bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation
Authors: Thériault Sébastien , Li Zhonglin , Abner Erik , Luan Jian’an , Manikpurage Hasanga D. , Houessou Ursula , Zamani Pardis , Briend Mewen ,   Estonian Biobank Research Team, Boudreau Dominique K. , Gaudreault Nathalie , Frenette Lily , Argaud Déborah , Dahmene Manel , Dagenais François , Clavel Marie-Annick , Pibarot Philippe , Arsenault Benoit J. , Boekholdt S. Matthijs , Wareham Nicholas J. , Esko Tõnu , Mathieu Patrick , Bossé Yohan 
Published: March 2024

AbstractThere is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry. We report 32 genomic loci, among which 20 are novel. RNA sequencing of 500 human aortic valves highlights an enrichment in expression regulation at these loci and prioritizes candidate causal genes. Homozygous genotype for a risk variant near TWIST1, a gene involved in endothelial-mesenchymal transition, has a profound impact on aortic valve transcriptomics. We identify five genes outside of GWAS loci by combining a transcriptome-wide association study, colocalization, and Mendelian randomization analyses. Using cross-phenotype and phenome-wide approaches, we highlight the role of circulating lipoproteins, blood pressure and inflammation in the disease process. Our findings pave the way for the development of novel therapies for CAVS.
Cryo-EM structures of type IV pili complexed with nanobodies reveal immune escape mechanisms
Authors: Fernandez-Martinez David , Kong Youxin , Goussard Sylvie , Zavala Agustin , Gastineau Pauline , Rey Martial , Ayme Gabriel , Chamot-Rooke Julia , Lafaye Pierre , Vos Matthijn , Mechaly Ariel , Duménil Guillaume 
Published: March 2024

AbstractType IV pili (T4P) are prevalent, polymeric surface structures in pathogenic bacteria, making them ideal targets for effective vaccines. However, bacteria have evolved efficient strategies to evade type IV pili-directed antibody responses. Neisseria meningitidis are prototypical type IV pili-expressing Gram-negative bacteria responsible for life threatening sepsis and meningitis. This species has evolved several genetic strategies to modify the surface of its type IV pili, changing pilin subunit amino acid sequence, nature of glycosylation and phosphoforms, but how these modifications affect antibody binding at the structural level is still unknown. Here, to explore this question, we determine cryo-electron microscopy (cryo-EM) structures of pili of different sequence types with sufficiently high resolution to visualize posttranslational modifications. We then generate nanobodies directed against type IV pili which alter pilus function in vitro and in vivo. Cryo-EM in combination with molecular dynamics simulation of the nanobody-pilus complexes reveals how the different types of pili surface modifications alter nanobody binding. Our findings shed light on the impressive complementarity between the different strategies used by bacteria to avoid antibody binding. Importantly, we also show that structural information can be used to make informed modifications in nanobodies as countermeasures to these immune evasion mechanisms.
Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment
Authors: Maggiorani Damien , Le Oanh , Lisi Véronique , Landais Séverine , Moquin-Beaudry Gaël , Lavallée Vincent Philippe , Decaluwe Hélène , Beauséjour Christian 
Published: March 2024

AbstractThe potential of immune checkpoint inhibitors (ICI) may be limited in situations where immune cell fitness is impaired. Here, we show that the efficacy of cancer immunotherapies is compromised by the accumulation of senescent cells in mice and in the context of therapy-induced senescence (TIS). Resistance to immunotherapy is associated with a decrease in the accumulation and activation of CD8 T cells within tumors. Elimination of senescent cells restores immune homeostasis within the tumor micro-environment (TME) and increases mice survival in response to immunotherapy. Using single-cell transcriptomic analysis, we observe that the injection of ABT263 (Navitoclax) reverses the exacerbated immunosuppressive profile of myeloid cells in the TME. Elimination of these myeloid cells also restores CD8 T cell proliferation in vitro and abrogates immunotherapy resistance in vivo. Overall, our study suggests that the use of senolytic drugs before ICI may constitute a pharmacological approach to improve the effectiveness of cancer immunotherapies.
Phenol as proton shuttle and buffer for lithium-mediated ammonia electrosynthesis
Authors: Fu Xianbiao , Xu Aoni , Pedersen Jakob B. , Li Shaofeng , Sažinas Rokas , Zhou Yuanyuan , Andersen Suzanne Z. , Saccoccio Mattia , Deissler Niklas H. , Mygind Jon Bjarke Valbæk , Kibsgaard Jakob , Vesborg Peter C. K. , Nørskov Jens K. , Chorkendorff Ib 
Published: March 2024

AbstractAmmonia is a crucial component in the production of fertilizers and various nitrogen-based compounds. Now, the lithium-mediated nitrogen reduction reaction (Li-NRR) has emerged as a promising approach for ammonia synthesis at ambient conditions. The proton shuttle plays a critical role in the proton transfer process during Li-NRR. However, the structure-activity relationship and design principles for effective proton shuttles have not yet been established in practical Li-NRR systems. Here, we propose a general procedure for verifying a true proton shuttle and established design principles for effective proton shuttles. We systematically evaluate several classes of proton shuttles in a continuous-flow reactor with hydrogen oxidation at the anode. Among the tested proton shuttles, phenol exhibits the highest Faradaic efficiency of 72 ± 3% towards ammonia, surpassing that of ethanol, which has been commonly used so far. Experimental investigations including operando isotope-labelled mass spectrometry proved the proton-shuttling capability of phenol. Further mass transport modeling sheds light on the mechanism.
The potential of urban irrigation for counteracting carbon-climate feedback
Authors: Li Peiyuan , Wang Zhi-Hua , Wang Chenghao 
Published: March 2024

AbstractGlobal climate changes, especially the rise of global mean temperature due to the increased carbon dioxide (CO2) concentration, can, in turn, result in higher anthropogenic and biogenic greenhouse gas emissions. This potentially leads to a positive loop of climate–carbon feedback in the Earth’s climate system, which calls for sustainable environmental strategies that can mitigate both heat and carbon emissions, such as urban greening. In this study, we investigate the impact of urban irrigation over green spaces on ambient temperatures and CO2 exchange across major cities in the contiguous United States. Our modeling results indicate that the carbon release from urban ecosystem respiration is reduced by evaporative cooling in humid climate, but promoted in arid/semi-arid regions due to increased soil moisture. The irrigation-induced environmental co-benefit in heat and carbon mitigation is, in general, positively correlated with urban greening fraction and has the potential to help counteract climate–carbon feedback in the built environment.
Predicting the optimal concentration of remifentanil for skull pin fixation with hemodynamic and analgesia nociception index monitoring
Authors: Kuo Yi-Wei , Chen Ying-Tzu , Lieu Ann-Shung , Lee Meei-Shyuan , Su Yu-Feng , Lai Hou-Chuan , Wu Zhi-Fu 
Published: March 2024

AbstractInadequate antinociception during skull pin fixation may cause hemodynamic instability in intracranial surgery. The optimal concentration of remifentanil to provide adequate antinociception and stable hemodynamics during skull pin fixation under analgesia nociception index monitoring is unknown. This study is to assess the 90% effective concentration of remifentanil for skull pin fixation under hemodynamic and analgesia nociception index monitoring. Twenty-six patients were enrolled for intracranial surgery, anesthesia was induced and maintained under total intravenous anesthesia using target-controlled infusion for remifentanil and propofol under analgesia nociception index and bispectral index monitoring. Skull pin fixation was performed at different effect-site concentrations of remifentanil required for Dixon's up-and-down method with a step size of 0.5 ng/ml under bispectral index 40–60. Inadequate antinociception is defined when either ANI < 30 or > 20% in hemodynamic changes from baseline (e.g. heart rate > 100 beats/min, or blood pressure > 180/100 mmHg) and the effect-site concentration of remifentanil is considered as failure. It is considered success as ANI > 30 and < 20% hemodynamic changes from baseline simultaneously. Seven pairs of failure/success were used for probit analysis. The 90% effective concentration of remifentanil for skull pin fixation with adequate antinociception and hemodynamic stability was 4.7 ng/ml.
Derivation of Dirac equation from the stochastic optimal control principles of quantum mechanics
Authors: Yordanov Vasil 
Published: March 2024

AbstractIn this paper, we present a stochastic approach to relativistic quantum mechanics. We formulate the three fundamental principles of this theory and derive the Dirac equations based on them. This approach enables us to bring more insight into the nature of Dirac’s spinors. Furthermore, we provide a physical interpretation of the stochastic optimal control theory of quantum mechanics.
Creation of a machine learning-based prognostic prediction model for various subtypes of laryngeal cancer
Authors: Wang Wei , Wang Wenhui , Zhang Dongdong , Zeng Peiji , Wang Yue , Lei Min , Hong Yongjun , Cai Chengfu 
Published: March 2024

AbstractDepending on the source of the blastophore, there are various subtypes of laryngeal cancer, each with a unique metastatic risk and prognosis. The forecasting of their prognosis is a pressing issue that needs to be resolved. This study comprised 5953 patients with glottic carcinoma and 4465 individuals with non-glottic type (supraglottic and subglottic). Five clinicopathological characteristics of glottic and non-glottic carcinoma were screened using univariate and multivariate regression for CoxPH (Cox proportional hazards); for other models, 10 (glottic) and 11 (non-glottic) clinicopathological characteristics were selected using least absolute shrinkage and selection operator (LASSO) regression analysis, respectively; the corresponding survival models were established; and the best model was evaluated. We discovered that RSF (Random survival forest) was a superior model for both glottic and non-glottic carcinoma, with a projected concordance index (C-index) of 0.687 for glottic and 0.657 for non-glottic, respectively. The integrated Brier score (IBS) of their 1-year, 3-year, and 5-year time points is, respectively, 0.116, 0.182, 0.195 (glottic), and 0.130, 0.215, 0.220 (non-glottic), demonstrating the model's effective correction. We represented significant variables in a Shapley Additive Explanations (SHAP) plot. The two models are then combined to predict the prognosis for two distinct individuals, which has some effectiveness in predicting prognosis. For our investigation, we established separate models for glottic carcinoma and non-glottic carcinoma that were most effective at predicting survival. RSF is used to evaluate both glottic and non-glottic cancer, and it has a considerable impact on patient prognosis and risk factor prediction.
Metamorphic turnover at 2 Ga related to two-stage assembly of Columbia
Authors: Volante Silvia , Kirscher Uwe 
Published: March 2024

AbstractUnderstanding the stabilization of cratons and how this is related to the onset of plate-tectonics is among the most important questions in geoscience. The assembly of Earth’s first supercontinent Columbia represents the first lines of evidence for a global subduction network, when the oldest, deep subduction-related rocks have been reported. We combine the low-, intermediate- and high-T/P global metamorphic record with the two-stage assembly of the Nuna-Columbia supercontinent to address the significance of the oldest “cold” rocks (low-T/P) and the related emergence of bimodal metamorphic belts. For this purpose, we analyse two examples from Laurentia (including Greenland) and Australia between 2.0–1.8 Ga and 1.8–1.6 Ga. Two main observations are: (i) a first-stage (2.0–1.8 Ga) amalgamation of the megacontinent Nuna (precursor to Columbia) is characterized by bimodal metamorphism along major mobile belts suturing the megacontinent’s center. In contrast, a second-stage (1.8–1.6 Ga) is dominated by the formation of soft collisional orogens during the final Columbia supercontinent assembly, recording intermediate- to high-T/P metamorphism; (ii) the metamorphic signature of the two assembly stages, featuring low- and intermediate-T/P rocks during Nuna assembly followed by their near absence during Columbia amalgamation, contrasts with the thermobaric ratios recorded by the Phanerozoic Gondwana-Pangea assembly, where intermediate and low-T/P rocks dominated the final stage of Pangea amalgamation. This discrepancy may signify substantial changes in intraplate metamorphism and minor rearrangements during Columbia assembly compared to major continent–continent collisions, such as the Appalachian-Variscan Orogen as well as production and fast exhumation of high- to ultra-high-pressure rocks during the assembly of the supercontinent Pangea. Furthermore, the variation of thermobaric ratios aligns with the concept of a two-stage mega-supercontinent formation, emphasizing differences between the potentially oldest and youngest supercontinent cycles.
Reduced influence of perceptual context in mild traumatic brain injury is not an illusion
Authors: Sidhu A. , Uiga L. , Langley B. , Masters R. S. W. 
Published: March 2024

AbstractPerceptual grouping is impaired following mild traumatic brain injury (mTBI). This may affect visual size perception, a process influenced by perceptual grouping abilities. We conducted two experiments to evaluate visual size perception in people with self-reported history of mTBI, using two different size-contrast illusions: the Ebbinghaus Illusion (Experiment 1) and the Müller-Lyer illusion (Experiment 2). In Experiment 1, individuals with mTBI and healthy controls were asked to compare the size of two target circles that were either the same size or different sizes. The target circles appeared by themselves (no-context condition), or were surrounded by smaller or larger circles (context condition). Similar levels of accuracy were evident between the groups in the no-context condition. However, size judgements by mTBI participants were more accurate in the context condition, suggesting that they processed the target circles separately from the surrounding circles. In Experiment 2, individuals with mTBI and healthy controls judged the length of parallel lines that appeared with arrowheads (context condition) or without arrowheads (no context condition). Consistent with Experiment 1, size judgements by mTBI participants were more accurate than size judgements by control participants in the context condition. These findings suggest that mTBI influences size perception by impairing perceptual grouping of visual stimuli in near proximity.
Exact solutions for nonlinear partial differential equations via a fusion of classical methods and innovative approaches
Authors: Mhadhbi Noureddine , Gana Sameh , Alsaeedi Mazen Fawaz 
Published: March 2024

AbstractThis paper presents a new approach for finding exact solutions to certain classes of nonlinear partial differential equations (NLPDEs) by combining the variation of parameters method with classical techniques such as the method of characteristics. Our primary focus is on NLPDEs of the form $$u_{tt}+a(x,t)u_{xt}+b(t)u_{t}=\alpha (x,t)+ G(u)(u_{t}+a(x,t)u_{x})e^{-\int b(t)dt}$$

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We provide numerical validation through several examples to ensure accuracy and reliability. Our approach enhances the applicability of analytical solution methods for a broader range of NLPDEs.
Feasibility and clinical value of linear endoscopic ultrasonography imaging in the lower gastrointestinal subepithelial lesions
Authors: Tao Li , Chen Yajun , Fang Qianqian , Xu Fan , Yu Qianwei , Zhang Lijiu , Hu Xiangpeng 
Published: March 2024

AbstractLinear endoscopic ultrasonography (EUS) has been extensively utilized as a novel diagnostic and therapeutic modality across various fields. However, there have been relatively few studies focusing on lower gastrointestinal lesions. The aim of our study was to investigate the feasibility, safety and clinical value of linear EUS in the lower gastrointestinal subepithelial lesions. This was a retrospective study involving patients with lower gastrointestinal subepithelial lesions diagnosed by linear EUS from August 2019 to April 2023 at the Second Affiliated Hospital of Anhui Medical University. The data, including basic clinical information, linear EUS features, technical success rate, complications, and follow-up, were retrospectively collected and analyzed. A total of 69 patients with lower gastrointestinal subepithelial lesions underwent examination by linear EUS. Excluding the rectum, the technical success rate of linear EUS was 90.6% (29/32). Apart from the 7 patients whose diagnosis remained unknown, 3 patients with no abnormal EUS findings, and 3 patients failed the procedure, 56 patients were included in the final diagnostic performance analysis. The most common locations of the lesions were the rectum (37/56, 66.1%) and sigmoid colon (7/56, 12.5%). Based on endoscopy findings and pathological results, the most prevalent types of subepithelial lesions in the lower gastrointestinal tract were neuroendocrine tumor (NET) (12/56, 20.3%), lipoma (8/56, 13.6%) and extraluminal compression (8/56, 13.6%). The majority of lesions ranged in diameter from 1 to 3 cm (χ2 = 18.750, p < 0.001). After undergoing linear EUS examination, 36 patients received EUS-FNA (3/36), biopsy (5/36), endoscopic resection (25/36), or surgical excision (3/36) respectively. The pathological results of 29 patients were entirely consistent with the diagnosis made using linear EUS, with an 80.6% (29/36) diagnostic accuracy rate. Follow-up indicated that the lesions remained unchanged within 6–36 months. All patients tolerated the procedure well without any complications. In conclusion, linear EUS demonstrates technical feasibility, safety, and a high diagnostic accuracy for subepithelial lesions in the lower gastrointestinal tract.
Transcatheter aortic valve replacement in patients with severe aortic stenosis reduced the frequency of intradialytic hypotension
Authors: Saigan Makoto , Miyasaka Masaki , Nagasawa Tasuku , Taguri Masataka , Satomi Natsuko , Watahiki Manami , Nakashima Masaki , Enta Yusuke , Toki Yusuke , Munehisa Yoshiko , Ito Jun , Hayatsu Yukihiro , Tada Norio 
Published: March 2024

AbstractIntradialytic hypotension (IDH) is a common complication during hemodialysis that increases cardiovascular morbidity and mortality. Aortic stenosis (AS) is a cause of IDH. Transcatheter aortic valve replacement (TAVR) has become an established treatment for patients with severe AS. However, whether TAVR reduce the frequency of IDH has not been investigated. This study aims to verify the efficacy of TAVR for reduction of the frequency of IDH. Consecutive hemodialysis patients who underwent TAVR at Sendai Kosei Hospital from February 2021 to November 2021 with available records 1 month before and 3 months after TAVR were included in the study. IDH was defined as a decrease in systolic blood pressure by 20 mmHg or a decrease in the mean blood pressure by 10 mmHg associated with hypotensive symptoms or requiring intervention. Patients with ≥ 3 episodes of IDH in ten hemodialysis sessions comprised the IDH group. Overall, 18/41 (43.9%) patients were classified into the IDH group. In ten hemodialysis sessions, IDH events were observed 2.1, 4.3, and 0.4 times in the overall cohort, IDH group, and non-IDH group, respectively. After TAVR, the incidence of IDH decreased from 43.2 to 10.3% (p < 0.0001) and IDH improved significantly in 15 patients in the IDH group. The result suggested that severe AS was the major cause of IDH in this cohort, and TAVR may be an effective treatment option for reduction of the frequency of IDH in patients with severe AS.
Transcript-specific induction of stop codon readthrough using a CRISPR-dCas13 system
Authors: Manjunath Lekha E , Singh Anumeha , Devi Kumar Sangeetha , Vasu Kirtana , Kar Debaleena , Sellamuthu Karthi , Eswarappa Sandeep M 
Published: March 2024

AbstractStop codon readthrough (SCR) is the process where translation continues beyond a stop codon on an mRNA. Here, we describe a strategy to enhance or induce SCR in a transcript-selective manner using a CRISPR-dCas13 system. Using specific guide RNAs, we target dCas13 to the region downstream of canonical stop codons of mammalian AGO1 and VEGFA mRNAs, known to exhibit natural SCR. Readthrough assays reveal enhanced SCR of these mRNAs (both exogenous and endogenous) caused by the dCas13-gRNA complexes. This effect is associated with ribosomal pausing, which has been reported for several SCR events. Our data show that CRISPR-dCas13 can also induce SCR across premature termination codons (PTCs) in the mRNAs of green fluorescent protein and TP53. We demonstrate the utility of this strategy in the induction of readthrough across the thalassemia-causing PTC in HBB mRNA and hereditary spherocytosis-causing PTC in SPTA1 mRNA. Thus, CRISPR-dCas13 can be programmed to enhance or induce SCR in a transcript-selective and stop codon-specific manner.
Flexible self-supporting inorganic nanofiber membrane-reinforced solid-state electrolyte for dendrite-free lithium metal batteries
Authors: Liu Weicui , Deng Nanping , Chen Shuang , Zhao Yixia , Gao Lu , Ju Jingge , Zhao Chunfeng , Kang Weimin 
Published: March 2024

The backbone effect of the 3D network structure in self-supporting Al2O3 nanofibrous membranes improves the mechanical properties of composite solid-state electrolytes, provides abundant Lewis acid sites and fast Li+ transport channels.