bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffusion models for conditional generation of hypothetical new families of superconductors
Authors: Yuan Samuel , Dordevic S. V. 
Published: May 2024

AbstractEffective computational search holds great potential for aiding the discovery of high-temperature superconductors (HTSs), especially given the lack of systematic methods for their discovery. Recent progress has been made in this area with machine learning, especially with deep generative models, which have been able to outperform traditional manual searches at predicting new superconductors within existing superconductor families but have yet to be able to generate completely new families of superconductors. We address this limitation by implementing conditioning—a method to control the generation process—for our generative model and develop SuperDiff, a denoising diffusion probabilistic model with iterative latent variable refinement conditioning for HTS discovery—the first deep generative model for superconductor discovery with conditioning on reference compounds. With SuperDiff, by being able to control the generation process, we were able to computationally generate completely new families of hypothetical superconductors for the very first time. Given that SuperDiff also has relatively fast training and inference times, it has the potential to be a very powerful tool for accelerating the discovery of new superconductors and enhancing our understanding of them.
The stress-responsive cytotoxic effect of diesel exhaust particles on lymphatic endothelial cells
Authors: Sakurai Yu , Oba Eiki , Honda Akiko , Tanaka Hiroki , Takano Hirohisa , Akita Hidetaka 
Published: May 2024

AbstractDiesel exhaust particles (DEPs) are very small (typically < 0.2 μm) fragments that have become major air pollutants. DEPs are comprised of a carbonaceous core surrounded by organic compounds such as polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs. Inhaled DEPs reach the deepest sites in the respiratory system where they could induce respiratory/cardiovascular dysfunction. Additionally, a previous study has revealed that a portion of inhaled DEPs often activate immune cells and subsequently induce somatic inflammation. Moreover, DEPs are known to localize in lymph nodes. Therefore, in this study we explored the effect of DEPs on the lymphatic endothelial cells (LECs) that are a constituent of the walls of lymph nodes. DEP exposure induced cell death in a reactive oxygen species (ROS)-dependent manner. Following exposure to DEPs, next-generation sequence (NGS) analysis identified an upregulation of the integrated stress response (ISR) pathway and cell death cascades. Both the soluble and insoluble components of DEPs generated intracellular ROS. Three-dimensional Raman imaging revealed that DEPs are taken up by LECs, which suggests internalized DEP cores produce ROS, as well as soluble DEP components. However, significant cell death pathways such as apoptosis, necroptosis, ferroptosis, pyroptosis, and parthanatos seem unlikely to be involved in DEP-induced cell death in LECs. This study clarifies how DEPs invading the body might affect the lymphatic system through the induction of cell death in LECs.
Predicting bladder cancer survival with high accuracy: insights from MAPK pathway-related genes
Authors: Cheng Guangyang , Zhou Zhaokai , Li Shiqi , Yang Shuai , Wang Yan , Ye Zhuo , Ren Chuanchuan 
Published: May 2024

AbstractThe mitogen-activated protein kinase (MAPK) pathway plays a critical role in tumor development and immunotherapy. Nevertheless, additional research is necessary to comprehend the relationship between the MAPK pathway and the prognosis of bladder cancer (BLCA), as well as its influence on the tumor immune microenvironment. To create prognostic models, we screened ten genes associated with the MAPK pathway using COX and least absolute shrinkage and selection operator (LASSO) regression analysis. These models were validated in the Genomic Data Commons (GEO) cohort and further examined for immune infiltration, somatic mutation, and drug sensitivity characteristics. Finally, the findings were validated using The Human Protein Atlas (HPA) database and through Quantitative Real-time PCR (qRT-PCR). Patients were classified into high-risk and low-risk groups based on the prognosis-related genes of the MAPK pathway. The high-risk group had poorer overall survival than the low-risk group and showed increased immune infiltration compared to the low-risk group. Additionally, the nomograms built using the risk scores and clinical factors exhibited high accuracy in predicting the survival of BLCA patients. The prognostic profiling of MAPK pathway-associated genes represents a potent clinical prediction tool, serving as the foundation for precise clinical treatment of BLCA.
Detection method for contact stress distribution of tapered roller bearings
Authors: Ji Ye , Ma Xinzhong , Zheng Haotian , Huang Kun , Wang Sheng , Zhang Danwen 
Published: May 2024

AbstractThe axle box of high-speed train adopts double row tapered roller bearings as transmission parts, and the reliability of bearings directly affects the safety of train operation. Tapered roller bearings can withstand axial and radial loads, their service life being closely related to the distribution of contact stress. The test object is the axle box bearing of high-speed train. According to bearing’s structural characteristics, based on the digital speckle correlation method (DSCM) and machine vision, the contact stress distribution detection devices for rollers and complete sets of bearings are developed respectively and an effective detection method is proposed. The contact stress data of the bearing which has reached the service life and the new bearing under the condition of no lubrication and grease lubrication are collected and normalized. Through the geometric relationship, based on the measured data of the selected detection points, the normal and tangential contact stress distribution of the roller and raceway under different contact conditions is obtained by data fitting. The test can be used as an evaluation basis for the effectiveness of bearing modification and provide reference for bearing design.
Multimodal data fusion using sparse canonical correlation analysis and cooperative learning: a COVID-19 cohort study
Authors: Er Ahmet Gorkem , Ding Daisy Yi , Er Berrin , Uzun Mertcan , Cakmak Mehmet , Sadee Christoph , Durhan Gamze , Ozmen Mustafa Nasuh , Tanriover Mine Durusu , Topeli Arzu , Aydin Son Yesim , Tibshirani Robert , Unal Serhat , Gevaert Olivier 
Published: May 2024

AbstractThrough technological innovations, patient cohorts can be examined from multiple views with high-dimensional, multiscale biomedical data to classify clinical phenotypes and predict outcomes. Here, we aim to present our approach for analyzing multimodal data using unsupervised and supervised sparse linear methods in a COVID-19 patient cohort. This prospective cohort study of 149 adult patients was conducted in a tertiary care academic center. First, we used sparse canonical correlation analysis (CCA) to identify and quantify relationships across different data modalities, including viral genome sequencing, imaging, clinical data, and laboratory results. Then, we used cooperative learning to predict the clinical outcome of COVID-19 patients: Intensive care unit admission. We show that serum biomarkers representing severe disease and acute phase response correlate with original and wavelet radiomics features in the LLL frequency channel (cor(Xu1, Zv1) = 0.596, p value < 0.001). Among radiomics features, histogram-based first-order features reporting the skewness, kurtosis, and uniformity have the lowest negative, whereas entropy-related features have the highest positive coefficients. Moreover, unsupervised analysis of clinical data and laboratory results gives insights into distinct clinical phenotypes. Leveraging the availability of global viral genome databases, we demonstrate that the Word2Vec natural language processing model can be used for viral genome encoding. It not only separates major SARS-CoV-2 variants but also allows the preservation of phylogenetic relationships among them. Our quadruple model using Word2Vec encoding achieves better prediction results in the supervised task. The model yields area under the curve (AUC) and accuracy values of 0.87 and 0.77, respectively. Our study illustrates that sparse CCA analysis and cooperative learning are powerful techniques for handling high-dimensional, multimodal data to investigate multivariate associations in unsupervised and supervised tasks.
Strong economic incentives of ship scrubbers promoting pollution
Authors: Lunde Hermansson Anna , Hassellöv Ida-Maja , Grönholm Tiia , Jalkanen Jukka-Pekka , Fridell Erik , Parsmo Rasmus , Hassellöv Jesper , Ytreberg Erik 
Published: May 2024

AbstractIn response to stricter regulations on ship air emissions, many shipowners have installed exhaust gas cleaning systems, known as scrubbers, allowing for use of cheap residual heavy fuel oil. Scrubbers produce large volumes of acidic and polluted water that is discharged to the sea. Due to environmental concerns, the use of scrubbers is being discussed within the International Maritime Organization. Real-world simulations of global scrubber-vessel activity, applying actual fuel costs and expenses related to scrubber operations, show that 51% of the global scrubber-fitted fleet reached economic break even by the end of 2022, with a surplus of €4.7 billion in 2019 euros. Within five years after installation, more than 95% of the ships with the most common scrubber systems reach break even. However, the marine ecotoxicity damage cost, from scrubber water discharge in the Baltic Sea Area 2014–2022, amounts to >€680 million in 2019 euros, showing that private economic interests come at the expense of marine environmental damage.
C–heteroatom coupling with electron-rich aryls enabled by nickel catalysis and light
Authors: Ni Shengyang , Halder Riya , Ahmadli Dilgam , Reijerse Edward J. , Cornella Josep , Ritter Tobias 
Published: May 2024

AbstractNickel photoredox catalysis has resulted in a rich development of transition-metal-catalysed transformations for carbon–heteroatom bond formation. By harnessing light energy, the transition metal can attain oxidation states that are difficult to achieve through thermal chemistry in a catalytic manifold. For example, nickel photoredox reactions have been reported for both the synthesis of anilines and aryl ethers from aryl(pseudo)halides. However, oxidative addition to simple nickel systems is often sluggish in the absence of special, electron-rich ligands, leading to catalyst decomposition. Electron-rich aryl electrophiles therefore currently fall outside the scope of many transformations in the field. Here we provide a conceptual solution to this problem and demonstrate nickel-catalysed C–heteroatom bond-forming reactions of arylthianthrenium salts, including amination, oxygenation, sulfuration and halogenation. Because the redox properties of arylthianthrenium salts are primarily dictated by the thianthrenium, oxidative addition of highly electron-rich aryl donors can be unlocked using simple NiCl2 under light irradiation to form the desired C‒heteroatom bonds.
E4BP4 in macrophages induces an anti-inflammatory phenotype that ameliorates the severity of colitis
Authors: Kajimura Yasuko , Taguchi Akihiko , Nagao Yuko , Yamamoto Kaoru , Masuda Konosuke , Shibata Kensuke , Asaoka Yoichi , Furutani-Seiki Makoto , Tanizawa Yukio , Ohta Yasuharu 
Published: May 2024

AbstractMacrophages are versatile cells of the innate immune system that work by altering their pro- or anti-inflammatory features. Their dysregulation leads to inflammatory disorders such as inflammatory bowel disease. We show that macrophage-specific upregulation of the clock output gene and transcription factor E4BP4 reduces the severity of colitis in mice. RNA-sequencing and single-cell analyses of macrophages revealed that increased expression of E4BP4 leads to an overall increase in expression of anti-inflammatory genes including Il4ra with a concomitant reduction in pro-inflammatory gene expression. In contrast, knockout of E4BP4 in macrophages leads to increased proinflammatory gene expression and decreased expression of anti-inflammatory genes. ChIP-seq and ATAC-seq analyses further identified Il4ra as a target of E4BP4, which drives anti-inflammatory polarization in macrophages. Together, these results reveal a critical role for E4BP4 in regulating macrophage inflammatory phenotypes and resolving inflammatory bowel diseases.
Midkine promotes renal fibrosis by stabilizing C/EBPβ to facilitate endothelial-mesenchymal transition
Authors: Xu Cuidi , Chen Juntao , Liang Lifei , Chen Siyue , Niu Xinhao , Sang Ruirui , Yang Cheng , Rong Ruiming 
Published: May 2024

AbstractNumerous myofibroblasts are arisen from endothelial cells (ECs) through endothelial to mesenchymal transition (EndMT) triggered by TGF-β. However, the mechanism of ECs transforms to a different subtype, or whether there exists an intermediate state of ECs remains unclear. In present study, we demonstrate Midkine (MDK) mainly expressed by CD31 + ACTA2+ECs going through partial EndMT contribute greatly to myofibroblasts by spatial and single-cell transcriptomics. MDK is induced in TGF-β treated ECs, which upregulates C/EBPβ and increases EndMT genes, and these effects could be reversed by siMDK. Mechanistically, MDK promotes the binding ability of C/EBPβ with ACTA2 promoter by stabilizing the C/EBPβ protein. In vivo, knockout of Mdk or conditional knockout of Mdk in ECs reduces EndMT markers and significantly reverses fibrogenesis. In conclusion, our study provides a mechanistic link between the induction of EndMT by TGF-β and MDK, which suggests that blocking MDK provides potential therapeutic strategies for renal fibrosis.
Genetic association analysis of human median voice pitch identifies a common locus for tonal and non-tonal languages
Authors: Di Yazheng , Mefford Joel , Rahmani Elior , Wang Jinhan , Ravi Vijay , Gorla Aditya , Alwan Abeer , Zhu Tingshao , Flint Jonathan 
Published: May 2024

AbstractThe genetic influence on human vocal pitch in tonal and non-tonal languages remains largely unknown. In tonal languages, such as Mandarin Chinese, pitch changes differentiate word meanings, whereas in non-tonal languages, such as Icelandic, pitch is used to convey intonation. We addressed this question by searching for genetic associations with interindividual variation in median pitch in a Chinese major depression case-control cohort and compared our results with a genome-wide association study from Iceland. The same genetic variant, rs11046212-T in an intron of the ABCC9 gene, was one of the most strongly associated loci with median pitch in both samples. Our meta-analysis revealed four genome-wide significant hits, including two novel associations. The discovery of genetic variants influencing vocal pitch across both tonal and non-tonal languages suggests the possibility of a common genetic contribution to the human vocal system shared in two distinct populations with languages that differ in tonality (Icelandic and Mandarin).
Circ-0075305 hinders gastric cancer stem cells by indirectly disrupting TCF4–β-catenin complex and downregulation of SOX9
Authors: Chen Qi-Yue , Xu Kai-Xiang , Huang Xiao-Bo , Fan Deng-Hui , Chen Yu-Jing , Li Yi-Fan , Huang Qiang , Liu Zhi-Yu , Zheng Hua-Long , Huang Ze-Ning , Lin Ze-Hong , Wang Yu-Xiang , Yang Jun-Jie , Zhong Qing , Huang Chang-Ming 
Published: May 2024

AbstractCircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a β-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4–β-catenin transcription complex through competitive to β-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/β-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing β-catenin signaling may serve as a potential therapeutic candidate.
Chemogenetic activation of mammalian brain neurons expressing insect Ionotropic Receptors by systemic ligand precursor administration
Authors: Iguchi Yoshio , Fukabori Ryoji , Kato Shigeki , Takahashi Kazumi , Eifuku Satoshi , Maejima Yuko , Shimomura Kenju , Mizuma Hiroshi , Mawatari Aya , Doi Hisashi , Cui Yilong , Onoe Hirotaka , Hikishima Keigo , Osanai Makoto , Nishijo Takuma , Momiyama Toshihiko , Benton Richard , Kobayashi Kazuto 
Published: May 2024

AbstractChemogenetic approaches employing ligand-gated ion channels are advantageous regarding manipulation of target neuronal population functions independently of endogenous second messenger pathways. Among them, Ionotropic Receptor (IR)-mediated neuronal activation (IRNA) allows stimulation of mammalian neurons that heterologously express members of the insect chemosensory IR repertoire in response to their cognate ligands. In the original protocol, phenylacetic acid, a ligand of the IR84a/IR8a complex, was locally injected into a brain region due to its low permeability of the blood-brain barrier. To circumvent this invasive injection, we sought to develop a strategy of peripheral administration with a precursor of phenylacetic acid, phenylacetic acid methyl ester, which is efficiently transferred into the brain and converted to the mature ligand by endogenous esterase activities. This strategy was validated by electrophysiological, biochemical, brain-imaging, and behavioral analyses, demonstrating high utility of systemic IRNA technology in the remote activation of target neurons in the brain.
Aging-regulated PNUTS maintains endothelial barrier function via SEMA3B suppression
Authors: Lozano-Vidal Noelia , Stanicek Laura , Bink Diewertje I. , Juni Rio P. , Hooglugt Aukie , Kremer Veerle , Phelp Philippa , van Bergen Anke , MacInnes Alyson W. , Dimmeler Stefanie , Boon Reinier A. 
Published: May 2024

AbstractAge-related diseases pose great challenges to health care systems worldwide. During aging, endothelial senescence increases the risk for cardiovascular disease. Recently, it was described that Phosphatase 1 Nuclear Targeting Subunit (PNUTS) has a central role in cardiomyocyte aging and homeostasis. Here, we determine the role of PNUTS in endothelial cell aging. We confirm that PNUTS is repressed in senescent endothelial cells (ECs). Moreover, PNUTS silencing elicits several of the hallmarks of endothelial aging: senescence, reduced angiogenesis and loss of barrier function. Findings are validate in vivo using endothelial-specific inducible PNUTS-deficient mice (Cdh5-CreERT2;PNUTSfl/fl), termed PNUTSEC-KO. Two weeks after PNUTS deletion, PNUTSEC-KO mice present severe multiorgan failure and vascular leakage. Transcriptomic analysis of PNUTS-silenced HUVECs and lungs of PNUTSEC-KO mice reveal that the PNUTS-PP1 axis tightly regulates the expression of semaphorin 3B (SEMA3B). Indeed, silencing of SEMA3B completely restores barrier function after PNUTS loss-of-function. These results reveal a pivotal role for PNUTS in endothelial homeostasis through a SEMA3B downstream pathway that provides a potential target against the effects of aging in ECs.
Palmitic acid induces lipid droplet accumulation and senescence in nucleus pulposus cells via ER-stress pathway
Authors: Chen Xi , Chen Kun , Hu Jun , Dong Yijun , Zheng Menglong , Jiang Jiang , Hu Qingsong , Zhang Wenzhi 
Published: May 2024

AbstractIntervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder affecting millions of adults worldwide, but a poor understanding of its pathogenesis has limited the effectiveness of therapy. In the current study, we integrated untargeted LC/MS metabolomics and magnetic resonance spectroscopy data to investigate metabolic profile alterations during IDD. Combined with validation via a large-cohort analysis, we found excessive lipid droplet accumulation in the nucleus pulposus cells of advanced-stage IDD samples. We also found abnormal palmitic acid (PA) accumulation in IDD nucleus pulposus cells, and PA exposure resulted in lipid droplet accumulation and cell senescence in an endoplasmic reticulum stress-dependent manner. Complementary transcriptome and proteome profiles enabled us to identify solute carrier transporter (SLC) 43A3 involvement in the regulation of the intracellular PA level. SLC43A3 was expressed at low levels and negatively correlated with intracellular lipid content in IDD nucleus pulposus cells. Overexpression of SLC43A3 significantly alleviated PA-induced endoplasmic reticulum stress, lipid droplet accumulation and cell senescence by inhibiting PA uptake. This work provides novel integration analysis-based insight into the metabolic profile alterations in IDD and further reveals new therapeutic targets for IDD treatment.
Structural origins of dielectric anomalies in the filled tetragonal tungsten bronze Sr2NaNb5O15
Authors: Tidey Jeremiah P. , Dey Urmimala , Sanchez Ana M. , Chen Wei-Tin , Chen Bo-Hao , Chuang Yu-Chun , Fernandez-Diaz Maria T. , Bristowe Nicholas C. , Beanland Richard , Senn Mark S. 
Published: May 2024

AbstractThe tetragonal tungsten bronze, Sr2NaNb5O15, shows promise for application in high-temperature high-efficiency capacitors vital for the sustainable energy revolution. Previously, the structural complexity of this and related materials has obscured the mechanisms underpinning two large anomalies in relative permittivity (εr) which give rise to their exceptionally broad dielectric response. Here, we comprehensively investigate the structural evolution from −173 to 627 °C, combining electron, X-ray and neutron diffraction, electron microscopy, and first principles electronic structure calculations to unambiguously identify the structural origins of both anomalies. The peak in εr at 305 °C is associated with a polar-nonpolar phase transition, wherein cations displace along the c axis. Guided by DFT, we identify a further transition upon cooling, associated with the second peak at −14 °C, linked to the softening of an in-plane polar distortion with a correlation length limited by ferroelastic nano-domains arising from rigid-unit-like tilting of NbO6 octahedra at high temperature, imparting relaxor-like behaviour. Thus, the two dielectric anomalies in Sr2NaNb5O15 are associated with two distinct crystallographic phase transitions and their interplay with a microstructure that arises from a third, non-polar structural distortion. Chemical control of these will enable development of tuneable materials with dielectric properties suitable for high-temperature energy storage applications.