bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behind the scenes: integrated pest management in a public garden
Authors: McDonald Rachel , Pantuliano Beth 
Published: November 2024

Abstract
Integrated pest management in a public garden poses unique challenges and opportunities. Longwood Gardens has 300 acres intensively managed by an integrated pest management team. Within that acreage, collections are managed for their aesthetic display quality, research, and conservation, as well as enjoyment by guests who come to the Gardens for classes, performances, and events or to enjoy a day of beauty and wonder. Each garden space has multiple uses, vast plant palettes, and historical legacies. The integrated pest management team must balance aesthetics, science, and human needs while looking to the future to prepare for potential new pest invaders. Every day is an adventure and lesson in prioritizing, patience, and tolerance. The integrated pest management practitioners are dedicated to finding the right integrated pest management tool, knowing when to use it and when to do nothing, and researching and learning new techniques and approaches to ensure the Garden continues to thrive.
Virtual reality exposure therapy for sexual aversion: a proof-of-concept study on acceptability, adequacy, and clinical effects
Authors: Lafortune David , Lapointe Valérie A , Dubé Simon , Bonneau Jonathan 
Published: November 2024

Abstract

Background
Sexual dysfunctions impair the intimate relationships of up to one-third of the population. Virtual reality (VR) offers innovative treatment options for both mental and sexual disorders, such as female orgasmic disorder and erectile disorder. Sexual aversion disorder (SAD)—the anxiety, disgust, and avoidance of sexual contexts—is a chronic condition commonly treated with anxiety-reducing strategies, such as exposure-based therapy. Despite exposure’s efficacy in reducing SAD symptoms, VR exposure therapy’s (VRET) effectiveness remains unexplored for this condition.

Aim
This proof-of-concept study examines the acceptability, adequacy, and clinical effects of a VRET’s simulation protocol for SAD.

Methods
In the laboratory, 15 adults suffering from SAD (Mage = 35.00; SD = 11.36) viewed 15 virtual sexual scenarios of increasing intensity (eg, flirting, nudity, genital stimulation) adjusted to their sexual preferences and gender identities.

Outcomes
Levels of anxiety, disgust, and catastrophizing beliefs were measured throughout the scenarios using standard self-report measures. Participants also completed validated questionnaires on sexual presence and simulation realism, as well as open-ended questions on scenarios’ representativeness and adequacy immediately after immersion. Six months after the laboratory visit, participants completed a negative effects questionnaire and were screened for SAD symptoms again. Repeated-measures ANOVAs and descriptive analyses were performed.

Results
Levels of anxiety and disgust significantly increased with the intensity of sexual scenarios. Catastrophizing levels were high and tended to augment with increasing exposure levels. A significant reduction in symptoms of SAD was found from pre-simulation to the 6-month follow-up assessment. Sexual presence and realism scores were moderate. Qualitative assessment revealed that all participants reported the sexual scenarios were representative of real-life situations that tend to elicit SAD symptoms for them. Reported negative effects were generally mild.

Clinical Implications
This proof-of-concept study suggests that VRET may have the potential to elicit self-reported emotional and cognitive manifestations of SAD (sex-related anxiety, disgust, and catastrophizing), while also hinting at its acceptability, adequacy, and benefits in alleviating SAD symptoms.

Strengths & Limitations
While this study marks the first exploration of the clinical relevance of gender-inclusive virtual sexual scenarios for SAD, its design and sample composition may impact observed effects and the generalizability of findings.

Conclusion
This study invites future clinical trials to assess VRET efficacy for SAD.
Sexual asylum regimes and politics of belonging: Narratives of deservingness in the political-public discourse in Switzerland
Authors: Schnell Mathis , Balsiger Philip , Dahinden Janine 
Published: November 2024

Abstract
This article explores the ways in which narratives of deservingness in the field of sexual asylum become crucial elements of national border drawing and boundary work, and important instruments of a politics of belonging. Switzerland is a particularly interesting case study in which to explore these issues due to the supposed humanitarian tradition on the one hand and conservative policies on gender and sexuality issues on the other hand. Drawing on literature on belonging and sexual nationalism, we conduct a qualitative analysis of textual data representing the political–public discourse. Four interconnected narratives of deservingness regarding the sexual asylum regime were isolated: (1) postcolonial geopolitics of national imaginaries; (2) Eurocentric/Western representations of queerness and a corresponding politics of the queer body; (3) hierarchizing categories of vulnerability; and (4) a general narrative of (dis)belief. We argue that the political–public discourse on sexual asylum should be understood as part of a broader moral economy concerned with the creation and definition of the Swiss community and its politics of belonging.
MFIB 2.0: a major update of the database of protein complexes formed by mutual folding of the constituting protein chains
Authors: Fichó Erzsébet , Pancsa Rita , Magyar Csaba , Kalman Zsofia E , Schád Éva , Németh Bálint Z , Simon István , Dobson Laszlo , Tusnády Gábor E 
Published: November 2024

Abstract
While the majority of proteins with available structures are able to fold independently and mediate interactions only after acquiring their folded state, a subset of the known protein complexes contains protein chains that are intrinsically disordered in isolation. The Mutual Folding Induced by Binding (MFIB) database collects and classifies protein complexes, wherein all constituent protein chains would be unstable/disordered in isolation but fold into a well-defined 3D complex structure upon binding. This phenomenon is often termed as cooperative folding and binding or mutual synergistic folding (MSF). Here we present a major update to the database: we collected and annotated hundreds of new protein complexes fulfilling the criteria of MSF, leading to an almost six-fold increase in the size of the database. Many novel features have also been introduced, such as clustering of the complexes based on structural similarity and domain types, assigning different evidence levels to each entry and adding the evidence coverage label that allowed us to include complexes of multi(sub)domain monomers with partial MSF. The MFIB 2.0 database is available at https://mfib.pbrg.hu.
Database resources of the National Center for Biotechnology Information in 2025
Authors: Sayers Eric W , Beck Jeffrey , Bolton Evan E , Brister J Rodney , Chan Jessica , Connor Ryan , Feldgarden Michael , Fine Anna M , Funk Kathryn , Hoffman Jinna , Kannan Sivakumar , Kelly Christopher , Klimke William , Kim Sunghwan , Lathrop Stacy , Marchler-Bauer Aron , Murphy Terence D , O’Sullivan Chris , Schmieder Erin , Skripchenko Yuriy , Stine Adam , Thibaud-Nissen Francoise , Wang Jiyao , Ye Jian , Zellers Erin , Schneider Valerie A , Pruitt Kim D 
Published: November 2024

Abstract
The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence repository and the PubMed® repository of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 31 distinct repositories and knowledgebases. The E-utilities serve as the programming interface for most of these. Resources receiving significant updates in the past year include PubMed, PubMed Central, Bookshelf, the NIH Comparative Genomics Resource, BLAST, Sequence Read Archive, Taxonomy, iCn3D, Conserved Domain Database, Pathogen Detection, antimicrobial resistance resources and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.
scProAtlas: an atlas of multiplexed single-cell spatial proteomics imaging in human tissues
Authors: Wang Tiangang , Chen Xuanmin , Han Yujuan , Yi Jiahao , Liu Xi , Kim Pora , Huang Liyu , Huang Kexin , Zhou Xiaobo 
Published: November 2024

Abstract
Spatial proteomics can visualize and quantify protein expression profiles within tissues at single-cell resolution. Although spatial proteomics can only detect a limited number of proteins compared to spatial transcriptomics, it provides comprehensive spatial information with single-cell resolution. By studying the spatial distribution of cells, we can clearly obtain the spatial context within tissues at multiple scales. Spatial context includes the spatial composition of cell types, the distribution of functional structures, and the spatial communication between functional regions, all of which are crucial for the patterns of cellular distribution. Here, we constructed a comprehensive spatial proteomics functional annotation knowledgebase, scProAtlas (https://relab.xidian.edu.cn/scProAtlas/#/), which is designed to help users comprehensively understand the spatial context within different tissue types at single-cell resolution and across multiple scales. scProAtlas contains multiple modules, including neighborhood analysis, proximity analysis and neighborhood network, to comprehensively construct spatial cell maps of tissues and multi-modal integration, spatial gene identification, cell-cell interaction and spatial pathway analysis to display spatial variable genes. scProAtlas includes data from eight spatial protein imaging techniques across 15 tissues and provides detailed functional annotation information for 17 468 394 cells from 945 region of interests. The aim of scProAtlas is to offer a new insight into the spatial structure of various tissues and provides detailed spatial functional annotation.
EPCO-02. HIGH CELLULAR PLASTICITY STATE OF HUMAN MEDULLOBLASTOMA LOCAL RECURRENCE AND DISTANT DISSEMINATION
Authors: Liu Hailong , Li Jiankang , Jiang Tao 
Published: November 2024

Abstract
Medulloblastoma (MB) is a heterogeneous pediatric brain tumor with variable clinical outcomes. Since current treatments facing limitations due to tumor resistance, less than 10% of relapsed patients survive beyond five years, with poorly understood recurrence mechanisms. To obtain cellular diversity and genetic characters in primary and recurrent MB, we conducted comprehensive analyses utilizing the single-cell/nucleus RNA sequencing (sc/snRNA-seq), snATAC-seq and spatial transcriptomics, complemented with bulk RNA sequencing and matched primary-recurrent whole exon profiles. SHH and Group_3 subgroups revealed distinct cellular subsets, including cycling, differentiated and quiescent tumor cells. Recurrent or disseminated MB displayed a dramatically different cellular ecosystem compared to primary tumors, with varying proportions of shared cell types. Local recurrence exhibited a higher enrichment of cycling tumor cells, while differentiated subset was notably present in disseminated lesions, indicating that local recurrences harbored the stronger proliferative capacity, whereas disseminations relatively well differentiated. Additionally, chromosomal alterations were assessed, reflecting distinct genetic subclones, such as chr7q gain and chr11 loss in Group_3 disseminations. Notably, the emergence of a subpopulation termed “high cellular plasticity (HCP)” during MB progression was noted, characterized by dynamic adaptability and stemness properties. As validated, HCP state was associated with increased chromatin accessibility, contributing to tumor recurrence and immune microenvironment remodeling. Functionally, inhibiting markers associated with HCP cells, such as PTPRZ1, efficiently suppressed MB metastasis in preclinical models. In conclusion, our findings fill the critical knowledge gaps in understanding the cellular diversity, chromosomal alterations and biological dynamics in MB recurrence and dissemination, offering potential therapeutic interventions.
EPCO-15. INTRA-TUMORAL HETEROGENEITY OF DNA METHYLATION PROFILING AND CELLULAR COMPOSITION IN GLIOBLASTOMA
Authors: Matsumoto Yuji , Singh Omkar , Garcia Jose , Kwak Sunwoo , Abdullaev Zied , Freeburg Nelson , Silverbush Dana , Aldape Kenneth , Davatzikos Christos , Nasrallah MacLean 
Published: November 2024

Abstract

BACKGROUND
DNA methylation profiling has become an important diagnostic and exploratory tool in neuro-oncology. Intra-tumoral molecular heterogeneity is a crucial factor in the treatment resistance of IDH-wildtype glioblastoma (GBM). However, the intra-tumoral heterogeneity of methylation profiles in GBM remains poorly elucidated. This study aimed to investigate the intra-tumoral heterogeneity of DNA methylation subclasses and deconvolve methylation profiles to infer the cellular composition of the tumor.

METHODS
We conducted genome-wide DNA methylation analysis and applied the DKFZ/Heidelberg CNS tumor classifier to FFPE tissue samples from a multi-sampling cohort with multiple samples per patient and a single-sampling cohort with one sample per patient. Only samples classified as GBM were included. We conducted two different methylation-based deconvolution analyses. Deconvolution 1 inferred the fractions of tumor subtypes (RTK_I, RTK_II, MES_TYP, and MES_ATYP) and cell types in the microenvironment. Deconvolution 2 estimated the abundance of malignant cell states (stem-like and differentiated cell components) and cell types in the microenvironment.

RESULTS
The multi-sampling cohort included 32 patients with 113 samples, and the single-sampling cohort included 87 patients with 87 samples. In the multi-sampling cohort, 8 patients (25%) exhibited intra-patient heterogeneity in methylation subclasses across their samples. Deconvolution 1 indicated that each tumor subclass component was heterogeneously distributed within samples, and the abundance of the myeloid cell component correlated with the MES_TYP component across samples. Deconvolution 2 similarly revealed heterogeneity in the immune component abundance across samples within patients. Integrating the results of Deconvolution 1 and Deconvolution 2 using the entire cohort revealed significant correlations between RTK_I and stem-like, RTK_II and differentiated, and MES_TYP and immune components. These findings were also replicated in TCGA dataset.

CONCLUSIONS
Our findings underscore the importance of considering intra-tumoral heterogeneity in methylation profiles and the biological characteristics of each methylation subclass in developing novel GBM therapies.
EPCO-18. DECIPHERING SPATIAL DIVERSITY OF GLIOBLASTOMA GENETIC ARCHITECTURE
Authors: Zhang Junyi , Joshi Tanvi , Hambardzumyan Dolores , Heiland Dieter Henrik 
Published: November 2024

Abstract
Glioblastoma (GBM) is hallmarked by profound inter- and intratumoral heterogeneity. Current research has mapped key genetic drivers to distinct transcriptional profiles within GBM. Nevertheless, the intricate interactions between genetic alterations and spatial-transcriptional heterogeneity remain elusive. We utilized nestin-Tva C57BL/6 mice to induce de novo GBM via oncogene overexpression alongside shRNA-mediated silencing or deletion of tumor suppressors. We modeled critical driver mutations: PDGFB, NF1, and EGFR. Employing 10X Genomics platform for single-cell RNA sequencing, combined with spatially resolved transcriptomics and proteomics (Nanostring GeoMx), we integrated data using both horizontal (mutual nearest neighbors) and vertical (weighted nearest neighbors) approaches, analyzed through the SPATA2 software. Advanced computational techniques, including graph neural networks and single-cell deconvolution, were leveraged to unravel the genotypic and spatial variability within tumors and their microenvironments. Our findings uncover persistent cellular heterogeneity across diverse genetic contexts. However, specific genetic mutations precipitated distinct dominant transcriptional states: NF1 and EGFR mutations drove mesenchymal and astrocytic-like states, respectively, whereas PDGFB fostered a neural progenitor/cell-like state. These transcriptional shifts were closely linked to unique microenvironmental modifications, such as elevated neuronal signaling in PDGFB-driven GBMs and significant immune infiltration in NF1 and EGFR models. Through weighted co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA) paired with spatial-niche deconvolution, we identified a mesenchymal transition leading to an immunosuppressive microenvironment in NF1-loss driven GBMs and increased lymphocyte presence around blood vessels in EGFR-amplified GBMs. These patterns were consistent with human spatially resolved transcriptomic data, emphasizing the genetic complexity and heterogeneity of human GBMs. Our genetically engineered mouse models serve as a robust platform for dissecting GBM with defined genetic mutations. Leveraging sophisticated analytical techniques and computational modeling, this study underscores the profound interplay between genetic drivers and the tumor microenvironment, paving the way for targeted therapeutic strategies and precision medicine in GBM.
EPCO-24. WHAT SCRNA SEQUENCING TAUGHT US ABOUT MGMT EXPRESSION IN GLIOBLASTOMA
Authors: Alnahhas Iyad , Shi Wenyin 
Published: November 2024

Abstract

INTRODUCTION
The promoter methylation status of O-6-methylguanine-DNA methyltransferase (MGMTp) is an established predictive and prognostic marker in GBM. Previous studies showed that the expression of MGMT based on immunohistochemistry was variable and lacked association with survival. This in part is because non-tumor cells including endothelial cells and macrophages express MGMT. Advanced technologies such as single-cell RNA (scRNA) sequencing have helped to elucidate the cellular composition of cancer and its microenvironment. scRNA sequencing allows to assess gene expression level in tumor cells specifically.

METHODS
We used publicly available data from two recent IDHwt GBM scRNA studies that included MGMTp methylation status data to explore and uncover details about MGMT expression at the single-cell level: CPTAC (13 primary samples) and Neftel (20 primary samples).

RESULTS
In the CPTAC study, MGMT gene expression ranged from 0.19%-1.43% in the MGMTp methylated group (median 0.82%), and from 2.17%-28.36% in the MGMTp unmethylated group (median 5.7%). It therefore appears that 2% is a reasonable expression cutoff to predict the MGMTp methylation status based on scRNA data. In the Neftel study, MGMT expression ranged from 0-1.26% in the MGMTp methylated group (median 0.59%), and from 0.3-27.67% in the MGMTp unmethylated group (median 12.44%). Three unmethylated samples (out of 16) did not follow the 2% rule. It is unclear if this is due to simply inaccurate annotation of these samples. Moreover, the Neftel paper did not specify the method used to detect MGMTp methylation. Alternatively, could it be that truly MGMTp unmethylated samples can have low MGMT expression? Could this explain why some unmethylated MGMTp GBM patients surpass the expected survival? Interestingly, gene set enrichment analysis shows that MGMT expressing cells are enriched with mesenchymal genes, whereas MGMT negative cells are enriched with proneural genes.

CONCLUSION
Fewer than 2% of GBM cells express MGMT if MGMTp is methylated.
EPCO-27. CHROMATIN REMODELING REPROGRAMS THE TRANSCRIPTION NETWORK IN GLIOBLASTOMA
Authors: Sun Xueqin Sherine , Mills Alea 
Published: November 2024

Abstract
Fundamentally, cancer arises from genetic and epigenetic alterations that interplay to reprogram gene expression networks, leading to unrestrained proliferation. Glioblastoma (GBM) is the most prevalent and aggressive primary brain cancer, with a median survival of approximately one year and a 5-year survival rate of just 5%. The standard care for GBM patients has remained unchanged for decades, underscoring the need for a better understanding of GBM biology to develop more effective therapies. The relatively low genetic mutation burden in GBM highlights the significant role of epigenetic mechanisms in its pathogenesis. Our recent work shows that chromatin remodeling plays pivotal roles in GBM pathogenesis. The BRD8-driven EP400 chromatin remodeling complex maintains GBM by crippling p53-mediated tumor suppression in an unprecedented way through hijacking the histone variant H2AZ at p53 target loci, enforcing a repressive chromatin state that prevents p53-mediated transactivation. Targeting BRD8 in TP53WT GBM, which makes up ~71% of all GBM cases, enhances chromatin accessibility by evicting H2AZ. This restores p53-mediated transactivation of its targets, reestablishes cell cycle arrest, inhibits gliomagenesis, and prolongs survival in xenograft models of TP53WT GBM. Conversely, the NuRD chromatin remodeling complex driven by CHD5 governs the MYC-mediated oncogenic network to prevent gliomagenesis. Mechanistically, CHD5 forms a CHD3-containing but CHD4-independent NuRD complex that directly binds to the MYC promoter and super enhancers. Chd5 loss triggers the remodeling of chromatin, enhances chromatin accessibility at Myc loci, augments Myc expression, significantly impairs NSCs differentiation while promotes proliferation, transformation, and gliomagenesis in vivo. Furthermore, reactivating CHD5 in human GBM xenograft models significantly extends survival. Thus, our findings reveal previously unappreciated epigenetic mechanisms by which GBM cells reprogram both tumor-suppressive and oncogenic transcription networks to facilitate their outgrowth. This sheds new light on our understanding of GBM malignancy and provides promising therapeutic opportunities for treating patients with this devastating malignancy.