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To investigate the diagnostic performance of fully automated radiomics-based models for multiclass classification of a single enhancing brain tumor among glioblastoma, central nervous system lymphoma, and metastasis.The training and test sets were comprised of 538 cases (300 glioblastomas, 73 lymphomas, and 165 metastases) and 169 cases (101 glioblastomas, 29 lymphomas, and 39 metastases), respectively. After fully automated segmentation, radiomic features were extracted. Three conventional machine learning classifiers, including least absolute shrinkage and selection operator (LASSO), adaptive boosting (Adaboost), and support vector machine with the linear kernel (SVC), combined with one of four feature selection methods, including forward sequential feature selection, F score, mutual information, and LASSO, were trained. Additionally, one ensemble classifier based on the three classifiers was used. The diagnostic performance of the optimized models was tested in the test set using the accuracy, F1-macro score, and the area under the receiver operating characteristic curve (AUCROC).The best performance was achieved when the LASSO was used as a feature selection method. In the test set, the best performance was achieved by the ensemble classifier, showing an accuracy of 76.3% (95% CI, 70.0-82.7), a F1-macro score of 0.704, and an AUCROC of 0.878.Our fully automated radiomics-based models for multiclass classification might be useful for differential diagnosis of a single enhancing brain tumor with a good diagnostic performance and generalizability.

This study aims to introduce a sea ice elevation dataset estimated by using a 3-D laser scanner during the ice camp of the 2022 Arctic summer field survey. The equipment used is FARO’s Laser scanner FOCUS 3D X 130 HDR. The observed sea ice floe is located in the Arctic Ocean (76°13' N, 174°35') and is a multi-year ice with several melt ponds and ice ridges. We scanned eight sections separately, considering the equipment’s maximum horizontal scan range and the ice surface’s topographic features. The raw data were co-registered based on the positions of reference spheres. The result indicated a significant level of accuracy with a target-based vertical mean error of 4.8 mm. The laser scanner data were merged into point clouds ranging from 160×210 m. As a result, sea ice elevation data were generated in 0 to 2.8 m based on the minimum vertical point in the observation range. Sea ice elevation data is an essential variable in estimating the various properties of sea ice, such as ice thickness and roughness. In addition, using climatic variables such as air temperature and energy budget observed simultaneously can help to understand the physical interaction between the sea ice surface and the atmosphere on a local scale.

Sea ice is monitored on a regular basis by satellite observation; however, image-based drift tracking is imprecise as the time interval forming the image-pair is too large to capture the actual trajectory of ice drift. In this study, drift trajectory and speed of an Arctic sea ice floe measured by a GPS tracker for 3 months and the characteristics of the relating device and data, are introduced.

The CoV2-001 Phase 1 randomized trial evaluated the safety and immunogenicity of the GLS-5310 bi-cistronic DNA vaccine through 48 weeks of follow-up.Forty-five vaccine-naïve participants were recruited between 31 December 2020 and 30 March 2021. GLS-5310, encoding for the SARS-CoV-2 spike (S) and ORF3a proteins, was administered intradermally at 0.6 mg or 1.2 mg per dose, followed by application of the GeneDerm suction device as part of a two-dose regimen spaced either 8 or 12 weeks between vaccinations.GLS-5310 was well tolerated with no SAE's reported. Antibody and T cell responses were dose-independent. Anti-S antibodies were induced in 95.5% of participants with average GMT of ∼480 four-weeks post-vaccination, and declined minimally through 48 weeks. Neutralizing antibodies were induced in 55.5% of participants with post-vaccination GMT of 28.4. T cell responses were induced in 97.8% of participants, averaged 716 SFU/10GLS-5310 administered with the GeneDerm suction device was well tolerated and induced high levels of binding antibodies and T-cell responses. Antibody responses were similar to other DNA vaccines, whereas T cell responses were many-fold greater than DNA and non-DNA vaccines.

In this work, we demonstrate the bioavailability of dietary sialyllactose by concentration–time profiles in an osteoarthritis mini-pig model and suggest a potential therapeutic effect of sialyllactose on osteoarthritis.

Periventricular nodular heterotopia (PNH) is a neuronal migration disorder that occurs during early brain development. Patients with PNH may be asymptomatic and have normal intelligence; however, PNH is also known to cause various symptoms such as seizures, dyslexia, and cardiovascular anomalies. PNH is not commonly diagnosed during early infancy because of the lack of clinical manifestations during this period. We present the case of a female infant diagnosed with PNH based on brain magnetic resonance imaging, who had symptomatic patent ductus arteriosus that had to be ligated surgically and had prolonged feeding cyanosis with frequent apneic spells.

High-grade serous ovarian cancer (HGSOC) represents the major histological type of ovarian cancer, and the lack of effective screening tools and early detection methods significantly contributes to the poor prognosis of HGSOC. Currently, there are no reliable diagnostic biomarkers for HGSOC. In this study, we performed liquid chromatography data-independent acquisition tandem mass spectrometry (MS) on depleted serum samples from 26 HGSOC cases and 24 healthy controls (HCs) to discover potential HGSOC diagnostic biomarkers. A total of 1,847 proteins were identified across all samples, among which 116 proteins showed differential expressions between HGSOC patients and HCs. Network modeling showed activations of coagulation and complement cascades, platelet activation and aggregation, neutrophil extracellular trap formation, toll-like receptor 4, insulin-like growth factor, and transforming growth factor β signaling, as well as suppression of lipoprotein assembly and Fc gamma receptor activation in HGSOC. Based on the network model, we prioritized 28 biomarker candidates and validated 18 of them using targeted MS assays in an independent cohort. Predictive modeling showed a sensitivity of 1 and a specificity of 0.91 in the validation cohort. Finally, in vitro functional assays on four potential biomarkers (FGA, VWF, ARHGDIB, and SERPINF2) suggested that they may play an important role in cancer cell proliferation and migration in HGSOC. All raw data were deposited in PRIDE (PXD033169).

Pulmonary vein stump thrombosis (PVST) is uncommonly encountered postoperative in-situ thrombosis in the stump of pulmonary veins after lung resection. Data regarding the incidence and clinical behaviour of PVST are scarce. Thus, this study aims to investigate the incidence, clinical characteristics and outcome of PVST after lung resection in patients with lung cancer. Follow-up enhanced chest computed tomography (CT) scans acquired after the surgery were retrospectively reviewed to determine PVST presence for patients with lung cancer who underwent lung resection in two tertiary referral centres. Out of the 1885 patients with lung cancer who underwent lobectomy or more extensive lung resection, PVST was observed in 37 patients (2.0%) on their follow-up chest CT. Most stump thrombi were observed in the left superior pulmonary vein [35 (94.6%)] and in patients who underwent left upper lobectomy [34 (91.9%)]. At the last CT follow-up of each patient, 33 (89.2%) exhibited complete resolution, three partial resolution and one stabilization. Eleven (29.7%) patients received anticoagulant therapy after the diagnosis. The rate of complete PVST resolution did not differ significantly between the anticoagulation and nonanticoagulation groups. None of the PVST patients experienced systemic embolic events, regardless of anticoagulation. The PVST incidence diagnosed at routine chest CT follow-up following lung cancer surgery was 2%. PVST was characterized by a benign clinical course without progression and systemic embolization, regardless of anticoagulation. However, further studies are required to determine individualized therapeutic strategies, including anticoagulation.

ObjectivesThis study used National Health Insurance claims data from Korea to report the prevalence of sleep disorders and treatment status, including traditional Korean medicine, in the last ten years.MethodsThis is a retrospective cohort study in Korea. All diagnosis and prescription data, including herbal medicine claims, from the Health Insurance Review and Assessment Service from 2011 to 2020 were reviewed. Prevalence estimation, direct medical expenses, and prescribed amounts for sleep disorders were recorded.ResultsThe prevalence of sleep disorders increased from 3,867,975 (7.62%) in 2011 to 7,446,846 (14.41%) in 2020, nearly doubling over 10 years. Insomnia was observed in 91.44% (n=9,011,692) of the patients. The mean number of hospital visits per patient for sleep disorders was 11.5 (±26.62). Benzodiazepines are the most commonly prescribed medications for sleep disorders, and gamma-isoyosan is the most frequently prescribed herbal medicine.ConclusionsSleep disorders are continuously increasing, as is the use of medical services – personal and social medical expenses are also increasing accordingly. Sleep disorders should be recognized as a significant health problem that needs to be actively addressed to improve quality of life.Strengths and limitations of this studyThis is a nationwide health insurance claims data for prevalence and the status of treatment on sleep disorders for ten years.This study will be meaningful because we have confirmed the current address of the prevalence and treatment of sleep disorders in the last 10 years.The data source has the limitation of being able to confirm only the items subject to health insurance benefits and review.The results of tests for the diagnosis of sleep disorders were not confirmed.

The purpose of this study was to identify differences in temporal parameters correlating to the presence of aspiration and the severity of penetration-aspiration scale (PAS) in patients with dysphagia after stroke. We also investigated whether there was a significant difference in temporal parameters based on the location of the stroke lesion. A total of 91 patient videofluoroscopic swallowing study (VFSS) videos of stroke patients with dysphagia were retrospectively analyzed. Various temporal parameters including oral phase duration, pharyngeal delay time, pharyngeal response time, pharyngeal transit time, laryngeal vestibule closure reaction time, laryngeal vestibule closure duration, upper esophageal sphincter opening duration and upper esophageal sphincter reaction time were measured. Subjects were grouped by the presence of aspiration, PAS score, and location of the stroke lesion. Pharyngeal response time, laryngeal vestibule closure duration, and upper esophageal sphincter opening duration were significantly prolonged in the aspiration group. These three factors showed positive correlation with PAS. In terms of stroke lesion, oral phase duration was significantly prolonged in the supratentorial lesion group, while upper esophageal sphincter opening duration was significantly prolonged in the infratentorial lesion group. We have demonstrated that quantitative temporal analysis of VFSS can be a clinically valuable tool identifying dysphagia pattern associated with stroke lesion or aspiration risk.

Background: Cardiac hemangiomas account for only 2.8% of primary cardiac tumors and are caused by the abnormal proliferation of endothelial cells and excess blood vessels. Typical radiological findings of cardiac hemangioma demonstrate intense contrast enhancement. Case Presentation: Here we report the case of a 69-year-old man who presented with a right atrial mass found incidentally with multimodal imaging findings, including echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI). This case presented with poor enhancement within right atrial mass on dynamic contrast-enhanced CT scan and gadolinium-enhanced first-pass perfusion image of cardiac MRI. After surgical resection, the pathologic diagnosis of cardiac capillary hemangioma was made. Conclusion: Cardiac hemangioma could be included in the differential diagnosis for cardiac neoplasms demonstrating poor enhancements on CT and MRI scans.

Supplementary Table 1. The IC50 values of bosutinib, gemcitabine, and cisplatin in biliary tract cancer cell lines.

S1- basal expression level S2- MTT Assay and Colony Forming Assay S3- Combination data S4- Trastuzumab monotherapy in vivo

Trastuzumab in combination with chemotherapy is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers. Several resistance mechanisms against anti-HER2 therapy have been proposed. Src activation has been suggested to be responsible for the resistance of HER2-positive breast cancer. In our study, we generated four trastuzumab-resistant (HR) cancer cell lines from HER2-amplified gastric and biliary tract cancer cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773). Elevated Src phosphorylation was detected in SNU2670HR and NCI-N87HR cell lines, but not in SNU216HR or SNU2773HR cell lines. In SNU216HR and SNU2773HR cell lines, phospho-FAK (focal adhesion kinase) was elevated. Bosutinib as a Src inhibitor suppressed growth, cell-cycle progression, and migration in both parental and HR cell lines. Specifically, Src interacted with FAK to affect downstream molecules such as AKT, ERK, and STAT3. Bosutinib showed more potent antitumor effects in Src-activated HR cell lines than parental cell lines. Taken together, this study suggests that Src inhibition may be an effective measure to overcome trastuzumab resistance in HER2-positive cancer. Mol Cancer Ther; 16(6); 1145–54. ©2017 AACR.

South Korea is one of the East Asian countries suffering severe ambient PM2.5 pollution which has been continuously reported to a risk factor driving both death and disability in many parts of the world. We investigated the associations of cause-specific mortality with both PM2.5 chemical constituents and source contributions in four metropolitan cities, namely Seoul, Daejeon, Gwangju and Ulsan, by applying the generalized linear model (GLM) to the results of the positive matrix factorization (PMF) modeling. The cities represent each of four air control zone designated as of April 2020 by the special law for controlling air pollution on a regional basis in South Korea. We found that that the interquartile range (IQR) increase in the concentration PM2.5 chemical constituents largely increased the relative risk (RR) of mortality, whereas the significance and strength of the associations were different among the cities. In addition, the effects of unit increase in source contributions also differed depending on regions. In conclusion, the results of this study suggest the PM2.5 compositional characteristics may have influenced the heterogeneous health of PM2.5 exposure among the cities. Therefore, the plans and policies based on the regional characteristics of PM2.5 composition and health risk need to be implemented along with the reduction of total mass concentration of PM2.5 for mitigating adverse health effects efficiently from a perspective of public health.

To determine whether imaging-based risk stratification enables prognostication in diffuse glioma, NOS (not otherwise specified).Data from 220 patients classified as diffuse glioma, NOS, between January 2011 and December 2020 were retrospectively included. Two neuroradiologists analyzed pre-surgical CT and MRI to assign gliomas to the three imaging-based risk types considering well-known imaging phenotypes (e.g., T2/FLAIR mismatch). According to the 2021 World Health Organization classification, the three risk types included (1) low-risk, expecting oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant, and 1p/19q-codeleted; (2) intermediate-risk, expecting astrocytoma, IDH-mutant; and (3) high-risk, expecting glioblastoma, IDH-wildtype. Progression-free survival (PFS) and overall survival (OS) were estimated for each risk type. Time-dependent receiver operating characteristic analysis using 10-fold cross-validation with 100-fold bootstrapping was used to compare the performance of an imaging-based survival model with that of a historical molecular-based survival model published in 2015, created using The Cancer Genome Archive data.Prognostication according to the three imaging-based risk types was achieved for both PFS and OS (log-rank test, p0.001). The imaging-based survival model showed high prognostic value, with areas under the curves (AUCs) of 0.772 and 0.650 for 1-year PFS and OS, respectively, similar to the historical molecular-based survival model (AUC = 0.74 for PFS and 0.87 for OS). The imaging-based survival model achieved high long-term performance in both 3-year PFS (AUC = 0.806) and 5-year OS (AUC = 0.812).Imaging-based risk stratification achieved histomolecular-level prognostication in diffuse glioma, NOS, and could aid in guiding patient referral for insufficient or unsuccessful molecular diagnosis.• Three imaging-based risk types enable distinct prognostication in diffuse glioma, NOS (not otherwise specified). • The imaging-based survival model achieved similar prognostic performance as a historical molecular-based survival model. • For long-term prognostication of 3 and 5 years, the imaging-based survival model showed high performance.

We investigated the safety and efficacy of pemetrexed monotherapy in patients with lung adenocarcinoma and various renal conditions, including chronic kidney disease. We also analyzed whether baseline renal function affected progression-free survival (PFS). We retrospectively analyzed 71 patients who received maintenance-and second-line pemetrexed monotherapy. Patients were divided into two groups according to estimated glomerular filtration rate (eGFR): fair eGFR (>60 mL/min/1.73 m2) and lower eGFR (59 mL/min/1.73 m2 or less). The safety and efficacy were evaluated for each group. Median ages were 73.2 years in the lower eGFR group (n=28) and 64.5 years in the fair eGFR group (n=43). Patients with a lower eGFR achieved a median PFS of 4.7 months, while the median PFS for patients with a fair eGFR was 2.7 months. The difference between the two groups was not statistically significant (p=0.075). Both groups showed treatment-related low-grade hematological and non-hematological adverse events. Pemetrexed monotherapy is safe and effective in patients with lung adenocarcinoma with a lower eGFR.

Background: This study aimed to identify the factors affecting smartphone overdependence among older adults.Methods: A cross-sectional descriptive study was conducted with 179 older adults using smartphones in B metropolitan city. A multiple regression analysis was performed to identify the effect of physical activity, social support, and depression on smartphone overdependence.Results: Factors that affect smartphone overdependence among the participants were as follows: (a) purpose of using smartphone (β=.23, p=.001), (b) age (β=.23, p=.002), (c) smartphone use time (β=.20, p=.004), (d) educational level (β=−.15, p=.027), and (e) social support (β=−.14, p=.048). The model explained for 19.0% (F=9.30, p＜.001).Conclusions: The findings of this study can be used as evidence to develop intervention programs and policy measures to prevent and manage smartphone overdependence, which has negative effects on the physical and mental health of older adults.

Here, we report a simple and general approach to fabricate free-standing two-dimensional (2D) sheets of nanoparticles by the simultaneous self-assembly of hydrophobic nanoparticles and hydrophilic polymers at the liquid-liquid interface. The nanoparticle-polymer interaction at the interface generates well-defined 2D sheets of densely packed nanoparticles with a lateral dimension of tens of micrometers. The nanosheets transferred in water are stable over months without any additional cross-linking step. The method is applicable for a broad range of nanoparticles including oxide, semiconductor, and metal nanoparticles as well as functional polymers.

A series of oligomeric chain extender-derived AEMs (QPP-b-PSK-w-TMA) are reported for AEMFC and AEMWE. Especially, the QPP-b-PSK-3.5-TMA-based AEMFC showed the highest specific power among the state-of-the-art AEMFCs with noble metal catalysts.

Purpose: The purpose of this study was to use shear-wave elastography (SWE) to assess testicular stiffness changes during the Valsalva maneuver in adolescents and young adults with varicocele, to compare these changes according to clinical severity, and to evaluate the role of SWE in the diagnosis of varicocele.Methods: This study included patients undergoing testicular ultrasonography for the diagnosis of varicocele or for post-varicocelectomy follow-up between June 2016 and February 2017. Fifty-four testicles of 27 consecutive patients (mean age, 15.9 years) were classified by clinical grade (grade 0-3). Using SWE, mean testicular stiffness (Emean) was measured at rest and during the Valsalva maneuver. The correlations between multiple ultrasonographic parameters (volume asymmetry, Emean at rest, and absolute and percentage changes in Emean during the Valsalva maneuver) and clinical grade were assessed using the Spearman correlation test.Results: The Emean at rest was similar across clinical grades. During the Valsalva maneuver, increased testicular stiffness was frequently observed in patients with grade 2 or 3 varicocele but rarely observed in those with grade 0 or 1 varicocele. The changes in Emean were positively correlated with the clinical grade (all P0.05).Conclusion: A transient, reversible increase in testicular stiffness during the Valsalva maneuver was observed in adolescents with high-grade varicocele, and the degree of stiffness change was correlated with the clinical grade. Stiffness change identified using SWE during the Valsalva maneuver is a potential surrogate indicator of venous congestion.

A hierarchically porous, biaxially woven carbon nanotube sheet was proposed in a cathode of anion-exchange membrane water electrolysis to increase surface area and enhance transports.

The subchronic toxicity of oral L-tryptophan produced by fermentation with metabolically engineered

Background/Aim: The majority of patients with early-stage endometrial cancer (EC) have a good prognosis, but recurrence does occur despite diagnosis at an early stage. There is a growing need for early diagnosis of EC and novel treatment options. Materials and Methods: Human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor receptor 2 (VEGFR) expression in microarrays of patient EC tissue was examined in association with clinicopathological data. HER2 and VEGFR2 expression in Ishikawa cells and differences in migration and proliferation of cells with HER2-knockdown were evaluated. Results: Higher expression of VEGFR2 was associated with lower International Federation of Obstetrics and Gynecology grades (p=0.044). The positive correlation between HER2 and VEFR2 expression was statistically significant in T1 stage (p=0.002) and International Federation of Obstetrics and Gynecology grade 1 tumors (p=0.004). Wound-healing assays revealed that HER2 loss in Ishikawa cells reduced confluence compared to that of control cells. Conclusion: The association of VEGFR2 and HER2 expression in early EC was elucidated. This study shows that the measurement of VEGFR2 expression may be useful in the preoperative assessment of EC and suggests the possibility of anti-HER2 therapy for EC.

Purpose: Histone deacetylase inhibitors (HDI) are promising anticancer therapies; however, drug resistance limits their efficacy. Here, we investigated the molecular mechanisms underlying HDI resistance, focusing on the mechanism of HDI-mediated induction of insulin-like growth factor 2 (IGF2) based on our previous study.Experimental Design: The methylation status of CCCTC-binding factor (CTCF)-binding sites in the IGF2/H19 imprinting control region (ICR) were determined by methylation-specific PCR and bisulfite sequencing. The effectiveness of single or combinatorial blockade of DNA methyltransferase 1 (DNMT1) and histone deacetylase (HDAC) was evaluated using cell viability assay and patient-derived tumor xenograft (PDX) model.Results: HDAC inhibition by vorinostat increased acetylated STAT3 (K685), resulting in transcriptional upregulation of DNMT1. DNMT1-mediated hypermethylation of CTCF-binding sites in the IGF2/H19 ICR decreased CTCF insulator activity, leading to a transcriptional upregulation of IGF2 and activation of the insulin-like growth factor 1 receptor (IGF-1R) pathway in cells with acquired or de novo vorinostat resistance. Strategies targeting DNMT1 diminished the IGF2 expression and potentiated vorinostat sensitivity in preclinical models of lung cancer with hypermethylation in the H19/IGF2 ICR. The degree of ICR hypermethylation correlated with vorinostat resistance in patient-derived lung tumors and in patients with hematologic malignancies.Conclusions: DNMT1-mediated transcriptional upregulation of IGF2 is a novel mechanism of resistance to HDIs, highlighting the role of epigenetic deregulation of IGF2 in HDI resistance and the potential value of the H19/IGF2 ICR hypermethylation and DNMT1 expression as predictive biomarkers in HDI-based anticancer therapies. Clin Cancer Res; 23(5); 1299–311. ©2016 AACR.

Supplementary Methods Supplementary Table S1. Enhanced phosphorylation of several protein kinases such as IGF-1R and Akt in vorinostat-resistant H1944R compared to its parental control (H1944). Supplementary Table S2. Synergistic effect of combinatorial treatment with erlotinib and linsitinib in H1944R cells. Supplementary Table S3. Primer sequences used for MSP. Supplementary Table S4. Primer sequences used for ChIP analysis. Supplementary Table S5. Primer sequences used for RT-PCR analysis.

Supplementary Figure S1. The involvement of the IGF-1R activation in acquired resistance to vorinostat. Supplementary Figure S2. Differential regulation of the CTCF binding to the CTCF6 site in the H19/IGF2 ICR according to vorinostat sensitivity. Supplementary Figure S3. Enhanced apoptosis by combinatorial treatment with vorinostat and Stattic. Supplementary Figure S4. The association of DNMT1 expression with vorinostat sensitivity in lymphoma cell lines.

Somatic mutational signatures elucidate molecular vulnerabilities to therapy and therefore detecting signatures and classifying tumors with respect to signatures has clinical value. However, identifying the etiology of the mutational signatures remains a statistical challenge, with both small sample sizes and high variability in classification algorithms posing barriers. As a result, few signatures have been strongly linked to particular risk factors. Here we presentDiffsig, a model and R package for estimating the association of risk factors with mutational signatures, suggesting etiologies for the pre-defined mutational signatures.Diffsigis a Bayesian Dirichlet-multinomial hierarchical model that allows testing of any type of risk factor while taking into account the uncertainty associated with samples with a low number of observations. In simulation, we found that our method can accurately estimate risk factor-mutational signal associations. We appliedDiffsigto breast cancer data to assess relationships between five established breast-relevant mutational signatures and etiologic variables, confirming known mechanisms of cancer development.Diffsigis implemented as an R package available at:https://github.com/jennprk/diffsig.

Background Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median survival of GBM patients remains poor (~ 1.5 years). For recurrent GBM, anti-angiogenic treatment is one of the common treatment approaches. However, current anti-angiogenic treatment modalities are not satisfactory because of the resistance to anti-angiogenic agents in some patients. Therefore, we sought to identify novel prognostic biomarkers that can predict the therapeutic response to anti-angiogenic agents in patients with recurrent glioblastoma. Methods We selected patients with recurrent GBM who were treated with anti-angiogenic agents and classified them into responders and non-responders to anti-angiogenic therapy. Then, we performed proteomic analysis using liquid-chromatography mass spectrometry (LC–MS) with formalin-fixed paraffin-embedded (FFPE) tissues obtained from surgical specimens. We conducted a gene-ontology (GO) analysis based on protein abundance in the responder and non-responder groups. Based on the LC–MS and GO analysis results, we identified potential predictive biomarkers for anti-angiogenic therapy and validated them in recurrent glioblastoma patients. Results In the mass spectrometry-based approach, 4957 unique proteins were quantified with high confidence across clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic patterns (n = 269 proteins) between responders and non-responders. The GO term enrichment analysis revealed a cluster of genes related to immune cell-related pathways (e.g., TMEM173, FADD, CD99) in the responder group, whereas the non-responder group had a high expression of genes related to nuclear replisome (POLD) and damaged DNA binding (ERCC2). Immunohistochemistry of these biomarkers showed that the expression levels of TMEM173 and FADD were significantly associated with the overall survival and progression-free survival of patients with recurrent GBM. Conclusions The candidate biomarkers identified in our protein analysis may be useful for predicting the clinical response to anti-angiogenic agents in patients with recurred GBM.

Purpose We aim to evaluate efficacy of immediate post-concurrent chemoradiotherapy (CCRT) advanced MRI in patients with glioblastoma to guide treatment decisions and improve survival outcomes. Methods This retrospective study included 168 patients with IDH wild-type glioblastoma who showed measurable enlarging enhancing lesion on MRI within 12 weeks after CCRT between January 2013 and August 2021. Patients were classified with positive MRI group when early progression was suspected on advanced MRI. The rate of switching to second-line treatment was compared between patients with positive and negative findings. Overall survival (OS) after adjustment with propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) was compared between patients continuing primary treatment and those switched to second-line treatment. Multivariable Cox proportional hazards analysis was performed on PSM patients. Results Among 168 patients, 110 exhibited positive findings and 58 showed negative findings on advanced MRI. The positive MRI group showed higher rate of switching to second-line treatment than negative MRI group (49% [54/110] vs. 2% [1/58]; p