bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Limits of the Law: Work in the Light of Capitalist Reproduction
Authors: Tzanakopoulou Maria 
Published: November 2024

ABSTRACT
The article explores alternatives to capitalist work from the point of view of reproduction of capitalist relations. The latter occurs in a cyclical manner as capitalist structures—the economic, juridico-political and ideological levels—co-constitute and reproduce one another. Given the difficulty inherent in breaking the cycle of reproduction, a reflection on alternatives to capitalist work requires that work is reconceptualised, to the extent possible, beyond current structures: as transformations at any one individual level cannot produce radical change, alternatives to capitalist work require a holistic reimagining of the social totality, transcending, for example, mere legal or mere political reform. The force that can disrupt the cycle of capitalist reproduction and open space for such holistic reimagination is class struggle. The latter becomes embedded in the process of redefining work in so far as it is the force that can precipitate structural and unforeseeable change. It also acts a reminder that the substantive redefinition of work is a collective process, and cannot be the task of any single individual situated externally to that struggle.
Pregnant women and healthcare workers’
perceptions on tuberculosis and screening: a cross-sectional study in Indonesia
Authors: Rahari Dzerlina Syanaiscara , Nurdiati Detty Siti , Thobari Jarir At , Suyanto Suyanto , Liabsuetrakul Tippawan 
Published: November 2024

Abstract

Background
There is a scarcity of studies regarding the obstacles in tuberculosis (TB) screening in pregnant women. This study aimed to assess the perceptions of TB as a disease and TB screening among pregnant women and healthcare workers, describe pregnant women's perceptions on specific TB screening methods and explore associations between the perceptions of TB with the intention to have TB screening by pregnant women.

Methods
A cross-sectional study was conducted at six primary healthcare centres in Yogyakarta Municipality, Indonesia among 240 pregnant women and 126 healthcare workers interviewed with a structured questionnaire about their perceptions. Perceptions were analysed as percentages and associated factors were tested by multivariable logistic regression.

Results
Most pregnant women and healthcare workers supported TB screening in pregnant women based on their perceptions of the susceptibility to or severity of TB and the benefits and risks of TB screening. Women who perceived the high susceptibility of TB disease and the benefits of TB screening were significantly more likely to have high intentions to accept TB screening in the future.

Conclusions
Pregnant women's perceptions of TB and TB screening influenced their intention to be screened; however, appropriate testing methods for universal TB screening in pregnant women in areas with a high prevalence of TB require further studies.
“Extremely Stupid Guidelines”: On The Development of Historical Questions Around Guru Tegh Bahadur’s Martyrdom
Authors: Judge Rajbir Singh 
Published: November 2024

ABSTRACT
In 1675, Mughal authorities beheaded Guru Tegh Bahadur, the ninth Sikh Guru and, today, the martyrdom has become a highly contested historical question within scholarly circles. This article investigates the emergence of the event as a historical question and how the emphasis of historical fact-finding refashioned scholarly approaches to the Sikh tradition in the colonial and postcolonial periods. I end by exploring how the famous Sikh intellectual and politician, Sirdar Kapur Singh (1909-1986), drew upon the Sikh tradition to challenge the very premises of such historiographical framing in his landmark essay, “Who Killed Guru Tegh Bahadur?” and the limits to his challenge. I ask: What do we make of Kapur Singh’s frustration and disgust at the history writing that came to dominate the Sikh tradition? I show how Kapur Singh does not transcend the epistemological constraints of history through a better or more accurate rendition of the past. Instead, he disrupts the historiographical operation in his frustration with history writing and what he calls its “extremely stupid guidelines.”
webTWAS 2.0: update platform for identifying complex disease susceptibility genes through transcriptome-wide association study
Authors: Cao Chen , Shao Mengting , Wang Jianhua , Li Zhenghui , Chen Haoran , You Tianyi , Li Mulin Jun , Ding Yijie , Zou Quan 
Published: November 2024

Abstract
Transcriptome-wide association study (TWAS) has successfully identified numerous complex disease susceptibility genes in the post-genome-wide association study (GWAS) era. Over the past 3 years, the focus of TWAS algorithms has shifted from merely identifying associations to understanding how single nucleotide polymorphisms (SNPs) regulate gene expression, with a growing emphasis on incorporating fine-mapping techniques. Additionally, the rapid increase in GWAS summary statistics, driven largely by the UK Biobank and other consortia, has made it essential to update our webTWAS resource. To address these challenges and meet the growing needs of researchers, we developed webTWAS 2.0, an updated platform for identifying susceptibility genes for human complex diseases using TWAS. Additionally, webTWAS 2.0 provides an online TWAS analysis tool that simplifies conducting TWAS analyses. The updated resource includes 7247 GWAS summary statistics covering 1588 complex human diseases from 192 publications. It also incorporates multiple TWAS methods, such as sTF-TWAS, 3′aTWAS and GIFT, along with an updated interactive visualization tool that allows users to easily explore significant associations across different methods. Other upgrades include a personalized online analysis tool for user-submitted GWAS data and a refined search function that makes it easier to identify relevant associations and meet diverse user needs more efficiently. webTWAS 2.0 is freely accessible at http://www.webtwas.net.
SoIR: a comprehensive Solanaceae information resource for comparative and functional genomic study
Authors: Liu Zhuo , Shen Shaoqin , Li Chunjin , Zhang Chenhao , Chen Xiang , Fu Yanhong , Yu Tong , Zhou Rong , Liu Dongxu , Yang Qing-Yong , Song Xiaoming 
Published: November 2024

Abstract
The Solanaceae family, which includes economically important crops such as tomatoes, potatoes and peppers, has experienced a rapid expansion in genomic data due to advancements in sequencing technologies. However, existing databases are limited by incomplete species representation, a lack of comprehensive comparative genomic tools and the absence of systematic pan-genomic analyses. To address these gaps, we developed the Solanaceae Information Resource (SoIR, https://soir.bio2db.com), a comprehensive genomics database for the Solanaceae family. SoIR integrates genomic data from 81 species and transcriptomic data from 41 species, encompassing a total of 3 908 408 gene annotations derived from Gene Ontology, nonredundant protein, Pfam, Swiss-Prot and TrEMBL databases. The resource also includes 3 437 115 CRISPR guide sequences, 212 395 transcription factors and 19 086 genes associated with methylation modification. In addition to species-specific analyses, SoIR provides extensive bioinformatics tools for investigating gene family evolution, phylogenetic relationships and karyotype reconstruction across 25 fully sequenced genomes. With advanced tools such as Blast, Synteny and Sequence Alignment, the platform provides users with interactive and intuitive visualizations for conducting cross-species comparative genomics. As the first comprehensive pan-genomic resource for the entire Solanaceae family, SoIR facilitates in-depth cross-species analysis, supporting global research initiatives in plant evolution, functional genomics and crop improvement.
PWOs repress gene transcription by regulating chromatin structures in Arabidopsis
Authors: Yang Tingting , Wang Dingyue , Luo Lingxiao , Yin Xiaochang , Song Zhihan , Yang Minqi , Zhou Yue 
Published: November 2024

Abstract
PWWP-DOMAIN INTERACTOR OF POLYCOMBS (PWO) family proteins play a vital role in regulating plant development. However, the molecular mechanisms of how PWOs regulate chromatin structure is elusive. Our data show that the PWO1 binding sites are enriched with positive modifications but exclusive with H3K27me3. Moreover, PWO1 binds to the H3K27me3-enriched compartment domain (H3K27me3-CD) boundary regions, and functions to maintain the boundary strength. Meanwhile, we found that PWOs and Polycomb repressive complex 2 (PRC2) function parallelly in maintaining H3K27me3-CDs’ structure. Loss of either PWOs or PRC2 leads to H3K27me3-CD strength reduction, B to A compartment switching as well as the H3K27me3-CD relocating away from the nuclear periphery. Additionally, PWOs and lamin-like proteins collaborate to regulate multiple chromatin structures to repress gene transcription within H3K27me3-CDs. We conclude that PWOs maintain H3K27me3-CDs’ repressive state and regulate their spatial position in the nucleus.
EPCO-01. FROM HIERARCHY TO GEOGRAPHY: MULTI-CLONES DRIVE THE CELLULAR DIVERSITY AND EVOLUTION OF HUMAN MEDULLOBLASTOMA
Authors: Liu Hailong , Li Jiankang , Jiang Tao 
Published: November 2024

Abstract
We’ve curated a comprehensive multi-omics database of medulloblastoma (MB) serving as a resource to understand spatiotemporal organization and guide therapeutic strategies. Herein, our analysis encompasses single-nucleus transcriptome (n = 51), chromatin accessibility (n = 46), and spatial transcriptomic profiles (n = 31) from human MB samples and patient-derived xenograft lines spanning four subgroups, augmented by bulk RNA (n = 322), whole-genome short-sequencing (n = 279), and bisulfite sequencing (n = 300) from matched samples. We delineate the malignant cellular hierarchy, identifying MB cancer stem-like cells (MB-CSCs), cycling cells, and more differentiated populations. Gene signatures of different cell subpopulations strongly correlate to clinical outcomes, while spatial character of patient-derived materials emphasizes the geographically heterogeneous nature of MB. Examination of somatic copy number variants (CNVs) and transcriptional signatures at single-nucleus resolution reveals geographically defined subclones harboring distinct CNVs, suggesting a competitive agglomeration of co-existing multi-clones for MB. Alongside the trajectorial transition, we observe distinct chromosomal alterations in apical MB-CSCs compared to more differentiated cells, indicative of extensive subclone-primed spatiotemporal evolution. Further analysis of reagent-gene interactions of subclonal lineages contributes to predicting the druggable candidates for treatment optimization. Integration of spatial architecture data highlights the recapitulation of subclone-determined niches through colocation with identified malignant lineages and their own inflammatory or fibrotic adaptions. Taken together, this comprehensive database, comprising five or six kinds of datatypes on the same MB cases, facilitates combinatorial analyses across different genomic modalities, offering genetic and geographic insights into therapeutic advancements.
EPCO-03. METABOLIC INSIGHT INTO GLIOMA HETEROGENEITY: MAPPING WHOLE EXOME SEQUENCING TOIN VIVO IMAGING WITH STEREOTACTIC LOCALIZATION AND DEEP LEARNING
Authors: Servati Mahsa , Cohen-Gadol Aaron A , Parker Jason G 
Published: November 2024

Abstract
Intra-tumoral heterogeneity (ITH) complicates the diagnosis and treatment of glioma, partly due to the diverse metabolic profiles driven by genomic alterations. While multiparametric imaging captures spatial and functional variations enabling ITH characterization, it falls short in assessing the metabolic activities underpinning phenotypic differences. This gap stems from the challenge of integrating easily accessible, co-located pathology and genomic data with metabolic insights. This study presents a multi-faceted approach combining stereotactic biopsy with clinical open-craniotomy for sample collection, voxel-wise analysis of MR images, regression-based GAM, and whole-exome sequencing. The aim is to demonstrate the potential of machine learning algorithms to predict variations in cellular and molecular tumor characteristics. This retrospective study enrolled ten treatment-naïve patients with radiologically confirmed glioma who underwent multiparametric MR scans (T1W, T1W-CE, T2W, T2W-FLAIR, DWI) prior to surgery. During craniotomy, at least one stereotactic biopsy was collected from each patient, with the screenshots of sample locations saved for spatial registration to pre-surgical MR data. Whole-exome sequencing was performed on flash-frozen tumor samples, prioritizing five glioma-related genes: IDH1, TP53, EGFR, PIK3CA, and NF1. Regression was implemented with a GAM using a univariate shape function for each predictor. Standard ROC analyses were used to evaluate detection, with AUC calculated for each gene target and MR contrast combination. Mean AUC for five gene targets and 31 MR contrast combinations was 0.75±0.11, with individual AUCs as high as 0.96 for IDH1 and TP53 with T2W-FLAIR and ADC, and 0.99 for EGFR with T2W and ADC. An average AUC of 0.85 across the five mutations was achieved using the combination of T1W, T2W-FLAIR, and ADC. These results suggest the possibility of predicting exome-wide mutation events from non-invasive, in vivo imaging by combining stereotactic localization of glioma samples with a semi-parametric deep learning method. This approach holds potential for refining targeted therapy by better addressing the genomic heterogeneity of glioma tumors.
EPCO-05. GENOMIC AND CLINICAL INSIGHTS FROM A LARGE-SCALE STUDY OF 172 RETINOBLASTOMAS
Authors: Abedalthagafi Malak , Maktabi Azza , Mesfer Saleh , Zauli Giorgio , Edward Deepak , Liu Yang , Hoehndorf Robert 
Published: November 2024

Abstract
Retinoblastoma, a pediatric ocular cancer, is the only central nervous system tumor visible without specialized tools, readily detectable with the naked eye. This rare childhood cancer is mainly driven by mutations in RB1 or MYCN amplification, posing significant challenges in pediatric oncology. We conducted whole exome sequencing on 172 retinoblastoma tumors along with matched blood DNA from 171 patients, which included 119 unilateral, 49 bilateral, and three trilateral cases. Our analysis identified pathogenic variants in RB1 in 76 patients and MYCN duplication in 79 cases, highlighting their crucial roles in the disease. Additionally, we found mutations in RPTOR and TSC2, components of the mTOR signaling pathway, in two patients. Notably, our copy number alteration analysis revealed recurrent arm-level changes, including gains on 1q (23.3%), 2p (20.9%), and especially 6p (41.3%), along with other changes such as 5p gain (8.1%), 17q gain (8.1%), and 16q loss (5.8%). Our findings link these genetic alterations to specific clinical features; for instance, 6p gains were associated with Rubeosis, subretinal seeds, and tumor LC beyond, while 17q gains were linked to Rubeosis. Furthermore, gene collapsing techniques identified MATR3 and CYP4F2 as additional novel retinoblastoma-related genes, and module identification analysis pinpointed retinoblastoma-associated modules including HLA-DRB1-CBL, LPAR2, RB1, and TRIM28. Our study, the largest cohort of its kind, underscores the importance of next-generation sequencing from understudied populations in uncovering the complex genetic landscape of retinoblastoma, emphasizing the potential of precision medicine to enhance therapeutic strategies and improve outcomes for retinoblastoma patients.
EPCO-09. DICER1-MUTANT PRIMARY INTRACRANIAL SARCOMA: ASSESSING THE ONCOGENIC ROLE OF MIRNA DYSREGULATION
Authors: Dasgupta Pushan , Gubbiotti Maria , Buchold Gregory , Wathoo Chetna , Joseph Jeena , Soomro Zaid , Zahid Anza , Ghia Amol , Ballester Leomar Y , Hirata Kirk , Macaulay Robert , Zhang Xinhai , Meredith David , Calin George , Puduvalli Vinay K 
Published: November 2024

Abstract
Cross-cancer profiling has shown that mutations in human DICER1 are recurrent in diverse cancers including intracranial sarcoma. Due to the rarity of these tumors, treatment options for these patients remain poorly defined. DICER1 encodes an endoribonuclease that processes the hairpin precursor microRNAs (miRNAs) into functionally mature miRNAs. In particular, hotspot mutations in the RNase IIIb domain of DICER1 are predicted to confer an oncogenic role although the precise mechanism is unknown. In a case of a 28-year-old male who presented with multicentric right frontal dural and parenchymal enhancing masses and underwent partial resection, pathology showed a DICER1-mutant primary intracranial sarcoma with a hotspot E1813G mutation in the RNase IIIb domain. Additionally, due to a family history of an unknown fatal brain tumor in his mother, the patient had additional molecular testing which revealed a germline BRCA2 mutation. After surgery, the patient received intensity-modulated radiation therapy followed by 6 cycles of ICE (ifosfamide, carboplatin, etoposide) chemotherapy with significant radiographic response and clinical improvement. He remains progression-free on radiological surveillance for 13 months since diagnosis. The treatment was well tolerated with clinically manageable myelosuppression (including grade 3 thrombocytopenia). This is the first reported case of an adult DICER1-mutant primary intracranial sarcoma patient with a germline BRCA2 mutation although the interaction between these oncogenic mechanisms is unclear. Based on the role of DICER1 in miRNA processing and to test the hypothesize that DICER1 mutations drive primary intracranial sarcoma through dysregulation of miRNA function, we have established a multi-institutional collaboration that is collecting and profiling DICER 1 mutant primary intracranial sarcoma cases from across the United States preliminary results of which will be presented. Identification of a miRNA-driven oncogenic mechanism in these tumors may yield novel targeted approaches beyond intensive chemotherapy for these patients.
EPCO-17. CARM1 METHYLATES GLIOBLASTOMA TUMOR SUPPRESSOR QUAKING TO REGULATE ITS TRANSCRIPTIONAL COACTIVATOR FUNCTION
Authors: Lu Kaylene , Wright Tanner , Shin Seula , Bedford Mark , Hu Jian 
Published: November 2024

Abstract
Glioblastoma (GBM) represents the most prevalent and deadly primary brain tumor in adults, and it remains highly refractory to current therapeutic interventions. Significant intratumor heterogeneity drives rapid invasion, immune escape, and therapeutic resistance. Therapeutic paradigms based on deconvoluting key molecular mechanisms driving gliomagenesis are urgently needed. Quaking (Qki, encoded by Qk) is frequently altered in GBM patients; Qk mutations or deletions occur in 35% percent of cases, and the Qki protein is absent in 50-60% of cases. Our lab has characterized Qki as important tumor suppressor in GBM, where deletion of Qk enables pre-malignant neural stem cells to expand outside their niche and develop into tumors that recapitulate human GBM. We discovered that Qki functions as a transcriptional coactivator of lipid metabolism genes, whereby Qki loss disrupts lipid homeostasis and compromises the integrity of various membrane structures. Several downstream processes governed by Qki have been delineated; however, upstream regulators of Qki have yet to be identified. Recurrent cancer mutations to specific Qki arginine sites implicate the dysregulation of arginine methylation, a common post-translational modification catalyzed by protein arginine methyltransferases (PRMTs). Leveraging in vitro methylation assays, we demonstrate that Qki is selectively methylated by the PRMT coactivator-associated arginine methyltransferase 1 (CARM1), specifically in the Quaking regulatory domain where cancer mutations are reported. We observe that Qki interacts with known CARM1 substrates, functioning in the transcriptional complex assembled by CARM1. Through mutagenesis studies, we identified arginine 242 (R242) and arginine 256 (R256) as specific CARM1-mediated methylation sites on Qki. Importantly, mutations to these sites compromise Qki’s activity as a transcriptional coactivator. Moreover, brain-specific deletion of CARM1 in vivo results in neurological phenotypes reminiscent of Qki deletion. Altogether, we provide evidence that CARM1 represents a novel tumor suppressor in GBM that functions through the arginine methylation of Qki.
EPCO-22. DEEP PHENOTYPING IDENTIFIES TRUNCATING MUTATIONS IN THE NF2 LINKER DOMAIN ASSOCIATED WITH DISEASE SEVERITY IN NEUROFIBROMATOSIS TYPE II
Authors: Asuzu David , Celano Emma , Mullaney Dustin , Mandal Debjani , Elkahloun Abdel , Johnson Kory , Chittiboina Prashant 
Published: November 2024

Abstract

INTRODUCTION
Neurofibromatosis type 2 (NF2) is an autosomal dominant tumor syndrome with protean presentation and variable penetrance. Our objective was to perform deep phenotypic and genetic analysis of a diverse NF2 population to identify predictors of worse clinical outcome.

METHODS
We evaluated 167 patients with NF2 and followed them for a mean duration of 4.5 years. Detailed clinical and radiographic characteristics were collected on each patient, and Karnofsky performance scale (KPS) scores and within-study mortality were monitored. CLIA certified genotyping was supplemented with a custom sequencing panel targeting NF2 and other schwannomatosis-related genes. Outcome predictors were assessed using multivariable linear or logistic regression.

RESULTS
Germline mutations (nonsense 36%, splice-site 16%, and large deletions 16%) were grouped by predicted protein effect (truncating 41%, non-truncating 27%, and mosaic 33%) and mapped to the NF2chromosomal locus. Patients with truncating NF2 mutations had lower mean age of diagnosis (19.9 versus 25.7, P = 0.01) and faster tumor growth rates (2.4% versus 1.1% for all tumors, P = 0.01). Patients whose truncating mutations occurred within the NF2 linker domain (exons 8, 11 and 12) had more total tumors (adjusted coefficient 15.0, 95% CI 0.8 – 29.0, P = 0.04), and specifically more schwannomas (adjusted coefficient 7.0, 95% CI 0.2 – 13.9, P = 0.04). Presence of a-helical domain mutations predicted higher within-study mortality (adjusted OR 4.3, 95% CI 1.1 – 16.2, P = 0.03).

CONCLUSIONS
The NF2 linker domain functions a hinge, facilitating binding between the tail domain and the LATS binding site within the FERM domain. In our study, truncating mutations in the NF2 linker domain were associated with higher tumor burden and over four-fold within-study mortality. The linker domain may constitute a novel therapeutic target in patients with NF2.