bluuebunny/crossref_metadata_2025 huggingface dataset:
CFD Predictions of Fire Spread over Wood Cribs in Large Open-plan Compartments: New Insights
Authors: Liu C , Dai X , Ming X M , Welch S
Published: November 2024

A CFD-based numerical simulator, coupled with a multi-component pyrolysis model established for an isolated wood crib fire test, successfully predicts fire spread behaviours and the evolution in compartment boundary conditions in a large-scale test with an extended, uniform fuel bed. Five distinct fire spread modes are identified, showing a gradual transition from 2D to 1D planar fire spread patterns. Our new model is no longer constrained to follow prescribed burning rates and an analysis of the drivers of fire spread at the level of the individual wood sticks shows linear correlations of burning rates with the incident heat fluxes at the fire’s leading edge, and similar within the crib during the main travelling fire phase, but higher rates when preheating effects dominate later in the fire. There is also relative insensitivity to exposures on the surface of the crib at the trailing edge, and it is believed that burning rates here are effectively isolated from preheating effects by the development of rigid char layer with high thermal resistance, thereby decoupling them from the compartment boundary conditions. This is a feature long recognised in experimental studies, but which is very challenging to corroborate through direct experimental measurements.
Thermodynamic roles of quantum environments: from heat baths to work reservoirs
Authors: Colla Alessandra , Breuer Heinz-Peter
Published: November 2024

Environments in quantum thermodynamics usually take the role of heat baths. These baths are Markovian, weakly coupled to the system, and initialized in a thermal state. Whenever one of these properties is missing, standard quantum thermodynamics is no longer suitable to treat the thermodynamic properties of the system that result from the interaction with the environment. Using a recently proposed framework for open system quantum thermodynamics which is valid for arbitrary couplings and non-Markovian effects, we show that within the very same model, described by a Fano–Anderson Hamiltonian, the environment can take three different thermodynamic roles: a standard heat bath, exchanging only heat with the system, a work reservoir, exchanging only work, and a hybrid environment, providing both types of energy exchange. The exact role of the environment is determined by the strength and structure of the coupling, and by its initial state. The latter also dictates the long time behaviour of the open system, leading to thermal equilibrium for an initial thermal state and to a nonequilibrium steady state when there are displaced environmental modes.
Creation and annotation of a code-mixed Kannada english dataset with accurate labels for detecting depression and major depressive disorder categories
Authors: Shwetha C H , Pushpalatha K
Published: November 2024

The research addresses mental health challenges within multilingual communities, with focus on individuals who frequently share their emotion, feelings and depressive thoughts by blending Kannada and English languages. The study includes creating a dataset that will be annotated with a label to detect depression and major depressive disorder categories. A code-mixed dataset was collected from various sources to construct the dataset. After data collection, it is processed using multilingual tools, and clinical experts provide guidance in annotating the dataset to accurately detect the depressive disorders. By examining key linguistic features related to depression—including emotional tone, grammatical structures, and code-switching patterns—the study offers a valuable insight into how depression is expressed across languages. The labelled dataset is crucial for developing deep learning models capable of accurately identifying and quantifying depression, particularly in multilingual environments. Additionally, the study emphasizes the role of language in mental health discourse and its potential impact on clinical practices and interventions for linguistically diverse populations. The practical implications of the research include using the dataset for digital mental health monitoring, supporting clinical decision-making, and creating culturally mental health tools for underrepresented multilingual communities.
Indo-Pak Cricketing Relations in the Shadow of the Rise of Hindutva
Authors: Khan Ali
Published: November 2024

This chapter seeks to trace the changing relations between India and Pakistan, paying particular attention to how the changing political influences in both countries have affected the cricket teams and the cricketing relations between them. More specifically, the chapter examines the recent decline in relations which is acutely influenced by Pakistan’s worsening security situation as a result of increased terrorist activity in the country following the war on terror. This was most dramatically demonstrated in the attack on the Sri Lankan cricket team which subsequently led to Pakistan losing the right to hold cricket matches at home. It also manifested itself in the Mumbai attacks that led to the severance of cricket relations between India and Pakistan in 2008. Relations have also been affected by the dramatic rise of extremist Hindu ideology in India and more specifically under Narendra Modi’s Bharatiya Janata Party government since 2014. An analysis of these political changes is key to understanding the plummeting cricketing relations between India and Pakistan. Where in the past support from the Asian bloc had guaranteed Pakistan would not be isolated, today the rupture in political relations with India has meant Pakistan has been increasingly sequestered. There have also been significant economic changes that have seen the meteoric rise of India as the financial powerhouse of the global cricketing world. This has meant that India is able to use the withdrawal of cricketing relations as a means of further punishing and isolating Pakistan.
A V-shaped analog of ITIC with a small exciton binding energy
Authors: Wang Kai , Jinnai Seihou , Ie Yutaka
Published: November 2024

The exciton binding energy (Eb) of organic semiconductors is a key parameter that determines the performance of organic optoelectronic devices. Here, we focus on ITIC, a representative organic semiconductor used in organic photovoltaics (OPVs), and investigate the influence of molecular structure on Eb by developing io-ITIC, a V-shaped isomer of ITIC. Experimental results reveal that io-ITIC exhibits a small Eb compared to ITIC. However, OPVs based on io-ITIC showed moderate photovoltaic characteristics. Theoretical studies including molecular dynamics simulations indicate that the stacking configuration of io-ITIC affects Eb and OPV characteristics.
Lower serum magnesium levels are associated with a higher risk of fractures and vascular calcifications in hemodialysis patients
Authors: Matias Patrícia João , Ávila Gonçalo , Domingos Diogo , Gil Célia , Ferreira Aníbal
Published: November 2024

Background

Magnesium (Mg) deficiency seems to be associated with altered bone metabolism and vascular calcifications (VC). This study aimed to evaluate the association between serum Mg levels and incident bone fragility fractures and VC in a cohort of prevalent hemodialysis (HD) patients.

Methods

We performed a retrospective study of 206 patients, with a mean age of 68.3 ± 13.1 years; 121 (59%) were male, and the median follow-up time was 58 months.

Results

Thirty-seven episodes of fragility fractures were identified with a median HD vintage of 42 months—an incidence rate of 29 per 1000 person-years. Patients with fractures showed lower Mg levels compared with those without fractures (P < .001) and more VC (P = .01). In a Cox regression analysis, time to fragility fracture was independently associated with serum Mg <2.2 mg/dL (P < .001), in a model adjusted to age, female gender, HD vintage, diabetes mellitus, body mass index, albumin, parathyroid hormone, active vitamin D therapy and the presence of VC. Patients with Mg serum levels <2.2 mg/dL had a 1.32-fold higher risk of fragility fractures (P < .001).

Conclusions

This study showed that the incidence of bone fragility fractures in HD patients is high and is significantly associated with lower Mg levels and with the presence of more VC.
Lipid-lowering therapies for aortic stenosis: a drug-target Mendelian randomization study
Authors: Ciofani Jonathan L , Han Daniel , Rao Karan , Gill Dipender , Woolf Benjamin , Rahimi Kazem , Allahwala Usaid K , Bhindi Ravinay
Published: November 2024

Introduction

Large observational and Mendelian randomization (MR) studies have demonstrated a strong association between both elevated LDL cholesterol (LDL-c) and triglycerides (TG) with risk of aortic stenosis (AS), although randomized trials showed no benefit of statins for AS. It consequently remains uncertain whether lipid-lowering therapies have a role to prevent or treat AS. We used a drug-target MR approach to investigate the genetically predicted effect of lipid-lowering therapies on risk of AS.

Methods and results

We collected summary statistics for LDL-c, TG, and AS from genome-wide association studies (GWAS) including 1 320 016, 1 253 277, and 412 181 European participants from the Global Lipids Genetics Consortium and FinnGen study, respectively. We identified genetic proxies for PCSK9 inhibitors, statins, bempedoic acid, and ezetimibe as single nucleotide polymorphisms in or within 200 kb of the target genes (PCSK9, HMGCR, ACLY, and NPC1L1, respectively), which were also significantly associated with LDL-c at P < 5 × 10−8. We used a similar approach to identify genetic proxies for the TG-lowering agents fenofibrates, APOC3 inhibitors, and ANGPTL3 inhibitors using the target genes PPARA, APOC3, and ANGPTL3, respectively. Inverse variance-weighted was the primary analysis method. Sensitivity analyses included weighted median, weighted mode, and MR-Egger, followed by the outlier-exclusion approaches MR-PRESSO and Cook's distance. We also performed multivariable analyses to evaluate whether the predicted effect of PCSK9 inhibition may be mediated by lipoprotein(a). We performed replication and negative control analyses using GWAS of AS and height including 653 867 and 408 112 participants, respectively. Genetically proxied PCSK9 inhibition was significantly associated with reduced AS risk (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.52–0.72, P < 0.0001) on main, replication, and all sensitivity analyses. Genetically proxied ezetimibe (OR 0.49, 95% CI 0.31–0.78, P = 0.003), bempedoic acid (OR 0.0054, 95% CI 0.0002–0.12, P = 0.0009), and statins (OR 0.61, 95% CI 0.46–0.81, P = 0.0006) were similarly associated with reduced AS risk, although the latter were not significant on replication analyses. Amongst the TG-lowering agents, genetically proxied APOC3 inhibition was associated with reduced AS risk (OR 0.78, 95% CI 0.70–0.88, P < 0.0001), but fenofibrate (OR 0.64, 95% CI 0.09–4.53, P = 0.65) and ANGPTL3 inhibitors (OR 1.05, 95% CI 0.77–1.43, P = 0.74) were not.

Conclusions

Genetically proxied lipid-lowering therapies are significantly associated with reduced risk of AS. Early initiation and sustained administration of lipid-lowering therapies may prevent AS progression and warrants further research in the clinical trial setting.
Seasonal shifts and land-use impact: unveiling the gut microbiomes of bank voles (Myodes glareolus) and common voles (Microtus arvalis)
Authors: Kauer Lea , Imholt Christian , Jacob Jens , Berens Christian , Kühn Ralph
Published: November 2024

Gut microbial diversity influences the health and vitality of the host, yet it is itself affected by internal and external factors, including land-use. The impact of land-use practices on wild rodents’ gut microbiomes remains understudied, despite their abundance and potential as reservoirs for zoonotic pathogens. We examined the bacterial and fungal gut microbiomes of bank voles (Myodes glareolus) and common voles (Microtus arvalis) across grassland and forest habitats with varying land-use intensities and types. We collected rodents seasonally and used 16S rRNA and ITS amplicon sequencing for microbe identification. We found significant differences in alpha and beta diversities between the species, with M. arvalis exhibiting higher diversity. Seasonality emerged as a prominent factor influencing microbial diversity, with significant variations between sampling months. While land-use affects the gut microbiome, its impact is subordinate to seasonal variations. Differential abundance analysis underscores the dynamic nature of microbial composition, with seasonal changes playing a predominant role. Overall, our findings highlight the significant influence of seasonality on gut microbiome diversity and composition in wild rodents, reflecting dietary shifts associated with seasonal changes. Understanding the interplay between environmental factors and microbial communities in wild rodents enahnces our knowledge of ecosystem health and resilience, warranting further investigation.
Diacylglycerol metabolism and homeostasis in fungal physiology
Authors: Mondal Sudipta , Pal Biswajit , Sankaranarayanan Rajan
Published: November 2024

Diacylglycerol (DAG) is a relatively simple and primitive form of lipid, which does not possess a phospholipid headgroup. Being a central metabolite of the lipid metabolism network, DAGs are omnipresent in all life forms. While the role of DAG has been established in membrane and storage lipid biogenesis, it can impart crucial physiological functions including membrane shapeshifting, regulation of membrane protein activity, and transduction of cellular signalling as a lipid-based secondary messenger. Besides, the chemical diversity of DAGs, due to fatty acyl chain composition, has been proposed to be the basis of its functional diversity. Therefore, cells must regulate DAG level at a spatio-temporal scale for homeostasis and adaptation. The vast network of eukaryotic lipid metabolism has been unravelled majorly by studying yeast models. Here, we review the current understanding and the emerging concepts in metabolic and functional aspects of DAG regulation in yeast. The implications can be extended to understand pathogenic fungi and mammalian counterparts as well as disease aetiology.
A unified VCF dataset from nearly 1,500 diverse maize accessions and resources to explore the genomic landscape of maize
Authors: Andorf Carson M , Ross-Ibarra Jeffrey , Seetharam Arun S , Hufford Matthew B , Woodhouse Margaret R
Published: November 2024

Efforts to capture and analyze maize nucleotide diversity have ranged widely in scope, but differences in reference genome version and software algorithms used in these efforts inhibit comparison, and these data are generally not available in an easy-to-use visualization platform for quick access and analysis. To address these issues, The Maize Genetics and Genomics Database has collaborated with maize researchers to offer variant data from a diverse set of 1,498 inbred lines, traditional varieties, and teosintes through a standardized variant-calling pipeline against version 5 of the B73 reference genome. The output was filtered for mapping quality, completeness, and linkage disequilibrium, and annotated based on variant effects relative to the B73 RefGen_v5 gene annotations. MaizeGDB has also updated a web tool, SNPversity 2.0, to filter, visualize, and download genotype sets based on genomic locations and accessions of interest, and added external datasets to demonstrate SNPversity 2.0's broad usage. MaizeGDB plans to host annual updates of these resources as additional resequencing data become available, with plans to expand to all publicly available sequence data.
Cis-regulatory Variation in Relation to Sex and Sexual Dimorphism in Drosophila melanogaster
Authors: Mishra Prashastha , Barrera Tania S , Grieshop Karl , Agrawal Aneil F
Published: November 2024

Much of sexual dimorphism is likely due to sex-biased gene expression, which results from differential regulation of a genome that is largely shared between males and females. Here, we use allele-specific expression to explore cis-regulatory variation in Drosophila melanogaster in relation to sex. We develop a Bayesian framework to infer the transcriptome-wide joint distribution of cis-regulatory effects across the sexes. We also examine patterns of cis-regulatory variation with respect to two other levels of variation in sexual dimorphism: (i) across genes that vary in their degree of sex-biased expression and (ii) among tissues that vary in their degree of dimorphism (e.g. relatively low dimorphism in heads vs. high dimorphism in gonads). We uncover evidence of widespread cis-regulatory variation in all tissues examined, with female-biased genes being especially enriched for this variation. A sizeable proportion of cis-regulatory variation is inferred to have sex-specific effects, with sex-dependent cis effects being much more frequent in gonads than in heads. Finally, we find some genes where 1 allele contributes to more than 50% of a gene's expression in heterozygous males but <50% of its expression in heterozygous females. Such variants could provide a mechanism for sex-specific dominance reversals, a phenomenon important for sexually antagonistic balancing selection. However, tissue differences in allelic imbalance are approximately as frequent as sex differences, perhaps suggesting that sexual conflict may not be particularly unique in shaping patterns of expression variation.
A Note on the Spectral Gap for Log-Concave Probability Measures on Convex Bodies
Authors: Bonnefont Michel , Joulin Aldéric
Published: November 2024

In this paper, we provide explicit lower bounds with respect to some quantities of interest (parameters of the underlying distribution, dimension, geometrical characteristics of the domain, position of the origin, etc.) on the spectral gap of log-concave probability measures on convex bodies. Our results are illustrated by some classical and less classical examples.
Motivic Classes of Curvilinear Hilbert Schemes and Igusa Zeta Functions
Authors: Rossinelli Ilaria
Published: November 2024

This paper delves into the study of curvilinear Hilbert schemes associated with a singular variety $(X,0)$ and the relationship between their motivic classes and the motivic measure on the arc scheme $X_\infty $ of $X$ introduced by Denef and Loeser. We introduce an Igusa zeta function specifically tailored for curvilinear Hilbert schemes for which we provide an explicit formulation in terms of an embedded resolution of the singularity, and we consequently obtain a recursive formula to compute the motivic classes of curvilinear Hilbert schemes in terms of the resolution. In addition, the paper explores and analyzes the geometry and combinatorics of curvilinear Hilbert schemes in the context of plane curve singularities and their topological invariants.
Paenibacillus oenotherae W2-3 degraded Welan gum to produce growth-promoting oligosaccharides
Authors: Fu Yang , Luan Jing , Jiang Lin , Li Xianzhen , Yang Fan , Yu Zhimin
Published: November 2024

Based on the biodegradation of Welan gum, this paper studies the properties of Welan gum degrading enzymes, degradation rules, and the application of Welan gum oligosaccharides. In order to study the biodegradation of Welan gum, a strain W2-3 capable of degrading Welan gum, was isolated from soil and identified as Paenibacillus sp. The properties of Welan gum degrading enzymes, degradation rules, and the application of Welan gum oligosaccharides were studied. After degradation, the average molecular weight of Welan gum oligosaccharides could be degraded to 500 Da, and the molecular weight distribution range was wide. Through the hydroponic culture of barley seedlings, it was proved that the degradation products of Welan gum had a positive effect on plant growth. The results showed that Welan gum oligosaccharides could significantly increase the root length, plant height, and fresh weight of barley, and could be used as a growth regulator in agricultural production.
Characteristics of heterotrophic endophytic bacteria in four kinds of edible raw vegetables: species distribution, antibiotic resistance, and related genes
Authors: Zhang Chong-Miao , Yuan Qiao-Qiao , Li Yong-Qiang , Liu An
Published: November 2024

This study aimed to explore antibiotic resistance characteristics and species of heterotrophic endophytic bacteria (HEB) in four kinds of edible raw vegetables, including radishes, lettuces, onions, and tomatoes. A total of 144 HEB were isolated and tested for resistance to sulfamethoxazole (SMZ), tetracycline (TET), cefotaxime (CTX), and ciprofloxacin (CIP), and their species were identified by 16S rRNA gene sequencing. Antibiotic resistance genes (ARGs) and class I integron in antibiotic-resistant isolates were analyzed by polymerase chain reaction. The results showed radishes had the highest, while tomatoes had the lowest concentration of antibiotic-resistant HEB. SMZ and CTX were predominant antibiotic-resistant phenotypes in HEB. The multi-resistant phenotypes, the combinations SMZ-TET-CTX and SMZ-TET-CIP, accounted for 9.34% of all antibiotic-resistant phenotypes, mainly in radishes and lettuces. Bacillus, Pseudomonas, Staphylococcus, and Stenotrophomonas showed resistance to two antibiotics and existed in more than one kind of vegetable, and were the main carriers of sul1, sul2, blaTEM, and intI1 genes. Therefore, these four genera were considered potential hosts of ARGs in edible raw vegetables. The study provides an early warning regarding health risks associated with ingesting antibiotic-resistant bacteria through raw vegetable consumption.
Modulating gut microbiota for treating antibiotic-associated diarrhea from Clostridium difficile infection: insights from Lizhong decoction and its polysaccharide component
Authors: Rong XinQian , Shu QingLong
Published: November 2024

To investigate whether the polysaccharide component of the Traditional Chinese Medicine (TCM) formula Lizhong decoction (LZD) has therapeutic effects and regulates gut microbiota in antibiotic-associated diarrhea (AAD) related to Clostridium difficile infection, a polysaccharide was extracted from LZD, consisting of rhamnose, five monosaccharides, arabinose, galactose, glucose, and galacturonic acid in a molar ratio of 1.12:8.49:4.06:80.67:5.66. An AAD model related to C. difficile infection was established using clindamycin gavage and oral colonization with C. difficile. Subsequently, oral treatment experiments with LZD polysaccharides and different doses of the decoction were conducted. The results indicated that the polysaccharide showed the best therapeutic effect on AAD related to C. difficile infection, with post-treatment gut microbiota clustering closest to the normal control group. The polysaccharide from LZD has therapeutic effects on AAD related to C. difficile infection, possibly achieved through the regulation of gut microbiota. It modulates the dominant gut microbiota, specifically increasing the abundance of beneficial bacteria by adjusting the ratio of Bacteroidetes and Firmicutes, thereby reversing the dysbiosis caused by C. difficile infection and antibiotics. Thus, LZD polysaccharide may be one of the important active components for gut microbiota regulation in this TCM formula.
The distribution of galactic neighbours of X-ray-selected active galactic nuclei
Authors: Jones James R , Watson Michael G , Birchall Keir L , Starling Rhaana L C
Published: November 2024

We combine X-ray data from the X-ray Multi-Mirror Mission 12th data release (4XMM DR12) and the extended ROentgen Survey with an Imaging Telescope Array (eROSITA) Final Equatorial-Depth Survey (eFEDS) early data release catalogues with the Galaxy and Mass Assembly spectroscopic galaxy survey to form a sample of 526 local ($0.05\le z \le 0.3$), moderately luminous active galactic nuclei (AGNs; $L_{\rm X} \ge 10^{42}$ erg s-1). We compare the distribution of AGN hosts with that of the general galaxy population, finding no evidence of AGNs being preferentially hosted within over/underdense environments at a 7-Mpc scale. Next, we compare the distances to nearest-neighbour galaxies and find that AGN host galaxies are separated from their neighbours by the same distance as galaxies in a matched non-AGN sample. Finally, we consider mid-IR colour, provided by the All-WISE survey, the $L_{\rm X}/L_{6\, \mu \mathrm{m}}$ ratio, and X-ray hardness as tracers of AGN obscuration, to explore whether there is a change in the galaxy environment for obscured AGNs. We find no evidence of increasing AGN obscuration with decreasing separation in close galaxy pairs. We conclude that close galaxy–galaxy interactions may not be sufficiently disruptive to cause any observable increase in AGN activity.
10211- GEN-12 IDENTIFICATION OF PROGNOSIS-RELATED METHYLATION PROFILES AND METHYLATION BIOMARKERS IN IDH-WILD-TYPE GLIOBLASTOMA
Authors: Saito Kuniaki , Satomi Kaishi , Shimizu Saki , Kugasawa Kazuha , Sasaki Nobuyoshi , Kobayashi Keiichi , Shibahara Junji , Ichimura Koichi , Nakotmi Hirofumi , Nagane Motoo
Published: November 2024

BACKGROUND

Genome-wide DNA methylation analysis is currently available and is used to diagnose brain tumors. Although MGMT promoter hypermethylation is a strong biomarker in glioblastoma (GBM), there are few reports of DNA methylation profiles associated with prognosis or other DNA methylation biomarkers. In this study, we examined DNA methylation profiles correlated with prognosis and DNA methylation biomarkers.

METHODS

We selected 20 long-term survivors (LS) and 20 short-term survivors (SS) from 407 patients with newly diagnosed IDH-wild-type GBM treated at our institution, divided by MGMT methylation status (methylated; M/unmethylated; U), and adjusted for age. DNA methylation analysis was performed by EPIC array, and DKFZ classifier, tSNE analysis, and copy number analysis were performed. DNA methylation data and DNA methylation profiles were compared between LS and SS groups.

RESULTS

There were no significant differences in age and sex between the LS and SS groups in the M and U groups, respectively. Median OS (months) in the M group was 62.1/17.3 in LS/SS and 28.1/6.8 in the U group. Differentially methylated genes in the promoter region between LS/SS groups in the M group were HOXD13 and HAGH (methylated in LS), KCTD14 and ALPK3 (methylated in SS). Those in the U group were KLF14 and HOXB4 (methylated in LS), ZMYND10 and SLFN13 (methylated in SS). Gene Ontology analysis revealed that the genes with a hypermethylated promoter in the LS are enriched in G protein-coupled receptor signaling pathway and plasma membrane in the M group and Homeobox antennapedia and sequence-specific double-stranded DNA binding in the U group.

CONCLUSION

We identified DNA methylation biomarkers and key pathways involved in the prognosis of GBM with methylated and unmethylated MGMT promoter. Multi-omics analysis is necessary to validate the mechanism related to the prognosis of GBM.
10022- ET-2 DEVELOPMENT OF MICROSURGICAL FORCEPS EQUIPPED WITH HAPTICS TECHNOLOGY FOR IN SITU DIFFERENTIATION OF BRAIN TUMORS DURING MICROSURGERY
Authors: Ezaki Taketo , Kishima Kohki , Shibao Shunsuke , Matsunaga Takuya , Pareira Eriel Sandika , Nakayama Yuji , Tsuda Noboru , Kitamura Yohei , Takahara Kento , Iwama Takashi , Sampetrean Oltea , Ohnishi Kouhei , Shimono Tomoyuki , Sasaki Hikaru
Published: November 2024

The stiffness of human cancers may be corelated with their pathology, and can be used as a biomarker for diagnosis, malignancy prediction, molecular expression, and postoperative complications. Neurosurgeons perform tumor resection based on tactile sensations. However, it takes years of surgical experience to appropriately distinguish brain tumors from surrounding parenchymal tissue. Haptics is a technology related to the touch sensation. Haptic technology can amplify, transmit, record, and reproduce real sensations, and the physical properties (e.g., stiffness) of an object can be quantified. In the present study, glioblastoma (SF126-firefly luciferase-mCherry [FmC], U87-FmC, U251-FmC) and malignant meningioma (IOMM-Lee-FmC, HKBMM-FmC) cell lines were transplanted into nude mice, and the stiffness of tumors and normal brain tissues were measured using our newly developed surgical forceps equipped with haptic technology. We found that all five brain tumor tissues were stiffer than normal brain tissue (p<0.001), and that brain tumor pathology (three types of glioblastomas, two types of malignant meningioma) was significantly stiffer than normal brain tissue (p<0.001 for all). While glioblastomas showed no significant stiffness differences (p=0.468), IOMM-Lee-FmC was stiffer than HKBMM-FmC among meningiomas (p=0.032). Histologically, compared with IOMM-Lee-FmC, HKBMM-FmC showed abundant necrotic foci (i.e., similar to glioblastoma), which may explain the differences in stiffness.
10025- ET-3 IDENTIFICATION OF A NEW MOLECULAR TARGET FOR MESENCHYMAL GLIOBLASTOMA AND ITS FUNCTION
Authors: Miyazono Kohei , Tanabe Ryo , Matsumoto Takehisa
Published: November 2024

In order to identify molecular target(s) for treatment of glioblastoma multiforme (GBM), we searched for genes characteristically expressed in mesenchymal (MES)-type GBM and identified HVEM (herpes virus entry mediator, also known as TNF receptor superfamily 14), whose expression is higher in brain tumor tissue than in normal brain, especially in MES-type GBM. Furthermore, a significant correlation between HVEM expression and prognosis of GBM patients was found. Using GBM cells from HGCC (human glioblastoma cell culture) bank, the effect of HVEM was analyzed. Knockdown of HVEM expression in MES-type GBM cells resulted in a significant reduction in proliferative and sphere-forming capacity in vitro and loss of stem cell-like characteristics was observed. In an intracranial transplantation study in nude mice, tumor-forming capacity was also inhibited in MES-type GBM cells in which HVEM expression was knocked down, and mouse survival was significantly prolonged. For targeting HVEM, we generated alpaca-derived anti-human HVEM VHH (variable domain of heavy chain of heavy chain antibody) antibody, and analyzed the effects of the VHH antibody on MES-type GBM cells in vitro and in vivo. Currently, we are conducting preclinical studies using the VHH antibody targeting human HVEM and promoting research for future clinical application of human HVEM antibodies to MES-type GBM (This work has been conducted in collaboration with Drs. Carl-Henrik Heldin and Bengt Westermark, Uppsala University, Sweden).
10309- ACT-18 A PHASE 1, RANDOMIZED, PERIOPERATIVE TRIAL OF VORASIDENIB AND IVOSIDENIB IN DIFFUSE GLIOMA WITH AN IDH1 MUTATION: UPDATED RESULTS
Authors: Cloughesy Timothy F , Mellinghoff Ingo K , Wen Patrick Y , Taylor Jennie W , Maher Elizabeth A , Arrillaga-Romany Isabel , Ellingson Benjamin M , Mahboub-Johnson Paria , Baron Eric , Hassan Islam , Steelman Lori , Clarke Jennifer L
Published: November 2024

INTRODUCTION

Vorasidenib (VOR) and ivosidenib (IVO) showed clinical activity in patients with isocitrate dehydrogenase mutant (mIDH) gliomas. We evaluated both agents in a Phase 1, randomized, open-label perioperative trial (NCT03343197). Pharmacodynamics, pharmacokinetics and preliminary objective response rate (ORR) data as of April-29, 2020 were previously reported (Mellinghoff et al. Nat Med 2023). Progression-free survival (PFS) data were not mature at publication time. Herein, we report longer-term follow-up results, including mature PFS.

METHODS

Patients with grade 2/3 non-enhancing mIDH1 R132H mutant gliomas were randomized to VOR (50 or 10 mg QD), IVO (500 or 250 mg BID), or no treatment (control) for 4 weeks prior to planned surgery, with the option to continue treatment with VOR or IVO postsurgery. Secondary objectives included PFS, ORR assessed by investigator in the postsurgery period, and safety profile of VOR and IVO.

RESULTS

Enrollment completed in April-2019. Of the 49 patients randomized, 46 (24 oligodendroglioma, 20 astrocytoma, one anaplastic oligodendroglioma, one anaplastic oligoastrocytoma) received treatment with either VOR (n=24) or IVO (n=22) after surgery. As of data cutoff (September-23, 2023), 11 (46%) and five (20%) patients remained on treatment for VOR and IVO, respectively. Median (range) post-operative treatment duration was 44.7 months (0.9–62.7) for VOR, 23.9 months (0–62.7) for IVO. Median (95% CI) PFS was 41.4 months (9.3–NE) for VOR, 38.6 months (18.3–NE) for IVO. ORR per Response Assessment in Neuro-Oncology in low-grade gliomas was 46% for VOR and 27% for IVO. Longer safety follow-up will also be presented.

CONCLUSIONS

These results provide further evidence of prolonged response using IVO and VOR immediately following surgery in predominantly non-enhancing gliomas. This longer-term follow-up is consistent with Phase 3 INDIGO study results in which VOR demonstrated PFS benefit with manageable safety, compared with placebo, in patients with non-enhancing mIDH gliomas.
10100- NQPC-4 ACTIVITIES OF OITA UNIVERSITY NEUROSURGICAL UNIT TO ESTABLISH ACP SUPPORT FRAMEWORK FOR BRAIN TUMOR PATIENTS
Authors: Fudaba Hirotaka , Satou Chizuru , Abe Kayo , Momii Yasutomo , Kawasaki Yukari , Takao Kunpei , Yanagida Masayuki , Anan Mitsuhiro , Hata Nobuhiro , Inoue Ryo , Fujiki Minoru
Published: November 2024

BACKGROUND

Advance care planning (ACP) involves thinking ahead about desired medical treatment and care at the end of life and discussing and sharing this information with the medical and care team. Our facility in Oita Prefecture, which performs surgery and induction chemoradiotherapy for malignant brain tumors, has been providing ACP support for brain tumor patients since 2019. We report on our multidisciplinary collaboration activities and evaluation, including creating a brain tumor-specific ACP leaflet in July 2022.

METHODS

We organized an “ACP Support Team for Brain Tumor Patients” and began bi-weekly ACP conferences. We analyzed 79 patients using the achievement rate of each ACP step and the number of times the process was repeated during hospitalization. Additionally, a questionnaire survey was conducted to assess changes in “nursing practice regarding decision support” for patients with malignant brain tumors and their families due to ACP conferences.

RESULTS

Forty-eight patients were supported by the leaflet, and 31 were not. Both groups mostly achieved confirmation of their priorities and selection of a decision-making representative. However, the achievement rate of discussion and documentation steps in ACP significantly improved after the leaflet’s introduction. The questionnaire survey revealed changes in nursing practices, including “intentional information gathering based on the progress of the brain tumor,” “reflection on nursing practice,” “sharing the patient’s intention with the whole team,” and a “positive attitude toward ACP practice.”

CONCLUSION

The brain tumor-specific ACP leaflet was effective in supporting ACP for brain tumor patients. Additionally, the ACP conference raised awareness of the importance of ACP in nursing practice from the early stages of the disease. Multidisciplinary cooperation played a crucial role in decision-making support.
10116- NQPC-6 USEFULNESS OF THE NEUROPSYCHOLOGICAL QUICK ASSESSMENT IN THE EVALUATION OF NEUROPSYCHOLOGICAL COMPLICATIONS IN PATIENTS WITH PEDIATRIC BRAIN TUMORS
Authors: Tabata Ami , Ueda Keita , Nukui Megumi , Komaki Misa , Arakawa Yoshiki
Published: November 2024

BACKGROUND

Neuropsychological complications impair the qualitative prognosis of patients with pediatric brain tumors. However, multifaceted evaluation cannot be conducted for all patients owing to various issues, such as time constraints or burden on patients. The Neuropsychological Quick Assessment (NQA) was devised by the Japan Children’s Cancer Group as a screening assessment tool for neuropsychological complications, but without reliability and validity. In this study, we examined the usefulness of NQA in the assessment of neuropsychological complications in patients with pediatric brain tumors.

METHODS

Patients with pediatric brain tumors treated at Kyoto University Hospital were enrolled. The NQA and functional outcomes (neurocognitive outcome; WISC-IV/WAIS-IV, motor coordination outcome; BOT-2, fatigue; CFS, social behavior outcome; CBCL/ABCL) were assessed (approved by the Kyoto University Graduate School and Faculty of Medicine, Ethics Committee; R1580). We categorized the NQA into five subscales according to the content of the assessments: Neurocognitive, Directional Attention, Coordination, Fatigue, and Social Behavior. The correlations between each subscale score (except Directional Attention) of the NQA and functional outcomes were calculated using Spearman rank correlations.

RESULTS

This study included 17 patients with pediatric brain tumors with a median age of 14.0 years. The FSIQ (WISC-IV/WAIS-IV) and the Total Motor Composite (BOT-2) strongly negatively correlated with the Neurocognitive score and the Coordination score (ρ=-0.7851, -0.7746; p=0.0002, 0.0007, respectively). Moreover, the score of CFS and the Total T-score (CBCL/ABCL) positively correlated with the Fatigue score and the Social Behavior score (ρ=0.5127, 0.5488; p=0.0353, 0.0225, respectively).

CONCLUSIONS

Each subscale score of the NQA showed a strong correlation with each functional outcome. Therefore, we believe that the NQA is a simple and clinically useful method for assessing neuropsychological complications in patients with pediatric brain tumors. One limitation of this study is its small sample size; therefore, further investigation is required.
10153- NQPC-7 ADVANCING COGNITIVE ASSESSMENT IN GLIOBLASTOMA TREATMENT WITH MOLECULAR IMAGING (THK5351 PET)
Authors: Miyake Keisuke , Tatano Masaki , Kanda Takahiro , Suzuki Kenta , Fujimori Takeshi , Ogawa Daisuke , Hatakeyama Tetsuhiro , Okauchi Masanobu , Kawanishi Masahiko
Published: November 2024

INTRODUCTION

Cancer treatment-related higher brain dysfunction significantly impacts quality of life (QOL) and social life. This study investigates the relationship between PET accumulation areas and advancing cognitive assessment in glioblastoma IDH-wild type (GBM) patients using the PET tracer THK5351, developed to detect tau protein.

METHODS

Twenty-four GBM patients who underwent changes in tumor to normal ratio (TNR) and metabolic tumor volume (MTV) for THK5351 evaluation before and after temozolomide (TMZ), bevacizumab (Bev), and radiation therapy from February 2020 to March 2024 were included. Cognitive assessments included the Mini-Mental State Examination (MMSE), Trail Making Test (TMT), Frontal Assessment Battery (FAB), Raven’s Coloured Progressive Matrices (RCPM), and Kohs block-design test (Kohs), administered at admission and discharge.

RESULTS

The mean age of the patients was 70.5 years (14 males, 10 females). All patients were diagnosed with GBM and received TMZ, Bev, and radiation therapy. In 11 patients, a reduction in THK5351 MTV correlated with MMSE improvement. However, 5 patients showed TMT deterioration, with a significant increase in THK5351 TNR change. FAB scores increased in 3 patients, while RCPM and Kohs scores deteriorated in 1 patient, alongside an increase in THK5351 TNR change. Among the 13 patients with enlarged THK5351 MTV, 5 showed decreased MMSE scores, and 3 showed decreased TMT and FAB scores. These cases exhibited an increased THK5351 TNR change, with accumulation expanding from the medial thalamus to the anterior nuclei of the thalamus, hypothalamus, caudate nucleus, hippocampus, and corpus callosum. Patients with reduced THK5351 TNR but enlarged THK5351 MTV had improved MMSE scores but decreased motivation and cognitive function.

CONCLUSION

Improving the GBM removal rate and preserving function requires attention to THK5351 accumulation in the corpus callosum, hippocampus, and hypothalamus for advancing cognitive assessment.
10003- MET-1 NEOADJUVANT STEREOTACTIC RADIOTHERAPY FOLLOWED BY SURGICAL RESECTION FOR BRAIN METASTASES: EFFICACY AND SAFETY STUDY (NEO-TACTICS TRIAL)
Authors: Mitsuya Koichi , Motimura Kazuya , Kibe Yuji , Otake Takumi
Published: November 2024

BACKGROUND

Postoperative stereotactic radiosurgery (SRS) for resected brain metastases (BM) improves local control compared to observation, while also preserving neurocognitive function in comparison to whole brain radiation therapy. However, even with surgery and SRS, rates of local recurrence at 1 year may be as high as 40%, especially for larger cavities, and there is also a known risk of leptomeningeal disease after surgery. The safety and effectiveness of neoadjuvant fractionated stereotactic radiotherapy (SRT) before piecemeal resection of large BM remains unknown.

METHODS

We retrospectively reviewed 20 consecutive patients with BM who underwent neoadjuvant fractionated SRT followed by piecemeal resection between July 2019 and March 2021. The prescribed dose regimens were as follows: 30 Gy or 35 Gy in five fractions.

RESULTS

The mean follow-up duration was 7.8 months. The median age was 67 years. Fourteen patients were male. All patients were symptomatic. All tumors were located in the supratentorial compartment. The median maximum diameter and volume were 3.7 cm and 17.6 cm3 respectively. The median time from the end of SRT to resection was 4 days. Nausea (CTCAE Grade 2) occurred in one patient and simple partial seizures (Grade 2) in two patients during radiation therapy. Gross total removal was performed in seventeen patients and sub-total removal in three patients. Postoperative complications were deterioration of paresis in two patients. Local recurrence was found in one patient (5%) who underwent sub-total resection at 2 months after craniotomy. Distant recurrence was found in six patients (30%) at a median of 6.9 months. Leptomeningeal disease recurrence was found in one patient (5%) at 3 months. No radiation necrosis developed.

CONCLUSIONS

Neoadjuvant SRT appears to be a safe and effective approach for patients with BM requiring piecemeal resection. Now, a multi-institutional prospective trial (NEO-TACTICS trial) is ongoing. (jRCT s042220014)
10213- MET-17 A CASE OF METASTATIC BRAIN TUMOR FROM HER2-POSITIVE PAROTID CARCINOMA WITH LOCALIZED MENINGEAL DISSEMINATION
Authors: Tabei Yusuke , Ishikawa Hisashi , Suma Takeshi , Ooyama Kenichi , Matsuno Akira , Nomura Ryutarou
Published: November 2024

A 30s-year-old man was undergoing chemotherapy with intravenous trastuzumab for recurrent HER2-positive parotid carcinoma. Gamma knife therapy was given to a metastatic brain tumor of left frontal lobe in February X. The lesion was temporarily reduced in size, but in November X, local re-growth and a new lesion in the right frontal lobe were observed. He underwent ZAP-X fractionated stereotactic radiotherapy 24 Gray per 3 fractions for the left frontal lobe lesion and 20 Gray for the right temporal lobe lesion. In February X+1, he received ZAP-X stereotactic radiotherapy for a new lesion near the Sylvian fissure. He was admitted to the hospital with a diagnosis of meningeal carcinomatosis due to contrast findings in the cerebral gyrus from the left Sylvian fissure. Whole brain irradiation was avoided, and intrathecal methotrexate was administered. MRI scan in June X+1 showed multiple intraparenchymal brain metastases with surrounding brain edema and recurrent headaches, so steroids were prescribed and palliative care was continued. The number of cases of localized meningeal dissemination is expected to increase with advances in chemotherapy and the widespread use of stereotactic radiotherapy. The indication of Trastuzumab deruxtecan has been expanded to HER2-positive metastatic solid tumors abroad. It is expected to be available in Japan as soon as possible.
10080- COT-9 HIGH EXPRESSION OF COX-2 PREDICTS IMPROVED OVERALL SURVIVAL OUTCOME IN BEVACIZUMAB-TREATED HIGH-GRADE GLIOMA PATIENTS
Authors: Kesumayadi Irfan , Kambe Atsushi , Kanda Haruto , Hosoya Tomohiro , Sakamoto Makoto , Kurosaki Masamichi
Published: November 2024

INTRODUCTION

Studies have shown that bevacizumab (BEV) improves progression-free survival (PFS) but not overall survival (OS) in high-grade glioma (HGG) patients. Here we evaluate the potential of cyclooxygenase-2 (COX-2), a rate-limiting enzyme involved in inflammation and tumor progression by producing prostaglandin E2, as a differentiating factor for the subset of participants who benefit from BEV treatment.

METHODS

We performed a retrospective study on newly diagnosed HGG patients who received Temozolomide (TMZ) alone or TMZ+BEV chemotherapy. We assessed the expression of COX-2 using immunohistochemistry staining prior to receiving chemotherapy. An immunoreactivity score > 3 is considered high. We performed survival analysis on PFS and OS among patients with high vs. low expression.

RESULTS

A total of 60 patients were enrolled in our study, with 28 treated with TMZ only and 32 treated with TMZ+BEV. We found 36 patients with low expression and 24 patients with high expression. High expression of COX-2 is known to be associated with poor prognosis for HGG patients. Here we found no significant differences in median PFS and OS between low and high expression of COX-2 among those receiving TMZ+BEV (PFS: 22 vs. 18 months, p=0.95; OS: 25 vs. 25 months, p=0.53). Interestingly, among patients with high expression of COX-2, those receiving TMZ+BEV showed significantly higher median PFS and OS than the TMZ only group (PFS: 18 vs. 8 months, p=0.001; OS: 25 vs. 14 months, p=0.022). This difference was not identified in patients with low expression of COX-2 between the TMZ+BEV vs. TMZ only groups (PFS: 22 vs. 10 months, p=0.16; OS: 25 vs. 20 months, p=0.09).

CONCLUSION

Our data demonstrate the benefit of BEV chemotherapy for HGG patients with high expression of COX-2, thus supporting the use of COX-2 as a predictive biomarker for determining which HGG patients are likely to benefit from BEV chemotherapy.
10110- COT-11 EVALUATING SHORT-TERM SURVIVORS OF GLIOBLASTOMA: A PROPOSAL BASED ON SEER REGISTRY DATA
Authors: Tomita Yusuke , Otani Yoshihiro , Omae Ryo , Mizuta Ryo , Ishida Joji , Hirotsune Nobuyuki , Tanaka Shota
Published: November 2024

BACKGROUND

Glioblastomas (GBMs) are central nervous system tumors with a poor prognosis and limited treatment options. Although small subsets of GBM patients survive longer than 3 years, there is little evidence regarding the prognostic factors of GBM. Therefore, we conducted a thorough characterization of GBM in the United States.

METHODS

We queried the Surveillance, Epidemiology and End Results database (SEER) between 2000 and 2021 to extract age-adjusted incidence rates (AAIR), age-adjusted mortality rates (AAMR), and survival data for GBM. Age group comparisons for each measure varied depending on the available SEER data. We compared trends in AAIR, AAMR, and survival time across age groups 0-14, 15-39, 40-69, and 70+ years. Also, we employed the Fine-Gray competing risk model among short-term survivors (STSs), defined as those with a survival time of 6 months or less, and long-term survivors (LTSs), defined as those with a survival time of 3 years or more.

RESULTS

This study included 16,625 STSs and 4,197 LTSs between 2000 and 2021. The mortality-to-incidence ratio was constant among STSs, whereas it increased with age among LTSs. Higher age and male sex were significantly associated with GBM-specific death among LTSs, whereas non-Hispanic White, subtotal resection/biopsy, no radiation therapy, and no chemotherapy were associated with GBM-specific death among STSs. Interestingly, higher age was significantly associated with other causes of death among STSs.

CONCLUSIONS

STSs partially consist of populations who died from causes other than GBM. It is important to include only GBM-specific deaths in STS groups to conduct reproducible research comparing STSs and LTSs.