bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can FSRQ 3C 345 be a very high energy blazar candidate?
Authors: Dar Athar A , Sahayanathan Sunder , Shah Zahir , Iqbal Naseer 
Published: December 2023

ABSTRACT
The recent detection of very high energy (VHE) emissions from flat spectrum radio quasars (FSRQs) at high redshifts has revealed that the universe is more transparent to VHE γ-rays than it was expected. It has also questioned the plausible VHE emission mechanism responsible for these objects. Particularly for FSRQs, the γ-ray emission is attributed to the external Compton (EC) process. We perform a detailed spectral study of Fermi-detected FSRQ 3C 345 using synchrotron, synchrotron self-Compton, and EC emission mechanisms. The simultaneous data available in optical, ultraviolet, X-ray, and γ-ray energy bands is statistically fitted under these emission mechanisms using the χ2-minimization technique. Three high flux states and one low flux state are chosen for spectral fitting. The broad-band spectral energy distribution during these flux states is fitted under different target photon temperatures, and the model VHE flux is compared with the 50 h Cherenkov Telescope Array sensitivity. Our results indicate a significant VHE emission could be attained during the high flux state from MJD 59635−59715 when the target photon temperature is within 900–1200 K. Furthermore, our study shows a clear trend of variation in the bulk Lorentz factor of the emission region as the source transits through different flux states. We also note that during high γ-ray flux states, an increase in external photon temperature demands high bulk Lorentz factors, while this behaviour reverses in case of low γ-ray flux state.
Dust evolution in a supernova interacting with the ISM
Authors: Vasiliev Evgenii O , Shchekinov Yuri A 
Published: December 2023

ABSTRACT
Supernovae (SNe) explosions are thought to be an important source of dust in galaxies. At the same time strong shocks from SNe are known as an efficient mechanism of dust destruction via thermal and kinetic sputtering. A critically important question of how these two hypotheses of SNe activity control the dust budget in galaxies is still not quite clearly understood. In this paper, we address this question within 3D multifluid hydrodynamical simulations, treating separately the SNe injected dust and the dust pre-existed in ambient interstellar gas. We focus primarily on how the injected and the pre-existing dust is destroyed by shock waves and hot gas in the SN bubble depending on the density of ambient gas. Within our model, we estimate an upper limit of the SN-produced dust mass which can be supplied into interstellar medium. For an SN progenitor mass of 30 M⊙ and the ejected dust mass Md = 1 M⊙, we constrain the dust mass that can be delivered into the ISM as ≥0.13 M⊙, provided that the SN has injected large dust particles with a ≥ 0.1 µm.
Constraints on sub-terrestrial free-floating planets from Subaru microlensing observations
Authors: DeRocco William , Smyth Nolan , Profumo Stefano 
Published: December 2023

ABSTRACT
The abundance of protoplanetary bodies ejected from their parent star system is presently poorly constrained. With only two existing optical observations of interstellar objects in the 108–1010 kg mass range and a small number of robust microlensing observations of free-floating planets (FFPs) in the 1024–1025 kg mass range, there is a large range of masses for which there are no existing measurements of the unbound population. The three primary microlensing surveys currently searching for FFPs operate at a cadence greater than 15 min, which limits their ability to observe events associated with bodies with a mass much below an Earth mass. We demonstrate that existing high-cadence observations of M31 with the Subaru Hyper Suprime-Cam place constraints on the abundance of unbound objects at sub-terrestrial masses, with peak sensitivity at 10−4 M⊕ for Milky Way lenses and 10−1 M⊕ for lenses in M31. For a fiducial $\frac{dn}{dM}\propto M^{-2}$ mass distribution, we find that the abundance of unbound objects is constrained to $n_\text{unbound} \lt 1.4 \times 10^{7} ~\rm {pc}^{-3}$ for masses within 1 dex of 10−4 M⊕. Additionally, we compute limits on an artificial ‘monochromatic’ distribution of unbound objects and compare to existing literature, demonstrating that the assumed spatial distribution of lenses has very significant consequences for the sensitivity of microlensing surveys. While the observations ultimately do not probe abundances suggested by current models of planetary formation, our limits place direct observational constraints on the unbound population in the sub-terrestrial mass range and motivate new observational strategies for microlensing surveys.
10005-ANGI-1 REGULATION OF ALTERNATIVE ANGIOGENIC FACTORS IN BEVACIZUMAB THERAPY FOR GLIOBLASTOMA
Authors: Ezaki Taketo , Tanaka Toshihide , Tamura Ryota , Yamamoto Yohei , Takei Jun , Morimoto Yukina , Imai Ryotaro , Kuranari Yuki , Akasaki Yasuharu , Murayama Yuichi , Miyake Keisuke , Sasaki Hikaru 
Published: December 2023

Abstract
The elucidation of the mechanism of action and resistance is imperative to overcome resistance to Bev and develop a more effective therapy. This study aims to investigate the status and change of alternative angiogenic factors regarding Bev usage using human specimens. The present study used 54 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naive Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory/autopsied Bev group). Importantly, naive Bev-refractory Bev of 22 specimens in 11 cases (including 4 autopsy specimens and 7 salvage surgery specimens) were obtained as paired specimens from the same patient. The expression of alternative angiogenic factors including basic fibroblast growth factor (bFGF), placental growth factor (PlGF), Angiopoietin1 (Ang-1), Angiopoietin2(Ang-2) and EphrinA2 were investigated via immunohistochemistry. PlGF expression was higher in the effective group than in the Naive group (p=0.048), and Ang-2 (0.047) and EphA2 (p=0.028) were higher in the relapse group than in the Naive group. Interestingly, in paired specimens, PlGF expression was higher in the refractory group than in the Naive group (p=0.036). This suggests that angiogenic factors other than VEGF are involved in recurrence. We provide the first clinicopathological evidence of the status of alternative angiogenic pathway after the Bev usage. These in situ observations will help to optimize therapy.
10006-PEDT-1 PEDIATRIC LOWER GRADE GLIOMA SURGERY IN THE ERA OF GENOMIC MEDICINE
Authors: Gomi Akira , Oguma Hirofumi , Kawai Kensuke 
Published: December 2023

Abstract

INTRODUCTION
In the new WHO Brain Tumor Classification of 2021, pediatric-type gliomas are classified separately from adult-type tumors. Additionally, with the advancement of cancer genomics, treatment options have expanded. Here we consider surgery for pediatric low-grade gliomas.

METHODS
We retrospectively analyzed 41 cases of low-grade gliomas or glioneuronal tumors in patients under 18 years of age who underwent surgery at our institute from 2002 to March 2023. We discussed surgical strategies based on molecular classification.

RESULTS
Among the cases, there were 34 gliomas and 7 glioneuronal tumors. According to the new WHO classification, they corresponded to 1) Adult-type diffuse gliomas, 2) Pediatric-type diffuse low-grade gliomas, 3) Circumscribed astrocytic tumors, or 4) Glioneuronal and neuronal tumors. Cases without molecular diagnosis were also considered in light of the new WHO classification.

DISCUSSION
Among molecularly diagnosed astrocytomas involving the cerebral hemisphere, brain stem, spinal cord, there were no cases of 1), and 2) 3) were the main cases. It is important in surgical selection to note that these cases generally have a more favorable prognosis compared to the adult type and have usefulness in diagnosing MAPK pathway abnormalities leading to the selection of molecularly targeted drugs. 3) includes pilocytic astrocytoma, subependymal giant cell astrocytoma, and pleomorphic xanthoastrocytoma. Among these, in the treatment of pilocytic astrocytomas located in the optic pathway and hypothalamus, biopsy becomes necessary for molecular diagnosis and the selection of appropriate therapeutic agents. Conversely, for unilateral optic nerve gliomas, options other than resection may be considered. 4) is primarily associated with epilepsy-related tumors. Surgical resection holds the promise of controlling epilepsy in these cases. However, various genetic abnormalities have been identified, which could prove useful in diagnosis and treatment.

CONCLUSION
Based on the new WHO classification, a reevaluation of treatment strategies for pediatric brain tumors is necessary.
10008-CBMS-1 THE NOVEL MDM4 INHIBITOR CEP-1347 ACTIVATES THE P53 PATHWAY AND BLOCKS MALIGNANT MENINGIOMA GROWTH IN VITRO AND IN VIVO
Authors: Mitobe Yuta , Sonoda Yukihiko , Kitanaka Chifumi 
Published: December 2023

Abstract
A significant proportion of meningiomas are clinically aggressive, but there is currently no effective chemotherapy for meningiomas. An increasing number of studies have been conducted to develop targeted therapies, yet none have focused on the p53 pathway as a potential target. In this study, we aimed to determine the in vitro and in vivo effects of CEP-1347, a small-molecule inhibitor of MDM4 with known safety in humans. The effects of CEP-1347 and MDM4 knockdown on the p53 pathway in human meningioma cell lines with and without p53 mutation were examined by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 was examined in vitro and in a mouse xenograft model of meningioma. In vitro, CEP-1347 at clinically relevant concentrations inhibited MDM4 expression, activated the p53 pathway in malignant meningioma cells with wild-type p53, and exhibited preferential growth inhibitory effects on cells expressing wild-type p53, which was mostly mimicked by MDM4 knockdown. CEP-1347 effectively inhibited the growth of malignant meningioma xenografts at a dose that was far lower than the maximum dose that could be safely given to humans. Our findings suggest targeting the p53 pathway with CEP-1347 represents a novel and viable approach to treating aggressive meningiomas.
10014-CBMS-2 CONCURRENT TARGETING OF MDM4 AND MDM2 USING CEP-1347 AS AN EFFECTIVE THERAPEUTIC STRATEGY FOR P53 WILD-TYPE MALIGNANT BRAIN TUMORS
Authors: Mitobe Yuta , Sonoda Yukihiko , Kitanaka Chifumi 
Published: December 2023

Abstract
The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study using CEP-1347, an inhibitor of MDM4 protein expression. The effects of CEP-1347, the genetic and/or pharmacological inhibition of MDM2, and their combination on the p53 pathway in malignant brain tumor cell lines expressing wild-type p53 were investigated by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 alone or in combination with MDM2 inhibition were examined by dye exclusion and/or colony formation assays. The treatment of malignant brain tumor cell lines with CEP-1347 markedly increased MDM2 protein expression, while blocking CEP-1347-induced MDM2 overexpression by genetic knockdown augmented the effects of CEP-1347 on the p53 pathway and cell growth. Blocking the MDM2-p53 interaction using the small molecule MDM2 inhibitor RG7112, but not MDM2 knockdown, reduced MDM4 expression. Consequently, RG7112 effectively cooperated with CEP-1347 to reduce MDM4 expression, activate the p53 pathway, and inhibit cell growth. The present results suggest CEP-1347-induced MDM2 overexpression combined with the selective inhibition of MDM2's interaction with p53, while preserving its ability to inhibit MDM4 expression, as a novel and rational strategy to effectively reactivate p53 in wild-type p53 cancer cells.
10018-COT-4 COMPARATIVE VOLUMETRIC ANALYSES FOLLOWING BEVACIZUMAB THERAPY FOR A PATIENT WITH CO- INCIDENCE OF GLIOBLASTOMA, MENINGIOM
Authors: Teshigawara Akihiko , Tanaka Toshihide , Tomoto Kyoichi , Hasegawa Yuzuru , Murayama Yuichi 
Published: December 2023

Abstract

BACKGROUND
Given that glioblastoma, meningioma and dural arteriovenous fistura (dAVF) represent angiogenic disease mainly caused by high expression of vascular endothelial growth factor (VEGF), bevacizumab is expected to be effective for these diseases. We experienced a patient with co-incidence of these 3 diseases was given neoadjuvant bevacizumab which provided a volume reduction of glioblastoma with improvement of clinical symptoms.

CASE REPORT
An eighty five year-old man has suffered from aphasia and dementia. Brain MRI showed a ring enhanced intraaxial tumor with perifocal edema in left temporal lobe, a dural-attached extraaxial tumor in the left sphenoid ridge and dAVF at left transverse-sigmoid sinus. Due to elderly with poor general condition, he was treated by administrate bevacizumab rather than the resection to confirm histological diagnosis. Three days after the administration, he began to walk and speech.

RESULTS
For comparison of the reactivity to bevacizumab among these three diseases, we calculated the volumetric quantitative assessment of glioblastoma and meningioma by the contrast-enhanced MRI and made a qualitative assesment for the dAVF by digital subtraction angiography (DSA) and MRA with comparison between before and afterbevacizumab administration. The volume reduction rates 1 and 5 months later after bevacizumab administration in glioblastoma and in meningioma were 0.34% and 94.5%, 13.7%, 6.8%, respectively. The volume reduction rate of glioblastoma was significantly larger than of Mg. The DSA showed the dAVF did not change even though bevacizumab therapy.

DISCUSSION
As previously reported, the VEGF concentration in the glioblastoma was significantly higher than that in other types of tumors including meningioma. In dAVF, other angiogenic factors would be produced in addition to VEGF.

CONCLUSIONS
Based on these evidences and the current rare case with co-incidence of glioblastoma, meningioma, and dAVF, it suggested that the effectiveness of bevacizumab therapy would be depend on the expression level of the VEGF concentration.
10025-MPC-3 DIFFERENCE AMONG GENERATIONS IN PATIENTS WITH HISTONE H3-MUTATED GLIOMAS
Authors: Fukai Junya , Hayashi Nobuhide , Nakatogawa Hirokazu , Kawaji Hiroshi , Kodama Yoshinori , Shofuda Tomoko , Yoshioka Ema , Kanematsu Daisuke , Katsuma Asako , Sumida Miho , Kijima Noriyuki , Okita Yoshiko , Mori Kanji , Kanemura Yonehiro 
Published: December 2023

Abstract

OBJECT
This study investigates clinical and molecular features, including the survival outcomes, of patients with histone H3-mutant gliomas and the differences among generations: children (-13 years), adolescence and young adult (AYA) (14-39 years), and older adult (40- years) patients. Particularly, we focused on the older adult cases.

METHODS
We collected pediatric and adult glioma cases harboring histone H3 mutations (K27M and G34R/G34V) enrolled in Kansai Network (118 cases) and retrospectively analyzed clinical characteristics and genetic status, including overall survival times (OS). Additionally, the differences between the older adult (40- years) and the younger generations (-39 years) were evaluated.

RESULTS
The older adult patients were not infrequently enrolled in the H3 K27-mutant glioma group (n = 47) (40-79 years old)), although H3 G34-mutant glioma cases belonged to around AYA generation (11-45 years old). Most popular location was brainstem in children (8/15, 53%) and thalamus in AYA (29/56, 52%), while cerebrum as well as brainstem and thalamus were common in the older adults (15/47, 32%; 15/47, 32%; 11/47, 24%). Histologically, diagnosis of non-GBM was not uncommon (63/105, 60%). There were no significant age-specific differences in genetic status (IDH1/2, TERT promoter, MGMT promoter, TP53, BRAF, FGFR1, EGFR). In general, tumor biopsy followed by radiation and chemotherapy was the main treatment regimen regardless of patient age (92/115, 80%). Particularly in the H3 K27-mutant gliomas, there was no statistically significant difference in OS among generations (median OS of children/AYA/older adult, 16.6/18.4/15.9 months).

CONCLUSIONS
We report clinicopathological features and survival outcomes of histone H3-mutated glioma patients in Kansai Network cohort. Histone H3 mutation could exist in the older adult cases with diffuse gliomas at cerebral location. There was a little difference in clinical and pathological features among generations. The prognosis of the older adults was as poor as those of children and AYA.
10027-CBMS-3 POSTOPERATIVE EPILEPTOGENICITY IN GLIOBLASTOMA ARE ACHIEVED AS THE RESULT OF INTERACTIVE FLUCTUATIONS OF GLUTAMATE AND STEM CELL MARKER
Authors: Kusakabe Kosuke , Inoue Akihiro , Ohnishi Takanori , Nakamura Yawara , Ohtsuka Yoshihiro , Nishikawa Masahiro , Yano Hajime , Tanaka Junya , Watanabe Hideaki , Kunieda Takeharu 
Published: December 2023

Abstract

BACKGROUND AND OBJECTIVE
In our recent Glioblastoma multiforme (GBM) cases, postoperative epilepsy mostly occurred later than twenty-eight days after surgery. CD44, a stem cell marker, is known to relate with tumor cell invasiveness, however, little are known with epilepsy nor glutamate (Glu). We investigated the relationship between CD44 and the pathophysiology of this post operative late-phase epilepsy.

MATERIALS AND METHODS
A total of 10 GBM cases received surgery and postoperative treatment at our institute were divided into two groups; 4 cases of epilepsy onset, group E, and 6 cases without, group NE. In each group, the tumor was separated into core and periphery, from which Glu was measured (Amino Acid Analyzer L8900; Hitachi High-Tech Corporation) with expression of xCT, EAAT2 and CD44 examined (Western blot). The same objects were also examined on our three glioma stem-like cell (GSC) lines. In addition, we figured Factor X (F-X) as a key related factor, and evaluated the same objects on the GSCs under conditioned F-X (under submission).

RESULTS
Group E showed higher Glu than group NE both in the core and periphery. CD44 expression was significantly higher in group E in the periphery, and xCT was higher in group E both in the core and periphery. EAAT2 was lower in group E both in the core and periphery. Among the GSCs, GSC-2 had the highest CD44 expression while having the lowest xCT and extracellular Glu, and the highest EAAT2. In addition, CD44 knockdown in GSC-2 resulted in significant increase of xCT expression and extracellular Glu. Furthermore, changing the concentration of F-X low to high led to decreased expression of CD44 and increased xCT.

CONCLUSION
The postoperative epileptogenicity could be gained by the increase of Glu which results from the alterations of CD44, xCT and EAAT2. F-X could enhance the ability of Glu discharge.
10031-GGE-2 GENOMIC ANALYSIS OF MENINGIOMA USING GENE PANEL TESTING
Authors: Ohba Shigeo , Sugihara Eiji , Yamada Seiji , Kojima Daijiro , Nakao Kazutaka , Fujiwara Eiji , Kumon Masanobu , Joko Masahiro , Nishiyama Yuya , Muto Jun , Nakae Shunsuke , Adachi Kazuhide , Abe Masato , Saya Hideyuki , Hirose Yuichi 
Published: December 2023

Abstract
Recently, cancer gene panel tests have been covered by insurance and their usefulness has been reported. In addition to the cancer gene panel tests covered by insurance, we are conducting the PleSSision-Rapid test, a cancer gene panel test that can measure 143 genes, as a clinical research project. The former has been used for 14 cases brain tumors, and the latter has been used for brain tumors in about 100 cases, respectively. The PleSSision-Rapid test has now completed analysis of 87 cases, with gliomas accounting for 33, meningiomas for 29, and metastatic brain tumors for 14 cases. Tumor mutation burden (TMB) was high in 18 cases, and microsatellite instability was high in none. NTRK gene fusion was observed in 1 case. Of the 29 meningiomas, 9 were male and 20 female, ranging in age from 31 to 79 years (mean 57). Twenty of the cases were located at the skull base. Twenty four were primary cases, whereas 5 were recurrent cases. WHO grade 1, 2, and 3 were 23, 4, and 2, respectively. There was no difference in TMB among grades, and Ki-67 values increased with increasing grade. Comparing grade 1 and grade 2/3, NF2 and KDM6A were found to be significantly different in the rate of gene mutations. Grade 2/3 patients had a significantly higher frequency of copy number aberrations such as genes related to DNA repair, histone modification, and chromatin remodeling, than grade 1 patients,
10033-IM-2 IDENTIFICATION OF THERAPEUTIC TARGET ANTIGENS USING PATIENT DERIVED GLIOBLASTOMA AND THEIR APPLICATION TO CAR-T THERAPY
Authors: Kuroda Hideki , Kijima Noriyuki , Tachi Tetsuro , Murakami Koki , Nakagawa Kanji , Kawamoto Yuki , Utsugi Reina , Hirayama Ryuichi , Okita Yoshiko , Kagawa Naoki , Hosen Naoki , Kishima Haruhiko 
Published: December 2023

Abstract
Introduction: New therapies for glioblastoma (GBM) are urgently needed due to its poor prognosis and chimeric antigen receptor T (CAR-T) cell therapy is one of the promising strategies. CAR-T cell therapy targeting EGFRvIII,HER2, and IL13Rα2 have been tested for GBM, but have limited efficacies. To further develop CAR-T cell therapy, cell surface targets that is highly specific for GBM cells are needed. In this study, we applied this strategy to search for GBM-specific cell surface targets using patient derived tumor spheres. Methods: Patient derived tumor spheres was established from GBM surgical specimens, and immunized to Balb/c mice. The B cells from the mice were fused with myeloma cells, immortalized, and cultured nonclonally to obtain a number of monoclonal antibodies reacted GBM cells. The obtained antibodies were reacted with GBM cells and normal brain cells, and those that specifically react to GBM were selected by flowcytometry to obtain antibody candidates that could be specifically expressed on the surface of GBM cells. Then, we generated CAR-T cells derived from the obtained antibody and confirmed anti-tumor effect of CAR-T cells in vitro by ELISA. Results: Approximately 25,000 antibody-producing strains were generated. Within these candidates, we identified antibody X, which reacted with several GBM samples and does not reacted with several normal brain cells. The antibody X is a reported to be a cell adhesion molecule. The CAR-T cells derived from the antibodies X produced IL-2 and IFNγ significantly in co-culture with GBM cells. Conclusion: In this study, we identified antigen X and analyzed its anti-tumor effect in vitro. The antigen X has been reported to be associated with the progression of solid tumors and is expected to be a tumor-specific antigen. Further studies are necessary to examine whether the CAR-T cells targeting antigen X have anti-tumor effect in vivo.