RESUMEN
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.
Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Masculino , Femenino , Glioma/complicaciones , Glioma/genética , Glioma/cirugía , Glioma/patología , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Anciano , Estudios de Cohortes , Adulto JovenRESUMEN
Previous studies on exposure to violence lack a nuanced understanding of the causal effects of different exposure types on offending behaviors. This study, drawing on Pathways to Desistance Study (PDS) data tracking 1354 adjudicated youths aged 14-18 over 7 years, explores the contemporaneous (cross-sectional), acute (after 1 year), enduring (after 3 years), and long-term (after 6 years) causal effects of violence exposure on property and violent offending. The sample, predominantly male (86%), consisted of White (20%), Black (42%), and other (38%) individuals. The generalized propensity score is used to match unbalanced covariates across multiple exposure types, namely noninvolved (n = 392), witnessed (n = 577), experienced (n = 31), and experienced-witnessed violence (n = 305). Results demonstrate the contemporaneous, acute, enduring, and long-term effects of violence exposure on both violent and property offending, with varying durations and strengths across exposure types. The most pronounced risk effects are immediate, diminishing over time and potentially reversing in the long term as youth transition into adulthood. Among exposure types, experienced-witnessed violence exhibits the most potent effects on offending, followed by witnessed violence and then experienced violence-a pattern consistent across the observed time points. Noteworthy is the finding that the impact of violence exposure is more pronounced for violent offending, diminishing more rapidly compared to the effects on property offending.
Asunto(s)
Exposición a la Violencia , Delincuencia Juvenil , Humanos , Adolescente , Masculino , Femenino , Exposición a la Violencia/psicología , Estudios Transversales , Delincuencia Juvenil/psicología , Crimen/psicología , Crimen/estadística & datos numéricos , Violencia/psicología , Factores de RiesgoRESUMEN
SARS-CoV-2 NSP12, the viral RNA-dependent RNA polymerase (RdRp), is required for viral replication and is a therapeutic target to treat COVID-19. To facilitate research on SARS-CoV-2 NSP12 protein, we developed a rat monoclonal antibody (CM12.1) against the NSP12 N-terminus that can facilitate functional studies. Immunoblotting and immunofluorescence assay (IFA) confirmed the specific detection of NSP12 protein by this antibody for cells overexpressing the protein. Although NSP12 is generated from the ORF1ab polyprotein, IFA of human autopsy COVID-19 lung samples revealed NSP12 expression in only a small fraction of lung cells including goblet, club-like, vascular endothelial cells, and a range of immune cells, despite wide-spread tissue expression of spike protein antigen. Similar studies using in vitro infection also generated scant protein detection in cells with established virus replication. These results suggest that NSP12 may have diminished steady-state expression or extensive posttranslation modifications that limit antibody reactivity during SARS-CoV-2 replication.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Animales , Ratas , SARS-CoV-2/metabolismo , Anticuerpos Monoclonales , Células Endoteliales , ARN Polimerasa Dependiente del ARN/genética , Antivirales/metabolismoRESUMEN
OBJECTIVES: Developed to keep youth in school and out of court, the Philadelphia Police School Diversion Program allows youth to avoid arrest for specified school-based summary and misdemeanor offenses. This study examined whether diverted youth were also less likely to experience exclusionary discipline, both in response to the referring incident and in the following calendar year. HYPOTHESES: We predicted that diverted youth-compared to youth arrested in schools the year before program implementation-would have been less likely to receive a suspension for their school-based incident, receive a suspension in the year following the incident, and be referred for permanent school removal in the year following the incident. METHOD: Using a quasi-experimental design, we examined data from 1,281 diverted youth and 531 comparable youth arrested in Philadelphia schools in the year before program implementation. These 1,812 students (67% male, 75% Black) ranged from 10 to 22 years of age. After using propensity score matching techniques, we conducted mixed-effects logistic regression analyses to compare the matched groups on 3 outcomes: incident-related suspension, postincident suspension, and postincident referral for permanent school removal. RESULTS: No statistically significant group differences in likelihood of incident-related suspension emerged; however, age and gender moderated the relationship between diverted/arrested status and incident-related suspension. Diverted youth were less likely than matched arrested youth to experience both postincident suspension and postincident permanent school removal referral. CONCLUSIONS: The Philadelphia Police School Diversion Program shows promise in reducing the likelihood that youth will experience future exclusionary discipline following a school-based incident. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Asunto(s)
Policia , Instituciones Académicas , Adolescente , Femenino , Humanos , Aplicación de la Ley , Masculino , Philadelphia , EstudiantesRESUMEN
OBJECTIVES: Created to combat the school-to-prison pipeline, the Philadelphia Police School Diversion Program offers voluntary community-based services to eligible youth accused of minor school-based offeses in lieu of arrest. This study evaluated program effectiveness in accomplishing goals related to reductions in school-based arrests, serious behavioral incidents, and recidivism. HYPOTHESES: We expected the annual number of school-based arrests in Philadelphia schools to decrease over the program's first 5 years and predicted that the annual number of serious behavioral incidents would not increase. Further, we expected that diverted youth-compared to youth arrested in schools the year before Diversion Program implementation-would have significantly lower rates of recidivism arrests in the 2 years following their school-based incidents. METHOD: Using a quasi-experimental design, we examined data from 2,302 public school students (67.0% male; 76.1% Black; age range: 10-22 years) who were either diverted from arrest through the Diversion Program or arrested in Philadelphia schools in the year prior to Diversion Program implementation. We compared rate of recidivism arrest, number of arrests, and time to arrest between diverted and arrested youth. We also used district-wide descriptive statistics to examine 5-year trends in school-based arrests and serious behavioral incidents. RESULTS: Since program implementation, the annual number of school-based arrests in Philadelphia has declined by 84% and the number of serious behavioral incidents has declined by 34%. Diverted youth demonstrated less recidivism than arrested youth in the 2 years following their initial incident; however, after propensity score matching, we no longer observed significant differences. CONCLUSIONS: Findings indicate that a prearrest diversion program can safely reduce school-based arrests and suggest a need for future research regarding the role of demographic and incident-related characteristics in recidivism outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Asunto(s)
Delincuencia Juvenil/prevención & control , Aplicación de la Ley/métodos , Evaluación de Programas y Proyectos de Salud , Reincidencia/prevención & control , Adolescente , Niño , Femenino , Humanos , Delincuencia Juvenil/estadística & datos numéricos , Masculino , Philadelphia , Puntaje de Propensión , Reincidencia/estadística & datos numéricos , Instituciones Académicas , Adulto JovenRESUMEN
Family processes, adolescent religious involvement, and self-control may serve as important mechanisms that mediate the relationship between parental religious involvement and delinquency. However, at present no study has systematically investigated the relationships among these factors and how these mediating mechanisms work. To address this gap, path analyses are conducted to test the hypothesized pathways whereby parental religious involvement operates to discourage delinquent behaviors of offspring. The study variables are taken from three waves of the study of the National Longitudinal Survey of Youth 1979 and its descendent NLSY79 Child and Young Adults at two year intervals (2000, 2002, and 2004). 1020 American adolescents who are 10-14 years old in 2002 are selected for final analyses. The findings suggest that parental religious involvement does not affect adolescent delinquency four years later directly, but indirectly through its influence on adolescent religious involvement, parenting practices, inter-parental conflict, and their interactions with adolescent self-control.
Asunto(s)
Relaciones Familiares/psicología , Delincuencia Juvenil/prevención & control , Responsabilidad Parental/psicología , Religión , Adolescente , Conducta del Adolescente/fisiología , Desarrollo del Adolescente , Niño , Femenino , Humanos , Delincuencia Juvenil/psicología , Estudios Longitudinales , Masculino , Autocontrol , Adulto JovenRESUMEN
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.
RESUMEN
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.
RESUMEN
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.
Asunto(s)
Astrocitoma , Imagen por Resonancia Magnética , Mutación , Clasificación del Tumor , Organización Mundial de la Salud , Humanos , Astrocitoma/genética , Astrocitoma/clasificación , Astrocitoma/patología , Astrocitoma/diagnóstico por imagen , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Imagen por Resonancia Magnética/métodos , Pronóstico , Isocitrato Deshidrogenasa/genética , Neoplasias del Sistema Nervioso Central/clasificación , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Anciano , Adulto Joven , Neoplasias Encefálicas/clasificación , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/mortalidad , AdolescenteRESUMEN
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.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Calidad de Vida , Glioma/patología , Mutación , Organización Mundial de la Salud , Isocitrato Deshidrogenasa/genéticaRESUMEN
Nickel-iron based hydr(oxy)oxides have been well recognized as one of the best oxygen-evolving catalysts in alkaline water electrolysis. A crucial problem, however, is that iron leakage during prolonged operation would lead to the oxygen evolution reaction (OER) deactivation over time, especially under large current densities. Here, the NiFe-based Prussian blue analogue (PBA) is designed as a structure-flexible precursor for navigating an electrochemical self-reconstruction (ECSR) with Fe cation compensation to fabricate a highly active hydr(oxy)oxide (NiFeOx Hy ) catalyst stabilized with NiFe synergic active sites. The generated NiFeOx Hy catalyst exhibits the low overpotentials of 302 and 313 mV required to afford large current densities of 500 and 1000 mA cm-2 , respectively. Moreover, its robust stability over 500 h at 500 mA cm-2 stands out among the NiFe-based OER catalysts reported previously. Various in/ex situ studies indicate that the Fe fixation by dynamic reconstruction process can reinforce the Fe-activated effect on the OER amenable to the industrial-level large current conditions against the Fe leakage. This work opens up a feasible strategy to design highly active and durable catalysts via thermodynamically self-adaptive reconstruction engineering.
RESUMEN
ABSTRACT: Purpose: To evaluate significant risk variables for sepsis incidence and develop a predictive model for rapid screening and diagnosis of sepsis in patients from the emergency department (ED). Methods: Sepsis-related risk variables were screened based on the PIRO (Predisposition, Insult, Response, Organ dysfunction) system. Training (n = 1,272) and external validation (n = 568) datasets were collected from Peking Union Medical College Hospital (PUMCH) and Beijing Tsinghua Changgung Hospital (BTCH), respectively. Variables were collected at the time of admission. Sepsis incidences were determined within 72 h after ED admissions. A predictive model, Early Assessment of Sepsis Engagement (EASE), was developed, and an EASE-based nomogram was generated for clinical applications. The predictive ability of EASE was evaluated and compared with the National Early Warning Score (NEWS) scoring system. In addition, internal and external validations were performed. Results: A total of 48 characteristics were identified. The EASE model, which consists of alcohol consumption, lung infection, temperature, respiration rate, heart rate, serum urea nitrogen, and white blood cell count, had an excellent predictive performance. The EASE-based nomogram showed a significantly higher area under curve (AUC) value of 86.5% (95% CI, 84.2%-88.8%) compared with the AUC value of 78.2% for the NEWS scoring system. The AUC of EASE in the external validation dataset was 72.2% (95% CI, 66.6%-77.7%). Both calibration curves of EASE in training and external validation datasets were close to the ideal model and were well-calibrated. Conclusions: The EASE model can predict and screen ED-admitted patients with sepsis. It demonstrated superior diagnostic performance and clinical application promise by external validation and in-parallel comparison with the NEWS scoring system.
Asunto(s)
Sepsis , Humanos , Pronóstico , Curva ROC , Sepsis/diagnóstico , Recuento de Leucocitos , Hospitalización , Servicio de Urgencia en Hospital , Estudios RetrospectivosRESUMEN
BACKGROUND: Spinal cord stimulation (SCS) is a surgical technique used in patients with chronic intractable pain, and its effectiveness and safety have been validated by multiple studies. However, to maintain an optimal and steady long-term effect is still challenging. Here, we report a new management paradigm integrating smartphone application and remote programming. Chronic pain patients with SCS implants can monitor their pain status on the phone and change stimulation parameters accordingly. The PreMaSy study is a randomized controlled trial to evaluate the clinical effectiveness and safety of this precise management system. METHODS: Patients with chronic intractable pain will be screened for eligibility, and 82 participants are anticipated to be enrolled in this trial. After the electrode implantation, the stimulation effectiveness will be tested. Participants with a reduction of more than 50% in the visual analog scale (VAS) will receive implantation of an implantable pulse generator and randomized (1:1) into the experimental group or control group. All participants will be asked to take online follow-ups and complete assessments using a smartphone application. Daily pain characteristic assessments and monthly quality of life questionnaires are integrated into the App, and participants will be required to complete these assessments. The daily VAS for pain intensity will be monitored and a threshold will be set based on baseline VAS score. The interventional appointment will be scheduled once the threshold is reached. The primary outcome is the health condition and quality of life assessed by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). Utility values of EQ-5D-5L will be assessed at baseline and 1, 3, and 6 months post-operative. DISCUSSION: The PreMaSy study aims to evaluate the effectiveness and safety of a novel App-based, patient-centered, self-assessment management system for chronic intractable pain. A randomized controlled trial is designed to test the non-inferiority of this precise management system compared to the monthly online follow-ups. It is also expected to yield valuable experiences regarding precision medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT05761392. Registered on March 07, 2023.
Asunto(s)
Dolor Crónico , Dolor Intratable , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/efectos adversos , Dolor Crónico/diagnóstico , Dolor Crónico/terapia , Calidad de Vida , Prótesis e Implantes , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
4E-BP1 is a tumor suppressor regulating cap-dependent translation that is in turn controlled by mechanistic target of rapamycin (mTOR) or cyclin-dependent kinase 1 (CDK1) phosphorylation. 4E-BP1 serine 82 (S82) is phosphorylated by CDK1, but not mTOR, and the consequences of this mitosis-specific phosphorylation are unknown. Knock-in mice were generated with a single 4E-BP1 S82 alanine (S82A) substitution leaving other phosphorylation sites intact. S82A mice were fertile and exhibited no gross developmental or behavioral abnormalities, but the homozygotes developed diffuse and severe polycystic liver and kidney disease with aging, and lymphoid malignancies after irradiation. Sublethal irradiation caused immature T-cell lymphoma only in S82A mice while S82A homozygous mice have normal T-cell hematopoiesis before irradiation. Whole genome sequencing identified PTEN mutations in S82A lymphoma and impaired PTEN expression was verified in S82A lymphomas derived cell lines. Our study suggests that the absence of 4E-BP1S82 phosphorylation, a subtle change in 4E-BP1 phosphorylation, might predispose to polycystic proliferative disease and lymphoma under certain stressful circumstances, such as aging and irradiation.
Asunto(s)
Proteína Quinasa CDC2 , Linfoma , Ratones , Animales , Proteína Quinasa CDC2/genética , Proteína Quinasa CDC2/metabolismo , Fosforilación , Serina/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linfoma/genéticaRESUMEN
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.
Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Glioblastoma , Humanos , Proteína Proto-Oncogénica N-Myc , Isocitrato Deshidrogenasa/genética , Mutación , Astrocitoma/genética , Neoplasias del Sistema Nervioso Central/genética , Organización Mundial de la SaludRESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
Adopting the integrated model of General Strain Theory (GST), the current study tested the relations between cyberbullying roles (i.e., cyberbully, cybervictim, and cyberbully-victim) and delinquent behaviors (i.e., physical fighting and substance use), as well as the potential mediating effects of delinquent peer association and perceived social attachment from parents, friends, and teachers. This was conducted in a cross-sectional sample of 12,642 American adolescents via the use of structural equation models. The results indicated that being involved in cyberbullying might be not only directly associated with an increase in delinquent behaviors, but also indirectly via delinquent peer associations and perceived social attachment from parents, friends, and teachers. Furthermore, both direct and indirect (mediating) relationships between cyberbullying and delinquency might depend upon specific cyberbullying roles and the types of delinquency. Potential implications for prevention and intervention strategies were discussed.
Asunto(s)
Conducta del Adolescente , Ciberacoso , Delincuencia Juvenil , Adolescente , Estudios Transversales , Amigos , Humanos , Grupo ParitarioRESUMEN
In large-scale observational data with a hierarchical structure, both clusters and interventions often have more than two levels. Popular methods in the binary treatment literature do not naturally extend to the hierarchical multilevel treatment case. For example, most K-12 and universities have moved to an unprecedented hybrid learning module during the COVID-19 pandemic where learning modes include hybrid and fully remote learning, while students were clustered within a class and school region. It is challenging to evaluate the effectiveness of the learning outcomes of the multilevel treatments in a hierarchically data structured. In this paper, we study a covariates matching method and develop a generalized propensity score matching method to reduce the bias of estimation in the intervention effect. We also propose simple algorithms to assess the covariates balance for each approach. We examine the finite sample performance of the methods via simulation studies and apply the proposed methods to analyze the effectiveness of learning modes during the COVID-19 pandemic.