bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling Form Roughness Induced by Tidal Sand Waves
Authors: Portos‐Amill Laura , Roos Pieter C. , Damveld Johan H. , Hulscher Suzanne J. M. H. 
Published: April 2024

AbstractTide‐dominated sandy shelf seas, such as the Dutch North Sea, are covered by sand waves. Yet, basin‐scale hydrodynamic models do not include any sand wave information because their grid sizes are too coarse to resolve sand waves individually. We explore the possibility of parametrizing the effects of sand waves on the larger‐scale tidal flow by means of a form roughness. Specifically, our aim is to see to what extent the flow over a sand wave field can be reproduced by that over a flat seabed with an increased effective roughness (accounting for both grain and form roughness). To do so, we use two process‐based hydrodynamic models: a second order perturbation approach, and Delft3D. Both models demonstrate that the presence of sand waves causes amplitude decrease and phase shift of the tidal flow. We explore the dependencies of form roughness on different sand wave characteristics (wavelength, height and asymmetry). Shorter and higher sand waves cause a higher form roughness, while our analysis does not reveal any dependency on sand wave asymmetry. Notably, the consideration of a tidal flow, characterized by several tidal constituents, each represented by an amplitude and a phase, results in a more complex form roughness analysis than in a fluvial setting, where the flow is unidirectional and steady. We thus obtain an amplitude‐based form roughness and a phase‐based form roughness, each yielding a different value, yet displaying the same qualitative dependencies.
Characterization of Relativistic Electron Precipitation Events Observed by the CALET Experiment Using Self‐Organizing‐Maps
Authors: Vidal‐Luengo Sergio E. , Blum Lauren W. , Bruno Alessandro , Ficklin Anthony W. , de Nolfo Georgia , Guzik T. Gregory , Bortnik Jacob , Kataoka Ryuho , Torii Shoji 
Published: April 2024

AbstractRelativistic electron precipitation (REP) is a relatively high‐latitude phenomenon where high‐energy electrons trapped in the outer radiation belt are lost into the Earth’s atmosphere. REP events observed at low Earth orbit show varying temporal profiles and global distributions. While the precipitation origin has been attributed to specific wave modes or scattering sources, the sorting of REP events by type or driver remains an unsolved challenge. In this study, we analyze the temporal profile of relativistic electron precipitation events observed by the CALorimetric Electron Telescope (CALET) experiment on board the International Space Station. We use an unsupervised machine learning technique called Self‐Organizing‐Maps (SOM) to automatically detect and then classify relativistic electron events observed by the two scintillator layers at the top of the apparatus, sensitive to electrons with energies >1.5 MeV and >3.4 MeV, respectively. We calculate the power spectral density (PSD) of the count rates observed by both sensors and use them as an input for the SOM. The SOM technique groups the PSDs by their similarity, resulting in a classification of relativistic electron events by the periodicity of the observed precipitation. We investigate the L‐shell and magnetic local time distribution of the resulting classification, and energy spectral index associated with the observations. Clear precipitation patterns are observed and compared to past precipitation categorization attempts as well as known distributions of various scattering mechanisms. The classification reveals features through the sorting of the variability of the rapid precipitation, allowing the identification of different precipitation populations with varying properties.
Advancing insights into in vivo meningeal lymphatic vessels with stereoscopic wide-field photoacoustic microscopy
Authors: Yang Fei , Wang Zhiyang , Shi Wenbin , Wang Miao , Ma Rui , Zhang Wuyu , Li Xipeng , Wang Erqi , Xie Wenjie , Zhang Zhan , Shen Qi , Zhou Feifan , Yang Sihua 
Published: April 2024

AbstractMeningeal lymphatic vessels (mLVs) play a pivotal role in regulating metabolic waste from cerebrospinal fluid (CSF). However, the current limitations in field of view and resolution of existing imaging techniques impede understanding the stereoscopic morphology and dynamic behavior of mLVs in vivo. Here, we utilized dual-contrast functional photoacoustic microscopy to achieve wide-field intravital imaging of the lymphatic system, including mLVs and glymphatic pathways. The stereoscopic photoacoustic microscopy based on opto-acoustic confocal features has a depth imaging capability of 3.75 mm, facilitating differentiation between mLVs on the meninges and glymphatic pathways within the brain parenchyma. Subsequently, using this imaging technique, we were able to visualize the dynamic drainage of mLVs and identify a peak drainage period occurring around 20–40 min after injection, along with determining the flow direction from CSF to lymph nodes. Inspiringly, in the Alzheimer’s disease (AD) mouse model, we observed that AD mice exhibit a ~ 70% reduction in drainage volume of mLVs compared to wild-type mice. With the development of AD, there is be continued decline in mLVs drainage volume. This finding clearly demonstrates that the AD mouse model has impaired CSF drainage. Our study opens up a horizon for understanding the brain’s drainage mechanism and dissecting mLVs-associated neurological disorders.
Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets
Authors: Fleishman Joshua S. , Kumar Sunil 
Published: April 2024

AbstractBile acids, once considered mere dietary surfactants, now emerge as critical modulators of macronutrient (lipid, carbohydrate, protein) metabolism and the systemic pro-inflammatory/anti-inflammatory balance. Bile acid metabolism and signaling pathways play a crucial role in protecting against, or if aberrant, inducing cardiometabolic, inflammatory, and neoplastic conditions, strongly influencing health and disease. No curative treatment exists for any bile acid influenced disease, while the most promising and well-developed bile acid therapeutic was recently rejected by the FDA. Here, we provide a bottom-up approach on bile acids, mechanistically explaining their biochemistry, physiology, and pharmacology at canonical and non-canonical receptors. Using this mechanistic model of bile acids, we explain how abnormal bile acid physiology drives disease pathogenesis, emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic diseases. We provide an in-depth summary on pre-existing bile acid receptor modulators, explain their shortcomings, and propose solutions for how they may be remedied. Lastly, we rationalize novel targets for further translational drug discovery and provide future perspectives. Rather than dismissing bile acid therapeutics due to recent setbacks, we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.
MiR-134-5p inhibits the malignant phenotypes of osteosarcoma via ITGB1/MMP2/PI3K/Akt pathway
Authors: Yan Lei , Zhou Ruhao , Feng Yi , Li Ruoqi , Zhang Long , Pan Yongchun , Qiao Xiaochen , Li Pengcui , Wei Xiaochun , Xu Chaojian , Li Yuan , Niu Xiaochen , Sun Xiaojuan , Lv Zhi , Tian Zhi 
Published: April 2024

AbstractMicro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.
Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition
Authors: Shendy Noha A. M. , Bikowitz Melissa , Sigua Logan H. , Zhang Yang , Mercier Audrey , Khashana Yousef , Nance Stephanie , Liu Qi , Delahunty Ian M. , Robinson Sarah , Goel Vanshita , Rees Matthew G. , Ronan Melissa A. , Wang Tingjian , Kocak Mustafa , Roth Jennifer A. , Wang Yingzhe , Freeman Burgess B. , Orr Brent A. , Abraham Brian J. , Roussel Martine F. , Schonbrunn Ernst , Qi Jun , Durbin Adam D. 
Published: April 2024

AbstractChemical discovery efforts commonly target individual protein domains. Many proteins, including the EP300/CBP histone acetyltransferases (HATs), contain several targetable domains. EP300/CBP are critical gene-regulatory targets in cancer, with existing high potency inhibitors of either the catalytic HAT domain or protein-binding bromodomain (BRD). A domain-specific inhibitory approach to multidomain-containing proteins may identify exceptional-responding tumor types, thereby expanding a therapeutic index. Here, we discover that targeting EP300/CBP using the domain-specific inhibitors, A485 (HAT) or CCS1477 (BRD) have different effects in select tumor types. Group 3 medulloblastoma (G3MB) cells are especially sensitive to BRD, compared with HAT inhibition. Structurally, these effects are mediated by the difluorophenyl group in the catalytic core of CCS1477. Mechanistically, bromodomain inhibition causes rapid disruption of genetic dependency networks that are required for G3MB growth. These studies provide a domain-specific structural foundation for drug discovery efforts targeting EP300/CBP and identify a selective role for the EP300/CBP bromodomain in maintaining genetic dependency networks in G3MB.
The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids
Authors: Holmberg Sandra M. , Feeney Rachel H. , Prasoodanan P.K. Vishnu , Puértolas-Balint Fabiola , Singh Dhirendra K. , Wongkuna Supapit , Zandbergen Lotte , Hauner Hans , Brandl Beate , Nieminen Anni I. , Skurk Thomas , Schroeder Bjoern O. 
Published: April 2024

AbstractBeneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.
Functional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy
Authors: Luo Audrey C. , Sydnor Valerie J. , Pines Adam , Larsen Bart , Alexander-Bloch Aaron F. , Cieslak Matthew , Covitz Sydney , Chen Andrew A. , Esper Nathalia Bianchini , Feczko Eric , Franco Alexandre R. , Gur Raquel E. , Gur Ruben C. , Houghton Audrey , Hu Fengling , Keller Arielle S. , Kiar Gregory , Mehta Kahini , Salum Giovanni A. , Tapera Tinashe , Xu Ting , Zhao Chenying , Salo Taylor , Fair Damien A. , Shinohara Russell T. , Milham Michael P. , Satterthwaite Theodore D. 
Published: April 2024

AbstractHuman cortical maturation has been posited to be organized along the sensorimotor-association axis, a hierarchical axis of brain organization that spans from unimodal sensorimotor cortices to transmodal association cortices. Here, we investigate the hypothesis that the development of functional connectivity during childhood through adolescence conforms to the cortical hierarchy defined by the sensorimotor-association axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3355; ages 5–23 years): the Philadelphia Neurodevelopmental Cohort (n = 1207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1126). Across datasets, the development of functional connectivity systematically varied along the sensorimotor-association axis. Connectivity in sensorimotor regions increased, whereas connectivity in association cortices declined, refining and reinforcing the cortical hierarchy. These consistent and generalizable results establish that the sensorimotor-association axis of cortical organization encodes the dominant pattern of functional connectivity development.
WindSeer: real-time volumetric wind prediction over complex terrain aboard a small uncrewed aerial vehicle
Authors: Achermann Florian , Stastny Thomas , Danciu Bogdan , Kolobov Andrey , Chung Jen Jen , Siegwart Roland , Lawrance Nicholas 
Published: April 2024

AbstractReal-time high-resolution wind predictions are beneficial for various applications including safe crewed and uncrewed aviation. Current weather models require too much compute and lack the necessary predictive capabilities as they are valid only at the scale of multiple kilometers and hours – much lower spatial and temporal resolutions than these applications require. Our work demonstrates the ability to predict low-altitude time-averaged wind fields in real time on limited-compute devices, from only sparse measurement data. We train a deep neural network-based model, WindSeer, using only synthetic data from computational fluid dynamics simulations and show that it can successfully predict real wind fields over terrain with known topography from just a few noisy and spatially clustered wind measurements. WindSeer can generate accurate predictions at different resolutions and domain sizes on previously unseen topography without retraining. We demonstrate that the model successfully predicts historical wind data collected by weather stations and wind measured by drones during flight.
Vegetation dieback in the Mississippi River Delta triggered by acute drought and chronic relative sea-level rise
Authors: Elsey-Quirk Tracy , Lynn Austin , Jacobs Michael Derek , Diaz Rodrigo , Cronin James T. , Wang Lixia , Huang Haosheng , Justic Dubravko 
Published: April 2024

AbstractVegetation dieback and recovery may be dependent on the interplay between infrequent acute disturbances and underlying chronic stresses. Coastal wetlands are vulnerable to the chronic stress of sea-level rise, which may affect their susceptibility to acute disturbance events. Here, we show that a large-scale vegetation dieback in the Mississippi River Delta was precipitated by salt-water incursion during an extreme drought in the summer of 2012 and was most severe in areas exposed to greater flooding. Using 16 years of data (2007–2022) from a coastwide network of monitoring stations, we show that the impacts of the dieback lasted five years and that recovery was only partial in areas exposed to greater inundation. Dieback marshes experienced an increase in percent time flooded from 43% in 2007 to 75% in 2022 and a decline in vegetation cover and species richness over the same period. Thus, while drought-induced high salinities and soil saturation triggered a significant dieback event, the chronic increase in inundation is causing a longer-term decline in cover, more widespread losses, and reduced capacity to recover from acute stressors. Overall, our findings point to the importance of mitigating the underlying stresses to foster resilience to both acute and persistent causes of vegetation loss.
Cortex-wide transcranial localization microscopy with fluorescently labeled red blood cells
Authors: Zhou Quanyu , Glück Chaim , Tang Lin , Glandorf Lukas , Droux Jeanne , El Amki Mohamad , Wegener Susanne , Weber Bruno , Razansky Daniel , Chen Zhenyue 
Published: April 2024

AbstractLarge-scale imaging of brain activity with high spatio-temporal resolution is crucial for advancing our understanding of brain function. The existing neuroimaging techniques are largely limited by restricted field of view, slow imaging speed, or otherwise do not have the adequate spatial resolution to capture brain activities on a capillary and cellular level. To address these limitations, we introduce fluorescence localization microscopy aided with sparsely-labeled red blood cells for cortex-wide morphological and functional cerebral angiography with 4.9 µm spatial resolution and 1 s temporal resolution. When combined with fluorescence calcium imaging, the proposed method enables extended recordings of stimulus-evoked neuro-vascular changes in the murine brain while providing simultaneous multiparametric readings of intracellular neuronal activity, blood flow velocity/direction/volume, and vessel diameter. Owing to its simplicity and versatility, the proposed approach will become an invaluable tool for deciphering the regulation of cortical microcirculation and neurovascular coupling in health and disease.
Group IV topological quantum alloy and the role of short-range order: the case of Ge-rich Ge1–xPbx
Authors: Liang Yunfan , Chen Shunda , Jin Xiaochen , West Damien , Yu Shui-Qing , Li Tianshu , Zhang Shengbai 
Published: April 2024

AbstractDespite the explosion of interest in topological materials over the last decades, their applications remain limited due to challenges in growth and incorporation with today’s microelectronics. As a potential bridge to close this gap, we investigate the group-IV alloy Ge1–xPbx, in the Ge-rich condition using density functional theory and show that relatively low concentrations of Pb (~9.4%) can lead to a topological phase transition. Furthermore, the calculation of the Z2 invariant for both the random alloy and the alloy with short-range order (SRO) indicate that the topological phase of the material can be directly modified by the degree of SRO. These findings are understood in terms of local structural relaxation, which decreases the bandgap in the random alloy. However, in the SRO case, the mutual avoidance of Pb leads to minimal structural relaxation, alleviating strain. Our findings not only highlight the emerging importance of SRO in alloy properties but also indicate the possibility of constructing topological interfaces between materials of identical composition (and nominally identical structure). Moreover, they uncover a viable avenue toward the monolithic integration of quantum materials with today’s semiconductor industry.
Full-length transcriptome analysis of a bloom-forming dinoflagellate Prorocentrum shikokuense (Dinophyceae)
Authors: Pan Xiaohui , Liu Hang , Feng Leili , Zong Yanan , Cao Zihao , Guo Li , Yang Guanpin 
Published: April 2024

AbstractProrocentrum shikokuense (formerly P. donghaiense) is a pivotal dinoflagellate species associating with the HABs in the East China Sea. The complexity of its large nuclear genome hindered us from understanding its genomic characteristics. Full-length transcriptome sequencing offers a practical solution to decipher the physiological mechanisms of a species without the reference genome. In this study, we employed single-molecule real-time (SMRT) sequencing technology to sequence the full-length transcriptome of Prorocentrum shikokuense. We successfully generated 41.73 Gb of clean SMRT sequencing reads and isolated 105,249 non-redundant full-length non-chimeric reads. Our trial has led to the identification of 11,917 long non-coding RNA transcripts, 514 alternative splicing events, 437 putative transcription factor genes from 17 TF gene families, and 34,723 simple sequence repeats. Additionally, a total of 78,265 open reading frames were identified, of them 15,501 were the protein coding sequences. This dataset is valuable for annotating P. shikokuense genome, and will contribute significantly to the in-depth studies on the molecular mechanisms underlining the dinoflagellate bloom formation.
A real-world pharmacovigilance study of amivantamab-related cardiovascular adverse events based on the FDA adverse event reporting system (FAERS) database
Authors: Sun Rui , Ning Zhen , Qin Henan , Zhang Wenhe , Teng Yibin , Jin Chenxing , Liu Jiwei , Wang Aman 
Published: April 2024

AbstractAmivantamab is the first dual-specificity antibody targeting EGFR and MET, which is approved for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. Cardiovascular toxicities related to amivantamab have not been reported in the CHRYSALIS study. However, the occurrence of cardiovascular events in the real world is unknown. To comprehensively investigate the clinical characteristics, onset times, and outcomes of cardiovascular toxicities associated with amivantamab. The Food and Drug Administration Adverse Event Reporting System (FAERS) database from 1st quarter of 2019 to the 2nd quarter of 2023 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with amivantamab. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage trans-formation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0 with at least 3 reports was considered statistically significant. A total of 20,270,918 eligible records were identified, among which 98 records were related to cardiovascular events associated with amivantamab. 4 categories of cardiovascular events exhibited positive signals: venous thrombotic diseases, abnormal blood pressure, arrhythmia, and pericardial effusion. Venous thrombotic diseases and abnormal blood pressure were the two most common signals. The median time to onset (TTO) for cardiovascular AEs was 33 days. The cumulative incidence within 90 days was 100% for cardiac failure, 75% for stroke, 63.16% for arrhythmia, 50% for sudden death, and 44.18% for venous thrombotic diseases. Death accounted for 16.3% of all cardiovascular AEs associated with amivantamab. The mortality rates for Major Adverse Cardiovascular Events (MACE) were up to 60%. This pharmacovigilance study systematically explored the cardiovascular adverse events of amivantamab and provided new safety signals based on past safety information. Early and intensified monitoring is crucial, and attention should be directed towards high-risk signals.