H3K27M is the most frequent mutation in brainstem gliomas (BSGs), and it has great significance in the differential diagnosis, prognostic prediction and treatment strategy selection of BSGs. There ...has been a lack of reliable noninvasive methods capable of accurately predicting H3K27M mutations in BSGs.
A total of 151 patients with newly diagnosed BSGs were included in this retrospective study. The H3K27M mutation status was obtained by whole-exome, whole-genome or Sanger’s sequencing. A total of 1697 features, including 6 clinical parameters and 1691 imaging features, were extracted from pre- and post-contrast T1-weighted and T2-weighted images. Using a random forest algorithm, 36 selected MR image features were integrated with 3 selected clinical features to generate a model that was predictive of H3K27M mutations. Additionally, a simplified prediction model comprising the Karnofsky Performance Status (KPS) at diagnosis, symptom duration at diagnosis and edge sharpness on T2 was established for practical clinical utility using the least squares estimation method.
H3K27M mutation was an independent prognostic factor that conferred a worse prognosis (p = 0.01, hazard ratio = 3.0, 95% confidence interval CI, 1.57–5.74). The machine learning-based model achieved an accuracy of 84.44% (area under the curve AUC = 0.8298) in the test cohort. The simplified model achieved an AUC of 0.7839 in the test cohort.
Using conventional MRI and clinical features, we established a machine learning-based model with high accuracy and a simplified model with improved clinical utility to predict H3K27M mutations in BSGs.
AIM:To compare the prognostic ability of inflammation scores for patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)undergoing transarterial ...chemoembolization(TACE).METHODS:Data of 224 consecutive patients who underwent TACE for unresectable HBV-related HCC from September 2009 to November 2011 were retrieved from a prospective database.The association of inflammation scores with clinicopathologic variables and overall survival(OS)were analyzed,and receiver operating characteristic curves were generated,and the area under the curve(AUC)was calculated to evaluate the discriminatory ability of each inflammation score and staging system,including tumor-node-metastasis,Barcelona Clinic Liver Cancer,and Cancer of the Liver Italian Program(CLIP)scores.RESULTS:The median follow-up period was 390 d,the one-,two-,and three-year OS were 38.4%,18.3%,and 11.1%,respectively,and the median OS was 390d.The Glasgow Prognostic Score(GPS),modifed GPS,neutrophil-lymphocyte ratio,and Prognostic Index were associated with OS.The GPS consistently had a higher AUC value at 6 mo(0.702),12 mo(0.676),and24 mo(0.687)in comparison with other inflammation scores.CLIP consistently had a higher AUC value at6 mo(0.656),12 mo(0.711),and 24 mo(0.721)in comparison with tumor-node-metastasis and Barcelona Clinic Liver Cancer staging systems.Multivariate analysis revealed that alanine aminotransferase,GPS,and CLIP were independent prognostic factors for OS.The combination of GPS and CLIP(AUC=0.777)was superior to CLIP or GPS alone in prognostic ability for OS.CONCLUSION:The prognostic ability of GPS is superior to other inflammation scores for HCC patients undergoing TACE.Combining GPS and CLIP improved the prognostic power for OS.
In this study, the authors aimed to create a nomogram for precisely predicting the 5-year prospective hemorrhage risk in brainstem cavernous malformations (BSCMs).
Patients with confirmed BSCMs in a ...single-center prospective observational series from January 2012 to December 2016 were included in the present study for nomogram building and validation. The concordance index (C-index), calibration curves, and decision curve analysis were used to evaluate the predictive accuracy, discriminative ability, and clinical usefulness of the nomogram. Then, a nomogram-based risk stratification model for untreated BSCMs was developed.
In total, 600 patients were included in the study; 417 patients who had been enrolled before July 2015 were divided into the training and validation cohorts, and 183 subsequently enrolled patients were used as the external validation cohort. By applying a backward stepwise procedure in the multivariable Cox model, variables, including prior hemorrhage (HR 1.69), hemorrhage on admission (HR 3.33), lesion size > 1.5 cm (HR 1.84), lesion depth (HR 2.35), crossing the axial midpoint (HR 1.94), and developmental venous anomaly (HR 2.62), were incorporated to develop a nomogram. The Harrell C-index values for a 5-year prospective hemorrhage were 0.752 (95% CI 0.687-0.816), 0.801 (95% CI 0.665-0.936), and 0.758 (95% CI 0.674-0.842) in the training, internal validation, and external validation cohorts, respectively. The nomogram performed well in terms of consistency between prediction and actual observation according to the calibration curve. The patients could be classified into three distinct (low, medium, and high) risk groups using the final score of this nomogram.
Independent predictors of the 5-year hemorrhage risk in untreated BSCMs were selected to create the first nomogram for predicting individual prospective hemorrhage. The nomogram was able to stratify patients into different risk groups and assist in clinical decision-making.
Purpose
Diffuse low-grade and intermediate-grade gliomas, also known as lower-grade gliomas (LGGs), are a class of central nervous system tumors. Overall survival varies greatly between patients, ...highlighting the importance of evaluating exact outcomes to facilitate individualized clinical management. We aimed to identify an mRNA-based prognostic signature to predict the survival of patients with LGGs.
Methods
A total of 874 LGGs from two public datasets were included. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most prognostic mRNAs and build a risk score. A nomogram incorporating the risk score and clinical factors was established for individualized survival prediction. The performance of the nomogram was assessed in the training set (329 patients), internal validation set (140 patients), and external validation set (405 patients).
Results
21 most prognostic mRNAs remained following the LASSO Cox regression. The 21-mRNA signature successfully stratified patients into high- and low-risk groups (P < 0.001 for all datasets in Kaplan–Meier analysis). Subsequent gene set enrichment analysis identified 19 essential biological processes in high-risk LGGs. Furthermore, a nomogram incorporating the risk score, age, grade, and 1p/19q status was developed with favorable calibration and high predictive accuracy in the training set and validation sets (C-index: 0.877, 0.878, and 0.812, respectively).
Conclusion
The 21-mRNA signature has reliable prognostic value for LGGs and might facilitate the effective stratification and individualized management of patients.
Argonaute 2 (Ago2) protein is the major vehicle of microRNAs (miRNAs)‐guided gene repression and silencing processes. Although the crystal structure of human Ago2 (hAgo2) has recently been disclosed, ...the information of dynamically structural character of protein–RNA recognition is still lacking. Molecular dynamics simulations were used to systematically explore hAgo2 in the presence and absence of RNA duplex. Stable direct and water‐mediated hydrogen bonds were observed between guide RNA backbone atoms and hAgo2, especially for nucleotides 2–7. In addition, water‐mediated hydrogen bonds are indicated to be critical in the specific recognition between hAgo2 and the conserved adenine in position 1 of target RNA. The core domains (N, PAZ, MID, and PIWI) possess rigid body movements during the simulations. The motions of N‐PAZ and PIWI‐MID are negatively correlated with or without RNA binding and PAZ domain is identified as the most mobile domain in both systems. The reorientation of PAZ domain not only influences the binding of helix‐7 and RNA duplex, the initial pairing process, but also the shape of N‐PAZ cleft, where the supplemental base pairing occurs. It is speculated that PAZ domain could be a key regulator in hAgo2‐mediated miRNA‐induced gene regulation.
Large conformational changes were detected in hAgo2‐free system comparing to RNA bounded hAgo2, especially for PAZ domain. The reorientation of PAZ domain not only influences the binding of helix‐7 and RNA duplex, the initial pairing process, but also the shape of N‐PAZ cleft, where the supplemental base pairing occurs. We speculate that PAZ domain played important role in hAgo2‐mediated miRNA‐induced gene regulation.
Aliphatic poly(monothiocarbonate)s synthesized by alternating copolymerization of carbonyl sulfide (COS) and epoxides are a new type of crystalline polymers. In this work, the isothermal ...crystallization behavior and spherulite morphology of poly(trimethylene monothiocarbonate) (PTMMTC) and poly(ethylene monothiocarbonate) (PEMTC) are studied. PTMMTC tends to form banded spherulites, especially at low crystallization temperatures, while PEMTC forms non-banded spherulites. The overall crystallization rate and spherulitic growth rate of PTMMTC are larger than those of PEMTC at the same degree of supercooling. PTMMTC with longer alkane segment in the main chain has a higher equilibrium melting temperature (Tm0) than PEMTC. Both polymers exhibit double melting peaks, but the formation mechanisms are different for PTMMTC and PEMTC. Small-angle X-ray scattering (SAXS) result reveals that more amorphous phases are located in interlamellae of PTMMTC, leading to a larger long period (L) and a thicker amorphous layers (la), which can account for the stronger tendency of PTMMTC to form banded spherulites. The melting enthalpies of PTMMTC and PETMC crystals with 100% crystallinity (ΔHm0) are obtained by extrapolating the melting enthalpies of the samples with different crystallinities. The free energy of the folding surface (σe) of PTMMTC is larger than that of PETMC, indicating that the PTMMTC chain is stiffer. The higher Tm0 and larger ΔHm0 and σe of PTMMTC can be attributed to its stronger interchain interaction.
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•The isothermal crystallization kinetics and morphology of poly(monothiocarbonate)s are presented for the first time.•The basics data, such as Tm0, ΔHm0 and G of poly(monothiocarbonate)s are firstly reported.•The effect of chain structure on crystallization behavior and morphology of PTMMTC and PEMTC is disclosed.
The controversy of adjuvant radiotherapy of meningiomas is at least partially due to the insufficient understanding on meningioma cells' response to irradiation and the shortage of ...radiosensitivity-promotion methods.
MicroRNA-221
and
microRNA-222
were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in meningiomas has yet to be confirmed. Therefore, the malignant meningioma IOMM-Lee cells were adopted, transfected with
microRNA-221/222
mimics or inhibitors, and irradiated with different dosages. The effects of radiation and
microRNA-221/222
were then assessed
in vitro
and
in vivo
. Radiation dose increases and
microRNA-221/222
downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression, and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the
microRNA-221/222
expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee's radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for malignant meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the
microRNA-221/222
level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.
Objective. Sick sinus syndrome (SSS) is one of the most common causes of cardiac impairment necessitating pacemaker implantation. However, studies of SSS pathogenesis are neither comprehensive nor ...conclusive due to limited success in achieving a stable rat SSS model. Here, we modified pinpoint press permeation to establish a stable rat SSS model. Methods. We randomly assigned 138 male Sprague-Dawley rats into three groups: normal control (n = 8), sham (n = 10), and SSS (n = 120). Postoperatively, the SSS group was further divided into SSSA (n = 40), SSSB (n = 40), and SSSC (n = 40), based on reduction in heart rates by 20–30%, 31–40%, and 41–50%, respectively. We also assessed histomorphological characteristics and hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) expression in the sinoatrial node (SAN) at 1, 2, 3, and 4 weeks after surgery. Results. Mortality was statistically higher in SSSC compared to SSSA and SSSB (7.5% versus 90.0% and 87.5%; P < 0.05). Heart rate in SSSA was gradually restored to preoperative levels by week 4 after surgery. In contrast, heart rate in SSSB was stable at 2–3 weeks after surgery. However, we observed that the tissues and cells in SAN were severely injured and also found a time-dependent increase in collagen content and atrium myocardium in SSSB. HCN4 expression was significantly reduced at all 4 time points in SSSB, with statistically significant differences among the groups (P < 0.01). Conclusion. We successfully developed a rat SSS model that was sustainable for up to 4 weeks.
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