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ObjectivesTo identify existing DNA methylation-based prognostic biomarkers and prediction models for colorectal cancer (CRC) prognosis and to validate them in a large external cohort.DesignSystematic review and external validation study.Data sourceSystematic search in PubMed and Web of Science until October 2022 to identify epigenome-wide studies reporting methylation at CpG sites (CpGs) associated with survival among CRC patients. Validation data were drawn from the 2310 CRC patients of the DACHS study recruited from 22 hospitals in the Rhine-Neckar region in the southwest of Germany.Main outcome measuresOverall survival (OS) in CRC patients.ResultsWe identified 200 unique CpGs and 10 CpG-based prognostic models derived from 15 studies. In the external validation analysis, 1252 of 2310 patients died during follow-up (median 10.4 years). Thirty-nine CpGs (20%) and five prognostic models (50%) were independently associated with overall survival after adjustment for clinical variables. The five models had unsatisfactory discrimination ability, with area under the receiver operating characteristic curves at five years ranging from 0.54 to 0.60. The calibration accuracy of the five models using recalibrated baseline survival was also poor, and no relevant added prognostic value to traditional clinical variables was observed. Based on the Prediction Model Risk of Bias Assessment Tool, all models were rated as high risk of bias.ConclusionsOnly 20% of published CpGs associated with survival in CRC patients could be externally validated. So far derived published CpG-based prognostic models for CRC do not seem to be useful for clinical practice.Summary boxWhat is already known on this topicSeveral studies have suggested that DNA methylation biomarkers could have the potential to improve prognostic accuracy for patients with colorectal cancer (CRC), but these studies mostly did not include large-scale external validationMany CpG sites associated with CRC prognosis and prognostic models based on these CpGs have been proposedAn independent study to validate these biomarkers and prediction models is essential for assessing their utility in clinical practice, but has not yet performedWhat this study addsThis external validation study verified the prognostic relevance of a fraction of existing DNA methylation-based prognostic biomarkers for CRCPublished CpG-based prognostic models all performed poorly in our external validation and were rated as at high risk of bias, so they do not seem to be useful for clinical practice

SummaryBackgroundDNA methylation biomarkers have great potential in improving prognostic classification systems for patients with cancer. Machine learning (ML)-based analytic techniques might help overcome the challenges of analyzing high-dimensional data in relatively small sample sizes. This systematic review summarizes the current use of ML-based methods in epigenome-wide studies for the identification of DNA methylation signatures associated with cancer prognosis.MethodsWe searched three electronic databases including PubMed, EMBASE, and Web of Science for articles published until 8 June 2022. ML-based methods and workflows used to identify DNA methylation signatures associated with cancer prognosis were extracted and summarized. Two authors independently assessed the methodological quality of included studies by a seven-item checklist adapted from relevant guidelines.ResultsSeventy-six studies were included in this review. Three major types of ML-based workflows were identified: 1) unsupervised clustering, 2) supervised feature selection, and 3) deep learning-based feature transformation. For the three workflows, the most frequently used ML techniques were consensus clustering, least absolute shrinkage and selection operator (LASSO), and autoencoder, respectively. The systematic review revealed that the performance of these approaches has not been adequately evaluated yet and that methodological and reporting flaws were common in the identified studies using ML techniques.ConclusionsThere is great heterogeneity in ML-based methodological strategies used by epigenome-wide studies to identify DNA methylation markers associated with cancer prognosis. Benchmarking studies are needed to compare the relative performance of various approaches for specific cancer types. Adherence to relevant methodological and reporting guidelines is urgently needed.

Introduction: The growth rate of meningiomas varies greatly (0.01 to 2.58 cm3/year).An inappropriate ‘wait and see’ treatment strategy, such as a follow-up interval of MRI longer than 2 years, for rapid growing meningioma (RGM) may seriously increase the risk of subsequent surgery and may eliminate the opportunity for operation. Our purpose was to compare the MR imaging features of slow-growing meningiomas (SGMs) and RGMs and identify the factors that could predict RGM.Methods: We retrospectively collected SGM and RGM data between 2016 and 2021 in Beijing Tiantan Hospital and then used IBM SPSS software to analyze the clinical and MR imaging features between the two groups.Results: Eighty-seven SGM and 78 RGM were collected in our study. Male sex had a 2.896-fold risk of predicting RGM in multivariate analysis (P = 0.048). Patient age, tumor shape and location showed no significant difference between the two groups (P = 0.562, P = 0.514, P = 0.094, respectively). Meningiomas with diameters > 2.5 cm had a higher risk of growing rapidly (multivariate analysis, HR: 3.484, P = 0.006). The presence of peritumoral edema and absence of hypointensity on T2W-MRI were significantly associated with RGM (multivariate analysis; HR: 6.990, P < 0.001; HR: 3.753, P = 0.008;, respectively).Conclusions: Male sex, peritumoral edema, tumor size > 2.5 cm and absence of hypointensity on T2W-MRI may indicate the potential for rapid growth of meningiomas.

Conductive hydrogels have attached considerable attention due to their good stretchability, excellent conductivity when they are applied in soft electronics. However, to fabricate a flexible hydrogel sensor with excellent toughness and good self-healing properties remains a challenge. In this work, we assembled a dual physical-crosslinking (DPC) ionic conductive polyacrylamide/carrageenan double-network (DN) hydrogel. This hydrogel has excellent fracture tensile stress and toughness, and demonstrates rapid self-recovery and self-healing ability due to the unique dual physical-crosslinking structures. Besides, the hydrogel is highly conductive by adding some conductive ions. As a result, the hydrogel-based sensor can stably detect human motions and physiological signals. The work provides novel ideas for the development of flexible sensing devices.

Adropin is a recently discovered peptide hormone that plays a vital role in metabolism and cardiovascular-cerebrovascular function. The purpose of this study is to investigate the role of circulating adropin levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and further determine the relationship between serum adropin concentration and endothelial dysfunction in patients with OSAHS. Forty polysomnography-diagnosed patients with OSAHS and 21 age and sex-matched healthy controls were enrolled in the current study. Serum adropin level, endothelial function parameters including flow-mediated dilatation (FMD) of brachial artery, endothelin-1 (ET-1), and nitric oxide (NO) were measured in all participants. Serum adropin levels were significantly lower in patients with OSAHS compared to the control subjects. FMD was lower and serum ET-1 levels were higher in patients with OSAHS compared to control subjects. No significant difference was seen in serum NO levels between the two groups. Multivariate linear regression analysis revealed that serum adropin level was positively associated with FMD and negatively correlated with AHI. Additionally, serum adropin levels were lower in patients with OSAHS who had endothelial dysfunction compared with those patients without endothelial dysfunction. The receiver operating characteristic (ROC) analysis showed that area under the curve (AUC) for serum adropin in predicting endothelial dysfunction status in patients with OSAHS was 0.815 (95% CI 0.680–0.951, p = 0.001). The cutoff value of serum adropin level was less than 235.0 pg/mL, which provided the sensitivity and specificity of 81% and 75%, respectively, for the detection of endothelial dysfunction in patients with OSAHS. Lower circulating adropin levels are closely associated with endothelial dysfunction in patients with OSAHS. Circulating adropin level may serve as an early biomarker to predict the development of endothelial dysfunction before the emergence of clinical symptoms in patients with OSAHS.

The capture of the xenon and krypton from nuclear reprocessing off-gas is essential to the treatment of radioactive waste. Although various porous materials have been employed to capture Xe and Kr, the development of high-performance adsorbents capable of trapping Xe/Kr at very low partial pressure as in the nuclear reprocessing off-gas conditions remains challenging. Herein, we report a self-adjusting metal-organic framework based on multiple weak binding interactions to capture trace Xe and Kr from the nuclear reprocessing off-gas. The self-adjusting behavior of ATC-Cu and its mechanism have been visualized by the in-situ single-crystal X-ray diffraction studies and theoretical calculations. The self-adjusting behavior endows ATC-Cu unprecedented uptake capacities of 2.65 and 0.52 mmol g

Tracheal defects lead to devastating problems, and practical clinical substitutes that have complex functional structures and can avoid adverse influences from exogenous bioscaffolds are lacking. Herein, a modular strategy for scaffold-free tracheal engineering is developed. A cartilage sheet (Cart-S) prepared by high-density culture is laminated and reshaped to construct a cartilage tube as the main load-bearing structure in which the chondrocytes exhibit a stable phenotype and secreted considerable cartilage-specific matrix, presenting a native-like grid arrangement. To further build a tracheal epithelial barrier, a temperature-sensitive technique is used to construct the monolayer epithelium sheet (Epi-S), in which the airway epithelial cells present integrated tight junctions, good transepithelial electrical resistance, and favorable ciliary differentiation capability. Epi-S can be integrally transferred to inner wall of cartilage tube, forming a scaffold-free complex tracheal substitute (SC-trachea). Interestingly, when Epi-S is attached to the cartilage surface, epithelium-specific gene expression is significantly enhanced. SC-trachea establishes abundant blood supply via heterotopic vascularization and then is pedicle transplanted for tracheal reconstruction, achieving 83.3% survival outcomes in rabbit models. Notably, the scaffold-free engineered trachea simultaneously satisfies sufficient mechanical properties and barrier function due to its matrix-rich cartilage structure and well-differentiated ciliated epithelium, demonstrating great clinical potential for long-segmental tracheal reconstruction.

Object Epilepsy is one of the most common clinical manifestations of primary brain tumors. Intraoperative electrocorticography (ECoG) has been widely used in tumor resection. We aim to describe the indication and utility of ECoG during brain tumor surgery. Methods We performed a systematic review of the literature on the prognosis of tumor-related epilepsy surgery guided by intraoperative ECoG. The published studies were searched in PubMed, Embase, and Web of Science using the keyword ‘seizure’ or ‘epilepsy’ and ‘electrocorticography’ or ‘ECoG’. Two reviewer authors screened studies and extracted data independently. Results Thirteen studies included 569 patients were finally selected, of which eight investigated medically intractable epilepsy. Three publications described temporal tumor-related epilepsy. All included studies were retrospective, and the age of all patients ranged from 1-71 years. The duration of epilepsy ranged from 1 month to 30 years. Patients with tumor-related epilepsy underwent surgical treatment with Engel I outcomes ranging from 56.5%-100%. Conclusion Intraoperative ECoG is generally considered a useful technique in delineating epileptogenic areas and improving the prognosis of surgical treatment of tumor-related epilepsy. However, large-scale randomized control trials are still needed to verify these findings and formulate appropriate surgical strategies.

OBJECTIVE Diffuse gliomas are the most common primary gliomas with a poor prognosis. This study aimed to develop and validate prognostic models for predicting the survival probability in newly diagnosed lower-grade glioma (LGG) patients. METHODS Detailed data were obtained for newly diagnosed LGG from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts. Survival was assessed using Cox proportional hazards regression with adjustment for known prognostic factors. The model was established using the TCGA cohort, and independently validated using the CGGA cohort, to predict the 3-, 5-, and 10-year survival probabilities of patients. RESULTS Data from 293 patients with newly diagnosed LGG from the TCGA cohort were used to establish a prognostic model, and from 232 patients with primary LGG in the CGGA cohort to validate the model. Age, tumor grade, molecular subtype, tumor resection, and preoperative neurological deficits were included in the prediction model. The Cox regression model had a satisfactory corrected concordance index of 0.8508, 0.8510, and 0.8516 in the internal bootstrap validation at 3, 5, and 10 years, respectively. The calibration plots demonstrated high consistency of the predicted and observed outcomes. The CGGA cohort was used for external validation and showed satisfactory discrimination of 0.7776, 0.7682, and 0.7051 at 3, 5, and 10 years, respectively. The calibration plots demonstrated an acceptable calibration capability in the external validation. CONCLUSIONS This study established and validated a prognostic model to predict the survival probability of patients with newly diagnosed LGG. The model performed well in discrimination and calibration with ease of use, speed, accessibility, interpretability, and generalizability. An easily used nomogram based on the Cox model was established for clinical application. Moreover, a free, easy-to-use software interface based on the nomogram is provided online.

To determine the association of molecular biomarkers with tumor growth in patients with high-grade gliomas (HGGs), the tumor growth rates and molecular biomarker status in 109 patients with HGGs were evaluated. Mean tumor diameter was assessed on at least two pre-surgical T2-weighted and contrast-enhancement T1-weighted magnetic resonance images (MRIs). Tumor growth rates were calculated based on tumor volume and diameter using various methods. The association of biomarkers with increased or decreased tumor growth was calculated using linear mixed-effects models. HGGs exhibited rapid growth rates, with an equivalent volume doubling time of 63.4 days and an equivalent velocity of diameter expansion of 51.6 mm/year. The WHO grade was an independent clinical factor of eVDEs. TERT promoter mutation C250T and MGMT promoter methylation was significantly associated with tumor growth in univariable analysis but not in multivariable analysis. Molecular groups of IDH1, TERT, and 1p/19q and IDH1 and MGMT were independently associated with tumor growth. In addition, tumor enhanced area had a faster growth rate than a tumor entity in incomplete enhanced HGGs (p = 0.006). Our findings provide crucial information for the prediction of preoperative tumor growth in HGGs, and aided in the decision making for aggressive resection and adjuvant treatment strategies.

Supplemental material, Supplemental_data.docxTAO for Procedure-specific prognostic impact of micropapillary subtype may guide resection strategy in small-sized lung adenocarcinomas: a multicenter study by Hang Su, Huikang Xie, Chenyang Dai, Shengnan Zhao, Dong Xie, Yunlang She, Yijiu Ren, Lei Zhang, Ziwen Fan, Donglai Chen, Feng Jiang, Jinshi Liu, Quan Zhu, Jie Yao, Honggang Ke, Lei Zhang, Chunyan Wu, Gening Jiang and Chang Chen in Therapeutic Advances in Medical Oncology

The newly proposed putamen classification system shows good prognostic value in patients with insular LGGs, yet no study towards the molecular profiles of putamen involved LGGs has been proposed. Clinical information and imaging data of patients diagnosed with insular low-grade gliomas were collected retrospectively. Genetic information of the 34 tumors was assessed using RNA-sequencing. Gene set enrichment analysis was further performed to identify the genes showing differential expression between putamen-involved tumors and putamen non-involved tumors. The level of Ki-67 expression was also evaluated. There were 843 genes identified to be differentially expressed between putamen-involved and non-involved gliomas. Specifically, Gene set enrichment analysis discovered 13 Kyoto Encyclopedia of Genes and Genomes pathways and 37 Gene Ontology Biological Process term were upregulated in putamen-involved low-grade glioma cells. The enriched GO sets with the highest gene counts included cell cycle (42 genes), mitotic cell cycle (24 genes), and cell division (19 genes). Furthermore, high expression of Ki-67 was associated with putamen involvement in insular gliomas. There is clear genetic variation between putamen-involved and non-involved insular low-grade gliomas. The differential expression of genes related to the processes of cell proliferation, cell migration, or DNA repair may lead to putamen involvement. The findings suggest that among the two subtypes, putamen-involved insular low-grade gliomas have higher malignancy, and the clinical treatment towards the putamen-involved insular low-grade gliomas should be more active.

For hydrogels, toughness and adhesiveness are contradictable. However, the simultaneous requirement for both is very urgent in some practical applications, such as robotic joints, wound dressing, and surgical bandages. Herein, milk casein as a protein model was introduced into polyacrylamide (PAAm) hydrogel, which resulted in adequate adhesiveness and mechanical strength. Surprisingly, casein-PAAm hydrogel could repeatedly adhere to the surface of various solid materials and biological tissues by possible physical interactions. A maximum peeling force of 378 N m−1 for casein-PAAm hydrogel on an aluminum surface was measured. Moreover, casein-PAAm hydrogel exhibited adequate mechanical performance with fracture stress of 180 kPa at fracture strain of 2000%. Therefore, the strategy based on tough and adhesive hydrogels assisted by protein would broaden the direction to fabricate a new generation of soft materials with multiple adhesive properties and tough mechanical properties.

Nicosulfuron is a common environmental pollutant, posing a great threat to aquatic systems and causing significant damage to crops. This study reported a cold-adapted strain Oceanisphaera psychrotolerans LAM-WHM-ZC, which efficiently degrades nicosulfuron over a wide range of temperatures (5 to 40 °C). The Box-Behnken design method was used to optimize the degradation conditions. O. psychrotolerans LAM-WHM-ZC can degrade 92.4% and 74.6% of initially supplemented 100 mg/L nicosulfuron under the optimum and low temperature of 18.1 and 5 °C, respectively, within 7 days. O. psychrotolerans LAM-WHM-ZC was found to be highly efficient in degrading cinosulfuron, chlorsulfuron, rimsulfuron, bensulfuron methyl, and ethametsulfuron methyl. Metabolites from nicosulfuron degradation were identified by UPLC-MS, and a possible degradation pathway was proposed. Furthermore, O. psychrotolerans LAM-WHM-ZC can also degrade nicosulfuron in soil; 78.6% and 67.4% of the initial nicosulfuron supplemented at 50 mg/kg were removed at 18.1 and 5 °C, respectively, within 15 days.

This study aimed to investigate the relationship between lymph node micrometastasis and histologic patterns of adenocarcinoma, with a particular focus on their joint effect on prognosis. We retrospectively reviewed 235 patients with stage I adenocarcinoma from January 2009 to December 2009. Lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin (AE1/AE3) and thyroid transcription factor-1. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis on prognosis. Lymph node micrometastasis was observed in 35 patients (15%). Patients with micrometastasis had significantly worse recurrence-free survival (P

Supplemental material for Reversible physical crosslinking strategy with optimal temperature for 3D bioprinting of human chondrocyte-laden gelatin methacryloyl bioink by Yawei Gu, Lei Zhang, Xiaoyu Du, Ziwen Fan, Long Wang, Weiyan Sun, Yu Cheng, Yufang Zhu and Chang Chen in Journal of Biomaterials Applications

Objectives Tumor spread through air spaces (STAS) is a novel invasive pattern in lung adenocarcinoma (ADC). The effects of the combination of STAS and tumor size on survival have not been well studied. Methods A total of 383 patients with ADC 3 cm or smaller (stage IA) and 161 patients with stage IB ADC were identified from 2009 to 2010. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients as stratified by STAS and tumor size. A validation cohort was included in this study. Results STAS was observed in 116 ADCs 3 cm or smaller (30.3%). In cases involving ADCs 3 cm or smaller, patients with STAS had worse RFS ( p = 0.006) and OS rates ( p p = 0.091) and OS ( p = 0.443) rates were observed in patients with ADCs 3 cm or smaller with STAS present and those with stage IB ADC. Multivariate analysis revealed STAS to be an independent prognostic factor in ADCs 3 cm or smaller (RFS, p = 0.043; OS, p = 0.009). Among patients with ADCs larger than 2 to 3 cm, STAS still stratified the prognosis. Moreover, the unfavorable prognosis of patients with ADCs larger than 2 to 3 cm with STAS present was similar to that of patients with stage IB ADC. Among patients with ADCs 2 cm or smaller, STAS failed to stratify the prognosis significantly. Similar results were obtained in the validation cohort. Conclusions These results provide preliminary evidence that STAS could be considered as a factor in a staging system to predict prognosis more precisely, especially in ADCs larger than 2 to 3 cm.