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BACKGROUND: The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. METHODS: Patients diagnosed with astrocytoma, IDH-mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2-3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. RESULTS: A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki-67 index (p < 0.001) of pathological examination were statistically different in the WHO grade 2-3 group (n = 27) and WHO grade 4 group (n = 33). CDK6 (p = 0.004), FGFR2 (p = 0.003), and MYC (p = 0.004) alterations showed an enrichment in the WHO grade 4 group. Patients with higher grade showed shorter mOS (mOS = 75.9 m, 53.6 m, 26.4 m for grade 2, 3, and 4, respectively, p = 0.01). CONCLUSIONS: Patients diagnosed as WHO grade 4 according to the 5th edition WHO classification based on molecular alterations are more likely to have poorer prognosis. Therefore, treatment should be tailored to their individual needs. Further research is needed for the management of IDH-mutant astrocytoma is needed in the future.
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Astrocitoma , Imageamento por Ressonância Magnética , Mutação , Gradação de Tumores , Organização Mundial da Saúde , Humanos , Astrocitoma/genética , Astrocitoma/classificação , Astrocitoma/patologia , Astrocitoma/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Imageamento por Ressonância Magnética/métodos , Prognóstico , Isocitrato Desidrogenase/genética , Neoplasias do Sistema Nervoso Central/classificação , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Idoso , Adulto Jovem , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/mortalidade , AdolescenteRESUMO
BACKGROUND: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups. CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.
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Neoplasias Encefálicas , Glioma , Humanos , Masculino , Feminino , Glioma/complicações , Glioma/genética , Glioma/cirurgia , Glioma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Idoso , Estudos de Coortes , Adulto JovemRESUMO
This study aimed to investigate correlation between mitochondrial reactive oxygen species and Porphyromonas gingivalis in the process of cementoblast pyroptosis. Lactate dehydrogenase activity assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry analysis were utilized to explore whether Porphyromonas gingivalis triggered pyroptosis in cementoblasts. Reactive oxygen species and mitochondrial reactive oxygen species were detected using flow cytometry and fluorescence staining. The effect of mitochondrial reactive oxygen species on the Porphyromonas gingivalis-induced pyroptosis of cementoblasts was assessed by Mito-Tempo, mitochondrion-targeted superoxide dismutase mimetic. Phosphorylation levels of p65 were measured by western blotting. SC75741, a nuclear factor-kappa B inhibitor, was added to block the nuclear factor-kappa B in the Porphyromonas gingivalis-infected cementoblasts. Porphyromonas gingivalis triggered pyroptosis of cementoblasts, and an elevation in reactive oxygen species generation in the mitochondria was observed. Inhibition of mitochondrial reactive oxygen species reduced pyroptosis and nuclear factor-kappa B signaling pathway mediated the pyroptotic cell death in Porphyromonas gingivalis-infected cementoblasts. Together, our findings demonstrate that mitochondrial reactive oxygen species increased by Porphyromonas gingivalis participated in the pyroptosis of cementoblasts. Targeting mitochondrial reactive oxygen species may offer therapeutic strategies for root surface remodeling or periodontal regeneration.
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Lead(II) is a potential carcinogen of heavy-metal ions (HIs). With the wide application of Pb-bearing products including lead alloy products, and new-energy lead-ion batteries, lead pollution has become a tricky problem. To solve such a difficulty, novel ultrathin MoS2-vinyl hybrid membranes (MVHMs) with a "spring" effect were synthesized via co-polymerization of acrylic acid, styrene and molybdenum disulfide (MoS2) and their adsorptions for HIs were explored. The "spring" effect derived from the interaction between the tendency of the short polyacrylic acid (PAA) chain connected with MoS2 to spread outward and the coulomb force between layers from MoS2 (s-MoS2), which enlarge the spacing of MoS2 layers without changing the number of layers after membrane formation, which changes the swelling membrane to a dense membrane and reduces the original thickness from 0.5 cm to 0.011 mm in the thickness direction. The adsorption experiment revealed that these MVHMs had super adsorption performance and high selectivity for Pb2+ by comparison with other five metal ions: Cu2+, Cd2+, Ni2+, Cr3+ and Zn2+. Especially, the adsorption quantity of MVHMs for Pb2+ could approach 2468 mg/g and the maximum adsorption ratio of qe[Pb2+]/qe[Cu2+] can reach 10.909. These values were much larger than the data obtained with the adsorbents reported in the last decade. A variety of models are applied to evaluate the effect of ionic groups. It was confirmed that -COOH plays a key role in adsorption of HIs and s-MoS2 also has a certain contribution. Conversely, ion exchange plays only a minor role during the period of adsorption process. Effective diffusion coefficient (Deff) of Pb(II) had the largest values among these metal ions. Hence, these hybrid membranes are promising adsorbents for the removal of Pb2+ from water containing various ions.
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Acrilatos , Dissulfetos , Chumbo , Molibdênio , Estireno , Molibdênio/química , Chumbo/química , Adsorção , Acrilatos/química , Dissulfetos/química , Estireno/química , Polimerização , Membranas Artificiais , Poluentes Químicos da Água/química , Metais Pesados/químicaRESUMO
Background: The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM). Purpose: This study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification. Methods: We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes. Results: 163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM. Conclusion: Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.
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Predictive markers and prognostic models are useful for the individualization of cancer treatment. In this study, we sought to identify clinical and molecular factors to predict overall survival in recurrent glioma patients receiving bevacizumab-containing regimens. A cohort of 102 patients was retrospectively collected from June 2011 to January 2022 at our institution. A nomogram was generated by Cox regression and feature selection algorithms based on 19 clinicopathological and 60 molecular variables. The model's performance was internally evaluated by bootstrapping in terms of discrimination and calibration. The median overall survival from the initiation of bevacizumab administration to death or last follow-up was 11.6 months (95% CI: 9.2-13.8 months) for all 102 patients, 10.2 months (95% CI: 6.4-13.3 months) for 66 patients with grade 4 tumors, and 13.8 months (lower limit of 95% CI: 11.5 months) for 36 patients with tumors of grade lower or not available. In the final model, a lower WHO 2021 grade (Grade lower or not available vs. Grade 4, HR: 0.398, 95% CI: 0.223-0.708, p = 0.00172), having received adjuvant radiochemotherapy (Yes vs. No, HR: 0.488, 95% CI: 0.268-0.888, p = 0.0189), and wildtype EGFR (Wildtype vs. Altered, HR: 0.193, 95% CI: 0.0506-0.733, p = 0.0157; Not available vs. Altered, HR: 0.386, 95% CI: 0.184-0.810, p = 0.0118) were significantly associated with longer overall survival in multivariate Cox regression. The overall concordance index was 0.652 (95% CI: 0.566-0.714), and the areas under the time-dependent curves for 6-, 12-, and 18-month overall survival were 0.677 (95% CI: 0.516-0.816), 0.654 (95% CI: 0.470-0.823), and 0.675 (95% CI: 0.491-0.860), respectively. A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-based therapy was established and internally validated. It could serve as a reference tool for clinicians to assess the extent the patients may benefit from bevacizumab and stratify their treatment response.
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Cognitive impairment is a common feature among patients with diffuse glioma. The objective of the study is to investigate the relationship between preoperative cognitive function and clinical as well as molecular factors, firstly based on the new 2021 World Health Organization's updated classification of central nervous system tumors. A total of 110 diffuse glioma patients enrolled underwent preoperative cognitive assessments using the Mini-Mental State Examination and Montreal Cognitive Assessment. Clinical information was collected from medical records, and gene sequencing was performed to analyze the 18 most influenced genes. The differences in cognitive function between patients with and without glioblastoma were compared under both the 2016 and 2021 WHO classification of tumors of the central nervous system to assess their effect of differentiation on cognition. The study found that age, tumor location, and glioblastoma had significant differences in cognitive function. Several genetic alterations were significantly correlated with cognition. Especially, IDH, CIC, and ATRX are positively correlated with several cognitive domains, while most other genes are negatively correlated. For most focused genes, patients with a low number of genetic alterations tended to have better cognitive function. Our study suggested that, in addition to clinical characteristics such as age, histological type, and tumor location, molecular characteristics play a crucial role in cognitive function. Further research into the mechanisms by which tumors affect brain function is expected to enhance the quality of life for glioma patients. This study highlights the importance of considering both clinical and molecular factors in the management of glioma patients to improve cognitive outcomes.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Qualidade de Vida , Glioma/patologia , Mutação , Organização Mundial da Saúde , Isocitrato Desidrogenase/genéticaRESUMO
ABSTRACT: Aging is a significant risk factor for various diseases, including asthma, and it often leads to poorer clinical outcomes, particularly in elderly individuals. It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage, resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases. The effects of aging affect not only the elderly but also those of younger ages, posing significant challenges to global healthcare. Thus, understanding the molecular mechanisms associated with aging in different diseases is essential. One intriguing factor is the aryl hydrocarbon receptor (AhR), which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process. Here, we review the literature on several major hallmarks of aging, including mitochondrial dysfunction, cellular senescence, autophagy, mitophagy, epigenetic alterations, and microbiome disturbances. Moreover, we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures, particularly in relation to the immune system. Furthermore, we explore how aging hallmarks affect clinical characteristics, inflammatory features, exacerbations, and the treatment of asthma. It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.
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Asma , Receptores de Hidrocarboneto Arílico , Humanos , Idoso , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Envelhecimento , Regulação da Expressão Gênica , LigantesRESUMO
The impact of Ba-modified peanut shell biochar (Ba-PSB) on Pb(II) removal was studied and BaCl2 was used as a modifier. It was shown that the PSB obtained at 750 °C had the best adsorption effect, and the Ba-PSB had a larger specific surface area and a good adsorption effect on Pb(II). At pH = 5, concentration was 400 mg/L, time was 14 h, and temperature was 55 °C, the loading amount of black peanut shell biochar (BPSB), red peanut shell biochar (RPSB), Ba-BPSB, and Ba-RPSB reached 128.050, 98.217, 379.330, and 364.910 mg/g, respectively. In addition, based on the non-linear fitting, it was found that the quasi-second-order kinetic model, and isothermal model could be applied to describe Pb(II) adsorption on PSB and Ba-PSB. The adsorption behavior of PSB unmodified and modified was a spontaneous process. Moreover, chemical modification of BPSB, RPSB, Ba-BPSB, and Ba-RPSB for hindering of -COOH and -OH groups revealed 81.81, 77.08, 86.90, and 83.65% removal of Pb(II), respectively, which was due to the participation of -COOH, while 17.61, 21.70, 12.77, and 15.06% was from -OH group, respectively. The increase of cation strength (Na+, K+, Ca2+, and Mg2+) will reduce the adsorption capacity of PSB for Pb(II).
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Arachis , Poluentes Químicos da Água , Chumbo , Adsorção , Água , Carvão Vegetal , Poluentes Químicos da Água/análise , CinéticaRESUMO
BACKGROUND: The latest fifth edition of the World Health Organization (WHO) classification of the central nervous system (CNS) tumors (WHO CNS 5 classification) released in 2021 defined astrocytoma, IDH-mutant, Grade 4. However, the understanding of this subtype is still limited. We conducted this study to describe the features of astrocytoma, IDH-mutant, Grade 4 and explored the similarities and differences between histological and molecular subtypes. METHODS: Patients who underwent surgery from January 2011 to January 2022, classified as astrocytoma, IDH-mutant, Grade 4 were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis. RESULTS: Altogether 33 patients with astrocytoma, IDH-mutant, Grade 4 were selected, including 20 with histological and 13 with molecular WHO Grade 4 astrocytoma. Tumor enhancement, intratumoral-necrosis like presentation, larger peritumoral edema, and more explicit tumor margins were frequently observed in histological WHO Grade 4 astrocytoma. Additionally, molecular WHO Grade 4 astrocytoma showed a tendency for relatively longer overall survival, while a statistical significance was not reached (47 vs. 25 months, p = 0.22). TP53, CDK6, and PIK3CA alteration was commonly observed, while PIK3R1 (p = 0.033), Notch1 (p = 0.027), and Mycn (p = 0.027) alterations may affect the overall survival of molecular WHO Grade 4 astrocytomas. CONCLUSIONS: Our study scrutinized IDH-mutant, Grade 4 astrocytoma. Therefore, further classification should be considered as the prognosis varied between histological and molecular WHO Grade 4 astrocytomas. Notably, therapies aiming at PIK3R1, Notch 1, and Mycn may be beneficial.
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Astrocitoma , Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioblastoma , Humanos , Proteína Proto-Oncogênica N-Myc , Isocitrato Desidrogenase/genética , Mutação , Astrocitoma/genética , Neoplasias do Sistema Nervoso Central/genética , Organização Mundial da SaúdeRESUMO
Background: Contemporary guidelines for managing nonvalvular atrial fibrillation (NVAF) include apixaban and rivaroxaban as first-line anticoagulation treatment options. Minimal guidance is available regarding selecting anticoagulants for patients with class I-III obesity. Objective: This study aims to evaluate the comparative effectiveness and safety of apixaban and rivaroxaban in both obese and morbidly obese patients with NVAF. Methods: A retrospective cohort study was conducted at an outpatient cardiovascular clinic after Institutional Review Board approval. Patients were eligible if they were ≥18 years of age, had a BMI ≥30 kg/m2, and took apixaban or rivaroxaban for NVAF for ≥3 months. The primary endpoint was the composite rate of stroke, transient ischemic attack (TIA), myocardial infarction (MI), or presence of atrial thrombosis. Bleeding events were evaluated as the primary safety endpoint. Results: Combined, the cohorts consisted of 303 obese or morbidly obese patients. The primary composite endpoint occurred in 3.8% of patients taking apixaban and 1.7% of patients taking rivaroxaban (P = .28). Both clinically relevant, non-major and major bleeding occurred more often in the apixaban arm, but this difference was not statistically significant; however, bleeding risk may have been skewed due to differences in baseline characteristics. Conclusion and Relevance: For obese and morbidly obese patients prescribed either apixaban or rivaroxaban for NVAF, rates of stroke, TIA, MI, and atrial thrombosis did not differ. The preferred DOAC for patients with class I-III obesity remains elusive, but current data points to a patient-centered approach for anticoagulant selection.
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BACKGROUND: To evaluate the incidence and severity of open gingival embrasures (OGEs) in adult patients treated with clear aligners and fixed appliances. METHODS: Two hundred non-extraction adult subjects with less than 5 mm of crowding (mean age, 24.6 ± 3.8 years) were enrolled in this retrospective study. The subjects were divided into the clear aligner (n = 100) and fixed appliance group (n = 100). The intraoral photographs were utilized to determine the incidence of OGEs in the upper arch between maxillary central incisors, as well as the lower arch between mandibular central incisors. Crown overlap, crown shape, posttreatment root angulation, the distance from the interproximal contact point (ICP) to the alveolar bone crest (ABC) after treatment and interproximal enamel reduction (IPR) were determined in the two groups. RESULTS: The incidence of OGEs between maxillary and mandibular central incisors after orthodontic treatment was 35.0% and 38.0% in the clear aligner group, respectively, significantly higher than that (18.0% and 24.0%) in the fixed appliance group (P < 0.05). The average area of an OGE after clear aligner treatment was larger both in the maxilla (0.16 ± 0.12mm2) and mandible (0.21 ± 0.24mm2) compared with that (0.05 ± 0.03mm2 and 0.05 ± 0.06mm2) after fixed appliance treatment (P < 0.05). No difference was found regarding pretreatment crown overlap, crown shape, treatment duration, posttreatment root angulation, amount and distribution of IPR and the distance from ICP to ABC. CONCLUSIONS: The incidence and severity of OGEs were higher in adults treated with clear aligners. Clinicians should be aware of the risk of OGEs during treatment with clear aligners.
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Má Oclusão , Aparelhos Ortodônticos Removíveis , Humanos , Adulto , Adulto Jovem , Estudos Retrospectivos , Incidência , Má Oclusão/terapia , Aparelhos Ortodônticos FixosRESUMO
Introduction: Glioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to the 2021 World Health Organization classification of central nervous system tumors. This study aimed to characterize the clinical, radiological, molecular, and survival features of GBM under the current classification scheme and explore survival determinants. Methods: We re-examined the genetic alterations of IDH-wildtype diffuse gliomas at our institute from 2011 to 2022, and enrolled GBMs for analysis after re-classification. Univariable and multivariable analyses were used to identify survival determinants. Results: Among 209 IDH-wildtype gliomas, 191 were GBMs, including 146 hist-GBMs (76%) and 45 mol-GBMs (24%). Patients with mol-GBMs were younger, less likely to develop preoperative motor dysfunction, and more likely to develop epilepsy than hist-GBMs. Mol-GBMs exhibited lower radiographic incidences of contrast enhancement and intratumoral necrosis. Common molecular features included copy-number changes in chromosomes 1, 7, 9, 10, and 19, as well as alterations in EGFR, TERT, CDKN2A/B, and PTEN, with distinct patterns observed between the two subtypes. The median overall survival (mOS) of GMB was 12.6 months. Mol-GBMs had a higher mOS than hist-GBMs, although not statistically significant (15.6 vs. 11.4 months, p=0.17). Older age, male sex, tumor involvement of deep brain structure or functional area, and genetic alterations in CDK4, CDK6, CIC, FGFR3, KMT5B, and MYB were predictors for a worse prognosis, while MGMT promoter methylation, maximal tumor resection, and treatment based on the Stupp protocol were predictive for better survival. Conclusion: The definition of GBM and its clinical, radiological, molecular, and prognostic characteristics have been altered under the current classification.
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Introduction: Elderly glioblastoma (GBM) patients is characterized by high incidence and poor prognosis. Currently, however, there is still a lack of adequate molecular characterization of elderly GBM patients. The fifth edition of the WHO Classification of Central Nervous System Tumors (WHO5) gives a new classification approach for GBM, and the molecular characteristics of elderly GBM patients need to be investigated under this new framework. Methods: The clinical and radiological features of patients with different classifications and different ages were compared. Potential prognostic molecular markers in elderly GBM patients under the WHO5 classification were found using Univariate Cox regression and Kaplan-Meier survival analysis. Results: A total of 226 patients were included in the study. The prognostic differences between younger and elderly GBM patients were more pronounced under the WHO5 classification. Neurological impairment was more common in elderly patients (p = 0.001), while intracranial hypertension (p = 0.034) and epilepsy (p = 0.038) were more common in younger patients. Elderly patients were more likely to have higher Ki-67(p = 0.013), and in elderly WHO5 GBM patients, KMT5B (p = 0.082), KRAS (p = 0.1) and PPM1D (p = 0.055) were each associated with overall survival (OS). Among them, KRAS and PPM1D were found to be prognostic features unique to WHO5 elderly GBM patients. Conclusion: Our study demonstrates that WHO5 classification can better distinguish the prognosis of elderly and younger GBM. Furthermore, KRAS and PPM1D may be potential prognostic predictors in WHO5 elderly GBM patients. The specific mechanism of these two genes in elderly GBM remains to be further studied.
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The present study aimed to examine whether and to what extent university student online learning performance was influenced by individual-technology fit (ITF), task-technology fit (TTF), environment-technology fit (ETF), and whether the influence was mediated by their behavioral, emotional, and cognitive engagement. A theoretical research model was developed by integrating the extended TTF theory and student engagement framework. The validity of the model was assessed using a partial least squares structural equation modeling approach based on data collected from 810 university students. Student learning performance was influenced by TTF (ß = 0.25, p < 0.001), behavioral engagement (ß = 0.25, p < 0.001), and emotional engagement (ß = 0.27, p < 0.001). Behavioral engagement was affected by TTF (ß = 0.31, p < 0.001) and ITF (ß = 0.41, p < 0.001). TTF, ITF, and ETF were observed as significant antecedents of emotional engagement (ß = 0.49, p < 0.001; ß = 0.19, p < 0.001; ß = 0.12, p = 0.001, respectively) and cognitive engagement (ß = 0.28, p < 0.001; ß = 0.34, p < 0.001; ß = 0.16, p < 0.001, respectively). Behavioral and emotional engagement served as mediators between fit variables and learning performance. We suggest the need for an extension to the TTF theory by introducing ITF and ETF dimensions and demonstrate the important role of these fit variables in facilitating student engagement and learning performance. Online education practitioners should carefully consider the fit between the individual, task, environment, and technology to facilitate student learning outcomes.
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Background: The World Health Organization (WHO) CNS5 classification system highlights the significance of molecular biomarkers in providing meaningful prognostic and therapeutic information for gliomas. However, predicting individual patient survival remains challenging due to the lack of integrated quantitative assessment tools. In this study, we aimed to design a WHO CNS5-related risk signature to predict the overall survival (OS) rate of glioma patients using machine learning algorithms. Methods: We extracted data from patients who underwent an operation for histopathologically confirmed glioma from our hospital database (2011-2022) and split them into a training and hold-out test set in a 7/3 ratio. We used biological markers related to WHO CNS5, clinical data (age, sex, and WHO grade), and prognosis follow-up information to identify prognostic factors and construct a predictive dynamic nomograph to predict the survival rate of glioma patients using 4 kinds machine learning algorithms (RF, SVM, XGB, and GLM). Results: A total of 198 patients with complete WHO5 molecular data and follow-up information were included in the study. The median OS time of all patients was 29.77 [95% confidence interval (CI): 21.19-38.34] months. Age, FGFR2, IDH1, CDK4, CDK6, KIT, and CDKN2A were considered vital indicators related to the prognosis and OS time of glioma. To better predict the prognosis of glioma patients, we constructed a WHO5-related risk signature and nomogram. The AUC values of the ROC curves of the nomogram for predicting the 1, 3, and 5-year OS were 0.849, 0.835, and 0.821 in training set, and, 0.844, 0.943, and 0.959 in validation set. The calibration plot confirmed the reliability of the nomogram, and the c-index was 0.742 in training set and 0.775 in validation set. Additionally, our nomogram showed a superior net benefit across a broader scale of threshold probabilities in decision curve analysis. Therefore, we selected it as the backend for the online survival prediction tool (Glioma Survival Calculator, https://who5pumch.shinyapps.io/DynNomapp/), which can calculate the survival probability for a specific time of the patients. Conclusion: An online prognosis predictor based on WHO5-related biomarkers was constructed. This therapeutically promising tool may increase the precision of forecast therapy outcomes and assess prognosis.
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Introduction: The fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors released in 2021 formally defines pediatric-type diffuse gliomas. However, there is still little understanding of pediatric-type diffuse gliomas, and even less attention has been paid to adult patients. Therefore, this study describes the clinical radiological, survival, and molecular features of adult patients with pediatric-type glioma. Methods: Adult patients who underwent surgery from January 2011 to January 2022, classified as pediatric-type glioma, were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis. Results: Among 596 adult patients, 20 patients with pediatric-type glioma were screened, including 6 with diffuse astrocytoma, MYB- or MYBL1-altered, 2 with diffuse midline glioma, H3 K27-altered, and 12 with diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. Pediatric high-grade glioma (pHGG) frequently showed tumor enhancement, peritumoral edema, and intratumoral necrosis. Adult patients with pHGG showed a longer life expectancy than adult patients with glioblastoma. Common molecular alterations included chromosome alterations and CDKN2A/B, PIK3CA, and PTEN, while altered KMT5B and MET were found to affect the overall survival. Conclusion: Our study demonstrated adult patients with pediatric-type glioma. Notably, our research aims to expand the current understanding of adult patients with pediatric-type diffuse gliomas. Furthermore, personalized therapies consisting of targeted molecular inhibitors for MET and VEGFA may exhibit beneficial effects in the corresponding population.
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Background: The 5th edition of the World Health Organization (WHO) classification of central nervous system tumors incorporated specific molecular alterations into the categorization of gliomas. The major revision of the classification scheme effectuates significant changes in the diagnosis and management of glioma. This study aimed to depict the clinical, molecular, and prognostic characteristics of glioma and its subtypes according to the current WHO classification. Methods: Patients who underwent surgery for glioma at Peking Union Medical College Hospital during 11 years were re-examined for tumor genetic alterations using next-generation sequencing, polymerase chain reaction-based assay, and fluorescence in situ hybridization methods and enrolled in the analysis. Results: The enrolled 452 gliomas were reclassified into adult-type diffuse glioma (ntotal=373; astrocytoma, n=78; oligodendroglioma, n=104; glioblastoma, n=191), pediatric-type diffuse glioma (ntotal=23; low-grade, n=8; high-grade, n=15), circumscribed astrocytic glioma (n=20), and glioneuronal and neuronal tumor (n=36). The composition, definition, and incidence of adult- and pediatric-type gliomas changed significantly between the 4th and the 5th editions of the classification. The clinical, radiological, molecular, and survival characteristics of each subtype of glioma were identified. Alterations in CDK4/6, CIC, FGFR2/3/4, FUBP1, KIT, MET, NF1, PEG3, RB1, and NTRK2 were additional factors correlated with the survival of different subtypes of gliomas. Conclusions: The updated WHO classification based on histology and molecular alterations has updated our understanding of the clinical, radiological, molecular, survival, and prognostic characteristics of varied subtypes of gliomas and provided accurate guidance for diagnosis and potential prognosis for patients.
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Carbon materials derived from bacterial cellulose have been studied in lithium-ion batteries due to their low cost and flexible characteristics. However, they still face many intractable problems such as low specific capacity and poor electrical conductivity. Herein, bacterial cellulose is used as the carrier and skeleton to creatively realize the composite of polypyrrole on its nanofiber surface. After carbonization treatment, three-dimensional carbon network composites with a porous structure and short-range ordered carbon are obtained for potassium-ion batteries. The introduction of nitrogen doping from polypyrrole can increase the electrical conductivity of carbon composites and provide abundant active sites, improving the comprehensive performance of anode materials. The carbonized bacterial cellulose@polypyrrole (C-BC@PPy) anode exhibits a high capacity of 248 mA h g-1 after 100 cycles at 50 mA g-1 and a capacity retention of 176 mA h g-1 even over 2000 cycles at 500 mA g-1. Combined with density functional theory calculations, these results indicate that the capacity of C-BC@PPy is contributed by N-doped and defect carbon composite materials as well as pseudocapacitance. This study provides a guideline for the development of novel bacterial cellulose composites in the energy storage field.