CONCLUSIONS: The TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC.
Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/mortality , Male , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Middle Aged , Aged , Prognosis , Retrospective Studies , Adult , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , RadiomicsABSTRACT
We consider the setting where (1) an internal study builds a linear regression model for prediction based on individual-level data, (2) some external studies have fitted similar linear regression models that use only subsets of the covariates and provide coefficient estimates for the reduced models without individual-level data, and (3) there is heterogeneity across these study populations. The goal is to integrate the external model summary information into fitting the internal model to improve prediction accuracy. We adapt the James-Stein shrinkage method to propose estimators that are no worse and are oftentimes better in the prediction mean squared error after information integration, regardless of the degree of study population heterogeneity. We conduct comprehensive simulation studies to investigate the numerical performance of the proposed estimators. We also apply the method to enhance a prediction model for patella bone lead level in terms of blood lead level and other covariates by integrating summary information from published literature.
Subject(s)
Computer Simulation , Humans , Linear Models , Biometry/methods , Lead/blood , Patella , Models, Statistical , Data Interpretation, StatisticalABSTRACT
Objective: This study aimed to identify prognostic signatures to predict the prognosis of patients with stomach adenocarcinoma (STAD), which is necessary to improve poor prognosis and offer possible treatment strategies for STAD patients. Methods: The overlapping genes between the key model genes that were screened by the weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) whose expression was different with significance between normal and tumor tissues were extracted to serve as co-expression genes. Then, enrichment analysis was performed on these genes. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression was performed to screen the hub genes among overlapping genes. Finally, we constructed a model to explore the influence of polygenic risk scores on the survival probability of patients with STAD, and interaction effect and mediating analyses were also performed. Results: DEGs included 2,899 upregulated genes and 2,896 downregulated genes. After crossing the DEGs and light-yellow module genes that were obtained by WGCNA, a total of 39 overlapping genes were extracted. The gene enrichment analysis revealed that these genes were enriched in the prion diseases, biosynthesis of unsaturated fatty acids, RNA metabolic process, hydrolase activity, etc. PIP5K1P1, PTTG3P, and SNORD15B were determined by LASSO-Cox. The prognostic prediction of the three-gene model was established. The Cox regression analysis showed that the comprehensive risk score for three genes was an independent prognosis factor. Conclusion: PIP5K1P1, PTTG3P, and SNORD15B are related to the prognosis and overall survival of patients. The three-gene risk model constructed has independent prognosis predictive ability for STAD.
ABSTRACT
BACKGROUND: Running exposes the body to physiological and mechanical stresses that generate musculoskeletal injuries, such as low back pain due to large spinal loading. Increasing running cadence may reduce impact forces and spinal shrinkage. RESEARCH QUESTION: This study aimed to determine the relationship between spinal loading and running cadence. METHODS: This cross-sectional study included 15 runners from the local community (36 ± 11 years; 23 ± 2â¯kg.m-2, and 8 ± 9 years of running experience) who ran for 30â¯min (R30) and 60â¯min (R60) at a constant speed (10â¯km.h-1). The spinal loading was assessed via fine stature variation measurements before the run (baseline) at R30 and R60. Cadence was monitored via a wristwatch. The cadence ranged from 150 to 180 steps.min-1. A t-test was used to compare stature loss between R30 and R60 (relative to baseline), and a stepwise linear regression equation was used to identify the relationship between cadence and stature variation in each instant. RESULTS: There was a stature loss throughout the race (R30 = 5.27 ± 1.92â¯mm and R60 =7.51 ± 2.51â¯mm). A linear regression analysis revealed a negative relationship between stature loss and cadence, indicating that running at a faster cadence produces smaller spinal loading than running at slower cadences after R60 (R2 = 0.38; p<0.05). SIGNIFICANCE: Increasing running cadence might cause less spinal loading than running with a slower cadence, which may reduce the risk of injury and back disorders in runners.
ABSTRACT
Uterine leiomyoma is a common condition affecting women that occurs in more than 70% of females. Women with leiomyomas overall have lower quality of life and deficiency in many specific spheres of life including work-related productivity, sexuality, relationships, social-emotional health, and physical well-being that might be present even in pre-and extended throughout early postmenopausal life. Choices for symptomatic fibroid management include medical, interventional radiology procedures, surgical, and expectant management. The uterine artery embolization (UAE) procedure has gained justified popularity for myoma management. Growth factors, vascular endothelial growth factor (VEGF) and tumor growth factor ß (TGF-ß), hold an important role in leiomyoma progression. However, blood levels of VEGF and TGF-ß in patients before and after UAE are not fully investigated and the possible relationship with myoma shrinkage has not been evaluated. Therefore, this study aims to assess menorrhagia score and quality of life improvement after UAE for uterine fibroids and compare blood levels of VEGF and TGF-ß in patients with uterine leiomyoma before and after UAE. This cross-sectional study will be performed at the University Medical Center, Astana, Kazakhstan. Women undergoing the UAE procedure for uterine leiomyoma will be involved in the study following the precisely defined inclusion/exclusion criteria. Uterine leiomyoma nodules' structural changes after UAE will be assessed along with the blood levels of growth factors (VEGF and TGF-ß), menorrhagia score, and quality of life. An important outcome of this project will be an investigation of the blood levels of growth factors (VEGF and TGF-ß) before and after the procedure and their association with leiomyoma shrinkage in correlation with the menorrhagia score and quality of life alterations among patients undergoing UAE.
ABSTRACT
The association between depth of response (DpR) and treatment outcomes has been documented across various types of cancer. Immune checkpoint inhibitor (ICI)-based treatment is globally used as first-line treatment for non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥ 50%. However, in this population, the significance of DpR is not elucidated. Patients with advanced NSCLC and PD-L1 expression ≥ 50% who received ICI-monotherapy or ICI plus chemotherapy were retrospectively enrolled into this study. Treatment responses were grouped into DpR 'quartiles' by percentage of maximal tumor reduction (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, and Q4 = ≥ 76%), and no tumor reduction (NTR). The association between DpR and survival rates were determined using hazard ratios (HR) generated by the Cox proportional hazards model. The Kaplan-Meier method was used to determine survival outcomes. A total of 349 patients were included, of which 214 and 135 patients received pembrolizumab monotherapy and ICI plus chemotherapy, respectively, as first-line treatments. The majority of the patients were male. All DpR quartiles, especially Q4, showed an association with progression-free survival (PFS)/overall survival (OS). In the Q4 cohort, patients who received pembrolizumab had a longer PFS than those who received ICI plus chemotherapy. High DpR was associated with longer PFS and OS, with a more pronounced effect observed with pembrolizumab monotherapy than with ICI plus chemotherapy.
ABSTRACT
Background: In the context of head-and-neck squamous cell carcinoma (HNSCC), dendritic cells (DCs) assume pivotal responsibilities, acting as architects of antigen presentation and conductors of immune checkpoint modulation. In this study, we aimed to identify hub genes associated with DCs in HNSCC and explore their prognostic significance and implications for immunotherapy. Methods: Integrated clinical datasets from The Cancer Genome Atlas (TCGA)-HNSCC and GSE65858 cohorts underwent meticulous analysis. Employing weighted gene co-expression network analysis (WGCNA), we delineated candidate genes pertinent to DCs. Through the application of random survival forest and least absolute shrinkage and selection operator (LASSO) Cox's regression, we derived key genes of significance. Lisa (epigenetic Landscape In Silico deletion Analysis and the second descendent of MARGE) highlighted transcription factors, with Dual-luciferase assays confirming their regulatory role. Furthermore, immunotherapeutic sensitivity was assessed utilizing the Tumor Immune Dysfunction and Exclusion online tool. Results: This study illuminated the functional intricacies of HNSCC DC subsets to tailor innovative therapeutic strategies. We leveraged clinical data from the TCGA-HNSCC and GSE65858 cohorts. We subjected the data to advanced analysis, including WGCNA, which revealed 222 DC-related candidate genes. Following this, a discerning approach utilizing random survival forest analysis and LASSO Cox's regression unveiled seven genes associated with the prognostic impact of DCs, notably ACP2 and CPVL, associated with poor overall survival. Differential gene expression analysis between ACP2 + and ACP2 - DC cells revealed 208 differential expressed genes. Lisa analysis identified the top five significant transcription factors as STAT1, SPI1, SMAD1, CEBPB, and IRF1. The correlation between STAT1 and ACP2 was confirmed through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Dual-luciferase assays in HEK293T cells. Additionally, TP53 and FAT1 mutations were more common in high-risk DC subgroups. Importantly, the sensitivity to immunotherapy differed among the risk clusters. The low-risk cohorts were anticipated to exhibit favorable responses to immunotherapy, marked by heightened expressions of immune system-related markers. In contrast, the high-risk group displayed augmented proportions of immunosuppressive cells, suggesting a less conducive environment for immunotherapeutic interventions. Conclusions: Our research may yield a robust DC-based prognostic system for HNSCC; this will aid personalized treatment and improve clinical outcomes as the battle against this challenging cancer continues.
ABSTRACT
The industrial production of cement contributes significantly to greenhouse gas emissions, making it crucial to address and reduce these emissions by using fly ash (FA) as a potential replacement. Besides, Graphene oxide (GO) was utilized as nanoparticle in concrete to augment its mechanical characteristics, deformation resistance, and drying shrinkage behaviours. However, the researchers used Response Surface Methodology (RSM) to evaluate the compressive strength (CS), tensile strength (TS), flexural strength (FS), modulus of elasticity (ME), and drying shrinkage (DS) of concrete that was mixed with 5-15% FA at a 5% increment, along with 0.05%, 0.065%, and 0.08% of GO as potential nanomaterials. The concrete samples were prepared by using mix proportions of design targeted CS of about 45 MPa at 28 days. From investigational outcomes, the concrete with 10% FA and 0.05% GO exhibited the greatest CS, TS, FS, and ME values of 62 MPa, 4.96 MPa, 6.82 MPa, and 39.37 GPa, on 28 days correspondingly. Besides, a reduction in the DS of concrete was found as the amounts of FA and GO increased. Moreover, the development and validation of response prediction models were conducted utilizing analysis of variance (ANOVA) at a significance level of 95%. The coefficient of determination (R2) values for the models varied from 94 to 99.90%. Research study indicated that including 10% fly ash (FA) as a substitute for cement, when combined with 0.05% GO, in concrete yields the best results. Therefore, this approach is an excellent option for the building sector.
ABSTRACT
OBJECTIVE: Tongue squamous cell carcinoma (TSCC) accounts for 43.4% of oral cancers in China and has a poor prognosis. This study aimed to explore whether radiomics features extracted from preoperative magnetic resonance imaging (MRI) could predict overall survival (OS) in patients with TSCC. METHODS: The clinical imaging data of 232 patients with pathologically confirmed TSCC at Xiangyang No. 1 People's Hospital were retrospectively analyzed from February 2010 to October 2022. Based on 2-10 years of follow-up, patients were categorized into two groups: control (healthy survival, n = 148) and research (adverse events: recurrence or metastasis-related death, n = 84). A training and a test set were established using a 7:3 ratio and a time node. Radiomics features were extracted from axial T2-weighted imaging, contrast-enhanced T1-weighted imaging, and diffusion-weighted imaging (DWI) sequences. The corresponding radiomics scores were generated using the least absolute shrinkage and selection operator algorithm. Kaplan-Meier and multivariate Cox regression analyses were used to screen for independent factors affecting adverse events in patients with TSCC using clinical and pathological results. A novel nomogram was established to predict the probability of adverse events and OS in patients with TSCC. RESULTS: The incidence of adverse events within 2-10 years after surgery was 36.21%. Kaplan-Meier analysis revealed that hot pot consumption, betel nut chewing, platelet-lymphocyte ratio, drug use, neutrophil-lymphocyte ratio, Radscore, and other factors impacted TSCC survival. Multivariate Cox regression analysis revealed that the clinical stage (P < 0.001), hot pot consumption (P < 0.001), Radscore 1 (P = 0.01), and Radscore 2 (P < 0.001) were independent factors affecting TSCC-OS. The same result was validated by the XGBoost algorithm. The nomogram based on the aforementioned factors exhibited good discrimination (C-index 0.86/0.81) and calibration (P > 0.05) in the training and test sets, accurately predicting the risk of adverse events and survival. CONCLUSION: The nomogram constructed using clinical data and MRI radiomics parameters may accurately predict TSCC-OS noninvasively, thereby assisting clinicians in promptly modifying treatment strategies to improve patient prognosis.
Subject(s)
Magnetic Resonance Imaging , Nomograms , Tongue Neoplasms , Humans , Male , Female , Middle Aged , Tongue Neoplasms/pathology , Tongue Neoplasms/mortality , Tongue Neoplasms/diagnostic imaging , Tongue Neoplasms/surgery , Retrospective Studies , Pilot Projects , Survival Rate , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/statistics & numerical data , Prognosis , Follow-Up Studies , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Aged , Adult , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/surgery , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/mortality , RadiomicsABSTRACT
INTRODUCTION: Marsupialization is a dependable choice for mandibular unicystic ameloblastoma (UA) management. However, investigations regarding its speed of shrinkage (SS) and reduction rate (RR) are lacking. This case report highlights the treatment of a huge mandibular UA with high SS and RR using marsupialization before secondary surgery. PRESENTATION OF CASE: A 45-year-old male patient presented with severe swelling of the right side of the mandible, resulting in prominent facial asymmetry. Panoramic radiograph revealed a unilocular, radiolucent lesion extending from the mandibular midline to the right ramus. Computed tomography (CT) revealed a large radiolucent lesion that expanded in the buccolingual direction. Incisional biopsy showed that the lesion was UA. After 1.5 years of marsupialization, an SS of 0.183 % per day was reached, leading to an impressive RR of 98.7 %. Treatment was followed by enucleation and peripheral osteotomy. No recurrence was observed at 1 year post-surgery. DISCUSSION: The treatment of mandibular UA remains controversial, ranging from conservative approaches to aggressive interventions. In the current case, marsupialization was highly effective in reducing the volume of the lesion, thereby facilitating a minimally invasive secondary surgery to preserve function. The intact periosteum, which has the potential to differentiate into various cell types, may be associated with the regeneration of new bone after marsupialization. CONCLUSION: Marsupialization remains a successful strategy for managing mandibular UA. Even the huge lesions causing facial deformity can be treated with marsupialization combined with secondary surgery, avoiding the aesthetic and functional disruptions associated with radical treatment.
ABSTRACT
Pollen is becoming an increasingly important subject for molecular researchers in genetic engineering, plant breeding, and environmental monitoring. To broaden the scope of these studies, it is essential to develop accessible methods for scientists who are not specialized in palynology. The article presents a simplified technical procedure for preparing pollen grains for scanning electron microscopy (SEM). The protocol is convenient for any molecular laboratory due to its small set of reagents, ease of execution, low cost, does not require special equipment, and takes only one hour to complete. The high penetrating ability of formaldehyde and the final delicate dehydration using hexamethyldisilazane (HMDS) instead of critical point drying allow for sufficient preservation of the architecture of the aperture, which is considered a gateway for the passage of biomolecules. The method was successfully applied to pollen grains of representatives of dicotyledons (beetroot, petunia, radish, tomato and tobacco) and monocotyledons (lily, onion, corn, rye and wheat). Species studied included insect-pollinated (entomophilous) and wind-pollinated (anemophilous) species. A comparative analysis of the sizes of fresh living pollen grains under a light microscope and those prepared for SEM showed some shrinkage. Quantitative analysis of the degree of pollen grain shrinkage showed that this process depends on the initial shape of dry pollen grains, and the number and structure of apertures. The results support the theoretical model of the folding/unfolding pathways of pollen grains.
ABSTRACT
The soft PBAT foam shows good flexibility, high elasticity, degradable nature, and it can be used as an environmental-friendly candidate for EVA and PU foams. Unfortunately, there are few reports on the application of PBAT as a soft foam. In this study, PBAT foam was fabricated by a pressure quenching method using CO2 as the blowing agent. A significant volume shrinkage of about 81% occurred, where the initial PBAT foam had an extremely high expansion ratio, of about 31 times. A 5-10 wt% PBS with high crystallinity was blended, and N2 with low gas solubility and diffusivity was mixed, with the aim of resisting foam shrinkage and preparing PBAT with a high final expansion ratio of 14.7 times. The possible mechanism behind this phenomenon was established, and the increased matrix modulus and decreased pressure difference within and outside the cell structure were the main reasons for the shrinkage resistance. The properties of PBAT and PBAT/PBS foams with a density of 0.1 g/cm3 were measured, based on the requirements for shoe applications. The 5-10 wt% PBS loading presented advantages in reducing thermal shrinkage at 75 °C/40 min, without compromising the hardness, elasticity, and the compression set, which ensures that PBAT/PBS foams have good prospects for use as soft foams.
ABSTRACT
In cold regions with high daily temperature gradients (>20 °C), the durability of cement-stabilized macadam (CSM) base materials is poor and prone to cracking. To effectively reduce the cracking of semi-rigid base layers in cold regions with high daily temperature gradients and extend fatigue life, this study focused on cracking and fatigue characteristics of CSM with a 10% commercial early strength agent (ESA) added by the external mixing method under different curing conditions. The ESA was manufactured by Jiangsu Subote New Materials Co., Ltd. (Nanjing, China). The curing conditions were divided into variable temperature (0-20 °C) and standard temperature (20 °C). CSM curing was carried out through a programmable curing box. The research results indicated that the variable temperature curing conditions reduced the strength and fatigue resistance of CSM and accelerated the modulus attenuation rate of CSM. At the same time, the drying shrinkage of CSM was greater. The temperature shrinkage coefficient and strain of CSM under variable temperature conditions were smaller than those under standard temperature conditions. The effect of variable temperature conditions on the cracking and durability of CSM could not be ignored in cold regions. Compared to standard temperature curing conditions, the indirect tensile strength of CSM reduced by 31.04% under variable temperature conditions, the coefficient of variation increased by 2.97 times, and the discrete type significantly increased. Compared with CSM without ESA, the dry and temperature shrinkage strains of CSM with 10% ESA were reduced by 24.65% and 26.10%, respectively. At a stress level of 0.6, compared to standard temperature curing conditions, the fatigue life of CSM decreased by 97.19% under variable temperature conditions. Under variable temperature conditions, the fatigue life of CSM with 10% ESA increased by 196 times compared to 0% ESA. Adding ESA enhanced the anti-shrinkage cracking, strength, and durability of CSM under variable temperatures. ESA incorporation effectively compensated for the weakened characteristics of CSM under variable temperature conditions. The study proposed a practical approach for boosting the durability of CSM in cold environments.
ABSTRACT
Biomass fly ash is a sustainable, eco-friendly cement substitute with economic and performance benefits, being renewable compared to coal fly ash. This study examines using biomass fly ash (BFA) as a sustainable cement substitute, comparing it with Class F fly ash (CFA). With a water-binder ratio of 0.5 and replacement rates of 10%, 15%, 20%, 25%, and 30% (by mass), the research highlights BFA's promising applications. BFA and CFA were mixed into cement paste/mortar to analyze their reactivity and properties, with hydration products CH and C-S-H evaluated at 7, 28, and 91 days. Compressive strength, micro-pore structure, and drying shrinkage (assessed from 7 to 182 days) were tested. Results showed BFA had similar pozzolanic reactions to CFA at later stages. While compressive strength decreased with higher BFA replacement rates, early-stage performance matched CFA; growth was CFA-10 (18 MPa) and BFA-10 (17.6 MPa). BFA mortars exhibited slightly better deformation properties. BFA-30 cement had superior performance, with a lower drying shrinkage rate of 65.7% from 14 to 56 days compared to CFA-10's 73.4% and a more stable shrinkage growth rate decrease to 8.4% versus CFA-10's 6.4% after 56 days. This study concluded that BFA, usable without preprocessing, performed best at a 10-15% replacement rate.
ABSTRACT
In this study, the characteristics of grout mixed with charcoal as an expansive agent were examined to reduce the pre-hardening shrinkage of cementitious materials. This study compared and reviewed the application of CSA, a conventional expansive agent, to grout. The setting time, fluidity, compressive strength, and pre-hardening shrinkage/expansion were evaluated to explore the usability of charcoal as an expansive agent. The test results confirmed that, as the incorporation rate of charcoal increased, the pre-hardening expansion rate of the grout also increased, making it more effective for pre-hardening expansion than the conventional expansive agent CSA. However, when charcoal was used as an expansive agent, the compressive strength decreased after hardening, indicating the need for caution regarding the amount of charcoal used. Furthermore, the pre-hardening shrinkage and expansion rates of the various types of charcoal used in this study showed some differences, suggesting the need for further research on the internal pore volume and pore size of the charcoal.
ABSTRACT
Lightweight concrete offers numerous advantages for modular construction, including easier construction planning and logistics, and the ability to offset additional dead loads induced by double-wall and double-slab features. In a previous study, authors proposed incorporating lightweight aggregate into foamed concrete instead of adding extra foam to achieve lower density, resulting in lightweight concrete with an excellent strength-to-density ratio. This paper further investigated the performance aspects of foamed concrete with lightweight aggregate beyond mechanical strength. To evaluate the effect of aggregate type and foam content, three mix compositions were designed for the lightweight concrete. Specimens were prepared for experimental tests on thermal conductivity and drying shrinkage of lightweight concrete. Results showed that while both the increase in foam volume and the incorporation of lightweight aggregate led to higher drying shrinkage, they also contributed to improved insulating properties and reduced potential of cracking. Using typical multi-storey modular residential buildings in Hong Kong and three other Chinese cities as case studies, simulations were performed to assess potential savings in annual cooling and heating loads by employing the proposed lightweight concrete. These findings demonstrate the practical benefits of using foamed concrete with lightweight aggregate in modular construction and provide valuable insights for further optimization and implementation.
ABSTRACT
To address shortages in construction materials for island engineering, tackle the accumulation of solid waste, and inhibit the shrinkage of geopolymers, coral waste was utilized as the internal curing material to prepare high-performance marine geopolymer concrete (MGC) with seawater, sea-sand, and normal limestone aggregate (LsA). The coral coarse aggregate (CorA) used in this investigation has a total porosity ranging from 50% to 58.3% with internal pore diameters spanning 50-400 µm. The water desorption of CorA followed a two-stage pattern within a relative humidity (RH) range of 75%-85%, becoming nonlinear above 90% RH, which released about 85% of its moisture within 200 h at 97% RH, demonstrating potential for internal curing. Adding a small amount of CorA to MGC increased slump and setting time by providing internal curing water. However, as CorA content exceeded 30%, the slump significantly decreased due to reduced mixing water and elevated activator concentration, while the initial setting time slightly decreased. Furthermore, the inclusion of saturated CorA in MGC significantly reduced autogenous shrinkage, with higher CorA contents (exceeding 30%) leading to slight expansion in the early stages and nearly eliminating shrinkage at contents above 40%. The greater drying shrinkage in geopolymer systems compared to ordinary Portland cement is due to capillary pressure compressing the product framework, converting larger gel pores into smaller ones. Additionally, the layered calcium aluminosilicate hydrate (C-A-S-H) gel exhibits more pronounced creep characteristics under low internal humidity conditions. The higher CorA content in MGC promoted the formation of hybrid C, N-A-S-H gel and hydrotalcite-like phases, and reduced carbonation issues. The interfacial transition zone (ITZ) between CorA and the geopolymer matrix formed a robust mechanical interlock, enhancing tensile strength and minimizing shrinkage-induced cracks. Based on overall performance and marine material utilization, an optimal substitution rate of CorA between 40% and 50% is recommended.
ABSTRACT
This paper tackles the challenge of estimating correlations between higher-level biological variables (e.g. proteins and gene pathways) when only lower-level measurements are directly observed (e.g. peptides and individual genes). Existing methods typically aggregate lower-level data into higher-level variables and then estimate correlations based on the aggregated data. However, different data aggregation methods can yield varying correlation estimates as they target different higher-level quantities. Our solution is a latent factor model that directly estimates these higher-level correlations from lower-level data without the need for data aggregation. We further introduce a shrinkage estimator to ensure the positive definiteness and improve the accuracy of the estimated correlation matrix. Furthermore, we establish the asymptotic normality of our estimator, enabling efficient computation of P-values for the identification of significant correlations. The effectiveness of our approach is demonstrated through comprehensive simulations and the analysis of proteomics and gene expression datasets. We develop the R package highcor for implementing our method.
ABSTRACT
The search for genetic variants that act as causative factors in human diseases by disrupting the normal splicing process has primarily focused on single nucleotide variants (SNVs). It is worth noting that insertions or deletions (indels) have also been sporadically reported as causative disease variants through their potential impact on the splicing process. In this study, to perform identification of indels inducing exon extension/shrinkage events, we used individual-specific genomes and RNA sequencing (RNA-seq) data pertaining to the corresponding individuals and identified 12 exon extension/shrinkage events that were potentially induced by indels that disrupted authentic splice sites or created novel splice sites in 235 normal individuals. By evaluating the impact of these abnormal splicing events on the resulting transcripts, we found that five events led to the generation of premature termination codons (PTCs), including those occurring within genes associated with genetic disorders. Our analysis revealed that the potential functions of indels have been underexamined, and it is worth considering the possibility that indels may affect splice site usage, using RNA-seq data to discover novel potentially disease-associated mutations.
ABSTRACT
BACKGROUND: Breast cancer patients exhibit various response patterns to neoadjuvant chemotherapy (NAC). However, it is uncertain whether diverse tumor response patterns to NAC in breast cancer patients can predict survival outcomes. We aimed to develop and validate radiomic signatures indicative of tumor shrinkage and therapeutic response for improved survival analysis. METHODS: This retrospective, multicohort study included three datasets. The development dataset, consisting of preoperative and early NAC DCE-MRI data from 255 patients, was used to create an imaging signature-based multitask model for predicting tumor shrinkage patterns and pathological complete response (pCR). Patients were categorized as pCR, nonpCR with concentric shrinkage (CS), or nonpCR with non-CS, with prediction performance measured by the area under the curve (AUC). The prognostic validation dataset (n = 174) was used to assess the prognostic value of the imaging signatures for overall survival (OS) and recurrence-free survival (RFS) using a multivariate Cox model. The gene expression data (genomic validation dataset, n = 112) were analyzed to determine the biological basis of the response patterns. RESULTS: The multitask learning model, utilizing 17 radiomic signatures, achieved AUCs of 0.886 for predicting tumor shrinkage and 0.760 for predicting pCR. Patients who achieved pCR had the best survival outcomes, while nonpCR patients with a CS pattern had better survival than non-CS patients did, with significant differences in OS and RFS (p = 0.00012 and p = 0.00063, respectively). Gene expression analysis highlighted the involvement of the IL-17 and estrogen signaling pathways in response variability. CONCLUSIONS: Radiomic signatures effectively predict NAC response patterns in breast cancer patients and are associated with specific survival outcomes. The CS pattern in nonpCR patients indicates better survival.