bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light chain mutations contribute to defining the fibril morphology in systemic AL amyloidosis
Authors: Karimi-Farsijani Sara , Pfeiffer Peter Benedikt , Banerjee Sambhasan , Baur Julian , Kuhn Lukas , Kupfer Niklas , Hegenbart Ute , Schönland Stefan O. , Wiese Sebastian , Haupt Christian , Schmidt Matthias , Fändrich Marcus 
Published: June 2024

AbstractSystemic AL amyloidosis is one of the most frequently diagnosed forms of systemic amyloidosis. It arises from mutational changes in immunoglobulin light chains. To explore whether these mutations may affect the structure of the formed fibrils, we determine and compare the fibril structures from several patients with cardiac AL amyloidosis. All patients are affected by light chains that contain an IGLV3-19 gene segment, and the deposited fibrils differ by the mutations within this common germ line background. Using cryo-electron microscopy, we here find different fibril structures in each patient. These data establish that the mutations of amyloidogenic light chains contribute to defining the fibril architecture and hence the structure of the pathogenic agent.
Single-molecule reconstruction of eukaryotic factor-dependent transcription termination
Authors: Xiong Ying , Han Weijing , Xu Chunhua , Shi Jing , Wang Lisha , Jin Taoli , Jia Qi , Lu Ying , Hu Shuxin , Dou Shuo-Xing , Lin Wei , Strick Terence R. , Wang Shuang , Li Ming 
Published: June 2024

AbstractFactor-dependent termination uses molecular motors to remodel transcription machineries, but the associated mechanisms, especially in eukaryotes, are poorly understood. Here we use single-molecule fluorescence assays to characterize in real time the composition and the catalytic states of Saccharomyces cerevisiae transcription termination complexes remodeled by Sen1 helicase. We confirm that Sen1 takes the RNA transcript as its substrate and translocates along it by hydrolyzing multiple ATPs to form an intermediate with a stalled RNA polymerase II (Pol II) transcription elongation complex (TEC). We show that this intermediate dissociates upon hydrolysis of a single ATP leading to dissociation of Sen1 and RNA, after which Sen1 remains bound to the RNA. We find that Pol II ends up in a variety of states: dissociating from the DNA substrate, which is facilitated by transcription bubble rewinding, being retained to the DNA substrate, or diffusing along the DNA substrate. Our results provide a complete quantitative framework for understanding the mechanism of Sen1-dependent transcription termination in eukaryotes.
Light regulates nuclear detainment of intron-retained transcripts through COP1-spliceosome to modulate photomorphogenesis
Authors: Zhou Hua , Zeng Haiyue , Yan Tingting , Chen Sunlu , Fu Ying , Qin Guochen , Zhao Xianhai , Heng Yueqin , Li Jian , Lin Fang , Xu Dongqing , Wei Ning , Deng Xing Wang 
Published: June 2024

AbstractIntron retention (IR) is the most common alternative splicing event in Arabidopsis. An increasing number of studies have demonstrated the major role of IR in gene expression regulation. The impacts of IR on plant growth and development and response to environments remain underexplored. Here, we found that IR functions directly in gene expression regulation on a genome-wide scale through the detainment of intron-retained transcripts (IRTs) in the nucleus. Nuclear-retained IRTs can be kept away from translation through this mechanism. COP1-dependent light modulation of the IRTs of light signaling genes, such as PIF4, RVE1, and ABA3, contribute to seedling morphological development in response to changing light conditions. Furthermore, light-induced IR changes are under the control of the spliceosome, and in part through COP1-dependent ubiquitination and degradation of DCS1, a plant-specific spliceosomal component. Our data suggest that light regulates the activity of the spliceosome and the consequent IRT nucleus detainment to modulate photomorphogenesis through COP1.
Multiscale and multidisciplinary analysis of aging processes in bone
Authors: Ravazzano Linda , Colaianni Graziana , Tarakanova Anna , Xiao Yu-Bai , Grano Maria , Libonati Flavia 
Published: June 2024

AbstractThe world population is increasingly aging, deeply affecting our society by challenging our healthcare systems and presenting an economic burden, thus turning the spotlight on aging-related diseases: exempli gratia, osteoporosis, a silent disease until you suddenly break a bone. The increase in bone fracture risk with age is generally associated with a loss of bone mass and an alteration in the skeletal architecture. However, such changes cannot fully explain increased fragility with age. To successfully tackle age-related bone diseases, it is paramount to comprehensively understand the fundamental mechanisms responsible for tissue degeneration. Aging mechanisms persist at multiple length scales within the complex hierarchical bone structure, raising the need for a multiscale and multidisciplinary approach to resolve them. This paper aims to provide an overarching analysis of aging processes in bone and to review the most prominent outcomes of bone aging. A systematic description of different length scales, highlighting the corresponding techniques adopted at each scale and motivating the need for combining diverse techniques, is provided to get a comprehensive description of the multi-physics phenomena involved.
Development and validation of a clinical breast cancer tool for accurate prediction of recurrence
Authors: Dhungana Asim , Vannier Augustin , Zhao Fangyuan , Freeman Jincong Q. , Saha Poornima , Sullivan Megan , Yao Katharine , Flores Elbio M. , Olopade Olufunmilayo I. , Pearson Alexander T. , Huo Dezheng , Howard Frederick M. 
Published: June 2024

AbstractGiven high costs of Oncotype DX (ODX) testing, widely used in recurrence risk assessment for early-stage breast cancer, studies have predicted ODX using quantitative clinicopathologic variables. However, such models have incorporated only small cohorts. Using a cohort of patients from the National Cancer Database (NCDB,n = 53,346), we trained machine learning models to predict low-risk (0-25) or high-risk (26-100) ODX using quantitative estrogen receptor (ER)/progesterone receptor (PR)/Ki-67 status, quantitative ER/PR status alone, and no quantitative features. Models were externally validated on a diverse cohort of 970 patients (median follow-up 55 months) for accuracy in ODX prediction and recurrence. Comparing the area under the receiver operating characteristic curve (AUROC) in a held-out set from NCDB, models incorporating quantitative ER/PR (AUROC 0.78, 95% CI 0.77–0.80) and ER/PR/Ki-67 (AUROC 0.81, 95% CI 0.80–0.83) outperformed the non-quantitative model (AUROC 0.70, 95% CI 0.68–0.72). These results were preserved in the validation cohort, where the ER/PR/Ki-67 model (AUROC 0.87, 95% CI 0.81–0.93,p = 0.009) and the ER/PR model (AUROC 0.86, 95% CI 0.80–0.92,p = 0.031) significantly outperformed the non-quantitative model (AUROC 0.80, 95% CI 0.73–0.87). Using a high-sensitivity rule-out threshold, the non-quantitative, quantitative ER/PR and ER/PR/Ki-67 models identified 35%, 30% and 43% of patients as low-risk in the validation cohort. Of these low-risk patients, fewer than 3% had a recurrence at 5 years. These models may help identify patients who can forgo genomic testing and initiate endocrine therapy alone. An online calculator is provided for further study.
Computational morphogenesis for liquid crystal elastomer metamaterial
Authors: Li Weichen , Zhang Xiaojia Shelly 
Published: June 2024

AbstractLiquid crystal elastomer (LCE) is a type of soft active material that generates large and reversible spontaneous deformations upon temperature changes, facilitating various environmentally responsive smart applications. Despite their success, most existing LCE metamaterials are designed in a forward fashion based on intuition and feature regular material patterns, which may hinder the reach of LCE’s full potential in producing complex and desired functionalities. Here, we develop a computational inverse design framework for discovering diverse sophisticated temperature-activated and -interactive nonlinear behaviors for LCE metamaterials in a fully controllable fashion. We generate intelligent LCE metamaterials with a wide range of switchable functionalities upon temperature changes. By sensing the environment, these metamaterials can realize maximized spontaneous area expansion/contraction, precisely programmable enclosed opening size change, and temperature-switchable nonlinear stress–strain relations and deformation modes. The optimized unit cells feature irregular LCE patterns and form complex and highly nonlinear mechanisms. The inverse design computational framework, optimized material patterns, and revealed underlying mechanisms fundamentally advance the design capacity of LCE metamaterials, benefiting environment-aware and -adaptive smart materials.
Dry immersion rapidly disturbs iron metabolism in men and women: results from the VIVALDI studies
Authors: Horeau Mathieu , Navasiolava Nastassia , Van Ombergen Angelique , Custaud Marc-Antoine , Robin Adrien , Ropert Martine , Antunes Inês , Bareille Marie-Pierre , Billette De Villemeur Rebecca , Gauquelin-Koch Guillemette , Derbré Frédéric , Loréal Olivier 
Published: June 2024

AbstractIron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in men. However, its impact on women remains unclear. This study aims to compare iron metabolism alterations in both sexes exposed to 5 days of dry immersion. Our findings demonstrate that women, similarly to men, experience increased systemic iron availability and elevated serum hepcidin levels, indicative of iron misdistribution after short-term exposure to simulated microgravity.
Tau seeding activity in skin biopsy differentiates tauopathies from synucleinopathies
Authors: Dellarole Ilaria Linda , Vacchi Elena , Ruiz-Barrio Inigo , Pinton Sandra , Raimondi Andrea , Rossi Stefania , Morandi Sara , Bianco Giovanni , Begum Bacinoglu Merve , Lombardo Annalisa , Celauro Luigi , Staedler Claudio , Galati Salvatore , Pagonabarraga Javier , Kulisevsky Jaime , Legname Giuseppe , Gobbi Claudio , Kaelin-Lang Alain , Moda Fabio , Melli Giorgia 
Published: June 2024

AbstractMost neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need. Since tau protein is highly expressed in skin of tauopathies patients, we aimed to exploit the ultrasensitive seeding activity assay (SAA) to assess tau seeding activity in skin of patients with tauopathies. In this multicentric, case-control study, patients with tauopathies and synucleinopathies were consecutively recruited and sex-matched to healthy controls (HC). Subjects underwent a double 3 mm skin biopsy in cervical area and ankle. Skin tau-SAA, using TauK18 and TauK19 as reaction substrates for 4R and 3R isoforms, seeding score, clinical scales, biochemical and morphological characterization of SAA end-products were evaluated. We analyzed 58 subjects: 24 tauopathies (18 progressive supranuclear palsy, PSP, and 6 corticobasal degeneration, CBD), 20 synucleinopathies (14 Parkinson’s disease, PD, and 6 multiple system atrophy, MSA), and 14 HC. PSP and CBD showed higher tau seeding activity at both anatomical sites. A greater sensitivity of 4R-SAA than 3R-SAA was observed. 4R tau-SAA identified tauopathies with 71% sensitivity and 93% specificity. Accuracy was higher for PSP than CBD: PSP vs HC / PD (AUC 0.825), while CBD vs HC / PD (AUC 0.797), and PSP vs MSA (AU 0.778). SAA end-products showed differences in biochemical and morphological characterization according to the anatomical site. Skin tau-SAA identifies tauopathies with good accuracy and can be used to implement the in-vivo clinical diagnosis of patients with neurodegenerative diseases. Further characterization of peripheral tau seed in skin may elucidate the structure of tau deposits in brain.
Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers
Authors: Tan Wenzhi , Thiruppathi Jayalakshmi , Hong Seol Hee , Puth Sao , Pheng Sophea , Mun Bo-Ram , Choi Won-Seok , Lee Kyung-Hwa , Park Hyun-Sun , Nguyen Duc Tien , Lee Min-Cheol , Jeong Kwangjoon , Zheng Jin Hai , Kim Young , Lee Shee Eun , Rhee Joon Haeng 
Published: June 2024

AbstractAlzheimer’s disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Because TauRD forms the structural core of tau aggregates, the development of immunotherapies that selectively target TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated recombinant TauRD polypeptide that form neurofibrillary tangle-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted the phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum also specifically recognized pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested its efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, as indicated by the amelioration of memory deficits, and alleviated tauopathy progression. Notably, the survival of the vaccinated mice was dramatically extended. In conclusion, we developed a mucosal vaccine that exclusively targets pathological tau conformers and prevents disease progression.
Immune escape of avian oncogenic Marek’s disease herpesvirus and antagonistic host immune responses
Authors: Zhu Zhi-Jian , Teng Man , Liu Yu , Chen Fu-Jia , Yao Yongxiu , Li En-Zhong , Luo Jun 
Published: June 2024

AbstractMarek’s disease virus (MDV) is a highly pathogenic and oncogenic alpha herpesvirus that causes Marek’s disease (MD), which is one of the most important immunosuppressive and rapid-onset neoplastic diseases in poultry. The onset of MD lymphomas and other clinical diseases can be efficiently prevented by vaccination; these vaccines are heralded as the first demonstration of a successful vaccination strategy against a cancer. However, the persistent evolution of epidemic MDV strains towards greater virulence has recently resulted in frequent outbreaks of MD in vaccinated chicken flocks worldwide. Herein, we provide an overall review focusing on the discovery and identification of the strategies by which MDV evades host immunity and attacks the immune system. We have also highlighted the decrease in the immune efficacy of current MD vaccines. The prospects, strategies and new techniques for the development of efficient MD vaccines, together with the possibilities of antiviral therapy in MD, are also discussed.
A multimodal framework for extraction and fusion of satellite images and public health data
Authors: Moukheiber Dana , Restrepo David , Cajas Sebastián Andrés , Montoya María Patricia Arbeláez , Celi Leo Anthony , Kuo Kuan-Ting , López Diego M. , Moukheiber Lama , Moukheiber Mira , Moukheiber Sulaiman , Osorio-Valencia Juan Sebastian , Purkayastha Saptarshi , Paddo Atika Rahman , Wu Chenwei , Kuo Po-Chih 
Published: June 2024

AbstractIn low- and middle-income countries, the substantial costs associated with traditional data collection pose an obstacle to facilitating decision-making in the field of public health. Satellite imagery offers a potential solution, but the image extraction and analysis can be costly and requires specialized expertise. We introduce SatelliteBench, a scalable framework for satellite image extraction and vector embeddings generation. We also propose a novel multimodal fusion pipeline that utilizes a series of satellite imagery and metadata. The framework was evaluated generating a dataset with a collection of 12,636 images and embeddings accompanied by comprehensive metadata, from 81 municipalities in Colombia between 2016 and 2018. The dataset was then evaluated in 3 tasks: including dengue case prediction, poverty assessment, and access to education. The performance showcases the versatility and practicality of SatelliteBench, offering a reproducible, accessible and open tool to enhance decision-making in public health.
The Global Historical Climatology Network Monthly Precipitation Dataset, Version 4
Authors: Applequist Scott , Durre Imke , Vose Russell 
Published: June 2024

AbstractThe Global Historical Climatology Network (GHCN) monthly precipitation dataset contains historical time series for thousands of land surface stations worldwide. Initially released in 1992 and revised in 1998, the dataset has been employed in a variety of applications over the past three decades, including operational monitoring, applied research, and international assessments. This paper describes the data and methods used to compile the latest edition (version 4), which has three major enhancements. The first enhancement is to the station network, which increased in size by a factor of five due to the inclusion of dozens of new source datasets, most notably GHCN Daily (GHCNd). The second improvement is the application of a rule-based algorithm to compare and merge records representing the same location. The third enhancement is to the quality assurance approach, now consisting of 18 new checks based on GHCNd and other operational systems. Updated monthly, the resulting dataset consists of time series of monthly precipitation totals at more than 120,000 worldwide stations, including more than 33,000 active observing sites.
Development of a model to predict the age at breast cancer diagnosis in a global population
Authors: Kim Ha Young , Mullaert Jimmy , Tondreau Ambre , Park Boyoung , Rouzier Roman 
Published: June 2024

AbstractKnowing the mean age at diagnosis of breast cancer (BC) in a country is important for setting up an efficient BC screening program. The aim of this study was to develop and validate a model to predict the mean age at diagnosis of BC at the country level. To develop the model, we used the CI5plus database from the IARC, which contains incidence data for 122 selected populations for a minimum of 15 consecutive years from 1993 to 2012 and data from the World Bank. The standard model was fitted with a generalized linear model with the age of the population, growth domestic product per capita (GDPPC) and fertility rate as fixed effects and continent as a random effect. The model was validated in registries of the Cancer Incidence in Five Continents that are not included in the CI5plus database (1st validation set: 1950–2012) and in the most recently released volume (2nd validation set: 2013–2017). The intercept of the model was 30.9 (27.8–34.1), and the regression coefficients for population age, GDPPC and fertility rate were 0.55 (95% CI: 0.53–0.58, p < 0.001), 0.46 (95% CI: 0.26–0.67, p < 0.001) and 1.62 (95% CI: 1.42–1.88, p < 0.001), respectively. The marginal R2 and conditional R2 were 0.22 and 0.81, respectively, suggesting that 81% percent of the variance in the mean age at diagnosis of BC was explained by the variance in population age, GDPPC and fertility rate through linear relationships. The model was highly accurate, as the correlations between the predicted age from the model and the observed mean age at diagnosis of BC were 0.64 and 0.89, respectively, and the mean relative error percentage errors were 5.2 and 3.1% for the 1st and 2nd validation sets, respectively. We developed a robust model based on population age and continent to predict the mean age at diagnosis of BC in populations. This tool could be used to implement BC screening in countries without prevention programs.
Interaction energy flow paths analysis of PMSG-based wind power integrated systems during LVRT and its parameter adjustment strategy
Authors: Xing Chao , Xi Xinze , He Xin , Deng Can , Zhang Mingqiang 
Published: June 2024

AbstractTo solve the problem of oscillation instability in permanent magnetic synchronous generator (PMSG)-based wind power connected systems during low-voltage ride through (LVRT) process, a parameter adjustment strategy based on interaction energy path optimization is proposed in this paper. Firstly, a modular state-space model of PMSG under fault transient conditions is constructed, and the system is divided into five subsystems. Then, the dynamic energy function of subsystems reflecting the oscillation stability of the system is derived. Based on that, the dynamic energy flow path is described considering the introduction of LVRT control. On this basis, the interaction energy between LVRT control links and subsystems is analyzed, and the coupling mechanism of voltage support and damping characteristics in the LVRT process is explained. Further, aiming at the optimal change rate of the total interaction energy in the LVRT process, the adjustment strategy of LVRT control parameters is constructed to meet voltage and damping requirements. Finally, a PMSG-connected system model is built on the MATLAB/Simulink platform to verify the effectiveness of the adjustment strategy. The results show that the proposed method can effectively improve the damping level under the fault transient condition, as well as supporting system voltage.
Novel CTD tag establishes shark fins as ocean observing platforms
Authors: Pagniello Camille M. L. S. , Castleton Michael R. , Carlisle Aaron B. , Chapple Taylor K. , Schallert Robert J. , Fedak Michael , Block Barbara A. 
Published: June 2024

AbstractAnimal-borne tags are effective instruments for collecting ocean data and can be used to fill spatial gaps in the observing network. We deployed the first conductivity, temperature, and depth (CTD) satellite tags on the dorsal fin of salmon sharks (Lamna ditropis) to demonstrate the potential of sharks to monitor essential ocean variables and oceanographic features in the Gulf of Alaska. Over 1360 km and 36 days in the summer of 2015, the salmon shark collected 56 geolocated, temperature-salinity profiles. The shark swam through a plume of anomalously salty water that originated from the “Blob” and encountered several mesoscale eddies, whose subsurface properties were altered by the marine heatwave. We demonstrate that salmon sharks have the potential to serve as submesoscale-resolving oceanographic platforms and substantially increase the spatial coverage of observations in the Gulf of Alaska.