bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency
Authors: Delling Jan Philipp , Bauer Helen Friedericke , Gerlach-Arbeiter Susanne , Schön Michael , Jacob Christian , Wagner Jan , Pedro Maria Teresa , Knöll Bernd , Boeckers Tobias M. 
Published: April 2024

AbstractSynaptic dysfunction is a key feature of SHANK-associated disorders such as autism spectrum disorder, schizophrenia, and Phelan-McDermid syndrome. Since detailed knowledge of their effect on synaptic nanostructure remains limited, we aimed to investigate such alterations in ex11|SH3 SHANK3-KO mice combining expansion and STED microscopy. This enabled high-resolution imaging of mosaic-like arrangements formed by synaptic proteins in both human and murine brain tissue. We found distinct shape-profiles as fingerprints of the murine postsynaptic scaffold across brain regions and genotypes, as well as alterations in the spatial and molecular organization of subsynaptic domains under SHANK3-deficient conditions. These results provide insights into synaptic nanostructure in situ and advance our understanding of molecular mechanisms underlying synaptic dysfunction in neuropsychiatric disorders.
Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk
Authors: Callander Natalie S. , Silbermann Rebecca , Kaufman Jonathan L. , Godby Kelly N. , Laubach Jacob , Schmidt Timothy M. , Sborov Douglas W. , Medvedova Eva , Reeves Brandi , Dhakal Binod , Rodriguez Cesar , Chhabra Saurabh , Chari Ajai , Bal Susan , Anderson Larry D. , Dholaria Bhagirathbhai R. , Nathwani Nitya , Hari Parameswaran , Shah Nina , Bumma Naresh , Holstein Sarah A. , Costello Caitlin , Jakubowiak Andrzej , Wildes Tanya M. , Orlowski Robert Z. , Shain Kenneth H. , Cowan Andrew J. , Pei Huiling , Cortoos Annelore , Patel Sharmila , Lin Thomas S. , Giri Smith , Costa Luciano J. , Usmani Saad Z. , Richardson Paul G. , Voorhees Peter M. 
Published: April 2024

AbstractIn the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10–5) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high–risk disease (≥2 HRCAs).
CK2α-mediated phosphorylation of GRP94 facilitates the metastatic cascade in triple-negative breast cancer
Authors: Kim Hye-Youn , Kim Young-Mi , Hong Suntaek 
Published: April 2024

Abstract
Distant metastasis is a significant hallmark affecting to the high death rate of patients with triple-negative breast cancer (TNBC). Thus, it is crucial to identify and develop new therapeutic strategies to hinder cancer metastasis. While emerging studies have hinted a pivotal role of glucose-regulated protein 94 (GRP94) in tumorigenesis, the exact biological functions and molecular mechanisms of GRP94 in modulating cancer metastasis remain to be elucidated. Our study demonstrated an increased expression of GRP94 in TNBC correlated with metastatic progression and unfavorable prognosis in patients. Functionally, we identified that GRP94 depletion significantly diminished TNBC tumorigenesis and subsequent lung metastasis. In contrast, GRP94 overexpression exacerbated the invasiveness, migration, and lung metastasis of non-TNBC cells. Mechanistically, we found that casein kinase 2 alpha (CK2α) active in advanced breast cancer phosphorylated GRP94 at a conserved serine 306 (S306) residue. This phosphorylation increased the stability of GRP94 and enhanced its interaction with LRP6, leading to activation of canonical Wnt signaling. From a therapeutic standpoint, we found that benzamidine, a novel CK2α inhibitor, effectively suppressed GRP94 phosphorylation, LRP6 stabilization, and metastasis of TNBC. Our results point to the critical role of CK2α-mediated GRP94 phosphorylation in TNBC metastasis through activation of Wnt signaling, highlighting GRP94 as a therapeutic target to impede TNBC metastasis.
Stable skyrmion bundles at room temperature and zero magnetic field in a chiral magnet
Authors: Zhang Yongsen , Tang Jin , Wu Yaodong , Shi Meng , Xu Xitong , Wang Shouguo , Tian Mingliang , Du Haifeng 
Published: April 2024

AbstractTopological spin textures are characterized by magnetic topological charges, Q, which govern their electromagnetic properties. Recent studies have achieved skyrmion bundles with arbitrary integer values of Q, opening possibilities for exploring topological spintronics based on Q. However, the realization of stable skyrmion bundles in chiral magnets at room temperature and zero magnetic field — the prerequisite for realistic device applications — has remained elusive. Here, through the combination of pulsed currents and reversed magnetic fields, we experimentally achieve skyrmion bundles with different integer Q values — reaching a maximum of 24 at above room temperature and zero magnetic field — in the chiral magnet Co8Zn10Mn2. We demonstrate the field-driven annihilation of high-Q bundles and present a phase diagram as a function of temperature and field. Our experimental findings are consistently corroborated by micromagnetic simulations, which reveal the nature of the skyrmion bundle as that of skyrmion tubes encircled by a fractional Hopfion.
Fabrication-induced even-odd discrepancy of magnetotransport in few-layer MnBi2Te4
Authors: Li Yaoxin , Wang Yongchao , Lian Zichen , Li Hao , Gao Zhiting , Xu Liangcai , Wang Huan , Lu Rui’e , Li Longfei , Feng Yang , Zhu Jinjiang , Liu Liangyang , Wang Yongqian , Fu Bohan , Yang Shuai , Yang Luyi , Wang Yihua , Xia Tianlong , Liu Chang , Jia Shuang , Wu Yang , Zhang Jinsong , Wang Yayu , Liu Chang 
Published: April 2024

AbstractThe van der Waals antiferromagnetic topological insulator MnBi2Te4 represents a promising platform for exploring the layer-dependent magnetism and topological states of matter. Recently observed discrepancies between magnetic and transport properties have aroused controversies concerning the topological nature of MnBi2Te4 in the ground state. In this article, we demonstrate that fabrication can induce mismatched even-odd layer dependent magnetotransport in few-layer MnBi2Te4. We perform a comprehensive study of the magnetotransport properties in 6- and 7-septuple-layer MnBi2Te4, and reveal that both even- and odd-number-layer device can show zero Hall plateau phenomena in zero magnetic field. Importantly, a statistical survey of the optical contrast in more than 200 MnBi2Te4 flakes reveals that the zero Hall plateau in odd-number-layer devices arises from the reduction of the effective thickness during the fabrication, a factor that was rarely noticed in previous studies of 2D materials. Our finding not only provides an explanation to the controversies regarding the discrepancy of the even-odd layer dependent magnetotransport in MnBi2Te4, but also highlights the critical issues concerning the fabrication and characterization of 2D material devices.
A global meta-analysis on the effects of organic and inorganic fertilization on grasslands and croplands
Authors: Shi Ting-Shuai , Collins Scott L. , Yu Kailiang , Peñuelas Josep , Sardans Jordi , Li Hailing , Ye Jian-Sheng 
Published: April 2024

AbstractA central role for nature-based solution is to identify optimal management practices to address environmental challenges, including carbon sequestration and biodiversity conservation. Inorganic fertilization increases plant aboveground biomass but often causes a tradeoff with plant diversity loss. It remains unclear, however, whether organic fertilization, as a potential nature-based solution, could alter this tradeoff by increasing aboveground biomass without plant diversity loss. Here we compile data from 537 experiments on organic and inorganic fertilization across grasslands and croplands worldwide to evaluate the responses of aboveground biomass, plant diversity, and soil organic carbon (SOC). Both organic and inorganic fertilization increase aboveground biomass by 56% and 42% relative to ambient, respectively. However, only inorganic fertilization decreases plant diversity, while organic fertilization increases plant diversity in grasslands with greater soil water content. Moreover, organic fertilization increases SOC in grasslands by 19% and 15% relative to ambient and inorganic fertilization, respectively. The positive effect of organic fertilization on SOC increases with increasing mean annual temperature in grasslands, a pattern not observed in croplands. Collectively, our findings highlight organic fertilization as a potential nature-based solution that can increase two ecosystem services of grasslands, forage production, and soil carbon storage, without a tradeoff in plant diversity loss.
Towards atom-level understanding of metal oxide catalysts for the oxygen evolution reaction with machine learning
Authors: Lunger Jaclyn R. , Karaguesian Jessica , Chun Hoje , Peng Jiayu , Tseo Yitong , Shan Chung Hsuan , Han Byungchan , Shao-Horn Yang , Gómez-Bombarelli Rafael 
Published: April 2024

AbstractGreen hydrogen production is crucial for a sustainable future, but current catalysts for the oxygen evolution reaction (OER) suffer from slow kinetics, despite many efforts to produce optimal designs, particularly through the calculation of descriptors for activity. In this study, we develop a dataset of density functional theory calculations of bulk and surface perovskite oxides, and adsorption energies of OER intermediates, which includes compositions up to quaternary and facets up to (555). We demonstrate that per-site properties of perovskite oxides such as Bader charge or band center can be tuned through element substitution and faceting, and develop a machine learning model that accurately predicts these properties directly from the local chemical environment. We leverage these per-site properties to identify promising perovskites with high theoretical OER activity. The identified design principles and promising materials provide a roadmap for closing the gap between current artificial catalysts and biological enzymes such as photosystem II.
Longitudinal cognitive decline characterizes the profile of non-PD-manifest GBA1 mutation carriers
Authors: Roeben Benjamin , Liepelt-Scarfone Inga , Lerche Stefanie , Zimmermann Milan , Wurster Isabel , Sünkel Ulrike , Schulte Claudia , Deuschle Christian , Eschweiler Gerhard W. , Maetzler Walter , Gasser Thomas , Berg Daniela , Brockmann Kathrin 
Published: April 2024

AbstractWith disease-modifying treatment for Parkinson’s disease (PD) associated with variants in the glucocerebrosidase gene (GBA1) under way, the challenge to design clinical trials with non-PD-manifest GBA mutation carriers (GBA1NMC) comes within close reach. To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1NMC, longitudinal data of 56 GBA1NMC carriers and 112 age- and sex-matched GBA1 wildtype participants (GBA1wildtype) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan–Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1NMC showed worse performance in Pegboard, 20 m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1NMC compared to GBA1wildtype, but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan–Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1NMC. Incidence of PD was significantly higher in GBA1NMC. In conclusion, our study extends data on GBA1NMC indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1NMC enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.
Interferon-induced transmembrane protein-1 competitively blocks Ephrin receptor A2-mediated Epstein–Barr virus entry into epithelial cells
Authors: Yang Yinggui , Ding Tengteng , Cong Ying , Luo Xiaomin , Liu Changlin , Gong Ting , Zhao Min , Zheng Xichun , Li Chenglin , Zhang Yuanbin , Zhou Jiayi , Ni Chuping , Zhang Xueyu , Ji Ziliang , Wu Tao , Yang Shaodong , Zhou Qingchun , Wu Dinglan , Gong Xinqi , Zheng Qingyou , Li Xin 
Published: April 2024

AbstractEpstein–Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1’s crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.
Multimodal cell atlas of the ageing human skeletal muscle
Authors: Lai Yiwei , Ramírez-Pardo Ignacio , Isern Joan , An Juan , Perdiguero Eusebio , Serrano Antonio L. , Li Jinxiu , García-Domínguez Esther , Segalés Jessica , Guo Pengcheng , Lukesova Vera , Andrés Eva , Zuo Jing , Yuan Yue , Liu Chuanyu , Viña José , Doménech-Fernández Julio , Gómez-Cabrera Mari Carmen , Song Yancheng , Liu Longqi , Xu Xun , Muñoz-Cánoves Pura , Esteban Miguel A. 
Published: April 2024

AbstractMuscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.
Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia
Authors: Dear Richard , Wagstyl Konrad , Seidlitz Jakob , Markello Ross D. , Arnatkevičiūtė Aurina , Anderson Kevin M. , Bethlehem Richard A. I. ,   Lifespan Brain Chart Consortium, Raznahan Armin , Bullmore Edward T. , Vértes Petra E. 
Published: April 2024

AbstractHuman brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1–C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development. Autism spectrum disorder and schizophrenia were specifically associated with C1/C2 and C3, respectively, across neuroimaging, differential expression and genome-wide association studies. Evidence converged especially in support of C3 as a normative transcriptional program for adolescent brain development, which can lead to atypical supragranular cortical connectivity in people at high genetic risk for schizophrenia.
Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation
Authors: Liu Julio C. Y. , Ackermann Leena , Hoffmann Saskia , Gál Zita , Hendriks Ivo A. , Jain Charu , Morlot Louise , Tatham Michael H. , McLelland Gian-Luca , Hay Ronald T. , Nielsen Michael Lund , Brummelkamp Thijn , Haahr Peter , Mailand Niels 
Published: April 2024

AbstractProtein SUMOylation provides a principal driving force for cellular stress responses, including DNA–protein crosslink (DPC) repair and arsenic-induced PML body degradation. In this study, using genome-scale screens, we identified the human E3 ligase TOPORS as a key effector of SUMO-dependent DPC resolution. We demonstrate that TOPORS promotes DPC repair by functioning as a SUMO-targeted ubiquitin ligase (STUbL), combining ubiquitin ligase activity through its RING domain with poly-SUMO binding via SUMO-interacting motifs, analogous to the STUbL RNF4. Mechanistically, TOPORS is a SUMO1-selective STUbL that complements RNF4 in generating complex ubiquitin landscapes on SUMOylated targets, including DPCs and PML, stimulating efficient p97/VCP unfoldase recruitment and proteasomal degradation. Combined loss of TOPORS and RNF4 is synthetic lethal even in unstressed cells, involving defective clearance of SUMOylated proteins from chromatin accompanied by cell cycle arrest and apoptosis. Our findings establish TOPORS as a STUbL whose parallel action with RNF4 defines a general mechanistic principle in crucial cellular processes governed by direct SUMO–ubiquitin crosstalk.
CROPGRIDS: a global geo-referenced dataset of 173 crops
Authors: Tang Fiona H. M. , Nguyen Thu Ha , Conchedda Giulia , Casse Leon , Tubiello Francesco N. , Maggi Federico 
Published: April 2024

AbstractCROPGRIDS is a comprehensive global geo-referenced dataset providing area information for 173 crops for the year 2020, at a resolution of 0.05° (about 5.6 km at the equator). It represents a major update of the Monfredaet al. (2008) dataset (hereafter MRF), the most widely used geospatial dataset previously available, covering 175 crops with reference year 2000 at 10 km spatial resolution. CROPGRIDS builds on information originally provided in MRF and expands it using 27 selected published gridded datasets, subnational data of 52 countries obtained from National Statistical Offices, and the 2020 national-level statistics from FAOSTAT, providing more recent harvested and crop (physical) areas for 173 crops at regional, national, and global levels. The CROPGRIDS data advance the current state of knowledge on the spatial distribution of crops, providing useful inputs for modelling studies and sustainability analyses relevant to national and international processes.
An annotated street view image dataset for automated road damage detection
Authors: Ren Miao , Zhang Xianfeng , Zhi Xiaobo , Wei Yuanjia , Feng Ziyuan 
Published: April 2024

AbstractRoad damage is a great threat to the service life and safety of roads, and the early detection of pavement damage can facilitate maintenance and repair. Street view images serve as a new solution for the monitoring of pavement damage due to their wide coverage and regular updates. In this study, a road pavement damage dataset, the Street View Image Dataset for Automated Road Damage Detection (SVRDD), was developed using 8000 street view images acquired from Baidu Maps. Based on these images, over 20,000 damage instances were visually recognized and annotated. These instances were distributed in five administrative districts of Beijing City. Ten well-established object detection algorithms were trained and assessed using the SVRDD dataset. The results have demonstrated the performances of these algorithms in the detection of pavement damages. To the best of our knowledge, SVRDD is the first public dataset based on street view images for pavement damages detection. It can provide reliable data support for future development of deep learning algorithms based on street view images.
Investigation of thrombin concentration at the time of clot formation in simultaneous thrombin and fibrin generation assays
Authors: Tarandovskiy Ivan D. , Surov Stepan S. , Parunov Leonid A. , Liang Yideng , Jankowski Wojciech , Sauna Zuben E. , Ovanesov Mikhail V. 
Published: April 2024

AbstractThrombin generation (TG) and fibrin clot formation represent the central process of blood coagulation. Up to 95% of thrombin is considered to be generated after the clot is formed. However, this was not investigated in depth. In this study, we conducted a quantitative analysis of the Thrombin at Clot Time (TCT) parameter in 5758 simultaneously recorded TG and clot formation assays using frozen plasma samples from commercial sources under various conditions of activation. These samples were supplemented with clotting factor concentrates, procoagulant lipid vesicles and a fluorogenic substrate and triggered with tissue factor (TF). We found that TCT is often close to a 10% of thrombin peak height (TPH) yet it can be larger or smaller depending on whether the sample has low or high TPH value. In general, the samples with high TPH are associated with elevated TCT. TCT appeared more sensitive to some procoagulant phenotypes than other commonly used parameters such as clotting time, TPH or Thrombin Production Rate (TPR). In a minority of cases, TCT were not predicted from TG parameters. For example, elevated TCT (above 15% of TPH) was associated with either very low or very high TPR values. We conclude that clotting and TG assays may provide complementary information about the plasma sample, and that the TCT parameter may serve as an additional marker for the procoagulant potential in plasma sample.