bluuebunny/crossref_metadata_2025_split huggingface dataset:
iModulonDB 2.0: dynamic tools to facilitate knowledge-mining and user-enabled analyses of curated transcriptomic datasets
Authors: Catoiu Edward A , Krishnan Jayanth , Li Gaoyuan , Lou Xuwen A , Rychel Kevin , Yuan Yuan , Bajpe Heera , Patel Arjun , Choe Donghui , Shin Jongoh , Burrows Joshua , Phaneuf Patrick V , Zielinski Daniel C , Palsson Bernhard O 
Published: November 2024

Abstract
iModulons—sets of co-expressed genes identified through independent component analysis (ICA) of high-quality transcriptomic datasets—provide an unbiased, modular view of an organism's transcriptional regulatory network. Established in 2020, iModulonDB (iModulonDB.org) serves as a centralized repository of curated iModulon sets, enabling users to explore iModulons and download the associated transcriptomic data. This update reflects a significant expansion of the database—19 new ICA decompositions (+633%) spanning 8 925 expression profiles (+1370%), 503 studies (+2290%) and 12 additional organisms (+400%)—and introduces new features to help scientists decipher the mechanisms governing prokaryotic transcriptional regulation. To facilitate comprehension of the underlying expression profiles, the updated user-interface displays essential information about each data-generating study (e.g. the experimental conditions and publication abstract). Dashboards now include condition-specific coloring and highlight data generated from genetically perturbed strains, enabling users to rapidly interpret disruptions in transcriptional regulation. New interactive graphs rapidly convey omics-derived indicators (e.g. the explained variance of ICA decompositions, genetic overlap between iModulons and regulons). Direct links to operon diagrams (BioCyc) and protein-protein interaction networks (STRING) provide users with seamless access to external resources for further assessment of iModulons. Lastly, a new suite of search-driven and species-wide analysis tools promotes user-engagement with iModulons, reinforcing iModulonDB’s role as a dynamic, interactive knowledgebase of prokaryotic transcriptional regulation.
A genomic database furnishes minimal functional glycyl-tRNA synthetases homologous to other, designed class II urzymes
Authors: Patra Sourav Kumar , Douglas Jordan , Wills Peter R , Betts Laurie , Qing Tang Guo , Carter Charles W 
Published: November 2024

Abstract
The hypothesis that conserved core catalytic sites could represent ancestral aminoacyl-tRNA synthetases (AARS) drove the design of functional TrpRS, LeuRS, and HisRS ‘urzymes’. We describe here new urzymes detected in the genomic record of the arctic fox, Vulpes lagopus. They are homologous to the α-subunit of bacterial heterotetrameric Class II glycyl-tRNA synthetase (GlyRS-B) enzymes. AlphaFold2 predicted that the N-terminal 81 amino acids would adopt a 3D structure nearly identical to our designed HisRS urzyme (HisCA1). We expressed and purified that N-terminal segment and the spliced open reading frame GlyCA1–2. Both exhibit robust single-turnover burst sizes and ATP consumption rates higher than those previously published for HisCA urzymes and comparable to those for LeuAC and TrpAC. GlyCA is more than twice as active in glycine activation by adenosine triphosphate as the full-length GlyRS-B α2 dimer. Michaelis–Menten rate constants for all three substrates reveal significant coupling between Exon2 and both substrates. GlyCA activation favors Class II amino acids that complement those favored by HisCA and LeuAC. Structural features help explain these results. These minimalist GlyRS catalysts are thus homologous to previously described urzymes. Their properties reinforce the notion that urzymes may have the requisite catalytic activities to implement a reduced, ancestral genetic coding alphabet.
CTR-DB 2.0: an updated cancer clinical transcriptome resource, expanding primary drug resistance and newly adding acquired resistance datasets and enhancing the discovery and validation of predictive biomarkers
Authors: Jiang Jianzhou , Ma Yajie , Yang Lele , Ma Shurui , Yu Zixuan , Ren Xinyi , Kong Xiangya , Zhang Xinlei , Li Dong , Liu Zhongyang 
Published: November 2024

Abstract
Drug resistance is a principal limiting factor in cancer treatment. CTR-DB, the Cancer Treatment Response gene signature DataBase, is the first data resource for clinical transcriptomes with cancer treatment response, and meanwhile supports various data analysis functions, providing insights into the molecular determinants of drug resistance. Here we proposed an upgraded version, CTR-DB 2.0 (http://ctrdb.ncpsb.org.cn). Around 190 up-to-date source datasets with primary resistance information (129% increase compared to version 1.0) and 13 acquired-resistant datasets (a new dataset type), covering 10 856 patient samples (111% increase), 39 cancer types (39% increase) and 346 therapeutic regimens (26% increase), have been collected. In terms of function, for the single dataset analysis and multiple-dataset comparison modules, CTR-DB 2.0 added new gene set enrichment, tumor microenvironment (TME) and signature connectivity analysis functions to help elucidate drug resistance mechanisms and their homogeneity/heterogeneity and discover candidate combinational therapies. Furthermore, biomarker-related functions were greatly extended. CTR-DB 2.0 newly supported the validation of cell types in the TME as predictive biomarkers of treatment response, especially the validation of a combinational biomarker panel and even the direct discovery of the optimal biomarker panel using user-customized CTR-DB patient samples. In addition, the analysis of users’ own datasets, application programming interface and data crowdfunding were also added.
Tumor purity estimated from bulk DNA methylation can be used for adjusting beta values of individual samples to better reflect tumor biology
Authors: Sasiain Iñaki , Nacer Deborah F , Aine Mattias , Veerla Srinivas , Staaf Johan 
Published: November 2024

Abstract
Epigenetic deregulation through altered DNA methylation is a fundamental feature of tumorigenesis, but tumor data from bulk tissue samples contain different proportions of malignant and non-malignant cells that may confound the interpretation of DNA methylation values. The adjustment of DNA methylation data based on tumor purity has been proposed to render both genome-wide and gene-specific analyses more precise, but it requires sample purity estimates. Here we present PureBeta, a single-sample statistical framework that uses genome-wide DNA methylation data to first estimate sample purity and then adjust methylation values of individual CpGs to correct for sample impurity. Purity values estimated with the algorithm have high correlation (&gt;0.8) to reference values obtained from DNA sequencing when applied to samples from breast carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Methylation beta values adjusted based on purity estimates have a more binary distribution that better reflects theoretical methylation states, thus facilitating improved biological inference as shown for BRCA1 in breast cancer. PureBeta is a versatile tool that can be used for different Illumina DNA methylation arrays and can be applied to individual samples of different cancer types to enhance biological interpretability of methylation data.
Multidisciplinary management strategies for recurrent brain metastasis after prior radiotherapy: An overview
Authors: Kotecha Rupesh , La Rosa Alonso , Brown Paul D , Vogelbaum Michael A , Navarria Pierina , Bodensohn Raphael , Niyazi Maximilian , Karschnia Philipp , Minniti Giuseppe 
Published: November 2024

Abstract
As cancer patients with intracranial metastatic disease experience increasingly prolonged survival, the diagnosis and management of recurrent brain metastasis pose significant challenges in clinical practice. Prior to deciding upon a management strategy, it is necessary to ascertain whether patients have recurrent/progressive disease vs adverse radiation effect, classify the recurrence as local or distant in the brain, evaluate the extent of intracranial disease (size, number and location of lesions, and brain metastasis velocity), the status of extracranial disease, and enumerate the interval from the last intracranially directed intervention to disease recurrence. A spectrum of salvage local treatment options includes surgery (resection and laser interstitial thermal therapy [LITT]) with or without adjuvant radiotherapy in the forms of external beam radiotherapy, intraoperative radiotherapy, or brachytherapy. Nonoperative salvage local treatments also range from single fraction and fractionated stereotactic radiosurgery (SRS/FSRS) to whole brain radiation therapy (WBRT). Optimal integration of systemic therapies, preferably with central nervous system (CNS) activity, may also require reinterrogation of brain metastasis tissue to identify actionable molecular alterations specific to intracranial progressive disease. Ultimately, the selection of the appropriate management approach necessitates a sophisticated understanding of patient, tumor, and prior treatment-related factors and is often multimodal; hence, interdisciplinary evaluation for such patients is indispensable.
Efficacy of 3D-TSE sequence-based radiosurgery in prolonging time to distant intracranial failure: A session-wise analysis in a histology-diverse patient cohort
Authors: Akdemir Eyub Y , Gurdikyan Selin , Rubens Muni , Abrams Kevin J , Sidani Charif , Chaneles Margaret C , Hall Matthew D , Press Robert H , Wieczorek D Jay , Tolakanahalli Ranjini , Gutierrez Alonso N , Gal Omer , La Rosa Alonso , Kutuk Tugce , McDermott Michael W , Odia Yazmin , Mehta Minesh P , Kotecha Rupesh 
Published: November 2024

Abstract

Background
Stereotactic radiosurgery (SRS) for patients with brain metastases (BM) is associated with a risk of distant intracranial failure (DIF). This study evaluates the impact of integrating dedicated 3D fast/turbo spin echo (3D-TSE) sequences to MPRAGE in BM detection and DIF prolongation in a histology-agnostic patient cohort.

Methods
The study population included adults treated with SRS from February 2019 to January 2024 who underwent MPRAGE alone or dual sequence with the addition of 3D-TSE starting from February 2020. Median times to DIF were estimated using the Kaplan–Meier method.

Results
The 216 study patients who underwent 332 SRS courses for 1456 BM imaged with MPRAGE and 3D-TSE (primary cohort) were compared to a control cohort (92 patients, 135 SRS courses, 462 BM). In the session-wise analysis, the median time to DIF between the cohorts was significantly prolonged in the primary vs. control cohorts (11.4 vs. 6.8 months, P = .029), more pronounced in the subgroups with 1–4 metastases (14.7 vs. 8.1 months, P = .008) and with solitary BM (36.4 vs. 10.9 months, P = .001). While patients relapsing on immunotherapy or targeted therapy did not significantly benefit from 3D-TSE (7.2 vs. 5.7 months, P = .280), those who relapsed on chemotherapy or who were off systemic therapy (including synchronous metastases) exhibited a trend toward longer time to DIF with 3D-TSE integration (14.7 vs. 7.9 months, P = .057).

Conclusions
Implementing 3D-TSE sequences into SRS practice increases BM detection across all patients and translates into clinical relevance by prolonging time to DIF, particularly in those with limited intracranial disease and those not receiving central nervous system-active agents.
Neighborhood disadvantage is associated with treatment access outcomes and survival among individuals with a primary brain tumor
Authors: Stockdill Macy L , Vo Jacqueline B , Celiku Orieta , Kim Yeonju , Karim Zuena , Vera Elizabeth , Miller Hope , Gilbert Mark R , Armstrong Terri S 
Published: November 2024

Abstract

Background
Neighborhood disadvantage is linked to lower rates of healthcare access. To understand how residence affects the primary brain tumor (PBT) population, we assessed neighborhood disadvantage and population density with treatment access outcomes among a cohort of 666 adult participants with a PBT and study entry data in a large observational study at the National Institutes of Health (NIH) (NCT#: NCT02851706).

Methods
We assessed neighborhood disadvantage (measured by the area deprivation index [ADI]) and population density with symptom duration before diagnosis and time to treatment using ordinal logistic and linear regression. Kaplan–Meier survival curves were estimated by population density and ADI, overall and stratified by residential distance to the NIH, tumor grade, and age.

Results
Among 666 participants, 24% lived in more disadvantaged areas. Among the overall sample, there were no associations between ADI or population density with symptom duration, but the time to any treatment was longer for patients living in more disadvantaged neighborhoods (β = 7.78; 95% confidence interval [CI] = 0.02, 15.55), especially among those with low-grade PBTs (β = 36.19; 95%CI = 12.17, 60.20). Time to treatment was longer for those in nonurbanized areas and further from the NIH (β = 0.63; 95% CI = 0.08, 1.17). Patients living in more disadvantaged neighborhoods had higher 5-year survival compared with patients living in less disadvantaged neighborhoods (P = .02).

Conclusions
Individuals with low-grade PBTs living in more disadvantaged neighborhoods and further from NIH had a longer time to treatment. Future efforts should focus on strategies to reach patients living in disadvantaged neighborhoods.
Pegylated liposomal doxorubicin in partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer: a prospective study
Authors: Zhang Ying , Yuan Zhen , Zhang Guo-Nan , Li Qing-Shui , Cui Man-Hua , Cheng Wen-Jun , Meng Yuan-Guang , Wu Xiao-Hua , Yue Ying , Wang Li , Hou Jian-Qing , Li Chang-Zhong , Qu Peng-Peng , Sun Li-Xin , Tao Guang-Shi , Li Gui-Ling , Chen Ya-Qing , Ren Fang , Cao Dong-Yan , Shen Keng 
Published: November 2024

Abstract

Background
This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) for patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer.

Methods
Patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer were recruited in this prospective, open-label, single-arm, multicenter study. Eligible patients were given 4-6 cycles of PLD (40 mg/m2 on day 1, every 4 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. Exploratory endpoints included the change trend of CA125 and platinum-free interval.

Results
Between June 2017 and November 2020, 167 eligible patients were included in the full analysis set. The median PFS and OS were 6.8 months (95% CI, 4.4-9.3 months) and 19.1 months (95% CI, 15.0-23.3 months), respectively. The ORR and DCR were 32.3% and 60.5%, respectively. The ORR (62.3 vs 22.5%) and DCR (84.9 vs 60.7%) of patients with a CA125 decrease after the first cycle were significantly higher than those without a CA125 decrease (all P &lt; .05). Grade ≥ 3 and serious adverse events were reported in 9.9% and 3.9% of patients, respectively. No treatment-related death was observed.

Conclusion
PLD showed promising efficacy and manageable tolerability in patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer.
ClinicalTrials.gov Identifier: Chinese Clinical Trial Registry, ChiCTR1900022962.
ALTERED MERISTEM PROGRAM1 impairs RNA silencing by repressing the biogenesis of a subset of inverted repeat-derived siRNAs
Authors: Li Jing , Le Brandon , Wang Xufeng , Xu Ye , Wang Suikang , Li Hao , Gao Lei , Mo Beixin , Liu Lin , Chen Xuemei 
Published: November 2024

Abstract
RNA silencing negatively regulates gene expression at the transcriptional and posttranscriptional levels through DNA methylation, histone modification, mRNA cleavage, and translational inhibition. Small interfering RNAs (siRNAs) of 21 to 24 nucleotides are processed from double-stranded RNAs by Dicer-like (DCL) enzymes and play essential roles in RNA silencing in plants. Here, we demonstrated that ALTERED MERISTEM PROGRAM1 (AMP1) and its putative paralog LIKE AMP1 (LAMP1) impair RNA silencing by repressing the biogenesis of a subset of inverted repeat (IR)-derived siRNAs in Arabidopsis (Arabidopsis thaliana). AMP1 and LAMP1 inhibit Pol II-dependent IR gene transcription by suppressing ARGONAUTE 1 (AGO1) protein levels. Genetic analysis indicates that AMP1 acts upstream of RNA polymerase IV subunit 1 (NRPD1), RNA-dependent RNA polymerase 2 (RDR2), and DCL4, which are required for IR-induced RNA silencing. We also show that AMP1 and LAMP1 inhibit siRNA-mediated silencing in a different mechanism from that of AGO4 and DCL3. Together, these results reveal two previously unknown players in siRNA biogenesis from IRs-AGO1, which promotes IR transcription, and AMP1, which inhibits IR transcription indirectly through the repression of AGO1 expression.
The Real Guarantee in De Se thought: How to characterize it?
Authors: García-Carpintero Manuel 
Published: November 2024

Abstract
Castañeda, Perry and Lewis argued that, among singular thoughts in general, thoughts about oneself ‘as oneself’—first-personal thoughts, which Lewis aptly called de se—have a distinctive character that traditional views of contents cannot characterize. Drawing on Anscombe, Annalisa Coliva has argued that a feature she calls Real Guarantee marks apart de se thoughts—as opposed to others including Immunity to Error through Misidentification that have been proposed for that role. I'll argue that, while her work points to a truly distinguishing feature of the de se, we need an account of the notion other than hers and Echeverri's recent development of it. I'll offer an alternative, drawing on Léa Salje's work. Finally, I'll briefly outline how, thus understood, the Real Guarantee feature could be adequately explained by theories of de se thoughts like the one I favour, even if it is an open option to just explain it away.
Ending a special relationship: Toward an ethics of divorce
Authors: Betzler Monika 
Published: November 2024

Abstract
Romantic partnerships are typically among the most important goods in our lives. But love sometime ends, and so too do relationships. Divorcing partners are particularly vulnerable to being wronged and harmed. The aim of this paper is to develop an ethics of divorce, by establishing that divorce is a condition for the possibility of the distinct value of romantic partnerships. Different sets of rights are specified here: the divorcee's right to explanation, the right to participation and the right to transitional goods; and the divorcer's right to relational freedom. Violations of these rights indicate the distinct wrongs and harms of divorce. The paper then explains the corresponding duties in divorce that might avoid these wrongs and mitigate these harms, and highlights the distinct status of these duties: while they continue to be special, they are residual duties grounded in the fact that the partners once committed to their partnership.
Post-intervention control in HIV immunotherapy trials
Authors: Sandel Demi A. , Rutishauser Rachel L. , Peluso Michael J. 
Published: November 2024

Purpose of review
While post-treatment control following interruption of standard-of-care antiretroviral therapy (ART) is well described, post-intervention control following immunotherapy in HIV cure-related clinical trials is less well understood. We provide an overview of recent studies that have identified post-intervention controllers and review the mechanisms that may drive this biologically important phenotype.

Recent findings
Post-intervention controllers have been identified in recent immunotherapy trials testing broadly neutralizing antibodies, immune modulators, modified T cells, checkpoint inhibitors, and gene therapy administered individually or in combination. Currently, there is substantial variability in how each trial defines post-intervention control, as well as in how the mechanisms underlying such control are evaluated. Such mechanisms include ongoing activity of both exogenous and autologous antibodies, as well as changes in HIV-specific T cell function.

Summary
While no therapeutic strategy to date has succeeded in definitively inducing HIV control, many studies have identified at least a small number of post-intervention controllers. The field would benefit from a standardized approach to defining and reporting this phenotype, as well as standardization in the approach to assessment of how it is achieved. Such efforts would allow for comparisons across clinical trials and could help accelerate efforts toward an HIV cure.
Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Liver Cirrhosis
Authors: Chou Tien-Shin , Lin Yuan , Tsai Ming-Lung , Tseng Chin-Ju , Dai Jhih-Wei , Yang Ning-I , Lin Chih-Lang , Chen Li-Wei , Hung Ming-Jui , Chen Tien-Hsing 
Published: November 2024

Objective:
Comparing direct oral anticoagulants (DOACs) and warfarin’s efficacy and safety in patients with nonvalvular atrial fibrillation (AF) and liver cirrhosis (LC).

Background:
Evidence of the pharmacodynamics of DOACs is limited in patients with AF and LC.

Methods:
A retrospective cohort study was conducted in the largest hospital system in Taiwan, involving patients with AF and LC for the years 2012 to 2021. Hazards of thromboembolic events (ischemic stroke, transient ischemic attack, and systemic embolism), intracranial hemorrhage, gastrointestinal, major bleeding, and all-cause mortality were investigated with a new-user, active comparator design. Inverse probability of treatment weighting was applied to balance potential confounders between treatment groups.

Results:
In total, 478 DOAC users and 247 warfarin users were included. DOACs and warfarin demonstrated similar trends in preventing thromboembolic events, namely ischemic stroke [adjusted hazard ratio (aHR), 1.05 (95% CI: 0.42-2.61)], transient ischemic attack [aHR, 1.36 (95% CI: 0.18-10.31)], and systemic embolism [aHR, 0.49 (95% CI: 0.14-1.70)]. DOAC use was associated with a similar risk of intracranial hemorrhage [aHR, 0.65 (95% CI: 0.26-1.59)] and gastrointestinal bleeding [aHR, 0.64 (95% CI: 0.39-1.03)], a decreased risk of major bleeding [aHR, 0.64 (95% CI: 0.42-0.99)], and a reduction in mortality [aHR, 0.73 (95% CI: 0.54-0.99)]. DOAC users exhibited a significant reduction in major bleeding risk in patients with Child-Pugh class A (aHR, 0.48; 95% CI: 0.33-0.70).

Conclusions:
DOACs showed potential safety advantages over warfarin for patients with nonvalvular AF and LC, particularly in reducing major bleeding risk in those with Child-Pugh class A.