The molecular signature and prognosis of glioma with preoperative intratumoral hemorrhage: a retrospective cohort analysis.

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.

Machine learning revealed stemness features and a novel stemness-based classification with appealing implications in discriminating the prognosis, immunotherapy and temozolomide responses of 906 glioblastoma patients.

Glioblastoma (GBM) is the most malignant and lethal intracranial tumor, with extremely limited treatment options. Immunotherapy has been widely studied in GBM, but none can significantly prolong the overall survival (OS) of patients without selection. Considering that GBM cancer stem cells (CSCs) play a non-negligible role in tumorigenesis and chemoradiotherapy resistance, we proposed a novel stemness-based classification of GBM and screened out certain population more responsive to immunotherapy. The one-class logistic regression algorithm was used to calculate the stemness index (mRNAsi) of 518 GBM patients from The Cancer Genome Atlas (TCGA) database based on transcriptomics of GBM and pluripotent stem cells. Based on their stemness signature, GBM patients were divided into two subtypes via consensus clustering, and patients in Stemness Subtype I presented significantly better OS but poorer progression-free survival than Stemness Subtype II. Genomic variations revealed patients in Stemness Subtype I had higher somatic mutation loads and copy number alteration burdens. Additionally, two stemness subtypes had distinct tumor immune microenvironment patterns. Tumor Immune Dysfunction and Exclusion and subclass mapping analysis further demonstrated patients in Stemness Subtype I were more likely to respond to immunotherapy, especially anti-PD1 treatment. The pRRophetic algorithm also indicated patients in Stemness Subtype I were more resistant to temozolomide therapy. Finally, multiple machine learning algorithms were used to develop a 7-gene Stemness Subtype Predictor, which were further validated in two external independent GBM cohorts. This novel stemness-based classification could provide a promising prognostic predictor for GBM and may guide physicians in selecting potential responders for preferential use of immunotherapy.

Ba-modified peanut shell biochar (PSB): preparation and adsorption of Pb(II) from water.

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).

Influence of Individual-technology-task-environment Fit on University Student Online Learning Performance: The Mediating Role of Behavioral, Emotional, and Cognitive Engagement.

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.

Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine-Induced Immunity in Older Adults.

BACKGROUND: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). RESULTS: Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. CONCLUSIONS: Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

Transcriptome-based identification and expression profiling of AP2/ERF members in Caragana intermedia and functional analysis of CiDREB3.

BACKGROUND: The AP2/ERF transcription factor family plays important roles in regulation of plant growth and development as well as the response of plants to stress. However, there are currently few studies focusing on the function of the AP2/ERF-type transcription factors in Caragana intermedia Kuang et H. C. Fu. Here, the expression pattern of AP2/ERF transcription factors family in different tissues and under four stress treatments were evaluated, and the function of CiDREB3 was examined. METHODS AND RESULTS: In this study, the genes encoding the AP2/ERF family of transcription factors were screened from the C. intermedia drought transcriptome database and subjected to bioinformatic analysis using the online tool and software. The expression pattern of the members of AP2/ERF transcription factors in C. intermedia were detected via quantitative real-time PCR (qRT-PCR). The function of CiDREB3 on growth, development and drought tolerance was evaluated by transgenic Arabidopsis. As a result, 22 sequences with complete ORFs were obtained and all sequences were divided into 13 sub-groups. Most of the AP2/ERF transcription factors exhibited tissue-specific expression and were induced by cold, heat, NaCl and mannitol treatments. Furthermore, heterologous expression of CiDREB3 altered the morphology of the transgenic Arabidopsis thaliana L. Heynh and improved its drought tolerance during seedlings development. CONCLUSIONS: Taken together, the results of the present study helped to better understand the function of the AP2/ERF family transcription factors in response to multiple abiotic stresses and uncovered the role of CiDREB3 in affecting the morphology and abiotic stress tolerance of Arabidopsis.

Comparison of Levothyroxine Dosing in Patients with and without Heart Failure.

Background: Evidence has shown that low thyroid hormone levels may lead to worse prognosis including a higher mortality rate in patients with heart failure (HF). Thyroid replacement increases cardiac output and exercise performance without causing significant adverse events. The purpose of this study is to compare levothyroxine doses in patients with and without HF.Methods: This single center, retrospective cohort study compared levothyroxine doses in ambulatory hypothyroid patients with a history of HF to those without a history of HF. Patients were stratified into three groups: no HF, HF with reduced ejection fraction (HFrEF, EF<40%), and other types of HF. The primary endpoint of average levothyroxine dose was analyzed using multivariable linear regression with variables determined a priori.Results: Three hundred patients were included in the study with 100 patients in each arm. Average levothyroxine doses (mcg/kg) were 1.5 ± 0.7, 1.6 ± 0.8, and 1.6 ± 0.9 for no HF, other types of HF, HFrEF, respectively (p= .61). Factors found to be significantly related to levothyroxine dosing included gender, drug-drug interactions, and the timing of clinic visit to lab draw. No differences were found in secondary outcomes including TSH levels, free T4, T3, and percentage of patients with elevated thyroid-stimulating hormone (TSH) among HFrEF, other types of HF, and no HF patients. Among HF patients, average ejection fractions were also similar comparing patients with elevated TSH, normal TSH, and low TSH.Conclusion: The dose of levothyroxine was not significantly different in HF patients compared to patients without HF.

Development of Agrobacterium-mediated transient expression system in Caragana intermedia and characterization of CiDREB1C in stress response.

BACKGROUND: The Agrobacterium-mediated transient transformation is a versatile and indispensable way of rapid analyzing gene function in plants. Despite this transient expression system has been successfully applied in a number of plant species, it is poorly developed in Caragana intermedia. RESULTS: In this study, we established an Agrobacterium-mediated transient expression system in C. intermedia leaves and optimized the effect of different Agrobacterial strains, several surfactants and the concentration of Silwet L-77, which would affect transient expression efficiency. Among the 5 Agrobacterial strains examined, GV3101 produced the highest GUS expression level. Besides, higher level of transient expression was observed in plants infiltrated with Silwet L-77 than with Triton X-100 or Tween-20. Silwet L-77 at a concentration of 0.001% greatly improved the level of GUS transient expression. Real-time PCR showed that expression of CiDREB1C was highly up-regulated in transiently expressed plants and reached the highest level at the 2nd day after infiltration. Based on this optimized transient transformation method, we characterized CiDREB1C function in response to drought, salt and ABA treatment. The results showed that transiently expressed CiDREB1C in C. intermedia leaves could enhance the survival rate and chlorophyll content, and reduce the lodging rate compared with the control seedlings under drought, salt and ABA treatments. Furthermore, the rate of leaf shedding of CiDREB1C transient expression seedlings was lower than that of the control under ABA treatment. CONCLUSIONS: The optimized transient expression condition in C. intermedia leaves were infiltrated with Agrobacterial strains GV3101 plus Silwet L-77 at a concentration of 0.001% added into the infiltration medium. Transiently expressed CiDREB1C enhanced drought, salt and ABA stress tolerance, indicated that it was a suitable and effective tool to determine gene function involved in abiotic stress response in C. intermedia.

Baloxavir Marboxil: The First Cap-Dependent Endonuclease Inhibitor for the Treatment of Influenza.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trials, and clinical implications of baloxavir marboxil. DATA SOURCES: A MEDLINE search was conducted using the terms baloxavir, baloxavir marboxil, cap-dependent endonuclease inhibitor, and polymerase acidic endonuclease inhibitor. Additional data were obtained from the prescribing information and relevant guidelines. STUDY SELECTION AND DATA EXTRACTION: All clinical trials were included. DATA SYNTHESIS: Baloxavir marboxil exploits a new mechanism of action of inhibiting cap-dependent endonuclease. Baloxavir was shown to be superior compared with placebo and noninferior compared with oseltamivir with regard to the primary end point. Baloxavir was well tolerated in the trials. A second phase III study investigating high-risk patients was completed with positive results. However, the full article is not yet published. Relevance to Patient Care and Clinical Practice: The small amount of literature limits baloxavir's use in certain patient populations. Baloxavir offers advantages such as single-dose regimen, eliminating adherence concerns and lack of cross-resistance, making it an alternative for resistant viruses. Several uncertainties remain. Baloxavir has not been studied in hospitalized patients, patients with symptoms for >48 hours, or in combination with other antiviral agents. Furthermore, resistance to baloxavir can develop after 1 dose. Clinical studies are ongoing to evaluate baloxavir in young pediatric patients, hospitalized patients, and in combination therapy with neuraminidase inhibitors to further elucidate baloxavir's place in therapy. CONCLUSION: Baloxavir is a new antiviral medication for the treatment of influenza. Given the new mechanism of action, baloxavir may be useful in treating patients with resistant viruses.

Analysis of Metabolite Accumulation Related to Pod Color Variation of Caragana intermedia.

Caragana intermedia, a leguminous shrub widely distributed in cold and arid regions, is rich in secondary metabolites and natural active substances, with high nutritional and medical values. It is interesting that the pods of C. intermedia often show different colors among individual plants. In this study, 10-, 20- and 30-day-old red and green pods of C. intermedia were used to identify and characterize important metabolites associated with pod color. A total 557 metabolites, which could be classified into 21 groups, were detected in the pod extracts using liquid chromatography coupled with ESI-triple quadrupole-linear ion trap mass spectrometer (LC-ESI-MS/MS). Metabolomics analysis revealed significant differences in 15 groups of metabolites between red and green pods, including amino acids, nucleotide derivatives, flavonoids, and phytohormones. Metabolic pathway analysis showed that the shikimic acid and the phytohormone metabolic pathways were extraordinarily active in red pods, and the difference between red and green pods was obvious. Moreover, red pods showed remarkable flavonoids, cytokinins, and auxin accumulation, and the content of total flavonoids and proanthocyanidins in 30-day-old red pods was significantly higher than that in green pods. This metabolic profile contributes to valuable insights into the metabolic regulation mechanism in different color pods.

Mitochondrial ROS participates in Porphyromonas gingivalis-induced pyroptosis in cementoblasts.

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.

Aryl hydrocarbon receptor: Linking environment to aging process in elderly patients with asthma.

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.

Synthesis of ultrathin hybrid membranes via the co-polymerization of acrylic acid, styrene and molybdenum disulfide and their high adsorption selectivity for lead(II) in the mixture of metal ions.

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.

Clinical features, MRI, molecular alternations, and prognosis of astrocytoma based on WHO 2021 classification of central nervous system tumors: A single-center retrospective study.

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.

Clinical roles of EGFR amplification in diffuse gliomas: a real-world study using the 2021 WHO classification of CNS tumors.

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.

A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-containing therapy.

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.

Molecular Determinants of Neurocognitive Deficits in Glioma: Based on 2021 WHO Classification.

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.

A Real-World Comparison of Apixaban and Rivaroxaban in Obese and Morbidly Obese Patients With Nonvalvular Atrial Fibrillation.

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.

Effectiveness and Safety Studies of Omalizumab in Children and Adolescents With Moderate-To-Severe Asthma.

Background: Omalizumab is currently approved for the treatment of moderate-to-severe allergic asthma in patients 6 years and older. Objective: To assess the effectiveness and safety of subcutaneous omalizumab as an add-on therapy option for moderate-severe allergic asthma in patients aged 6-20 years old. Methods: The studies published from July, 1970 to May, 2021 were searched from the electronic databases which followed keywords: ("anti-IgE" OR "anti-immunoglobulin E" OR "anti-IgE antibody" OR "omalizumab" OR "rhuMAb-E25" OR "Xolair") AND "asthma" AND ("child" OR "children" OR "adolescents" OR "youth" OR "teenager" OR "kids" OR "pediatric"). Thirteen studies were pooled to determine the effectiveness and safety of omalizumab. Efficacy endpoints were evaluated using a fixed-effects model or a random-effects model depending on heterogeneity. Safety endpoints were evaluated by odds ratio. Results: Thirteen studies were included. In this meta-analysis, our results showed that fractional exhaled nitric oxide and asthma control test scores were significantly improved with omalizumab treatment. Serum immunoglobulin E was also decreased in children with moderate-to-severe asthma after treatment with omalizumab. The analysis found that there was no significant difference between pre-and post-treatment in forced expiratory volume in one second/ forced vital capacity ratio, forced expiratory flow between 25 and 75% of vital capacity, or FEV1. Overall, more adverse events occurred with omalizumab compared to placebo. However, the degree was mild to moderate. Conclusion: This meta-analysis indicates that omalizumab is safe and effective to treat children and adolescents with moderate-to-severe asthma.

The incidence and severity of open gingival embrasures in adults treated with clear aligners and fixed appliances: a retrospective cohort study.

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.