bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical Properties of Quasi‐Periodic Electromagnetic Ion Cyclotron Waves: ULF Modulation Effects
Authors: Shahid Muhammad , Bashir M. Fraz , Artemyev A. V. , Zhang X.‐J. , Angelopoulos Vassilis , Murtaza G. 
Published: November 2024

AbstractElectromagnetic ion cyclotron (EMIC) waves effectively scatter relativistic electrons in Earth's radiation belts and energetic ions in the ring current. Empirical models parameterizing the EMIC wave characteristics are important elements of inner magnetosphere simulations. Two main EMIC wave populations included in such simulations are the population generated by plasma sheet injections and another population generated by magnetospheric compression due to the solar wind. In this study, we investigate a third class of EMIC waves, generated by hot plasma sheet ions modulated by compressional ultra‐low frequency (ULF) waves. Such ULF‐modulated EMIC waves are mostly observed on the dayside, between magnetopause and the outer radiation belt edge. We show that ULF‐modulated EMIC waves are weakly oblique (with a wave normal angle ) and narrow‐banded (with a spectral width of of the mean frequency). We construct an empirical model of the EMIC wave characteristics as a function of ‐shell and MLT. The low ratio of electron plasma frequency to electron gyrofrequency around the EMIC wave generation region does not allow these waves to scatter energetic electrons. However, these waves provide very effective (comparable to strong diffusion) quasi‐periodic precipitation of plasma sheet protons.
Variation of the Altitude of Auroral Emission During a Substorm Cycle: Stereoscopic Optical Observations During the LAMP Rocket Experiment
Authors: Hosokawa K. , Miyoshi Y. , Mcharg M. , Ledvina V. , Hampton D. , Lessard M. , Shumko M. , Asamura K. , Sakanoi T. , Mitani T. , Namekawa T. , Nosé M. , Ogawa Y. , Jaynes A. , Halford A. 
Published: November 2024

AbstractWe estimated the altitude of aurora by combining data from all‐sky cameras at multiple places which were obtained during the LAMP sounding rocket experiment in Alaska on 5 March 2022. During the launch window of the rocket, three high‐speed all‐sky cameras were operative at three stations immediately below the trajectory of the rocket: Poker Flat, Venetie and Fort Yukon. The all‐sky cameras captured all‐sky images with a temporal resolution of 100 Hz (80 Hz for the Fort Yukon case). The method of altitude determination is based on analyses of time‐series of the optical intensity obtained from the all‐sky cameras in Venetie and Poker Flat covering the downrange area of the rocket trajectory. The estimated altitude of pulsating aurora during the rocket experiment was found to be consistent with that derived from the in‐situ observation of precipitating electrons with a model of optical emission, which confirms the feasibility of deriving the emission altitude through correlation analyses using time‐series. The estimated altitude of aurora decreased after the expansion onset of the substorm and stayed slightly below 100 km during the interval of pulsating aurora in the recovery phase. In particular, prompt and brief lowering of the auroral emission, well down to around 90 km, was detected during a transition of auroral form from discrete to diffuse which occurred ∼10 min after the onset. This result implies an existence of a process causing harder electron precipitation operative soon after the start of the expansion phase of auroral substorm.
LncRNA MALAT1 promotes Erastin-induced ferroptosis in the HBV-infected diffuse large B-cell lymphoma
Authors: Bai Xiaofei , Li Jianguo , Guo Xuecong , Huang Yinghui , Xu Xu , Tan Ailing , Jia Yisha , Sun Qiaoyi , Guo Xudong , Chen Jie , Kang Jiuhong 
Published: November 2024

AbstractIn a retrospective analysis of clinical data from 587 DLBCL (diffuse large B-cell lymphoma) patients in China, 13.8% of cases were associated with HBV (hepatitis B virus) infection, leading to distinct clinical features and poorer prognosis. Moreover, HBV infection has a more pronounced impact on the survival of the GCB (germinal center B-cell-like) type DLBCL patients compared to the ABC (activated B-cell-like) type. In this study, we found that the expression of LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was downregulated in the HBV-infected GCB-type DLBCL patients, and the HBV core protein (HBX) directly inhibited the MALAT1 expression in DLBCL cells. Notably, the overexpression of HBX could attenuate the Erastin-induced ferroptosis in the GCB-type DLBCLs, while MALAT1 re-expression restored sensitivity in the HBX-overexpressing DLBCLs in vitro and in vivo. Mechanistically, MALAT1 competitively hindered SFPQ (splicing factor proline and glutamine-rich) from effectively splicing the pre-mRNA of SLC7A11 (solute carrier family 7 member 11), due to a shared TTGGTCT motif, which impeded the SLC7A11 pre-mRNA maturation and hence diminished its negative regulation on ferroptosis. Together, our study identified HBX’s role in inhibiting MALAT1 expression, promoting SFPQ-mediated splicing of SLC7A11 pre-mRNA, and reducing the GCB-type DLBCL sensitivity to Erastin-induced ferroptosis. Combined with the recent studies that ferroptosis may be involved in the occurrence and development of DLBCL, these findings explain our clinical data analysis that DLBCL patients with low expression of MALAT1 have poorer prognosis and shorter overall survival, and provide a valuable therapeutic target for the HBV-infected GCB-type DLBCL patients.
Cancer cells sense solid stress to enhance metastasis by CKAP4 phase separation-mediated microtubule branching
Authors: Sun Xing , Zhou Yangyang , Sun Shengjie , Qiu Siyuan , Peng Menglan , Gong Han , Guo Junxiao , Wen Chengcai , Zhang Yibin , Xie Yifang , Li Hui , Liang Long , Luo Guoyan , Wu Wencan , Liu Jing , Tan Weihong , Ye Mao 
Published: November 2024

AbstractSolid stress, originating from rigid and elastic components of extracellular matrix and cells, is a typical physical hallmark of tumors. Mounting evidence indicates that elevated solid stress drives metastasis and affects prognosis. However, the molecular mechanism of how cancer cells sense solid stress, thereby exacerbating malignancy, remains elusive. In this study, our clinical data suggest that elevated stress in metastatic solid tumors is highly associated with the expression of cytoskeleton-associated protein 4 (CKAP4). Intriguingly, CKAP4, as a sensitive intracellular mechanosensor, responds specifically to solid stress in a subset of studied tumor micro-environmental elements through liquid–liquid phase separation. These micron-scaled CKAP4 puncta adhere tightly onto microtubules and dramatically reorchestrate their curvature and branching to enhance cell spreading, which, as a result, boosts cancer cell motility and facilitates distant metastasis in vivo. Mechanistically, the intrinsically disordered region 1 (IDR1) of CKAP4 binds to microtubules, while IDR2 governs phase separation due to the Cav1.2-dependent calcium influx, which collectively remodels microtubules. These findings reveal an unprecedented mechanism of how cancer cells sense solid stress for cancer malignancy and bridge the gap between cancer physics and cancer cell biology.
Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial
Authors: Baretti Marina , Danilova Ludmila , Durham Jennifer N. , Betts Courtney B. , Cope Leslie , Sidiropoulos Dimitrios N. , Tandurella Joseph A. , Charmsaz Soren , Gross Nicole , Hernandez Alexei , Ho Won Jin , Thoburn Chris , Walker Rosalind , Leatherman James , Mitchell Sarah , Christmas Brian , Saeed Ali , Gaykalova Daria A. , Yegnasubramanian Srinivasan , Fertig Elana J. , Coussens Lisa M. , Yarchoan Mark , Jaffee Elizabeth , Azad Nilofer S. 
Published: November 2024

AbstractPancreatic ductal adenocarcinoma (PDA) is characterized by low cytotoxic lymphocytes, abundant immune-suppressive cells, and resistance to immune checkpoint inhibitors (ICI). Preclinical PDA models showed the HDAC inhibitor entinostat reduced myeloid cell immunosuppression, sensitizing tumors to ICI therapy. This phase II study combined entinostat with nivolumab (PD1 inhibitor) in patients with advanced PDA (NCT03250273). Patients received entinostat 5 mg orally once weekly for 14-day lead-in, followed by entinostat and nivolumab. The primary endpoint was the objective response rate (ORR) by RECIST v1.1. Secondary endpoints included safety, duration of response, progression free-survival and overall survival. Between November 2017 and November 2020, 27 evaluable patients were enrolled. Three showed partial responses (11% ORR, 95% CI, 2.4%-29.2%) with a median response duration of 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were, respectively, 1.89 (95% CI, 1.381-2.301) and 2.729 (95% CI, 1.841-5.622) months. Grade ≥3 treatment-related adverse events occurred in 19 patients (63%), including decreased lymphocyte count, anemia, hypoalbuminemia, and hyponatremia. As exploratory analysis, peripheral and tumor immune profiles changes were assessed using CyTOF, mIHC, and RNA-seq. Entinostat increased dendritic cell activation and maturation. Gene expression analysis revealed an enrichment in inflammatory response pathways with combination treatment. Although the primary endpoint was not met, entinostat and nivolumab showed durable responses in a small subset of PDA patients. Myeloid cell immunomodulation supported the preclinical hypothesis, providing a basis for future combinatorial therapies to enhance clinical benefits in PDA.
Mechanically Tunable, Compostable, Healable and Scalable Engineered Living Materials
Authors: Manjula-Basavanna Avinash , Duraj-Thatte Anna M. , Joshi Neel S. 
Published: November 2024

AbstractAdvanced design strategies are essential to realize the full potential of engineered living materials, including their biodegradability, manufacturability, sustainability, and ability to tailor functional properties. Toward these goals, we present mechanically engineered living material with compostability, healability, and scalability – a material that integrates these features in the form of a stretchable plastic that is simultaneously flushable, compostable, and exhibits the characteristics of paper. This plastic/paper-like material is produced in scalable quantities (0.5–1 g L−1), directly from cultured bacterial biomass (40%) containing engineered curli protein nanofibers. The elongation at break (1–160%) and Young’s modulus (6-450 MPa) is tuned to more than two orders of magnitude. By genetically encoded covalent crosslinking of curli nanofibers, we increase the Young’s modulus by two times. The designed engineered living materials biodegrade completely in 15–75 days, while its mechanical properties are comparable to petrochemical plastics and thus may find use as compostable materials for primary packaging.
Sequence variants associated with BMI affect disease risk through BMI itself
Authors: Einarsson Gudmundur , Thorleifsson Gudmar , Steinthorsdottir Valgerdur , Zink Florian , Helgason Hannes , Olafsdottir Thorhildur , Rognvaldsson Solvi , Tragante Vinicius , Ulfarsson Magnus O. , Sveinbjornsson Gardar , Snaebjarnarson Audunn S. , Einarsson Hafsteinn , Aegisdottir Hildur M. , Jonsdottir Gudrun A. , Helgadottir Anna , Gretarsdottir Solveig , Styrkarsdottir Unnur , Arnason Hannes K. , Bjarnason Ragnar , Sigurdsson Emil , Arnar David O. , Bjornsson Einar S. , Palsson Runolfur , Bjornsdottir Gyda , Stefansson Hreinn , Thorgeirsson Thorgeir , Sulem Patrick , Thorsteinsdottir Unnur , Holm Hilma , Gudbjartsson Daniel F. , Stefansson Kari 
Published: November 2024

AbstractMendelian Randomization studies indicate that BMI contributes to various diseases, but it’s unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement. Similar attenuation was observed for chronic kidney disease and stroke, though results varied. Findings were consistent across sexes, except for myocardial infarction. Residual effects may result from temporal BMI changes, pleiotropy, measurement error, non-linear relationships, non-collapsibility, or confounding. The attenuation extent of BMI genetic risk score on disease associations suggests the potential impact of reducing BMI on disease risk.
Leveraging ancient DNA to uncover signals of natural selection in Europe lost due to admixture or drift
Authors: Pandey Devansh , Harris Mariana , Garud Nandita R. , Narasimhan Vagheesh M. 
Published: November 2024

AbstractLarge ancient DNA (aDNA) studies offer the chance to examine genomic changes over time, providing direct insights into human evolution. While recent studies have used time-stratified aDNA for selection scans, most focus on single-locus methods. We conducted a multi-locus genotype scan on 708 samples spanning 7000 years of European history. We show that the G12 statistic, originally designed for unphased diploid data, can effectively detect selection in aDNA processed to create ‘pseudo-haplotypes’. In simulations and at known positive control loci (e.g., lactase persistence), G12 outperforms the allele frequency-based selection statistic, SweepFinder2, previously used on aDNA. Applying our approach, we identified 14 candidate regions of selection across four time periods, with half the signals detectable only in the earliest period. Our findings suggest that selective events in European prehistory, including from the onset of animal domestication, have been obscured by neutral processes like genetic drift and demographic shifts such as admixture.
Shareable artificial intelligence to extract cancer outcomes from electronic health records for precision oncology research
Authors: Kehl Kenneth L. , Jee Justin , Pichotta Karl , Paul Morgan A. , Trukhanov Pavel , Fong Christopher , Waters Michele , Bakouny Ziad , Xu Wenxin , Choueiri Toni K. , Nichols Chelsea , Schrag Deborah , Schultz Nikolaus 
Published: November 2024

AbstractDatabases that link molecular data to clinical outcomes can inform precision cancer research into novel prognostic and predictive biomarkers. However, outside of clinical trials, cancer outcomes are typically recorded only in text form within electronic health records (EHRs). Artificial intelligence (AI) models have been trained to extract outcomes from individual EHRs. However, patient privacy restrictions have historically precluded dissemination of these models beyond the centers at which they were trained. In this study, the vulnerability of text classification models trained directly on protected health information to membership inference attacks is confirmed. A teacher-student distillation approach is applied to develop shareable models for annotating outcomes from imaging reports and medical oncologist notes. ‘Teacher’ models trained on EHR data from Dana-Farber Cancer Institute (DFCI) are used to label imaging reports and discharge summaries from the Medical Information Mart for Intensive Care (MIMIC)-IV dataset. ‘Student’ models are trained to use these MIMIC documents to predict the labels assigned by teacher models and sent to Memorial Sloan Kettering (MSK) for evaluation. The student models exhibit high discrimination across outcomes in both the DFCI and MSK test sets. Leveraging private labeling of public datasets to distill publishable clinical AI models from academic centers could facilitate deployment of machine learning to accelerate precision oncology research.
HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling
Authors: Erinjeri Annmary Paul , Wang Xunyan , Williams Rhianna , Chiozzi Riccardo Zenezini , Thalassinos Konstantinos , Labbadia Johnathan 
Published: November 2024

AbstractIncreased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1. We find that hsf-1 overexpression leads to transcriptional downregulation of all components of the CDC-48-UFD-1-NPL-4 complex, which is central to both endoplasmic reticulum and mitochondria associated protein degradation, and that this is complemented by UBQL-1-dependent turnover of NPL-4.1. As a consequence, mitochondrial network dynamics are altered, leading to increased lifespan. Together, our data establish that HSF-1 mediates lifespan extension through mitochondrial network adaptations that occur in response to down-tuning of components associated with organellar protein degradation pathways.
A noncoding variant confers pancreatic differentiation defect and contributes to diabetes susceptibility by recruiting RXRA
Authors: Li Yinglei , Zheng Ran , Jiang Lai , Yan Chenchao , Liu Ran , Chen Luyi , Jin Wenwen , Luo Yuanyuan , Zhang Xiafei , Tang Jun , Dai Zhe , Jiang Wei 
Published: November 2024

AbstractHuman genetics analysis has identified many noncoding SNPs associated with diabetic traits, but whether and how these variants contribute to diabetes is largely unknown. Here, we focus on a noncoding variant, rs6048205, and report that the risk-G variant impairs the generation of PDX1+/NKX6-1+ pancreatic progenitor cells and further results in the abnormal decrease of functional β cells during pancreatic differentiation. Mechanistically, this risk-G variant greatly enhances RXRA binding and over-activates FOXA2 transcription, specifically in the pancreatic progenitor stage, which in turn represses NKX6-1 expression. Consistently, inducible FOXA2 overexpression could phenocopy the differentiation defect. More importantly, mice carrying risk-G exhibit abnormal pancreatic islet architecture and are more sensitive to streptozotocin or a high-fat diet to develop into diabetes eventually. This study not only identifies a causal noncoding variant in diabetes susceptibility but also dissects the underlying gain-of-function mechanism by recruiting stage-specific factors.
Sea-level rise and extreme Indian Ocean Dipole explain mangrove dieback in the Maldives
Authors: Carruthers Lucy , Ersek Vasile , Maher Damien , Sanders Christian , Tait Douglas , Soares Juliano , Floyd Matthew , Hashim Aminath Shaha , Helber Stephanie , Garnett Mark , East Holly , Johnson Jamie A. , Ponta Gheorghe , Sippo James Z. 
Published: November 2024

AbstractMangrove forests enhance Small Island Developing States’ resilience to climate change, yet in 2020, a mangrove dieback impacted ~ 25% of mangrove-containing islands in the Maldives. Using remote sensing, dendrology and sediment geochemistry, we document a significant decrease in mangrove health post-2020 (NDVI: 0.75 ± 0.09) compared to pre-2020 (0.85 ± 0.04; P < 0.0001). Dead trees showed reduced stomatal conductance (δ13C: − 26.21 ± 0.11 ‰) relative to living ones (− 27.66 ± 0.14 ‰), indicating salinity stress. Critically, sea-level rise (30.50 ± 23.30 mm/year) outpaced mangrove sediment accretion (6.40 ± 0.69 mm/year) five-fold between 2017 and 2020. We attribute this dieback to salinity stress driven by record-high sea levels in 2020, linked to an extreme positive Indian Ocean Dipole event. These findings reveal the vulnerability of mangrove ecosystems to rapid sea-level rise and highlights the urgent need for adaptive conservation strategies in Small Island Developing States.
Generating bat primary and immortalised cell-lines from wing biopsies
Authors: Alcock Dominic , Power Sarahjane , Hogg Bridget , Sacchi Carlotta , Kacprzyk Joanna , McLoughlin Sarah , Bertelsen Mads Frost , Fletcher Nicola F. , O’Riain Aidan , Teeling Emma C. 
Published: November 2024

AbstractBats are becoming recognised as new model species to study naturally evolved mammalian extended healthspan and disease tolerance. However, this research is limited by the lack of bat specific cellular resources. Here we describe an optimised protocol to develop both primary and immortalised fibroblast cell-lines from wing biopsy punches from the Egyptian fruit bat, Rousettus aegyptiacus. We show that the immortalised cell lines and primary cells show similar characteristics in their proliferative capacity and response to oxidative stress. They also exhibited a similar response in their NF-κB immune response to TLR agonists including SARS-CoV2. As wing punches can be acquired non-lethally, these methods can be used to develop primary and immortalised cells, from potentially any bat species, including those of conservation concern that cannot be sacrificed. This can expand the scope of bat species that can be studied in the future, and the development of key cellular resources required to functionally validate the regulators of bats’ unique longevity.
Correlative light and soft X-ray tomography of in situ mesoscale heterochromatin structure in intact cells
Authors: Gupta Rajshikhar , Goswami Yagyik , Yuan Luezhen , Roy Bibhas , Pereiro Eva , Shivashankar GV 
Published: November 2024

AbstractHeterochromatin organization is critical to many genome-related programs including transcriptional silencing and DNA repair. While super-resolution imaging, electron microscopy, and multiomics methods have provided indirect insights into the heterochromatin organization, a direct measurement of mesoscale heterochromatin ultrastructure is still missing. We use a combination of correlative light microscopy and cryo-soft X-ray tomography (CLXT) to analyze heterochromatin organization in the intact hydrated state of human mammary fibroblast cells. Our analysis reveals that the heterochromatin ultra-structure has a typical mean domain size of approximately 80 nm and a mean separation of approximately 120 nm between domains. Functional perturbations yield further insights into the molecular density and alterations in the mesoscale organization of the heterochromatin regions. Furthermore, our polymer simulations provide a mechanistic basis for the experimentally observed size and separation distributions of the mesoscale chromatin domains. Collectively, our results provide direct, label-free observation of heterochromatin organization in the intact hydrated state of cells.