bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAPK4 inhibits the early aberrant activation of B cells in rheumatoid arthritis by promoting the IRF4-SHIP1 signaling pathway
Authors: Huang Pei , Yang Guangli , Zhang Pingping , Zhu Yin , Guan Yaning , Sun Jian , Li Qian , An Yang , Shi Xiaoqi , Zhao Juanjuan , Liu Chaohong , He Zhixu , Chen Yan , Du Zuochen 
Published: January 2025

Abstract
The involvement of B lymphocytes in the pathogenesis of rheumatoid arthritis (RA) is well-established, with their early and aberrant activation being a crucial factor. However, the mechanisms underlying this abnormal activation in RA remain incompletely understood. In this study, we identified a significant reduction in MAPK4 expression in both RA patients and collagen-induced arthritis (CIA) mouse models, which correlates with disrupted B cell activation. Using MAPK4 knockout (KO) mice, we demonstrated that MAPK4 intrinsically promotes the differentiation of marginal zone (MZ) B cells. Loss of MAPK4 in KO mice enhances proximal BCR signaling and activates the PI3K-AKT-mTOR pathway, leading to heightened B cell proliferation. Notably, B cells from MAPK4 KO mice produce significantly higher levels of IL-6, a key pro-inflammatory cytokine in RA. Furthermore, MAPK4 KO mice exhibit impaired T cell-independent humoral immune responses. Mechanistically, MAPK4 inhibits the activation of the PI3K signaling pathway in B cells by activating the IRF4-SHIP1 pathway. Treatment with the MAPK4 agonist Vacquinol-1 enhances MZ B cell differentiation in WT mice and reduces IL-6 secretion in CIA mouse models. In summary, this study reveals the diverse roles of MAPK4 in regulating of B cell functions, with potential implications for developing therapeutic strategies for RA and related autoimmune diseases.
Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics
Authors: Rat Anaïs , Martinez Fernandez Veronica , Doumic Marie , Teixeira Maria Teresa , Xu Zhou 
Published: January 2025

Abstract
Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells. Simulations of yeast populations, where cells with varying proliferation capacities compete against each other, show that the distribution of telomere lengths of the initial population shapes population growth, especially through the distribution of cells’ shortest telomere lengths. We also quantified how factors influencing cell viability independently of telomeres can impact senescence rates. Overall, we demonstrate a temporal evolution in the composition of senescent cell populations—from a state directly linked to critically short telomeres to a state where senescence onset becomes stochastic. This population structure may promote genome instability and facilitate senescence escape.
Nonlinearity of the post-spinel transition and its expression in slabs and plumes worldwide
Authors: Dong Junjie , Fischer Rebecca A. , Stixrude Lars P. , Brennan Matthew C. , Daviau Kierstin , Suer Terry-Ann , Turner Katlyn M. , Meng Yue , Prakapenka Vitali B. 
Published: January 2025

Abstract
Phase transitions in the mantle control its internal dynamics and structure. The post-spinel transition marks the upper–lower mantle boundary, where ringwoodite dissociates into bridgmanite plus ferropericlase, and its Clapeyron slope regulates mantle flow across it. This interaction has previously been assumed to have no lateral spatial variations, based on the assumption of a linear post-spinel boundary in pressure and temperature. Here we present laser-heated diamond anvil cell experiments with synchrotron X-ray diffraction to better constrain this boundary, especially at higher temperatures. Combining our data with results from the literature, and using a global analysis based on machine learning, we find a pronounced nonlinearity in the post-spinel boundary, with its slope ranging from –4 MPa/K at 2100 K, to –2 MPa/K at 1950 K, and to 0 MPa/K at 1600 K. Changes in temperature over time and space can therefore cause the post-spinel transition to have variable effects on mantle convection and the movement of subducting slabs and upwelling plumes.
LDPC-cat codes for low-overhead quantum computing in 2D
Authors: Ruiz Diego , Guillaud Jérémie , Leverrier Anthony , Mirrahimi Mazyar , Vuillot Christophe 
Published: January 2025

Abstract
The main obstacle to large scale quantum computing are the errors present in every physical qubit realization. Correcting these errors requires a large number of additional qubits. Two main avenues to reduce this overhead are (i) low-density parity check (LDPC) codes requiring very few additional qubits to correct errors (ii) cat qubits where bit-flip errors are exponentially suppressed by design. In this work, we combine both approaches to obtain an extremely low overhead architecture. Assuming a physical phase-flip error probability ϵ ≈ 0.1% per qubit and operation, one hundred logical qubits can be implemented on a 758 cat qubit chip, with a total logical error probability per cycle and per logical qubit ϵ

L
≤ 10−8. Our architecture also features two major advantages. First, the hardware implementation of the code can be realised with short-range qubit interactions in 2D and low-weight stabilizers, under constraints similar to those of the popular surface code architecture. Second, we demonstrate how to implement a fault-tolerant universal set of logical gates with an additional layer of routing cat qubits stacked on top of the LDPC layer, while maintaining the local connectivity. Furthermore, our architecture benefits from a high capacity of parallelization for these logical gates.
Mechano-gated iontronic piezomemristor for temporal-tactile neuromorphic plasticity
Authors: Wei Xiao , Wu Zhixin , Gao Hanfei , Cao Shiqi , Meng Xue , Lan Yuqun , Su Huixue , Qin Zhenglian , Liu Hang , Du Wenxin , Wu Yuchen , Liu Mingjie , Zhao Ziguang 
Published: January 2025

Abstract
In bioneuronal systems, the synergistic interaction between mechanosensitive piezo channels and neuronal synapses can convert and transmit pressure signals into complex temporal plastic pulses with excitatory and inhibitory features. However, existing artificial tactile neuromorphic systems struggle to replicate the elaborate temporal plasticity observed between excitatory and inhibitory features in biological systems, which is critical for the biomimetic processing and memorizing of tactile information. Here we demonstrate a mechano-gated iontronic piezomemristor with programmable temporal-tactile plasticity. This system utilizes a bicontinuous phase-transition heterogel as a stiffness-governed iontronic mechanogate to achieve bidirectional piezoresistive signals, resulting in wide-span dynamic tactile sensing. By micro-integrating the mechanogate with an oscillatory iontronic memristor, it exhibits stiffness-induced bipolarized excitatory and inhibitory neuromorphics, thereby enabling the activation of temporal-tactile memory and learning functions (e.g., Bienenstock–Cooper–Munro and Hebbian learning rules). Owing to dynamic covalent bond network and iontronic features, reconfigurable tactile plasticity can be achieved. Importantly, bridging to bioneuronal interfaces, these systems possess the capacity to construct a biohybrid perception-actuation circuit. We anticipate that such temporal plastic piezomemristor devices for abiotic-biotic interfaces can serve as promising hardware systems for interfacing dynamic tactile behaviors into diverse neuromodulations.
Machine learning Hubbard parameters with equivariant neural networks
Authors: Uhrin Martin , Zadoks Austin , Binci Luca , Marzari Nicola , Timrov Iurii 
Published: January 2025

Abstract
Density-functional theory with extended Hubbard functionals (DFT + U + V) provides a robust framework to accurately describe complex materials containing transition-metal or rare-earth elements. It does so by mitigating self-interaction errors inherent to semi-local functionals which are particularly pronounced in systems with partially-filled d and f electronic states. However, achieving accuracy in this approach hinges upon the accurate determination of the on-site U and inter-site V Hubbard parameters. In practice, these are obtained either by semi-empirical tuning, requiring prior knowledge, or, more correctly, by using predictive but expensive first-principles calculations. Here, we present a machine learning model based on equivariant neural networks which uses atomic occupation matrices as descriptors, directly capturing the electronic structure, local chemical environment, and oxidation states of the system at hand. We target here the prediction of Hubbard parameters computed self-consistently with iterative linear-response calculations, as implemented in density-functional perturbation theory (DFPT), and structural relaxations. Remarkably, when trained on data from 12 materials spanning various crystal structures and compositions, our model achieves mean absolute relative errors of 3% and 5% for Hubbard U and V parameters, respectively. By circumventing computationally expensive DFT or DFPT self-consistent protocols, our model significantly expedites the prediction of Hubbard parameters with negligible computational overhead, while approaching the accuracy of DFPT. Moreover, owing to its robust transferability, the model facilitates accelerated materials discovery and design via high-throughput calculations, with relevance for various technological applications.
Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial
Authors: Kopetz Scott , Yoshino Takayuki , Van Cutsem Eric , Eng Cathy , Kim Tae Won , Wasan Harpreet Singh , Desai Jayesh , Ciardiello Fortunato , Yaeger Rona , Maughan Timothy S. , Beyzarov Elena , Zhang Xiaoxi , Ferrier Graham , Zhang Xiaosong , Tabernero Josep 
Published: January 2025

Abstract
Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403–4.253; 99.8% CI: 1.019–5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318–0.691; repeated CI: 0.166–1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421.
Genomic analysis of three medieval parchments from German monasteries
Authors: Heinrich Felix , Simianer Henner , Bölling Jörg , Röckelein Hedwig , Roos Christian , Reimer Christian , Schmitt Armin O. 
Published: January 2025

Abstract
In the last two decades there has been growing interest in the analysis of ancient DNA obtained from the parchment used in historic documents. The genetic insight that this data provides makes collections of historic documents an invaluable source for studying the development and spread of historical livestock populations. Additionally, the biological data may provide new information for the historical analysis that could be used to determine the provenance as well as the authenticity of these documents. In this study, we extracted DNA from three medieval parchments that were written in German monasteries in the twelfth century. The source animal of the parchments could be identified as cattle and we compared their genome sequences with those of modern populations that are part of the 1000 Bull Genomes Project. The three animals were found to carry mtDNA haplogroup T3 and show a closer genetic relationship to other historic animals than to modern breeds. We further identified 39 haplotypes and 132 SNPs variants, which are rare (

$$<0.1$$

<
0.1

) or even non-existent in modern breeds. Finally, the genetic distances between the parchment samples show a putative association with the dates when the documents were written, indicating the usefulness of genetic analysis for provenance research.
Imaging flow cytometry reveals the mechanism of equine arteritis virus entry and internalization
Authors: Kublicka Agata , Lorek Daria , Mikołajczyk-Martinez Agata , Chodaczek Grzegorz , Chwirot Aleksandra , Bażanów Barbara , Matczuk Anna Karolina 
Published: January 2025

Abstract
The process of viral entry into host cells is crucial for the establishment of infection and the determination of viral pathogenicity. A comprehensive understanding of entry pathways is fundamental for the development of novel therapeutic strategies. Standard techniques for investigating viral entry include confocal microscopy and flow cytometry, both of which provide complementary qualitative and quantitative data. Imaging flow cytometry, which integrates the advantages of both methodologies, offers significant potential in virological studies. In this investigation, we employed imaging flow cytometry coupled with immunostaining to monitor the entry of equine arteritis virus EAV into Vero cells via the endosomal trafficking route. Analysis provided an insight into the early infection dynamics across thousands of cells, revealing statistically significant alterations in internalization and uncoating process. Moreover, we evaluated the effectiveness of two inhibitors targeting cellular factors involved in facilitating viral entry: ammonium chloride, which disrupts endocytosis, and camostat mesylate, which inhibits the activity of serine proteases. The results demonstrated a clear distinction between effective and ineffective inhibitors. This study highlighted the potential of imaging flow cytometry to advance the study of viral entry and the evaluation of antiviral agents.
Lactiplantibacillus plantarum 22 A-3 ameliorates leaky gut in mice through its anti-inflammatory effects
Authors: Kobayashi Takashi , Kessoku Takaomi , Iwaki Michihiro , Nogami Asako , Yoneda Masato , Saito Satoru , Yamana Yoshie , Nishitani Yosuke , Kuwahara Hiroshige , Nakajima Atsushi 
Published: January 2025

Abstract
There are limited studies on the improvement of leaky gut with minor inflammation associated with various diseases. To explore the therapeutic potential of Lactiplantibacillus plantarum 22 A-3, a member of the Lactobacillus species, in addressing a leaky gut. Lactiplantibacillus plantarum 22 A-3 was administered to a leaky gut mice model with low dextran sulfate sodium concentrations. The Lactiplantibacillus plantarum 22 A-3-treated group exhibited amelioration of increased intestinal permeability, as indicated by lower blood fluorescein isothiocyanate-dextran levels compared with that of the control group. Furthermore, the messenger RNA expression of interleukin-10, an anti-inflammatory cytokine, was upregulated in the small intestine of Lactiplantibacillus plantarum 22 A-3-treated mice. Moreover, forkhead box P3 was upregulated in the small intestine and colon following Lactiplantibacillus plantarum 22 A-3 administration. Flow cytometry showed that forkhead box P3-positive regulatory T cells tended to increase in the small intestine and colon; however, this was not significant. Messenger RNA levels for the pro-inflammatory cytokines, interleukin-1 beta, and tumor necrosis factor-alpha showed no significant changes in the small intestine; however, their expressions significantly decreased in the colon. Blood fluorescein isothiocyanate-dextran levels showed that intestinal permeability also decreased in Lactiplantibacillus plantarum 22 A-3-dead bacteria. The bacterial component of Lactiplantibacillus plantarum 22 A-3 ameliorates increased intestinal permeability through its anti-inflammatory effect in the intestinal tract and may be a novel treatment for leaky gut.
Genetic analysis reveals the genetic diversity and zoonotic potential of Streptococcus dysgalactiae isolates from sheep
Authors: Stefańska Ilona , Kwiecień Ewelina , Didkowska Anna , Kizerwetter-Świda Magdalena , Chrobak-Chmiel Dorota , Sałamaszyńska-Guz Agnieszka , Żmuda Piotr , Anusz Krzysztof , Rzewuska Magdalena 
Published: January 2025

Abstract

Streptococcus dysgalactiae (S. dysgalactiae ) is a common pathogen of humans and various animals. However, the phylogenetic position of animal S. dysgalactiae isolates and their zoonotic potential remain unclear. Most molecular epidemiological studies explicate beta-hemolytic streptococci according to their MLST and M protein gene (emm) types. Although human S. dysgalactiae isolates are relatively well characterized, the data concerning animal isolates are scarce. Here, we report the molecular characteristics and antimicrobial resistance of S. dysgalactiae strains recovered from sheep and their genetic relationship with isolates from other animal hosts and humans. Overall, 11 PFGE pulsotypes, five MLST sequence types (STs), and two emm types were distinguished, with ST248 and stL1376 being the most prevalent, indicating genetic diversity among tested 17 ovine isolates. Some isolates exhibited resistance to doxycycline (59%), erythromycin (6%), ciprofloxacin (6%), and trimethoprim/sulfamethoxazole (6%), harboring various resistance determinants. Phylogenetic analysis showed that studied ovine isolates grouped together with human S. dysgalactiae isolates from the cases of zoonotic infections. Moreover, some ovine isolates shared identical STs and emm gene sequences with human non-invasive and invasive S. dysgalactiae strains. These findings suggest a possible link between human and ovine isolates and indicate the zoonotic potential of this pathogen.
Novel transcripts of EMT driving the malignant transformation of oral submucous fibrosis
Authors: Shetty Smitha Sammith , Ram Padam Kanaka Sai , Sharma Mohit , Kudva Adarsh , Patel Pratik , Radhakrishnan Raghu 
Published: January 2025

Abstract
Oral submucous fibrosis (OSF) is a chronic, progressive, and fibrotic condition of the oral mucosa that carries an elevated risk of malignant transformation. We aimed to identify and validate novel genes associated with the regulation of epithelial-to-mesenchymal transition (EMT) in OSF. Genes regulating EMT were identified through differential gene expression analysis, using a LogFC threshold of -1 and + 1 and a padj value < 0.05, based on data from GEO datasets and the TCGA-HNSC datasets. The curated EMT genes were correlated with functional cancer states and subjected to clustering to identify candidate genes. Integration of bioinformatics and proteomics led to the discovery of the EMT genes MMP9, SPARC, and ITGA5 as novel candidates. Comprehensive pathway and immunohistochemical analyses confirmed their roles in regulating EMT in OSF, oral squamous cell carcinoma (OSCC), and OSF-associated squamous cell carcinoma (OSFSCC). The significant roles of MMP9, SPARC, and ITGA5 in fibrosis and malignancy suggest a novel mechanism in which fibrosis-associated type 2 EMT undergoes transition to type 3 EMT, driving OSF towards malignancy.
Asymptomatic female softball pitchers have altered hip morphology and cartilage composition
Authors: Warden Stuart J. , Coburn Sally L. , Fuchs Robyn K. , Surowiec Rachel K. , Carballido-Gamio Julio , Kemp Joanne L. , Jalaie Peter K. , Hanff David F. , Palmer Antony J. R. , Fernquest Scott J. , Crossley Kay M. , Heerey Joshua J. 
Published: January 2025

Abstract
Few studies have explored hip morphology and cartilage composition in female athletes or the impact of asymmetric repetitive loading, such as occurs during softball pitching. The current cross-sectional study assessed bilateral bony hip morphology on computed tomography imaging in collegiate-level softball pitchers (‘Pitch1’, n = 25) and cross-country runners (‘Run’, n = 13). Magnetic resonance imaging was used to assess cartilage relaxation times in a second cohort of pitchers (‘Pitch2’, n = 10) and non-athletic controls (‘Con’, n = 4). Pitch1 had 52% greater maximum alpha angle than Run (p < 0.001) and were 21.3 (95% CI 2.4 to 192.0) times more likely to have an alpha angle ≥ 60° within at least one hip. Pitch2 had longer T2 relaxation times in the superior femoral cartilage of the drive leg (same side as the throwing arm) and stride leg than Con (all p < 0.02). The drive leg in Pitch2 had longer T1ρ and T2 relaxation times in the superior femoral cartilage compared to the stride leg (all p ≤ 0.03). Asymptomatic softball pitchers exhibit altered bony hip morphology and cartilage composition compared to cross-country runners and non-athletic controls, respectively. They also exhibit asymmetry in cartilage composition. Further studies with larger sample sizes are warranted and any potential long-term consequences of the changes in terms of symptom and osteoarthritis development requires investigation.
Shifted dominant flood drivers of an alpine glacierized catchment in the Tianshan region revealed through interpretable deep learning
Authors: Liang Wenting , Duan Weili , Chen Yaning , Fang Gonghuan , Zou Shan , Li Zhi , Qiu Zewei , Lyu Haodong 
Published: January 2025

Abstract
The Kumalak River, a typical alpine glacierized catchment in the Tianshan region, experiences complex flooding driven by glacier meltwater, snowmelt, and rainfall. However, the mechanisms driving these processes under climate change remain unclear. To address this, a SWAT-Glacier hydrological model and a degree–day factor model were used for snowmelt, glacier meltwater, and rainfall calculations. Two Long Short-Term Memory (LSTM) models (LSTM-SG and LSTM-DDF) were developed using these inputs, and additive decomposition and integrated gradient methods were applied to interpret flood mechanisms. Glacier meltwater was found to dominate annual maximum flood (AMF) events, while snowmelt drove annual spring maximum flood (AMFSp) events. For AMF events (1960–2018), contributions were 10.01–12.21% from snowmelt, 60.49–60.92% from glacier meltwater, and 26.86–29.50% from rainfall. For AMFSp events (1961–2018), contributions were 48.49–56.08% from snowmelt, 16.12–22.08% from glacier meltwater, and 27.79–29.42% from rainfall. These findings provide critical insights for enhancing flood prediction and optimizing water resource management.