bluuebunny/crossref_metadata_2025_split huggingface dataset:
10089- IM-5 CHARACTERIZATION OF HIF-1Α KNOCKOUT PRIMARY HUMAN NATURAL KILLER CELLS INCLUDING POPULATIONS IN ALLOGENEIC GLIOBLASTOMA
Authors: Yamada Kengo , Nakazawa Tasutomu , Morimoto Takayuki , Maeoka Ryosuke , Matsuda Ryosuke , Nakamura Mitsutoshi , Nishimura Fumihiko , Yamada Shuichi , Park Young-Soo , Tsujimura Takahiro , Nakagawa Ichiro 
Published: November 2024

Abstract
Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Natural killer cells (NK) are major innate effector cells with broad cytotoxicity against tumors. Accordingly, NK cells are ideal candidates for cancer immunotherapy, including glioblastoma (GBM). Hypoxia is a common feature of solid tumors, and tumor cells and normal cells adapt to the tumor microenvironment by upregulating the transcription factor hypoxia-inducible factor (HIF)-1α, which can be detrimental to anti-tumor effector immune cell function, including that of NK cells. We knocked out HIF-1α in human primary NK cells using clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9). Then, cellular characterizations were conducted in normoxic and hypoxic conditions. Electroporating two HIF-1α-targeting guide RNA-Cas9 protein complexes inhibited HIF-1α expression in expanded NK cells. HIF-1α knockout human NK cells, including populations in hypoxic conditions, enhanced the growth inhibition of allogeneic GBM cells and induced apoptosis in GBM-cell-derived spheroids. RNA-sequencing revealed that the cytotoxicity of HIF-1α knockout NK cells could be related to increased perforin and TNF expression. The results demonstrated that HIF-1α knockout human NK cells, including populations, enhanced cytotoxicity in an environment mimicking the hypoxic conditions of GBM. CRISPR-Cas9-mediated HIF-1α knockout NK cells, including populations, could be a promising immunotherapeutic alternative in patients with GBM.
10148- ACT-7 BORON NEUTRON CAPTURE THERAPY FROM TWO-DIRECTION FOR HIGH-GRADE MENINGIOMAS ACHIEVED BY PATIENT REPOSITIONING AND CONTINUOUS BPA ADMINISTRATION
Authors: Kashiwagi Hideki , Kawabata Shinji , Yoshimura Kohei , Fujikawa Yoshiki , Takeuchi Koji , Futamura Gen , Hiramatsu Ryo , Nonoguchi Naosuke , Furuse Motomasa , Hu Naonori , Sakurai Yoshinori , Tanaka Hiroki , Kondo Naoko , Suzuki Minoru , Ono Koji , Miyatake Shin-Ichi , Wanibuchi Masahiko 
Published: November 2024

Abstract

BACKGROUND
High-grade meningiomas are refractory to repeated surgery and radiotherapy. We have performed boron neutron capture therapy (BNCT) for high-grade meningiomas. We report on BNCT for extensive, deep or multiple lesions in recurrent high-grade meningiomas, using two-directional neutron irradiation in a single machine-time.

METHODS
BNCT was performed at a reactor power of 5 MW with the Heavy Water Neutron Irradiation Facility in the Institute for Integrated Radiation and Nuclear Science, Kyoto University. The boron compound used was boronophenylalanine (BPA), which was administered intravenously (200 mg/kg/h) for 2-hour before irradiation, followed by continuous BPA administration during irradiation. Those patients were repositioned between the first and second irradiations. Prescribed doses were calculated from the tolerable dose in normal brain and mucosal tissues.

RESULTS
Two-directional neutron irradiation was planned eight times. The irradiation durations were 40 ± 11.3 min for the first and 34.9 ± 8.7 min for the second. The irradiation interval was 36.7 ± 3.6 min. The second irradiation was interrupted or stopped at 2 cases. The factors for the two-directional irradiation were extensive tumor location, deep midline and multiple lesions. All patients developed treatment-related adverse events within one month, including increased amylase, fever, urine color change and dermatitis. Most adverse events resolved within six months.

CONCLUSIONS
Two-directional neutron irradiation reduces the dose to normal tissue and allows irradiation of multiple sites, thus ensuring tumor dose to deep midline lesions and allowing irradiation of large or multiple lesions. Adverse events were similar to those seen with BNCT for malignant gliomas at single neutron irradiation, suggesting the safety of two-directional neutron irradiation and continuous administration of BPA. This report may be a pioneer in the use of two-directional neutron irradiation.
10084- STMO-5 A CASE OF GLIOBLASTOMA SURGERY NEAR THE LANGUAGE AREA SAFELY REMOVED USING INTRAOPERATIVE LANGUAGE AREA MONITORING BASED ON GAMMA OSCILLATION REGULARITY ANALYSIS.
Authors: Kobayashi Yusuke , Satou Yosuke , Kawauchi Yuta , Kon Takashi , Takahashi Junichiro , Tanaka Kosuke 
Published: November 2024

Abstract
We have been performing safe and reliable brain tumor surgery by visualizing epileptic lesions and areas of reduced brain function using gamma oscillation regularity analysis. In this report, we describe our experience of surgery in a case of glioblastoma near the language area in which intraoperative language monitoring using this analysis enabled safe and aggressive removal of the tumor. The patient was a male in his 50s. He was rushed to another hospital due to a seizure. A contrast-enhanced MRI scan of the head showed a ring-shaped lesion with a maximum diameter of 70 mm in the left frontal to temporal lobes, which was suspected to be a glioblastoma, and the patient was transferred to our hospital for treatment. At the time of transfer, the patient had mild dysarthria and confusion symptoms, and the dominant language hemisphere was on the left side in the WADA test. Aphasia symptoms worsened while the patient was waiting for surgery, and the language area was evaluated intraoperatively using cortico-cortical evoked potential (CCEP) and gamma oscillation regularity analysis. Gamma oscillation regularity analysis revealed increased gamma oscillation regularity in areas that were excited by electrical stimulation via white matter fibers, and these areas were consistent with the language areas inferred by CCEP and could be better localized. Aggressive tumor resection was performed under intraoperative language area monitoring. There was no worsening of symptoms, and the preoperative aphasia symptoms resolved postoperatively. In this case, we were able to perform intraoperative language monitoring by taking advantage of the increase in gamma oscillation regularity in the areas excited by electrical stimulation via white matter fibers. Intraoperative gamma oscillation regularity analysis is very useful in brain tumor surgery and may become a new technique for intraoperative brain function monitoring.
10013- MPC-3 CHARACTERISTICS AND OUTCOMES OF HISTONE H3 K27M-MUTANT DIFFUSE MIDLINE AND NON-MIDLINE GLIOMAS IN THE KANSAI NETWORK COHORT
Authors: Fukai Junya 
Published: November 2024

Abstract

INTRODUCTION
Histone H3 K27M-mutant diffuse gliomas are observed at the midline and, rarely, non-midline locations (abbreviated as DMG and NDMG in this study, respectively). It may be unclear how NDMG should be classified in the 2021 WHO classification. This study investigates clinical and molecular characteristics as well as treatment outcomes of patients with NDMG in comparison with those of DMG.

METHODS
We collected histone H3 K27M-mutant diffuse glioma cases and enrolled in the Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and molecular characteristics and treatment outcomes were analyzed retrospectively and compared between NDMG and DMG cases.

RESULTS
Anatomical tumor locations were classified into five groups: cerebral hemisphere (16), thalamus (47), brainstem (24), spinal cord (12) and other midline locations (10); therefore, a total of 16 patients with NDMG and 93 patients with DMG were included in this study. Clinical and molecular characteristics of the study cohort (NDMG vs. DMG) included: median age 45 vs. 25 years, female sex (37 vs. 41%), lower-grade histology (6 vs. 56%), preoperative Karnofsky performance status (KPS) scores &gt;80 (50 vs. 49%), resection (50 vs. 36%), adjuvant radiation plus chemotherapy (81 vs. 83%), HIST1H3B p.K27M mutation (0 vs. 4%), TERT promoter mutation (0 vs. 3%), MGMT promoter methylation (25 vs. 9%), BRAF p.V600E mutation (6 vs. 1%), FGFR1 mutation (6 vs. 14%) and EGFR mutation (0 vs. 3%). Median overall survival time was 20.0 vs. 16.6 months. In DNA methylation analysis, NDMG clustered within or close to the reference group of DMG.

CONCLUSIONS
Diffuse gliomas harboring histone H3 K27M mutation can be observed at cerebral hemisphere in the older adults. NDMG shares many similarities with DMG, suggesting that they correspond to a rare anatomical presentation of DMG.
10195- MPC-19 CURRENT STATUS OF MULTICENTER STUDIES USING GLIOMA TAILORED CUSTOM DNA/RNA PANELS
Authors: Higa Nayuta , Akahane Toshiaki , Yonezawa Hajime , Yokoyama Seiya , Makino Ryutaro , Uchida Hiroyuki , Kirishima Mari , Yoshimoto Koji , Tanimoto Akihide , Hanaya Ryosuke 
Published: November 2024

Abstract

INTRODUCTION
In 2018, we developed a glioma specific next-generation sequencing NGS panel and analyzed over 500 cases. In April 2023, we have expanded our work to include a custom DNA/RNA panel capable of detecting fusion genes. A multicenter collaborative study utilizing this advanced panel has been in progress since October 2023. This report outlines the diagnostic and screening significance of our panel and provides an update on the ongoing multicenter study.

METHODS
The custom gene panel included a 51 gene DNA and 37 gene RNA panel. DNA and RNA were extracted from formalin fixed paraffin embedded specimens used for histopathological diagnosis. Mutations, copy number and fusion genes were detected using the Illumina NextSeq1000. A multicenter collaborative study is currently underway with 21 institutions, analyzing cases at 43,000 yen each. This system has analyzed 210 consecutive brain tumors cases.

RESULTS
Currently, 12 of the 21 facilities have contracted us for analysis. The average analysis time was 35 days. Of the 210 cases, 35 (16.7%) harbored fusion genes. Nineteen cases (9.0%) had therapeutic target genes, including NTRK1/2, FGFR1/3, MET, and BRAF fusion genes. Eighteen of 112 GBM cases (16.1%) harbored fusion genes. Among receptors tyrosine kinases, EGFR gene alterations were observed in 42% of GBMs, often with EGFR amplification in cases with EGFR fusion or variants. PDGFRA gene alterations were present in 18%. Additionally, 9.8% of the GBMs had FGFR gene alterations, with FGFR1 mutation confined to the kinase domain and FGFR3 exclusively showing fusion genes. No FGFR2 alterations were detected. DNA analysis revealed that 11 cases were molecular GBMs, TERTp mutations were found in nine cases.

CONCLUSION
Our system’s analysis aligns with the WHO 2021 brain tumor classification, demonstrating its value as a screening tool in genomic medicine.
10086- MET-8 A CASE OF METASTASIS OF LUNG CANCER TO INTRACRANIAL MENINGIOMA
Authors: Kohno Shohei , Shinji Yukei , Shinko Aiko , Takahashi Kazuya 
Published: November 2024

Abstract

INTRODUCTION
Meningiomas are the most common benign tumors, and are supplied with nutrients from various blood vessels, and have a very rich cerebral blood flow, making them a potential target for systemic cancer metastasis. We report a case of small cell lung cancer metastasis to a meningioma.

CASE
A 74-year-old man. He had been treated for small cell lung cancer and was under observation. He had gradually lost appetite one month ago and was hospitalized at his previous hospital. A head CT scan revealed a suspected brain tumor, and he was referred to our hospital for treatment. At the initial visit, he only had mild consciousness disorder. Head CT scan showed a tumorous lesion of about 5 cm in the right frontal region, adjacent to the dura mater, with surrounding cerebral edema. Brain MRI showed areas of uniform contrast and areas of poor contrast due to bleeding in the same area. Although the consciousness disorder improved with the administration of steroids, the tumor did not shrink and there was also surrounding edema, so an excision was performed. Intraoperative findings showed a tumor originating from the dura mater, with the anterior portion showing a tumorous lesion of a different nature, and the border with the surrounding brain was unclear. Pathology showed components of meningioma and lung cancer, and it was determined that the lung cancer had metastasized to the meningioma. After surgery, the patient received 30 Gy of whole brain irradiation and was discharged home.

CONCLUSION
Although meningiomas are benign tumors, they have an extremely abundant blood flow, and the survival time for systemic cancer has been increasing, so it is important to keep in mind that there is a possibility of metastasis to meningioma, as in this case.
10193- BT-8 4 CASES OF SECONDARY CANCER AFTER TREATMENT FOR PEDIATRIC MEDULLOBLASTOMA
Authors: Ohe Naoyuki , Tamura Takeaki , Kumagai Toshinobu , Shoda Kenji , Nakayama Noriyuki , Izumo Tsuyoshi 
Published: November 2024

Abstract

INTRODUCTION
The number of long-term survivors of medulloblastoma has increased due to advances in treatment, the occurrence of secondary neoplasms has become a new problem. We report four secondary neoplasms after medulloblastoma treatment.

PATIENTS
Of the 26 cases of pediatric cerebellar medulloblastomas that have undergone initial treatment in our department, four have developed secondary neoplasms. The ages of the patients who developed secondary cancers ranged from 17 to 48 years (mean 30 years), with two men and two women, and the ages ranged from 6 to 33 years (mean 21 years) after initial treatment. Two infratentorial glioblastomas, one DIPG, and one multiple meningiomas occurred. The radiation doses at the tumor site were 50.4 and 55.2 Gy for the cases of glioblastoma, 49.6 Gy for the case of DIGP, and 20.5 Gy for the case of multiple meningiomas.

RESULTS
The two patients with cerebellar glioblastoma underwent treatment, but they had dissemination from the time of onset and died 10 and 12 months after onset. The patient with multiple meningiomas underwent tumor resection and has maintained an independent social life. The patient with DIPG is currently undergoing detailed examination.

DISCUSSION
Secondary neoplasms occurred in 4 of 26 cases (15%) in our overall study, but the incidence rate increased to 2 cases (50%) in 4 long-term survivors who survived for more than 30 years after treatment for pediatric medulloblastomas. The incidence of secondary neoplasms increases over time if the latency period exceeds 10 years, and radiation exposure at a young age in particular is considered to be a risk factor for secondary cancer. It is also said that the incidence of secondary cancers increases in proportion to the radiation dose, but it is necessary to comprehensively evaluate the occurrence of secondary neoplasms, including not only the radiation dose but also chemotherapy, genetic predisposition.
Out-of-Africa migration and clonal expansion of a recombinant Epstein-Barr virus drives frequent nasopharyngeal carcinoma in southern China
Authors: Zhang Xinyi , Chen Yanhong , Liang Jingtong , Yang Yue , Chen Hui , Chen Zehui , Li Minhao , Chen Shuanghui , Chen Tingting , He Haopeng , Liu Yunsong , Liu Zhiyuan , Han Lu , Wu Dafei , Zou Zhengting , Qu Yanhua , Li Mingkun , Stoneking Mark , Fu Qiaomei , Xu Shuhua , Zeng Yi-Xin , Ma Liang , Liu Jianjun , Xu Miao , Zhai Weiwei 
Published: November 2024

Abstract
While Epstein-Barr virus (EBV) infection is ubiquitous globally, a high-risk EBV subtype associated with the extremely high incidence of nasopharyngeal carcinoma (NPC) was found in southern China, but the evolution history of EBV in humans and the origin of this high-risk subtype remains enigmatic. By obtaining one of the largest datasets of EBV genomes across the world, we found that EBV had an evolutionary history matching the out-of-Africa migration of humans. Within the high-risk subtype from southern China, we identified a rapidly expanding clonal strain originated from a recombination event between EBV strains from northern and southern Chinese around 4000 years ago, followed by strong Darwinian evolution with a fitness advantage of 4%. The clonal strain has almost doubled the risk for NPC compared to the high-risk subtype and explained around 66% of the NPCs, representing the highest risk factor for NPC identified so far. Taken together, we unraveled a strong co-evolution history between EBV and humans where human migration and admixture triggered subsequent recombination and expansion of a highly advantageous EBV strain, leading to a cancer epidemic in southern China.
Novel Dolutegravir and Lenacapavir Resistance Patterns in Human Immunodeficiency Virus Type 2 Infection: A Case Report
Authors: van Kampen Jeroen J A , van Nood Els , Mahmud Rizwan , Krullaars Zoë , Voskamp Tess , Voskamp Mike , Nijssen Tess , Voermans Jolanda J C , Charpentier Charlotte , Le Hingrat Quentin , van de Vijver David A M C , Gruters Rob A , Mesplède Thibault 
Published: November 2024

Abstract

Background
The treatment management of human immunodeficiency virus (HIV)-2 infection presents greater challenges compared to HIV-1 infection, primarily because of inherent resistance against non-nucleoside reverse transcriptase inhibitors. Integrase strand transfer inhibitors, particularly dolutegravir, have improved treatment outcomes for people with HIV-2. Lenacapavir, a novel and potent antiretroviral capsid inhibitor, offers additional therapeutic options. However, limited knowledge exists regarding HIV-2 resistance against dolutegravir and lenacapavir.

Methods
We report the case of a treatment-experienced individual who did not achieve virological suppression with regimens containing dolutegravir and lenacapavir. Clinical monitoring, genotypic and phenotypic resistance assays, and in silico structural modeling were performed.

Results
Lenacapavir was added to a failing regimen of boosted darunavir, twice daily dolutegravir, and 2 nucleoside reverse transcriptase inhibitors. Initially, this addition led to a decline in the viral load and increase in CD4+ T-cell count, despite the identification of a previously unreported combination of integrase resistance mutations. However, virological suppression was not achieved and viral load, although reduced, resumed increasing. This rebound was associated with the development of an N73D capsid substitution in HIV-2, which conferred resistance against lenacapavir. Based on cell-based assays predicting hypersusceptibility to bictegravir, the regimen was adjusted to oral lenacapavir plus bictegravir/emtricitabine/tenofovir alafenamide, resulting in a resumption in viral load decline.

Conclusions
Although lenacapavir demonstrated therapeutic potential, our case underscores the critical need to combine it with other fully active antiretroviral agents to prevent the rapid emergence of resistance and achieve long-term virological control in treatment-experienced individuals with HIV-2.
Fairness in policing: how does internal procedural justice translate to external procedural justice?
Authors: Yesberg Julia A , Sargeant Elise , Fenn Liam , Murphy Kristina , Madon Natasha 
Published: November 2024

Abstract
A growing body of research has shown the experience of fair treatment within police organizations (internal procedural justice) leads to a greater willingness among police officers to treat members of the public fairly (external procedural justice). Despite recent scholarship in this area, the associations between internal and external procedural justice, and the intervening mechanisms at play, are still not well understood. Using survey data from new police officers in England and Wales, we test the direct association between internal and external procedural justice, and indirect connections through self-efficacy, job satisfaction, and well-being. Self-efficacy, but not job satisfaction or well-being, was found to partially mediate the relationship between internal and external procedural justice. In other words, perceived internal procedural justice promoted external procedural justice through (in part) cultivating greater confidence in officers’ abilities to perform their job effectively.
Comparison analysis between standard polysomnographic data and in-ear-electroencephalography signals: a preliminary study
Authors: Palo Gianpaolo , Fiorillo Luigi , Monachino Giuliana , Bechny Michal , Wälti Michel , Meier Elias , Pentimalli Biscaretti di Ruffia Francesca , Melnykowycz Mark , Tzovara Athina , Agostini Valentina , Faraci Francesca Dalia 
Published: November 2024

Abstract

Study Objectives
Polysomnography (PSG) currently serves as the benchmark for evaluating sleep disorders. Its discomfort makes long-term monitoring unfeasible, leading to bias in sleep quality assessment. Hence, less invasive, cost-effective, and portable alternatives need to be explored. One promising contender is the in-ear-electroencephalography (EEG) sensor. This study aims to establish a methodology to assess the similarity between the single-channel in-ear-EEG and standard PSG derivations.

Methods
The study involves 4-hour signals recorded from 10 healthy subjects aged 18–60 years. Recordings are analyzed following two complementary approaches: (1) a hypnogram-based analysis aimed at assessing the agreement between PSG and in-ear-EEG-derived hypnograms; and (2) a feature- and analysis-based on time- and frequency-domain feature extraction, unsupervised feature selection, and definition of Feature-based Similarity Index via Jensen–Shannon Divergence (JSD-FSI).

Results
We find large variability between PSG and in-ear-EEG hypnograms scored by the same sleep expert according to Cohen’s kappa metric, with significantly greater agreements for PSG scorers than for in-ear-EEG scorers (p &lt; .001) based on Fleiss’ kappa metric. On average, we demonstrate a high similarity between PSG and in-ear-EEG signals in terms of JSD-FSI—0.79 ± 0.06—awake, 0.77 ± 0.07—nonrapid eye movement, and 0.67 ± 0.10—rapid eye movement—and in line with the similarity values computed independently on standard PSG channel combinations.

Conclusions
In-ear-EEG is a valuable solution for home-based sleep monitoring; however, further studies with a larger and more heterogeneous dataset are needed.