bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics analysis reveals prognostic and immune characteristics of cuproptosis in lung adenocarcinoma
Authors: Su Yongcheng , Wang Wenjun , Shen Qianwen , Lei Ziyu , Li Jiangquan , Zhang Wenqing , Zhang Fuxing , Xu Beibei , Hu Tianhui 
Published: April 2023

Abstract
Cuproptosis is a newly defined form of regulated cell death triggered by excess copper and is distinct from other known types of cell death. Currently, reliable prognostic signatures based on cuproptosis-related regulators are underdeveloped. Herein, we aimed to investigate the cuproptosis landscape in lung adenocarcinoma (LUAD). We downloaded gene expression data and corresponding clinical information from The Cancer Genome Atlas and Gene Expression Omnibus. Cuproptosis subtypes were identified using unsupervised clustering based on the expression of 10 cuproptosis-related regulatory genes, including seven positively (FDX1, LIAS, LIPT1, DLAT, DLD, PDHA1, and PDHB) and three negatively (CDKN2A, GLS, and MTF1) correlated genes. CDKN2A expression was detected using immunohistochemistry tissue microarrays. Unsupervised clustering revealed two LUAD cuproptosis-related subtypes (A and B). Patients with subtype B had a higher survival rate and were significantly enriched in innate immune cells compared to those with subtype A. We built a cuproptosis-related risk model (CRM) to calculate a risk score for each patient; the score was positively correlated with patient prognosis. Chemotherapy drug sensitivity analysis suggested that patients with a low score were more sensitive to elesclomol and bortezomib but less sensitive to axitinib, sorafenib, AZD6244, and AZD6482 than those with a high score. Somatic mutation landscape analysis revealed a significant negative relationship between tumor mutational burden (TMB) and the CRM score. Patients with both a low CRM score and TMB had the worst prognosis. Immune landscape analysis revealed that patients with a high CRM score had a higher tumor immune dysfunction and exclusion score, suggesting a poorer immunotherapy response rate. Single-cell CRM score quantification revealed its correlation with the enrichment of different immune cell types in LUAD. Our findings pave the way to innovative and effective treatment strategies for LUAD.
SteatoSITE: an Integrated Gene-to-Outcome Data Commons for Precision Medicine Research in NAFLD
Authors: Fallowfield Jonathan , Kendall Timothy , Jimenez-Ramos Maria , Turner Frances , Ramachandran Prakash , Minnier Jessica , McColgan Michael , Ellis Harriet , Dunbar Donald , Kohnen Gabriele , Konanahalli Prakash , Oien Karin , Bandiera Lucia , Menolascina Filippo , Juncker-Jensen Anna , Alexander Douglas , Mayor Charlie , Guha Indra 
Published: April 2023

Abstract
Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide and a growing healthcare burden. The pathobiology of NAFLD is complex, disease progression is variable and unpredictable, and there are no qualified prognostic biomarkers or licensed pharmacotherapies that can improve clinical outcomes; it represents an unmet precision medicine challenge. We established a retrospective multicentre national cohort of 940 patients, across the complete NAFLD spectrum, integrating quantitative digital pathology, hepatic RNA-sequencing and 5.67 million days of longitudinal electronic health record follow-up into a secure, searchable, open resource (SteatoSITE) to inform rational biomarker and drug development and facilitate personalised medicine approaches for NAFLD. A complementary web-based gene browser was also developed. Here, our initial analysis uncovers disease stage-specific gene expression signatures, pathogenic hepatic cell subpopulations and master regulator networks associated with disease progression in NAFLD. Additionally, we construct novel transcriptional risk prediction tools for the development of future hepatic decompensation events.
Spatial analysis and hazard assessment of Large-scale ancient landslides around the reservoir area of Wudongde Hydropower Station, China
Authors: Shao Xiaoyi , Xu Chong , Li Lei , Yang Zhiqiang , Yao Xianglong , Shao Bo , Liang Cheng , Xue Zhiwen , Xu Xiwei 
Published: April 2023

Abstract
The complex geological environment and strong tectonic movement have led to the development of a large number of ancient landslides along the Jinsha River. These landslides exhibit characteristics of large-scale, complex formation mechanisms, multiple sliding periods, and high potential hazards. In this study, we aim to construct an ancient landslide inventory and conduct potential landslide hazard assessment of the Wudongde hydropower station section and its surrounding areas, which is located in the downstream area of Jinsha River. We used the visual interpretation method to recognize large ancient landslides based on high-resolution remote sensing images on the GoogleEarth platform, and analyzed the correlations between the landslide abundance and different influencing factors. Our results show that there were 3126 ancient landslides in the study area, covering a total area of 502.64 km2. The statistical analysis indicated that the landslide occurrence is closely related to the slope gradient and topographic relief, and the landslide abundance index increases with the increase of above two influencing factors. In addition, the ancient landslides gradually decreases with the increase of the elevation, indicating that ancient landslides are more likely to occur in lower elevation areas, i.e., lower portion of the hillslopes. In addition, combining with machine learning method, the potential landslide hazard assessment of the study area was calculated by the hypothetical earthquake scenario of 10% exceedance probability in 50 years. The predicted result shows that the extremely high-hazard area of landslides appeared around the hydropower station, and the high-hazard area was mainly distributed within a 5-km range along both banks of the Jinsha River. This study provides basic data and important reference for the distribution characteristics and potential hazard assessment of ancient landslides in the reservoir area of Wudongde hydropower station.
Bioaccumulation, Bioindication and Health Risk Assessment of Heavy Metals in Cape Horse Mackerel (Trachurus trachurus) and Slinger Seabream (Chrysoblephus puniceus) in the Durban Basin and Cape Vidal, South Africa
Authors: Ogola Henry , Sanjeev Debipersadh , Mearns Kevin , Selvarajan Ramganesh 
Published: April 2023

Abstract
The bioaccumulation of heavy metals (HMs) in marine fish is a growing global concern due to potential health risks. The study analysed HM in the muscle tissue, gills, and gut of cape horse mackerel and slinger seabream caught in the polluted Durban Basin and pristine Cape Vidal from April 2018 to February 2019. Results revealed interspecific, spatial, and organ-specific variability in HM levels. In the Durban basin, slinger seabream had bioaccumulation (in mg/kg) of As (2.3± 0.2), Cr (2.6±0.2), Ni (2.0±0.1), and Pb (4.1±0.3) while cape horse mackerel had Ni (1.6±0.2), Pb (4.7±0.6), and Zn (52±3.01) exceeding WHO regulatory limits. Metal pollution index (MPI) values were also higher in Durban Basin (>5.13) than Cape Vidal (<3.32) for both species muscles. Liver and gills of slinger seabream and gut of cape horse mackerel exhibited higher HM accumulation patterns proportionate to the environmental concentrations, indicating the bioindicative potential of HM pollution by the two species. Risk assessment indicated that both fish species had target hazard quotient (THQ) > 1 for Cr, and target cancer risk (TR) < 10-4 for Pb, implying significant non-carcinogenic and carcinogenic health risks associated with fish consumption from the Durban Basin. The study recommends daily consumption limits of 16 g/day for slinger seabream and 14 g/day for cape horse mackerel to ensure health safety. The findings contribute to the understanding of HM pollution in the Durban basin and provide important information for decision-makers and policymakers in developing effective strategies to mitigate and manage HM contamination in fish populations.
Goldene: Free-standing Single-atom-thick Sheets of Gold
Authors: Kashiwaya Shun , Shi Yuchen , Lu Jun , Sangiovanni Davide , Andersson Mike , Rosen Johanna , Hultman Lars 
Published: April 2023

Abstract
The quest to make free-standing monolayer gold has hitherto been limited to free-standing several-atoms-thick layers, or monolayers but confined on or inside another template. Examples are monolayers diffused into double hydroxides1, membranes framed in alloys under electron irradiation2, nano-ribbons suspended in graphene3, quantum dots on hexagonal BN4, monolayers in between SiC wafers and monolayer graphene5, and fragments produced via thermal dewetting on sapphire6. Here, we report the synthesis of free-standing single-atom-thick 2D gold (named goldene) by wet-chemically etching away Ti3C2 from Ti3AuC2, a nano-laminated MAX-phase ceramic initially formed by substituting Si in Ti3SiC2 with Au7. The free-standing goldene layers are revealed by scanning transmission electron microscopy. While ab initio molecular dynamics simulations show that 2D goldene is inherently stable, the experiments reveal a tendency for curling and agglomeration at edges. Prospects for preparing goldene from a series of non-van der Waals Au-intercalated MAX-phases, including developing etching schemes, are also presented.
A positive feedback cycle between the alarmin S100A8/A9 and NLRP3 inflammasome-GSDMD signalling reinforces the innate immune response in Candida albicans keratitis
Authors: Fang Xiaolong , Lian Huifang , Liu Shuang , Dong Jingcun , Hua Xia , Li Wenguang , Liao Chunyang , Yuan Xiaoyong 
Published: April 2023

Abstract
Background Fungal keratitis is a severe sight-threatening ocular infection, without effective treatment strategies available now. Calprotectin S100A8/A9 has recently attracted great attention as a critical alarmin modulating the innate immune response against microbial challenges. However, the unique role of S100A8/A9 in fungal keratitis is poorly understood.Methods Experimental fungal keratitis was established in wild-type and gene knockout mice by infecting mouse corneas with Candida albicans. The degree of mouse cornea injuries was evaluated by clinical scoring. To interrogate the molecular mechanism in vitro, macrophage RAW264.7 cell line was challenged with Candida albicans or recombinant S100A8/A9 protein. Label-free quantitative proteomics, quantitative real-time PCR, western blotting and immunohistochemistry were conducted in this research.Results Herein, we characterized the proteome of mouse corneas infected with Candida albicans and found that S100A8/A9 was robustly expressed at the early stage of the disease. S100A8/A9 significantly enhanced disease progression by promoting NLRP3 inflammasome activation and Caspase-1 maturation, accompanied by increased accumulation of macrophages in infected corneas. In response to Candida albicans infection, toll-like receptor 4 (TLR4) sensed extracellular S100A8/A9 and acted as a bridge between S100A8/A9 and NLRP3 inflammasome activation in mouse corneas. Furthermore, the deletion of TLR4 resulted in noticeable improvement in fungal keratitis. Remarkably, NLRP3/GSDMD-mediated macrophage pyroptosis in turn facilitates S100A8/A9 secretion during Candida albicans keratitis, thus forming a positive feedback cycle that amplifies the proinflammatory response in corneas.Conclusions The present study is the first to reveal the critical roles of the alarmin S100A8/A9 in the immunopathology of Candida albicans keratitis, highlighting a promising approach for therapeutic intervention in the future.
Waveform Optimization for Improving Inkjet Printing Speed
Authors: Sui Chao , Zhou Wenchao 
Published: April 2023

Abstract
Inkjet has been widely used in different industrial applications for its high resolution and capability to print with multiple materials, but its printing speed has limited its use for high volume production. This paper presents a new approach to improve the speed of piezo inkjet printing through waveform optimization. We previously developed a model that can predict the effects of driving signal parameters on printing speed, and in this paper, we use optimization techniques to find the optimal signal parameters for maximum speed. We then validate these optimal parameters using a custom-designed experimental setup with a high-speed camera capable of capturing the dynamics of droplet formation. Our results show that our optimized signal achieves successful jetting with a five-time increase in equivalent printing speed compared to a benchmark commercial printhead (Xaar 128/80W).
Systematic pan-cancer analysis reveals XCR1 as a Prognostic and Immunological Biomarker
Authors: Cui Likun , Chen Jie , Li Chunzhen , Yu Yizhi , Xu Sheng 
Published: April 2023

Abstract
Background Chemokines and their receptors play an important role in immune monitoring and immune defense during the tumor growth and metastasis. However, their prognostic roles in pan-cancer were not elucidated. In this work, we screened all chemokine receptors in pan-cancer and discovered XCR1 as a reliable immunological and prognostic biomarker in pan-cancer using bioinformation.Methods The TCGA database served as the foundation for the primary research database analysis in this work. The screening of tumor patients' overall survival yielded XCR1, which had a favorable predictive connection. Further investigation into the connection between XCR1 expression and tumor development stage in tumor patients was done using the clinicopathological stage. The regulatory mechanism of XCR1 regulating tumor formation and as a prognostic molecule has also been discovered using enrichment analysis of XCR1-related genes. The spatial localization of XCR1 in tumor tissues was discovered by using single-cell databases.Result XCR1 was downregulated in tumors. Patients with reduced XCR1 showed worse prognoses and a concomitant decrease in immune cell infiltration (DCs and CD8 + T cells). According to gene enrichment study, XCR1 enhanced immune system performance by promoting T cell infiltration through the CXCL9-CXCR3 axis. In addition, XCR1 is mainly expressed on infiltrated DCs and some malignant cells in tumor tissues.Conclusion Our data revealed the important role of XCR1 in remodeling of the tumor microenvironment and predicting the survival prognosis, which could also be used as sensitive biomarker for tumor immunotherapy.
Development of a method to discriminate salt sensitivity in hypertension by single-nephron blood flow (SNBF) index and new insights into the relationship between SNBF and hypertension.
Authors: Kunimi Motoei , Takizawa Toshikazu , Tamura Koichi 
Published: April 2023

Abstract
More than 95% of hypertensive patients have essential hypertension, which can be divided into salt-resistant hypertension (SRH) and salt-sensitive hypertension (SSH). They differ in several aspects. If they can be easily diagnosed, treatment, complications and prognosis can be improved. But there is no easy way to differentiate them. We focused on renal salt excretion process and renal blood flow (RBF). RBF of SRH decreases by increasing renal vascular resistance, and RBF of SSH increases by fluid accumulation for decreasing salt excretion efficiency. Since both can be distinguished by measuring RBF, we created a renal blood flow index using uric acid. Then, we divided RBF into 2 categories: whole renal blood flow (WRBF) and single-nephron blood flow (SNBF). We studied in 26 SRH and 16 SSH patients from 3/1/ to 30/11, 2018. SSH was higher than SRH in WRBF and SNBF, with no significant difference in WRBF (81.3 ± 29.8 vs 73.3 ± 32.4, p = 0.43), but significant difference in SNBF (1.94 ± 0.75 vs 1.04 ± 0.39, P < 0.01), suggesting that SNBF can distinguish SSH and SRH. Therefore, SNBF allows differentiation between SRH and SSH, and this study showed that essential hypertension is an abnormal condition in which SNBF is increased or decreased from the physiological range of SNBF.
Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells
Authors: Elsayed Ahmed K. , Alajez Nehad M. , Abdelalim Essam M. 
Published: April 2023

Abstract
Background: Our recent studies have demonstrated the crucial involvement of FOXA2 in the development of human pancreas. Reduction of FOXA2 expression during the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic islets has been found to reduce α-and β-cell masses. However, the extent to which such changes are linked to alterations in the expression profile of long non-coding RNAs (lncRNAs) remains unraveled.
Methods: Here, we employed our recently established FOXA2-deficient iPSCs (FOXA2-/- iPSCs) to investigate changes in lncRNA profiles and their correlation with dysregulated mRNAs during the pancreatic progenitor (PP) and pancreatic islet stages. Furthermore, we constructed co-expression networks linking significantly downregulated lncRNAs with differentially expressed pancreatic mRNAs.
Results: Our results showed that 442 lncRNAs were downregulated, and 114 lncRNAs were upregulated in PPs lacking FOXA2 compared to controls. Similarly, 177 lncRNAs were downregulated, and 59 lncRNAs were upregulated in islet cells lacking FOXA2 compared to controls. At both stages, we observed a strong correlation between lncRNAs and several crucial pancreatic genes and TFs during pancreatic differentiation. Correlation analysis revealed 12 DE-lncRNAs that strongly correlated with key downregulated pancreatic genes in both PPs and islet cell stages. Selected DE-lncRNAs were validated using RT-qPCR.
Conclusions: Our data indicate that the observed defects in pancreatic islet development due to the FOXA2 loss is associated with significant alterations in the expression profile of lncRNAs. Therefore, our findings provide novel insights into the role of lncRNA and mRNA networks in regulating pancreatic islet development, which warrants further investigations.
Manufacturing Process and Clinical Application of Personalized 3D Printed Occlusal Guides for Maxillofacial Fractures
Authors: Wang Honghao , Chi Yifan , Hu Yukun , Huang Hanxiao , Hou Jun 
Published: April 2023

Abstract
Restoration of the occlusal relationship is critical in the treatment of maxillofacial fractures. Poor restoration of the occlusal relationship has a serious impact on the patient's oral function and physical and mental health. This study is based on computer-aided design and manufacturing and aimed to use computed tomography (CT) data to establish a maxillofacial bone model and perform virtual reduction of such fractures. The upper and lower dentition models were established and reconstructed via 3D printing. After the occlusal relationship was determined by the prosthodontist using the model, the occlusal relationship was obtained through an oral three-dimensional scanner. Based on the reconstructed occlusal relationship, an occlusal reduction guide plate was designed and manufactured to precisely reduce the occlusal relationship in patients with maxillofacial fractures. This study proposes a design process for occlusal guides for maxillofacial fractures that optimizes the traditional surgical processes and enhances surgical convenience. This study presents new ideas for the design of personalized surgical guides for maxillofacial fractures.
No intromission is involved in the mating of Eptesicus serotinus, a novel copulatory pattern in mammals.
Authors: Fasel Nicolas , Jeucken Jan , Kravchenko Kseniia , Fritze Marcus , Ruczynski Ireneusz , Komar Ewa , Moiseienko Marharyta , Shulenko Alona , Vlaschenko Anton , Christe Philippe , Glaizot Olivier , Holtze Susanne 
Published: April 2023

Abstract
Copulatory behaviours stand as cornerstones of sexual selection, yet they remain mysterious in many species, especially in bats. An extremely large penile erection with a heart-shape terminal swelling has been observed in the serotine bat (Eptesicus serotinus). The engorgement of the erectile tissues could take place after penetration to generate a copulatory lock. Alternatively, the erected penis, long and mobile, could be used to pass by the protective tail membrane to reach the vulva. In the latter scenario, the penis may however not be able to penetrate the vagina. In order to find out which of the two scenarios occurs, we investigated the morphology of female and male genitalia of E. serotinus. We found that the vagina is more than seven times shorter than the erected penis, supporting that the penis is used as a copulatory arm rather than an intromittent organ. We could confirm our hypothesis with direct observations of copulations. During mating, the male grasps the female in a dorsoventral position. The male probes the female’s ventral part with its erected penis until the penis is tightly pushed against the vulva. Afterward, the pair stops moving and can hold the position for several hours. In addition, the timing of copulations, which exhibits a peak in October, implies that visits to swarming sites throughout the year may serve other functions besides mating. This research reveals a novel copulatory behaviour that has not been previously documented in mammals and sheds light on the poorly understood area of bat reproduction.
The Changing Cholera-Climate Relationship in the Bengal Delta over the Past Century
Authors: Shackleton Debbie , Memon Fayyaz , Chen Albert , Dutta Shanta , Kanungo Suman , Deb Alok 
Published: April 2023

Abstract
Background: In the Bengal Delta, research has shown that climate and cholera are linked. One demonstration of this is the relationship between interannual ocean-atmospheric oscillations such as the El Niño Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD). What remains unclear in the present literature is how and if this relationship has changed over time.
Results: In this study, we analyse the changing relationship between climate and cholera over a recent (1999-2019) and historical (1897-1941) time interval using wavelet analysis to measure signal coherence. Significant and non-stationary coherence levels with cholera were observed in both time intervals for both climate oscillations. While a notable weakening of the relationship with ENSO over time was evident, the relationship with IOD remained strong. Our results suggest that temperature, and not rainfall or SST, is the mediating factor behind the association between cholera and both climate oscillations.
Conclusions: Despite consistent improvements to WASH infrastructure, the link between cholera and climate remains strong. Climate-change induced warming and strengthening of the IOD are likely to increase vulnerability to cholera in the region in the future.
The Impact of Vaccinations and Chronic Disease on COVID Death Rates
Authors: Doti James L. 
Published: April 2023

Abstract
This study presents a theoretical and empirical regression model to measure the efficacy of vaccinations in reducing COVID death rates across states over the 3/10/21 to 12/28/22 period. During that period, it was estimated that the availability of vaccinations resulted in a reduction of 427,000 COVID deaths in the nation. To arrive at that estimate, other covariants were held constant. In particular, it was found that chronic disease should be included as an explanatory variable to arrive at unbiased measures of the efficacy of vaccinations in reducing deaths. In addition, the percentage of people over the age of 65 was found to be highly significant. The only ethnic/racial characteristic that was significant in explaining COVID deaths was the percentage of American Indians/Alaska Natives residing in a state. Other ethnic/racial characteristics, as well as variables representing population, density, governmental stringency, and income, were not significant over the period tested. Finally, cumulative prior death and case rates tested were not significant in influencing COVID death rates during the period tested in this study.