bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ensemble‐Based Data Assimilation of GPM DPR Reflectivity: Cloud Microphysics Parameter Estimation With the Nonhydrostatic Icosahedral Atmospheric Model (NICAM)
Authors: Kotsuki Shunji , Terasaki Koji , Satoh Masaki , Miyoshi Takemasa 
Published: February 2023

AbstractDirect assimilation of Dual‐frequency Precipitation Radar (DPR) data of the Global Precipitation Measurement (GPM) core satellite is challenging mainly due to its long revisiting intervals relative to the time scale of precipitation, and precipitation location errors. This study explores a method for improving precipitation forecasts using GPM DPR through model parameter estimation. We developed a 28 km mesh global atmospheric data assimilation system that integrates the Nonhydrostatic ICosahedral Atmospheric Model (NICAM) and Local Ensemble Transform Kalman Filter (LETKF) coupled with a satellite radar simulator. Using the NICAM‐LETKF and GPM DPR observations, this study estimates a model cloud physics parameter corresponding to snowfall terminal velocity. To overcome the difficulties of long revisiting intervals and precipitation location errors, we propose a parameter estimation method based on a two‐dimensional histogram known as the contoured frequency by temperature diagram (CFTD). Parameter estimation effectively mitigated the gap between simulated and observed CFTD, resulting in improved 6 hr precipitation forecasts.
MAPK4 silencing in gastric cancer drives liver metastasis by positive feedback between cancer cells and macrophages
Authors: Li Shuang , Guo Dongyang , Sun Qiang , Zhang Lu , Cui Yun , Liu Min , Ma Xixi , Liu Yiman , Cui Wenyu , Sun Leimin , Teng Lisong , Wang Liangjing , Lin Aifu , Liu Wei , Zhuo Wei , Zhou Tianhua 
Published: February 2023

AbstractLiver metastasis is a major cause of death in gastric cancer patients, but the underlying mechanisms are poorly understood. Through a combination of in vivo screening and transcriptome profiling followed by quantitative RT-PCR and tissue array analyses, we found that mitogen-activated protein kinase 4 (MAPK4) downregulation in gastric cancer tissues from patients is significantly associated with liver metastasis and poor prognosis. The knockdown of MAPK4 in gastric cancer cells promotes liver metastasis in orthotopic mouse models. MAPK4 depletion in gastric cancer cells induces the secretion of macrophage migration inhibitory factor (MIF) to polarize tumor-associated macrophages (TAMs) in orthotopic xenograft tumors. Moreover, TAMs activate epithelial–mesenchymal transition of gastric cancer cells to suppress MAPK4 expression, which further increases MIF secretion to polarize TAMs. Taken together, our results suggest a previously undescribed positive feedback loop between cancer cells and macrophages mediated by MAPK4 silencing that facilitates gastric cancer liver metastasis.
B-lymphoid tyrosine kinase-mediated FAM83A phosphorylation elevates pancreatic tumorigenesis through interacting with β-catenin
Authors: Zhou Cefan , Zhu Xiaoting , Liu Nanxi , Dong Xueying , Zhang Xuewen , Huang Huili , Tang Yu , Liu Shicheng , Hu Mengyu , Wang Ming , Deng Xiaoling , Li Shi , Zhang Rui , Huang Yuan , Lyu Hao , Xiao Shuai , Luo Sang , Ali Declan William , Michalak Marek , Chen Xing-Zhen , Wang Zhentian , Tang Jingfeng 
Published: February 2023

AbstractAbnormal activation of Wnt/β-catenin-mediated transcription is closely associated with the malignancy of pancreatic cancer. Family with sequence similarity 83 member A (FAM83A) was shown recently to have oncogenic effects in a variety of cancer types, but the biological roles and molecular mechanisms of FAM83A in pancreatic cancer need further investigation. Here, we newly discovered that FAM83A binds directly to β-catenin and inhibits the assembly of the cytoplasmic destruction complex thus inhibiting the subsequent phosphorylation and degradation. FAM83A is mainly phosphorylated by the SRC non-receptor kinase family member BLK (B-lymphoid tyrosine kinase) at tyrosine 138 residue within the DUF1669 domain that mediates the FAM83A-β-catenin interaction. Moreover, FAM83A tyrosine 138 phosphorylation enhances oncogenic Wnt/β-catenin-mediated transcription through promoting β-catenin-TCF4 interaction and showed an elevated nucleus translocation, which inhibits the recruitment of histone deacetylases by TCF4. We also showed that FAM83A is a direct downstream target of Wnt/β-catenin signaling and correlates with the levels of Wnt target genes in human clinical pancreatic cancer tissues. Notably, the inhibitory peptides that target the FAM83A-β-catenin interaction significantly suppressed pancreatic cancer growth and metastasis in vitro and in vivo. Our results revealed that blocking the FAM83A cascade signaling defines a therapeutic target in human pancreatic cancer.
Targeting epigenetic regulators to overcome drug resistance in cancers
Authors: Wang Nan , Ma Ting , Yu Bin 
Published: February 2023

AbstractDrug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regulation have been well studied. Increasing evidence has shown that aberrant epigenetic regulations contribute to tumor resistance. Therefore, targeting epigenetic regulators represents an effective strategy to reverse drug resistance. In this review, we mainly summarize the roles of epigenetic regulation in tumor resistance. In addition, as the essential factors for epigenetic modifications, histone demethylases mediate the histone or genomic DNA modifications. Herein, we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family, the Jumonji C-domain-containing demethylase family, and the histone arginine demethylase family, and fully discuss their regulatory mechanisms related to cancer drug resistance. In addition, therapeutic strategies, including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance, are also described.
Association between children's resilience and practising oral habits: a cross-sectional study
Authors: Abd-Elsabour Mennat A. A. , Hanafy Rasha M. Hatem , Omar Ola M. 
Published: February 2023

AbstractIntroduction While resilience is the quality of being buffered against stressors, practising oral habits is suggested to be a maladaptive behaviour towards stressors. The relation between resilience and practising oral habits in children remains vague.Aims This study aims to investigate the association between practising oral habits and resilience in children aged 5-7 years.Materials and methods An electronic Google form questionnaire was distributed through social media among five schools' children's parents, utilising the Child and Youth Resilience Measure-Revised Person Most Knowledgeable version (PMK-CYRM-R) scale as a resilience assessment tool, and the third domain of interview part of the Nordic Orofacial Test-Screen (NOT-S) as a habit assessment tool. The questionnaire received 227 eligible responses which were divided into habit-free group (123; 54.19%) and habit-practising group (104; 45.81%). The third domain of the interview part of the NOT-S included sucking habit, bruxism and nail-biting habits. The mean PMK-CYRM-R scores were calculated for each group and statistical analysis was done using SPSS Statistics package.Results Total PMK-CYRM-R score was 46.05 ± 3.63 in the habit-free group and 44.10 ± 3.59 in the habit-practising group (p = 0.0001). Bruxism, nail-biting and sucking habit subgroups showed statistically significant lower personal resilience levels than the habit-free group.Conclusion The results of the current study suggest that children with low resilience levels may be more likely to practise oral habits.
XBP1 modulates endoplasmic reticulum and mitochondria crosstalk via regulating NLRP3 in renal ischemia/reperfusion injury
Authors: Ni Haiqiang , Ou Zhiyu , Wang Yuchen , Liu Yanna , Sun Kailun , Zhang Ji , Zhang Jiasi , Deng Wenfeng , Zeng Wenli , Xia Renfei , Xu Jian , Gong Nianqiao , Miao Yun 
Published: February 2023

AbstractThe functional status of mitochondria and the endoplasmic reticulum are central to renal ischemia/reperfusion injury (IRI). X-box binding protein 1 (XBP1) is an important transcription factor in endoplasmic reticulum stress. NLR family pyrin domain containing-3 (NLRP3) inflammatory bodies are closely related to renal IRI. In vivo and in vitro, we examined the molecular mechanisms and functions of XBP1-NLRP3 signaling in renal IRI, which influences ER-mitochondrial crosstalk. In this study, mice were subjected to 45 min of unilateral renal warm ischemia, the other kidney resected, and reperfusion was performed for 24 h in vivo. In vitro, murine renal tubular epithelial cells (TCMK-1) were exposed to hypoxia for 24 h and reoxygenation for 2 h. Tissue or cell damage was evaluated by measuring blood urea nitrogen and creatinine levels, histological staining, flow cytometry, terminal deoxynucleotidyl transferase-mediated nick-end labeling, diethylene glycol staining, and transmission electron microscopy (TEM). Western blotting, immunofluorescence staining, and ELISA were used to analyze protein expression. Whether XBP1 regulates the NLRP3 promoter was evaluated using a luciferase reporter assay. Kidney damage was reduced with decreasing blood urea nitrogen, creatinine, interleukin-1β, and interleukin-18 levels. XBP1 deficiency reduced tissue damage and cell apoptosis, protecting the mitochondria. Disruption of XBP1 was associated with reduced NLRP3 and cleaved caspase-1 levels and markedly improved survival. In vitro in TCMK-1 cells, XBP1 interference inhibited caspase-1-dependent mitochondrial damage and reduced the production of mitochondrial reactive oxygen species. The luciferase assay showed that spliced XBP1 isoforms enhanced the activity of the NLRP3 promoter. These findings reveal that XBP1 downregulation suppresses the expression of NLRP3, a potential regulator of endoplasmic reticulum mitochondrial crosstalk in nephritic injury and a potential therapeutic target in XBP1-mediated aseptic nephritis.
Rescue of neuropsychiatric phenotypes in a mouse model of 16p11.2 duplication syndrome by genetic correction of an epilepsy network hub
Authors: Forrest Marc P. , Dos Santos Marc , Piguel Nicolas H. , Wang Yi-Zhi , Hawkins Nicole A. , Bagchi Vikram A. , Dionisio Leonardo E. , Yoon Sehyoun , Simkin Dina , Martin-de-Saavedra Maria Dolores , Gao Ruoqi , Horan Katherine E. , George Alfred L. , LeDoux Mark S. , Kearney Jennifer A. , Savas Jeffrey N. , Penzes Peter 
Published: February 2023

AbstractNeuropsychiatric disorders (NPDs) are frequently co-morbid with epilepsy, but the biological basis of shared risk remains poorly understood. The 16p11.2 duplication is a copy number variant that confers risk for diverse NPDs including autism spectrum disorder, schizophrenia, intellectual disability and epilepsy. We used a mouse model of the 16p11.2 duplication (16p11.2dup/+) to uncover molecular and circuit properties associated with this broad phenotypic spectrum, and examined genes within the locus capable of phenotype reversal. Quantitative proteomics revealed alterations to synaptic networks and products of NPD risk genes. We identified an epilepsy-associated subnetwork that was dysregulated in 16p11.2dup/+mice and altered in brain tissue from individuals with NPDs. Cortical circuits from 16p11.2dup/+mice exhibited hypersynchronous activity and enhanced network glutamate release, which increased susceptibility to seizures. Using gene co-expression and interactome analysis, we show that PRRT2 is a major hub in the epilepsy subnetwork. Remarkably, correctingPrrt2copy number rescued aberrant circuit properties, seizure susceptibility and social deficits in 16p11.2dup/+mice. We show that proteomics and network biology can identify important disease hubs in multigenic disorders, and reveal mechanisms relevant to the complex symptomatology of 16p11.2 duplication carriers.
Increasing countries’ financial resilience through global catastrophe risk pooling
Authors: Ciullo Alessio , Strobl Eric , Meiler Simona , Martius Olivia , Bresch David N. 
Published: February 2023

AbstractExtreme weather events can severely impact national economies, leading the recovery of low- to middle-income countries to become reliant on foreign financial aid. Foreign aid is, however, slow and uncertain. Therefore, the Sendai Framework and the Paris Agreement advocate for more resilient financial instruments like sovereign catastrophe risk pools. Existing pools, however, might not fully exploit their financial resilience potential because they were not designed to maximize risk diversification and because they pool risk only regionally. Here we introduce a method that forms pools by maximizing risk diversification and apply it to assess the benefits of global pooling compared to regional pooling. We find that global pooling always provides a higher risk diversification, it better distributes countries’ risk shares in the pool’s risk and it increases the number of countries profiting from risk pooling. Optimal global pooling could provide a diversification increase to existing pools of up to 65 %.
Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity
Authors: Yang Liang , Shen Junfeng , Liu Chunhua , Kuang Zhonghua , Tang Yong , Qian Zhengjiang , Guan Min , Yang Yongfeng , Zhan Yang , Li Nan , Li Xiang 
Published: February 2023

AbstractImbalances in NAD+ homeostasis have been linked to aging and various diseases. Nicotine, a metabolite of the NAD+ metabolic pathway, has been found to possess anti-inflammatory and neuroprotective properties, yet the underlying molecular mechanisms remained unknown. Here we find that, independent of nicotinic acetylcholine receptors, low-dose nicotine can restore the age-related decline of NAMPT activity through SIRT1 binding and subsequent deacetylation of NAMPT, thus increasing NAD+ synthesis. 18F-FDG PET imaging revealed that nicotine is also capable of efficiently inhibiting glucose hypermetabolism in aging male mice. Additionally, nicotine ameliorated cellular energy metabolism disorders and deferred age-related deterioration and cognitive decline by stimulating neurogenesis, inhibiting neuroinflammation, and protecting organs from oxidative stress and telomere shortening. Collectively, these findings provide evidence for a mechanism by which low-dose nicotine can activate NAD+ salvage pathways and improve age-related symptoms.
Tracking the evolution of esophageal squamous cell carcinoma under dynamic immune selection by multi-omics sequencing
Authors: Cui Sijia , McGranahan Nicholas , Gao Jing , Chen Peng , Jiang Wei , Yang Lingrong , Ma Li , Liao Junfang , Xie Tian , Xie Congying , Enver Tariq , Wu Shixiu 
Published: February 2023

AbstractIntratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, it is discovered that genomic, epigenomic, and transcriptomic ITH are underpinned by ongoing chromosomal instability. Based on the RNA-seq data, we observe diverse levels of immune infiltrate across different tumor sites from the same tumor. We reveal genetic mechanisms of neoantigen evasion under distinct selection pressure from the diverse immune microenvironment. Overall, our work offers an avenue of dissecting the complex contribution of the multi-omics level to the ITH in ESCC and thereby enhances the development of clinical therapy.
Identifying the ground state structures of point defects in solids
Authors: Mosquera-Lois Irea , Kavanagh Seán R. , Walsh Aron , Scanlon David O. 
Published: February 2023

AbstractPoint defects are a universal feature of crystals. Their identification is addressed by combining experimental measurements with theoretical models. The standard modelling approach is, however, prone to missing the ground state atomic configurations associated with energy-lowering reconstructions from the idealised crystallographic environment. Missed ground states compromise the accuracy of calculated properties. To address this issue, we report an approach to navigate the defect configurational landscape using targeted bond distortions and rattling. Application of our workflow to eight materials (CdTe, GaAs, Sb2S3, Sb2Se3, CeO2, In2O3, ZnO, anatase-TiO2) reveals symmetry breaking in each host crystal that is not found via conventional local minimisation techniques. The point defect distortions are classified by the associated physico-chemical factors. We demonstrate the impact of these defect distortions on derived properties, including formation energies, concentrations and charge transition levels. Our work presents a step forward for quantitative modelling of imperfect solids.
MorphoSim: an efficient and scalable phase-field framework for accurately simulating multicellular morphologies
Authors: Kuang Xiangyu , Guan Guoye , Tang Chao , Zhang Lei 
Published: February 2023

AbstractThe phase field model can accurately simulate the evolution of microstructures with complex morphologies, and it has been widely used for cell modeling in the last two decades. However, compared to other cellular models such as the coarse-grained model and the vertex model, its high computational cost caused by three-dimensional spatial discretization hampered its application and scalability, especially for multicellular organisms. Recently, we built a phase field model coupled with in vivo imaging data to accurately reconstruct the embryonic morphogenesis of Caenorhabditis elegans from 1- to 8-cell stages. In this work, we propose an improved phase field model by using the stabilized numerical scheme and modified volume constriction. Then we present a scalable phase-field framework, MorphoSim, which is 100 times more efficient than the previous one and can simulate over 100 mechanically interacting cells. Finally, we demonstrate how MorphoSim can be successfully applied to reproduce the assembly, self-repairing, and dissociation of a synthetic artificial multicellular system - the synNotch system.
Effect of a combination of pea protein, grape seed extract and lactic acid in an in vivo model of bacterial vaginosis
Authors: Lanza Marika , Scuderi Sarah Adriana , Capra Anna Paola , Casili Giovanna , Filippone Alessia , Campolo Michela , Cuzzocrea Salvatore , Esposito Emanuela , Paterniti Irene 
Published: February 2023

AbstractBacterial vaginosis (BV) is a common vaginal dysbiosis characterized by a malodorous discharge and irritation. The imbalance of the vaginal microbiota plays a key role in the development of BV. It has been demonstrated that Gardnerella vaginalis (GV), a facultative anaerobic bacillus, is involved in BV. Due to the rising number of antimicrobial-resistant species, recurrence of BV is becoming more frequent in women; thus, alternative treatments to antibiotics are needed. Natural substances have recently shown a great efficacy for the treatment of vaginal dysbiosis. Thus, this study aimed to investigate the beneficial effect of a product containing pea protein (PP), grape seed extract (GS) and lactic acid (LA) in an in vivo model of Gardnerella vaginalis-induced vaginosis by intravaginal administration of GV suspension (1 × 106 CFU/20 µL saline). Our results demonstrated that the product containing PP, GS and LA significantly reduced GV proliferation. More specifically, it significantly preserved tissue architecture and reduced neutrophil infiltration, inflammatory markers and sialidase activity when used both as a pre- or a post-treatment. Moreover, the product displayed strong bioadhesive properties. Therefore, our data suggested that the product containing PP, GS and LA could be used as alternative preventive or curative treatment for the management of BV.
Hybrid feature engineering of medical data via variational autoencoders with triplet loss: a COVID-19 prognosis study
Authors: Mahdavi Mahdi , Choubdar Hadi , Rostami Zahra , Niroomand Behnaz , Levine Alexandra T. , Fatemi Alireza , Bolhasani Ehsan , Vahabie Abdol-Hossein , Lomber Stephen G. , Merrikhi Yaser 
Published: February 2023

AbstractMedical machine learning frameworks have received much attention in recent years. The recent COVID-19 pandemic was also accompanied by a surge in proposed machine learning algorithms for tasks such as diagnosis and mortality prognosis. Machine learning frameworks can be helpful medical assistants by extracting data patterns that are otherwise hard to detect by humans. Efficient feature engineering and dimensionality reduction are major challenges in most medical machine learning frameworks. Autoencoders are novel unsupervised tools that can perform data-driven dimensionality reduction with minimum prior assumptions. This study, in a novel approach, investigated the predictive power of latent representations obtained from a hybrid autoencoder (HAE) framework combining variational autoencoder (VAE) characteristics with mean squared error (MSE) and triplet loss for forecasting COVID-19 patients with high mortality risk in a retrospective framework. Electronic laboratory and clinical data of 1474 patients were used in the study. Logistic regression with elastic net regularization (EN) and random forest (RF) models were used as final classifiers. Moreover, we also investigated the contribution of utilized features towards latent representations via mutual information analysis. HAE Latent representations model achieved decent performance with an area under ROC curve of 0.921 (±0.027) and 0.910 (±0.036) with EN and RF predictors, respectively, over the hold-out data in comparison with the raw (AUC EN: 0.913 (±0.022); RF: 0.903 (±0.020)) models. The study aims to provide an interpretable feature engineering framework for the medical environment with the potential to integrate imaging data for efficient feature engineering in rapid triage and other clinical predictive models.