bluuebunny/crossref_metadata_2025_split huggingface dataset:
The epigenetic landscape of brain metastasis
Authors: Powell Aoibhín M. , Watson Louise , Luzietti Lara , Prekovic Stefan , Young Leonie S. , Varešlija Damir 
Published: February 2025

Abstract
Brain metastasis represents a significant challenge in oncology, driven by complex molecular and epigenetic mechanisms that distinguish it from primary tumors. While recent research has focused on identifying genomic mutation drivers with potential clinical utility, these strategies have not pinpointed specific genetic mutations responsible for site-specific metastasis to the brain. It is now clear that successful brain colonization by metastatic cancer cells requires intricate interactions with the brain tumor ecosystem and the acquisition of specialized molecular traits that facilitate their adaptation to this highly selective environment. This is best exemplified by widespread transcriptional adaptation during brain metastasis, resulting in aberrant gene programs that promote extravasation, seeding, and colonization of the brain. Increasing evidence suggests that epigenetic mechanisms play a significant role in shaping these pro-brain metastasis traits. This review explores dysregulated chromatin patterns driven by chromatin remodeling, histone modifications, DNA/RNA methylation, and other epigenetic regulators that underpin brain metastatic seeding, initiation, and outgrowth. We provide novel insights into how these epigenetic modifications arise within both the brain metastatic tumor and the surrounding brain metastatic tumor ecosystem. Finally, we discuss how the inherent plasticity and reversibility of the epigenomic landscape in brain metastases may offer new therapeutic opportunities.
PSMD14-mediated deubiquitination of CARM1 facilitates the proliferation and metastasis of hepatocellular carcinoma by inducing the transcriptional activation of FERMT1
Authors: Lu Jing , Wu Huita , Zhan Ping , Lu Yuyan , Fang Qinliang , Luo Changhong , Wang Fuqiang , Wen Jing , Xie Chengrong , Yin Zhenyu 
Published: February 2025

Abstract
Hepatocellular carcinoma (HCC) is a highly potent malignancy. The enzyme coactivator-associated arginine methyltransferase 1 (CARM1) is highly expressed in different types of cancer. However, the precise levels of expression, clinical significance, biological functions, and molecular mechanisms of CARM1 in HCC, particularly related to the downstream genes regulated by CARM1 through histone arginine methylation, remain unclear. In this study, we presented findings from the TCGA database and clinical samples, which collectively demonstrated the overexpression of CARM1 in HCC. Additionally, we found that the upregulation of CARM1 was mediated by PSMD14-induced deubiquitination. CARM1 promoted the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistic investigations further revealed that FERMT1 is a downstream gene of CARM1, and CARM1 activates the transcription of FERMT1 through the dimethylation of arginine 17 on histone 3 (H3R17me2). Additionally, administering SGC2085, a CARM1 inhibitor, effectively suppressed the malignant behaviors of HCC cells. To summarize, our findings provided strong evidence that CARM1 can serve as a key oncoprotein; thus, it holds promise as a therapeutic target for HCC.
MicroRNA-379-5p attenuates cancer stem cells and reduces cisplatin resistance in ovarian cancer by regulating RAD18/Polη axis
Authors: Shukla Devendra , Mishra Sanjay , Mandal Tanima , Charan Manish , Verma Ajeet Kumar , Khan Md Maqsood Ahamad , Chatterjee Nabanita , Dixit Amit Kumar , Ganesan Senthil Kumar , Ganju Ramesh K. , Srivastava Amit Kumar 
Published: February 2025

Abstract
Ovarian cancer (OC) is an aggressive malignancy of the female reproductive organs, associated with a low 5-year survival rate. Emerging evidence suggests the pivotal role of microRNAs (miRNAs) in regulating chemoresistance and metastasis in OC, primarily through cancer stem cells (CSCs), also known as cancer stem-like cells (CSLCs). Herein, we demonstrate that miR-379-5p is downregulated in several OC cell populations including both cell lines and patient tumor samples. Furthermore, overexpression of miR-379-5p effectively inhibits CSCs and counteracts cisplatin-induced expansion of CSCs. Further mechanistic investigations identify RAD18, a DNA repair protein involved in translesion DNA synthesis (TLS), as a direct target of miR-379-5p. Moreover, a negative correlation between miR-379-5p and RAD18 expression is observed in ovarian CSCs isolated from OC patients. The downregulation of RAD18 inhibits stem-like phenotypes and enhances the sensitivity of ovarian CSCs to cisplatin treatment. Importantly, miR-379-5p-mediated inhibition of RAD18 prevents the repair synthesis in CSCs by promoting the accumulation of DNA damage. In vivo studies further reveal that miR-379-5p enhances DNA damage, which, in turn, inhibits tumor cell proliferation in athymic nude mice. Remarkably, targeting of RAD18 by miR-379-5p prevents monoubiquitination of proliferating cell nuclear antigen (PCNA), resulting in reduced DNA Polymerase η (a TLS polymerase that helps to bypass DNA lesions) recruitment to lesion sites. In the absence of Polη, the persisting DNA lesions cause activation of cell cycle arrest and apoptosis pathway in CSCs. Therefore, our findings unveil a novel mechanism whereby miR-379-5p overexpression curtails CSCs by modulating the RAD18/Polη axis.
Predicting the need for diabetic macular oedema treatment from photographic screening in the Singapore Integrated Diabetic Retinopathy Programme (SiDRP)
Authors: Poh Stanley S. J. , Teo Kelvin Y. C. , Goh Rose Ann , Lee Qian Xin , Hamzah Haslina , Sim Serene S. C. , Tan Colin S. , Tan Ngiap Chuan , Wong Tien Yin , Tan Gavin S. W. 
Published: February 2025

Abstract

Objective
To identify diabetic maculopathy features from photographic screening that are predictive of treatment on referral to a tertiary care centre.

Methods
Retrospective review of participants who underwent screening by Singapore Integrated Diabetic Retinopathy Programme from 2015 to 2019. Participants underwent visual acuity (VA) test and non-stereoscopic retinal photographs. Maculopathy features include haemorrhages, microaneurysm and hard exudates (HE), stratified by inner and outer zone (1 and 1-2 disc diameter from fovea respectively) and VA of 6/12. Diabetic macular oedema (DMO) treatment was defined as intravitreal injection or macular photocoagulation up to 540 days from point of referral.

Results
16,712 patients screened had referable eye disease. Out of 3518 maculopathy suspects, 281 (8.0%) received DMO treatment within 540 days. Those treated for DMO had shorter duration of diabetes (6.90 vs. 9.13 years, p < 0.001), higher total cholesterol (4.65 ± 1.20 vs. 4.36 ± 1.13 mmol/L, p = 0.001) and LDL cholesterol (2.59 ± 1.05 vs. 2.37 ± 0.93 mmol/L, p < 0.05) than those without treatment. High-risk features, including inner zone haemorrhages with VA ≤ 6/12 (HR 12.0, 95% CI: 5.5–25.9) and inner zone hard exudates (HR 7.4, 95% CI: 3.4–15.8), significantly increased the likelihood of requiring DMO treatment compared to low-risk features. Higher body mass index is protective of DMO treatment in mild non-proliferative diabetic retinopathy (HR 0.84, 95% CI: 0.73–0.97).

Conclusion
Haemorrhages, microaneurysms and HE within inner zone are important photographic features predictive of DMO treatment. VA is an important stratification for screening especially in patients with only visible haemorrhages.
Direct observation of ultrafast symmetry reduction during internal conversion of 2-thiouracil using Coulomb explosion imaging
Authors: Jahnke Till , Mai Sebastian , Bhattacharyya Surjendu , Chen Keyu , Boll Rebecca , Castellani Maria Elena , Dold Simon , Frühling Ulrike , Green Alice E. , Ilchen Markus , Ingle Rebecca , Kastirke Gregor , Lam Huynh Van Sa , Lever Fabiano , Mayer Dennis , Mazza Tommaso , Mullins Terence , Ovcharenko Yevheniy , Senfftleben Björn , Trinter Florian , Atia-Tul-Noor  , Usenko Sergey , Venkatachalam Anbu Selvam , Rudenko Artem , Rolles Daniel , Meyer Michael , Ibrahim Heide , Gühr Markus 
Published: February 2025

Abstract
The photochemistry of heterocyclic molecules plays a decisive role for processes and applications like DNA photo-protection from UV damage and organic photocatalysis. The photochemical reactivity of heterocycles is determined by the redistribution of photoenergy into electronic and nuclear degrees of freedom, initially involving ultrafast internal conversion. Most heterocycles are planar in their ground state and internal conversion requires symmetry breaking. To lower the symmetry, the molecule must undergo an out-of-plane motion, which has not yet been observed directly. Here we show using the example of 2-thiouracil, how Coulomb explosion imaging can be utilized to extract comprehensive information on this molecular deformation, linking the extracted deplanarization of the molecular geometry to the previously studied temporal evolution of its electronic properties. Particularly, the protons of the exploded molecule are well-suited messengers carrying rich information on its geometry at distinct times after electronic excitation. We expect that our new analysis approach centered on these peripheral protons can be adapted as a general concept for future time-resolved studies of complex molecules in the gas phase.
Aspirin-responsive gene switch regulating therapeutic protein expression
Authors: Huang Jinbo , Teixeira Ana Palma , Gao Ting , Xue Shuai , Xie Mingqi , Fussenegger Martin 
Published: February 2025

Abstract
Current small-molecule-regulated synthetic gene switches face clinical limitations such as cytotoxicity, long-term side-effects and metabolic disturbances. Here, we describe an advanced synthetic platform inducible by risk-free input medication (ASPIRIN), which is activated by acetylsalicylic acid (ASA/aspirin), a multifunctional drug with pain-relieving, anti-inflammatory, and cardiovascular benefits. To construct ASPIRIN, we repurpose plant salicylic acid receptors NPR1 and NPR4. Through domain truncations and high-throughput mutant library screening, we enhance their ASA sensitivity. Optimized NPR1 fused with a membrane-tethering myristoylation signal (Myr-NPR1) forms a complex with NPR4, which is fused with a DNA binding domain (VanR) and a transactivation domain (VP16). ASA induces dissociation of the Myr-NPR1/NPR4-VanR-VP16 complex, allowing nuclear translocation of NPR4-VanR-VP16 to activate VanR-operator-controlled gene expression. In male diabetic mice implanted with microencapsulated ASPIRIN-engineered cells, ASA regulates insulin expression, restores normoglycemia, alleviates pain and reduces biomarkers of diabetic neuropathy and inflammation. We envision this system will pave the way for aspirin-based combination gene therapies.
Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma
Authors: Long Georgina V. , Shklovskaya Elena , Satgunaseelan Laveniya , Mao Yizhe , da Silva Inês Pires , Perry Kristen A. , Diefenbach Russell J. , Gide Tuba N. , Shivalingam Brindha , Buckland Michael E. , Gonzalez Maria , Caixeiro Nicole , Vergara Ismael A. , Bai Xinyu , Rawson Robert V. , Hsiao Edward , Palendira Umaimainthan , Phan Tri Giang , Menzies Alexander M. , Carlino Matteo S. , Quek Camelia , Grimmond Sean M. , Vissers Joseph H. A. , Yeo Dannel , Rasko John E. J. , Khasraw Mustafa , Neyns Bart , Reardon David A. , Ashley David M. , Wheeler Helen , Back Michael , Scolyer Richard A. , Drummond James , Wilmott James S. , Rizos Helen 
Published: February 2025

Abstract
Glioblastoma (GBM) is an aggressive primary adult brain tumor that rapidly recurs after standard-of-care treatments, including surgery, chemotherapy and radiotherapy. While immune checkpoint inhibitor therapies have transformed outcomes in many tumor types, particularly when used neoadjuvantly or as a first-line treatment, including in melanoma brain metastases, they have shown limited efficacy in patients with resected or recurrent GBM. The lack of efficacy has been attributed to the scarcity of tumor-infiltrating lymphocytes (TILs), an immunosuppressive tumor microenvironment and low tumor mutation burden typical of GBM tumors, plus exclusion of large molecules from the brain parenchyma. We hypothesized that upfront neoadjuvant combination immunotherapy, administered with disease in situ, could induce a stronger immune response than treatment given after resection or after recurrence. Here, we present a case of newly diagnosed IDH-wild-type, MGMT promoter unmethylated GBM, treated with a single dose of neoadjuvant triplet immunotherapy (anti-programmed cell death protein 1 plus anti-cytotoxic T-lymphocyte protein 4 plus anti-lymphocyte-activation gene 3) followed by maximal safe resection 12 days later. The anti-programmed cell death protein 1 drug was bound to TILs in the resected GBM and there was marked TIL infiltration and activation compared with the baseline biopsy. After 17 months, there is no definitive sign of recurrence. If used first line, before safe maximal resection, checkpoint inhibitors are capable of immune activation in GBM and may induce a response. A clinical trial of first-line neoadjuvant combination checkpoint inhibitor therapy in newly diagnosed GBM is planned (GIANT; trial registration no. NCT06816927).
An annotated haplotype-resolved genome sequence assembly of diploid German chamomile, Matricaria chamomilla
Authors: Cho Woohyeon , Feng Jiawu , Knauft Manuela , Albrecht Sebastian , Himmelbach Axel , Otto Lars-Gernot , Mascher Martin 
Published: February 2025

Abstract

Matricaria chamomilla L. (chamomile) is a medicinal plant that is widely used for treating skin infections and respiratory ailments. Chamomile belongs to the Asteraceae family of flowering plants and is a primarily outcrossing species with a heterozygous genome. Despite its extensive use, no reference genome has been available for chamomile until now. We present a chromosome-level genome sequence for chamomile which was assembled with TRITEX pipeline from PacBio accurate long reads and chromosome conformation capture sequencing data. The assembled pseudo-haploid genome has a total size of 2.75 Gb, organized into 9 chromosomes with a scaffold N50 of 285 Mb. This high-quality reference genome has a BUSCO value of 98.8% and includes 47,820 functional genes. Additionally, we assembled a haplotype-resolved genome, taking advantage of the high heterozygosity of chamomile. The haplotype assemblies have total sizes of 2.28 Gb and 2.34 Gb and cover 87.6% and 89.8% of the pseudo-haploid reference genome, respectively. Our assemblies provide a valuable resource for genetics and genomics works for chamomile and related members of the Asteraceae.
Enhanced object detection in remote sensing images by applying metaheuristic and hybrid metaheuristic optimizers to YOLOv7 and YOLOv8
Authors: Elgamily Khaled Mohammed , Mohamed M. A. , Abou-Taleb Ahmed Mohamed , Ata Mohamed Maher 
Published: February 2025

Abstract
Developments in object detection algorithms are critical for urban planning, environmental monitoring, surveillance, and many other applications. The primary objective of the article was to improve detection precision and model efficiency. The paper compared the performance of six different metaheuristic optimization algorithms including Gray Wolf Optimizer (GWO), Particle Swarm Optimization (PSO), Genetic Algorithm (GA), Remora Optimization Algorithm (ROA), Aquila Optimizer (AO), and Hybrid PSO–GWO (HPSGWO) combined with YOLOv7 and YOLOv8. The study included two distinct remote sensing datasets, RSOD and VHR-10. Many performance measures as precision, recall, and mean average precision (mAP) were used during the training, validation, and testing processes, as well as the fit score. The results show significant improvements in both YOLO variants following optimization using these strategies. The GWO-optimized YOLOv7 with 0.96 mAP 50, and 0.69 mAP 50:95, and the HPSGWO-optimized YOLOv8 with 0.97 mAP 50, and 0.72 mAP 50:95 had the best performance in the RSOD dataset. Similarly, the GWO-optimized versions of YOLOv7 and YOLOv8 had the best performance on the VHR-10 dataset with 0.87 mAP 50, and 0.58 mAP 50:95 for YOLOv7 and with 0.99 mAP 50, and 0.69 mAP 50:95 for YOLOv8, indicating greater performance. The findings supported the usefulness of metaheuristic optimization in increasing the precision and recall rates of YOLO algorithms and demonstrated major significance in improving object recognition tasks in remote sensing imaging, opening up a viable route for applications in a variety of disciplines.
Smart distributed data factory volunteer computing platform for active learning-driven molecular data acquisition
Authors: Ghukasyan Tsolak , Altunyan Vahagn , Bughdaryan Aram , Aghajanyan Tigran , Smbatyan Khachik , Papoian Garegin A. , Petrosyan Garik 
Published: February 2025

Abstract
This paper presents the smart distributed data factory (SDDF), an AI-driven distributed computing platform designed to address challenges in drug discovery by creating comprehensive datasets of molecular conformations and their properties. SDDF uses volunteer computing, leveraging the processing power of personal computers worldwide to accelerate quantum chemistry (DFT) calculations. To tackle the vast chemical space and limited high-quality data, SDDF employs an ensemble of machine learning (ML) models to predict molecular properties and selectively choose the most challenging data points for further DFT calculations. The platform also generates new molecular conformations using molecular dynamics with the forces derived from these models. SDDF makes several contributions: the volunteer computing platform for DFT calculations; an active learning framework for constructing a dataset of molecular conformations; a large public dataset of diverse ENAMINE molecules with calculated energies; an ensemble of ML models for accurate energy prediction. The energy dataset was generated to validate the SDDF approach of reducing the need for extensive calculations. With its strict scaffold split, the dataset can be used for training and benchmarking energy models. By combining active learning, distributed computing, and quantum chemistry, SDDF offers a scalable, cost-effective solution for developing accurate molecular models and ultimately accelerating drug discovery.
Equatorial convection controls boreal summer intraseasonal oscillations in the present and future climates
Authors: Kottapalli Aditya , Vinayachandran P. N. 
Published: February 2025

Abstract
The boreal summer intraseasonal oscillation (BSISO) is the major mode of tropical intraseasonal variability during the Indian summer monsoon (ISM), it partly controls the dry and wet spells of the ISM and thus is crucial for agricultural yield in the country. Understanding the future of BSISO is essential as it has been established recently that the large-scale BSISO environment enhances the probability of extreme rainfall events enormously. In this study, the ability of Coupled Model Inter Comparison Project Phase 6 (CMIP6) models to capture the northward propagation of boreal summer intraseasonal oscillation (BSISO) is examined using a counting algorithm. A composite moisture budget reveals the difference in moisture dynamics between the above-average-performing (AAPM) and below-average-performing (BAPM) models. The AAPM composite has a stronger horizontal moisture advection ahead of the convection centre than the BAPM composite. The weaker wind and moisture perturbations in the BAPM mainly cause this difference in the horizontal moisture advection between AAPM and BAPM. The BAPM composite shows a weaker equatorial convection signal compared to the AAPM composite, resulting in weaker wind and moisture perturbations and a lesser number of northward propagations. Finally, we understand the future of BSISO by examining the projections of Shared Socioeconomic Pathways 370 (SSP370) from the available AAPMs. The background moisture will be enhanced uniformly in the future, leading to no substantial change in gradients. The equatorial convection amplifies and broadens in the future projections, leading to very little change in the wind perturbations. This results in the enhancement of BSISO rainfall by 63% in the Bay of Bengal and 42% in the Arabian Sea. However, the proportion of northward propagations remains the same as moisture advection remains the same. The study implies that with a correct representation of BSISO’s equatorial convection, the prediction of BSISO and extreme rainfall associated with BSISOs becomes more reliable.
FABP5 is a key player in metabolic modulation and NF-κB dependent inflammation driving pleural mesothelioma
Authors: Vecchio Eleonora , Gallo Raffaella , Mimmi Selena , Gentile Debora , Giordano Caterina , Straface Emilio , Marino Rossana , Caiazza Carmen , Pastore Arianna , Ruocco Maria Rosaria , Arcucci Alessandro , Schiavone Marco , Palmieri Camillo , Iaccino Enrico , Stornaiuolo Mariano , Quinto Ileana , Mallardo Massimo , Martini Fernanda , Tognon Mauro , Fiume Giuseppe 
Published: February 2025

Abstract
Pleural mesothelioma (PM) poses a significant challenge in oncology due to its intricate molecular and metabolic landscape, chronic inflammation, and heightened oxidative stress, which contribute to its notorious resilience and clinical complexities. Despite advancements, the precise mechanisms driving PM carcinogenesis remain elusive, impeding therapeutic progress. Here, we explore the interplay between tumor growth dynamics, lipid metabolism, and NF-κB dysregulation in malignant pleural mesothelioma, shedding light on novel molecular mechanisms underlying its pathogenesis. Our study reveals distinctive growth dynamics in PM cells, characterized by heightened proliferation, altered cell cycle progression, and resistance to apoptosis. Intriguingly, PM cells exhibit increased intracellular accumulation of myristic, palmitic, and stearic acids, suggestive of augmented lipid uptake and altered biosynthesis. Notably, we identify FABP5 as a key player in driving metabolic alterations and inflammation through NF-κB dysregulation in mesothelioma cells, distinguishing them from normal mesothelial cells. Silencing of FABP5 leads to significant alterations in cell dynamics, metabolism, and NF-κB activity, highlighting its potential as a therapeutic target. Our findings unveil a reciprocal relationship between lipid metabolism and inflammation in PM, providing a foundation for targeted therapeutic strategies. Overall, this comprehensive investigation offers insights into the intricate molecular mechanisms driving PM pathogenesis and identifies potential avenues for therapeutic intervention.
Clinical lactation studies. Acting on key recommendations over the last decade
Authors: Rowland Yeo Karen , Gerhart Jacqueline , Sawant-Basak Aarti , Ojara Francis Williams , Kawuma Aida N. , Waitt Catriona 
Published: February 2025

Abstract
Including lactating women in clinical trials is imperative to generate relevant drug exposure and safety data needed to advise on clinical use of drugs in this understudied population. Recent changes in perspectives, regulatory guidance, and international networks which outline pragmatic approaches for advancing the conduct of clinical lactation studies are discussed. Case studies demonstrating successful application of modeling and simulation to complement clinical lactation data for enhanced knowledge of infant drug exposure are presented.