bluuebunny/crossref_metadata_2025_split huggingface dataset:
A large-scale comparison of human-written versus ChatGPT-generated essays
Authors: Herbold Steffen , Hautli-Janisz Annette , Heuer Ute , Kikteva Zlata , Trautsch Alexander 
Published: October 2023

AbstractChatGPT and similar generative AI models have attracted hundreds of millions of users and have become part of the public discourse. Many believe that such models will disrupt society and lead to significant changes in the education system and information generation. So far, this belief is based on either colloquial evidence or benchmarks from the owners of the models—both lack scientific rigor. We systematically assess the quality of AI-generated content through a large-scale study comparing human-written versus ChatGPT-generated argumentative student essays. We use essays that were rated by a large number of human experts (teachers). We augment the analysis by considering a set of linguistic characteristics of the generated essays. Our results demonstrate that ChatGPT generates essays that are rated higher regarding quality than human-written essays. The writing style of the AI models exhibits linguistic characteristics that are different from those of the human-written essays. Since the technology is readily available, we believe that educators must act immediately. We must re-invent homework and develop teaching concepts that utilize these AI models in the same way as math utilizes the calculator: teach the general concepts first and then use AI tools to free up time for other learning objectives.
Prediction method for the truck's fault time in open-pit mines based on exponential smoothing neural network
Authors: Liu Wei , Sun Jiayang , Huang Jinbiao , Liu Guangwei , Bai Runcai 
Published: October 2023

AbstractThe transport truck is one of the important equipment for open-pit mines, and predicting the truck's fault time is of great significance in improving the economic benefits of open-pit mines. In this paper, we discuss the reason for the large prediction error of the exponential smoothing method. Then, we propose a novel nonlinear exponential smoothing method (ESNN) for predicting the truck's fault time, and demonstrate the equivalence between our approach and the neural network structure. Finally, based on the augmented Lagrange function, the solving method of ESNN is proposed. We conduct experiments on real-world datasets and our results demonstrate the effectiveness of ESNN in comparison to existing state-of-the-art methods. Our approach makes it easier for maintenance personnel to predict fault situations in advance and provides a basis for enterprises to develop preventive maintenance plans.
Novel 3-phenylquinazolin-2,4(1H,3H)-diones as dual VEGFR-2/c-Met-TK inhibitors: design, synthesis, and biological evaluation
Authors: Hassan Abdelfattah , Mosallam Ahmed M. , Ibrahim Amal O. A. , Badr Mohamed , Abdelmonsef Aboubakr H. 
Published: October 2023

AbstractMultitarget anticancer drugs are more superior than single target drugs regarding patient compliance, drug adverse effects, drug-drug interactions, drug resistance as well as pharmaceutical industry economics. Dysregulation of both VEGFR-2 and c-Met tyrosine kinases (TKs) could result in development and progression of different human cancers. Herein, we reported a novel series of 3-phenylquinazolin-2,4(1H,3H)-diones with thiourea moiety as dual VEGFR-2/c-Met TKs. Compared to sorafenib, cabozantinib went behind VEGFR-2 inhibition to target c-Met TK. The dual VEGFR-2/c-Met inhibitory activity of cabozantinib is due to a longer HB domain than that of sorafenib. Based on pharmacophore of cabozantinib analogues, we designed new dual VEGFR-2/c-Met TKs. We synthesized the target compounds via a new single pot three-component reaction. The cytotoxic activity of synthesized compounds was conducted against HCT-116 colorectal cancer cell line. Compounds 3c and 3e exhibited the highest cytotoxic activity against HCT-116 cell line (IC50 1.184 and 3.403 µM, respectively). The in vitro enzyme inhibitory activity was carried out against both VEGFR-2 and c-Met TKs. Compound 3e has the highest inhibitory activity against both VEGFR-2/c-Met (IC50 = 83 and 48 nM, respectively). Docking studies showed that α-oxo moiety in quinazoline ring formed hydrogen bond HB with Met1160 residue in the adenine region of c-Met TK.
Primary breast tumor induced extracellular matrix remodeling in premetastatic lungs
Authors: Cai Ruoqing , Tressler Caitlin M. , Cheng Menglin , Sonkar Kanchan , Tan Zheqiong , Paidi Santosh Kumar , Ayyappan Vinay , Barman Ishan , Glunde Kristine 
Published: October 2023

AbstractThe premetastatic niche hypothesis proposes an active priming of the metastatic site by factors secreted from the primary tumor prior to the arrival of the first cancer cells. We investigated several extracellular matrix (ECM) structural proteins, ECM degrading enzymes, and ECM processing proteins involved in the ECM remodeling of the premetastatic niche. Our in vitro model consisted of lung fibroblasts, which were exposed to factors secreted by nonmalignant breast epithelial cells, nonmetastatic breast cancer cells, or metastatic breast cancer cells. We assessed ECM remodeling in vivo in premetastatic lungs of female mice growing orthotopic primary breast tumor xenografts, as compared to lungs of control mice without tumors. Premetastatic lungs contained significantly upregulated Collagen (Col) Col4A5, matrix metalloproteinases (MMPs) MMP9 and MMP14, and decreased levels of MMP13 and lysyl oxidase (LOX) as compared to control lungs. These in vivo findings were consistent with several of our in vitro cell culture findings, which showed elevated Col14A1, Col4A5, glypican-1 (GPC1) and decreased Col5A1 and Col15A1 for ECM structural proteins, increased MMP2, MMP3, and MMP14 for ECM degrading enzymes, and decreased LOX, LOXL2, and prolyl 4-hydroxylase alpha-1 (P4HA1) for ECM processing proteins in lung fibroblasts conditioned with metastatic breast cancer cell media as compared to control. Taken together, our data show that premetastatic priming of lungs by primary breast tumors resulted in significant ECM remodeling which could facilitate metastasis by increasing interstitial fibrillar collagens and ECM stiffness (Col14A1), disruptions of basement membranes (Col4A5), and formation of leaky blood vessels (MMP2, MMP3, MMP9, and MMP14) to promote metastasis.
Circulating DNA and frequency of colorectal cancer brain metastases in a presumed high-risk group
Authors: Callesen Louise Bach , Boysen Anders Kindberg , Andersen Rikke Fredslund , Dalby Rikke Beese , Spindler Karen-Lise Garm 
Published: October 2023

AbstractThis explorative prospective observational pilot study investigated if suggested risk factors, rectal cancer and lung metastases, could add to a relevant detection rate of asymptomatic brain metastases (BM) from colorectal cancer (CRC). Secondary, prognostic biological aspects were investigated by translational analysis of plasma samples. The study enrolled patients with rectal cancer and lung metastases. At inclusion, patients underwent a standard MRI scan of the brain. Cell-free DNA (cfDNA) level was measured by a direct fluorescence assay (DFA), and circulating tumor DNA (ctDNA) by ddPCR. BM was detected in one of twenty-nine included patients. Patients had higher cfDNA levels than healthy subjects (p < 0.01). Patients with the primary tumor in situ had higher cfDNA levels than those with resected primary tumor (p < 0.01). Patients with liver involvement had higher cfDNA levels (p = 0.12) and circulating tumor DNA levels (p = 0.01) than those without liver involvement. In conclusion, the modest incidence of BM does not justify routine MRI of the brain in this selected population. cfDNA by DFA could be a valuable tool when planning treatment and follow-up for CRC patients. Future studies should focus on identifying further characteristics and biomarkers associated with a high risk of BM, enhancing the possibility for early intervention.
Alzheimer’s disease: new insight in assessing of amyloid plaques morphologies using multifractal geometry based on Naive Bayes optimized by random forest algorithm
Authors: Amin Elshaimaa , Elgammal Yasmina M. , Zahran M. A. , Abdelsalam Mohamed M. 
Published: October 2023

AbstractAlzheimer’s disease (AD) is a physical illness, which damages a person’s brain; it is the most common cause of dementia. AD can be characterized by the formation of amyloid-beta (Aβ) deposits. They exhibit diverse morphologies that range from diffuse to dense-core plaques. Most of the histological images cannot be described precisely by traditional geometry or methods. Therefore, this study aims to employ multifractal geometry in assessing and classifying amyloid plaque morphologies. The classification process is based on extracting the most descriptive features related to the amyloid-beta (Aβ) deposits using the Naive Bayes classifier. To eliminate the less important features, the Random Forest algorithm has been used. The proposed methodology has achieved an accuracy of 99%, sensitivity of 100%, and specificity of 98.5%. This study employed a new dataset that had not been widely used before.
Experimental investigation and modelling of the mechanical properties of palm oil fuel ash concrete using Scheffe’s method
Authors: Akeke Godwin Adie , Inem Philip-Edidiong Udo , Alaneme George Uwadiegwu , Nyah Efiok Etim 
Published: October 2023

AbstractThis study explores the enhancement of mechanical properties in concrete blended with palm oil fuel ash (POFA) through Scheffe's optimization. The utilization of POFA as supplementary cementitious material in concrete has gained attention for its potential environmental benefits. Utilizing a (5,2) simplex-lattice design, a systematic approach is employed for optimizing mixture proportions based on response parameters. The laboratory tests to evaluate concrete's mechanical behavior were conducted using the computed mixture ratios from the design experimental points after 28 days of hydration. The results showed maximum flexural strength at 8.84 N/mm2and compressive strength at 31.16 N/mm2, achieved with a mix of 0.65:0.54:2.3:3.96:0.35 for cement, water, coarse aggregate, fine aggregate, and POFA. Additionally, maximum splitting tensile strength reached 8.84 N/mm2with a mix of 0.62:0.55:2.09:3.86:0.38 for the same components. Conversely, the minimum flexural, splitting tensile and compressive strength within the experimental factor space was 4.25, 2.08 and 19.82 N/mm2respectively. The results obtained indicated a satisfactory mechanical strength performance at POFA replacement of 35 percent in the concrete mixture. The developed mathematical model was statistically validated using analysis of variance (ANOVA) at a 95% confidence interval which showed satisfactory prediction performance. The findings from this study provide valuable insights into optimizing POFA-blended concrete for enhanced mechanical performance, offering potential sustainable solutions for the construction industry.
Clinical usefulness of urinary biomarkers for early prediction of acute kidney injury in patients undergoing transaortic valve implantation
Authors: Obata Yumi , Kamijo-Ikemori Atsuko , Shimmi Sachi , Inoue Soichiro 
Published: October 2023

AbstractThis study aimed to reveal the clinical usefulness of urinary biomarkers for the early prediction of AKI onset after transcatheter aortic valve implantation (TAVI) (n = 173). In this study, 22 (12.7%) patients had AKI, of which 21 had mild AKI and 1 had moderate AKI. Higher levels of urinary liver-type fatty acid binding protein (L-FABP), [tissue inhibitor of metalloproteinases-2] × [insulin-like growth factor-binding protein 7], clusterin and urinary albumin before, after and 4 h after TAVI were associated with AKI onset. However, the time point of higher urinary N-acetyl-β-d-glucosaminidase levels related to AKI onset was only before TAVI. No significant differences were found in the area under the receiver-operator characteristic curves (AUC) for predicting AKI onset between urinary biomarkers before TAVI. After TAVI, the AUC (0.81) of urinary albumin was significantly higher than those of any other urinary biomarkers. The sensitivity (0.86) in urinary albumin after TAVI and specificity (0.98) in urinary L-FABP before TAVI were the highest among urinary biomarkers. In conclusion, urinary biomarkers may be clinically useful for early differentiation of patients with a higher or lower risk for AKI onset or early prediction of post-TAVI onset of AKI.
Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma
Authors: Wu Qinjuan , Li Xin , Long Menghong , Xie Xianfeng , Liu Qing 
Published: October 2023

AbstractHistone lysine lactylation (Kla) plays a vital role in the tumorigenesis of hepatocellular carcinoma (HCC). Hence, we focused on Kla-specific genes to select novel therapeutic targets. Differentially expressed Kla-specific genes (DEKlaGs) were identified from TCGA with the cut-off criteria |log2(FlodChange (FC))| > 2, p-value < 0.05, following investigating the prognostic value. The correlation between lactate accumulation and prognostic DEKlaGs expression was further investigated. On the other hand, we explored the roles of Kla activation in the immune microenvironment, immunotherapy, and drug resistance. We conducted gene set enrichment analysis (GSEA) to predict the pathways influenced by Kla. The predictive power of Cox model was further identified in ICGC and GEO databases. A total of 129 DEKlaGs were identified, and 32 molecules might be potential prognostic biomarkers. A Cox model including ARHGEF37, MTFR2, NR6A1, NT5DC2, OSBP2, RNASEH2A, SFN, and UNC119B was constructed, which suggested unfavorable overall survival in high-risk score group, and risk score could serve as an indicator for large tumor size, poor pathological grade and advanced stage. NR6A1, OSBP2 and UNC119B could inhibit NK cell as well as TIL cell infiltration, and impair Type-I and II IFN responses in HCC, thereby contributing to unsatisfactory prognosis and immunotherapy resistance. OSBP2 and UNC119B were identified to be related to chemotherapy resistance. GSEA showed that WNT, MTOR, MAPK and NOTCH signaling pathways were activated, indicating that these pathways might play a crucial role during the Kla process. On the other hand, we showed that NR6A1 and OSBP2 were overexpressed in GEO. OSBP2 and UNC119B contributed to poor survival and advanced stage in ICGC. In summary, histone Kla was related to HCC prognosis and might serve as an independent biomarker. NR6A1, OSBP2 and UNC119B were associated with the prognosis, immunotherapy, and chemotherapy resistance, suggesting that NR6A1, OSBP2 and UNC119B might be novel candidate therapeutic targets for HCC.
Discovering golden ratio in the world’s first five-agent network in ancient China
Authors: Yang Ciann-Dong 
Published: October 2023

AbstractThe world’s first five-agent network, also called Wuxing network in ancient China, had been fully established in the second century BC. Surprisingly, the key to cracking the operation of Wuxing network is the golden ratio, the world’s most astonishing number originating from ancient Greece. Wuxing network is composed of five agents located on the vertices of a pentagon such that adjacent agents cooperate with each other, while spaced-apart agents oppose each other. Although it was proposed more than 2000 years ago, it is still an unparalleled network operation protocol. This article reveals the role of the golden ratio in the balance and stability of Wuxing network, and demonstrates how to detect the golden ratio experimentally in Wuxing electronic circuits and in Wuxing formation flight of drones.
Synthesis and physicochemical characterization of carbon quantum dots produced from folic acid
Authors: Fawaz Walaa , Hasian Jameela , Alghoraibi Ibrahim 
Published: October 2023

AbstractThe rising interest in carbon dots (c-dots) is driven by their remarkable potential in the field of biomedical applications. This is due to their distinctive and adjustable photoluminescence characteristics, outstanding physicochemical properties, excellent photostability, and biocompatibility. Herein, carbon dots were successfully produced via the heat synthesis method and characterization for physical and chemical properties using UV–Vis spectrophotometer, photoluminescence spectroscopy, Fourier Transform Infrared and Raman spectroscopy, Energy-dispersive X-ray analysis, and quantum yield. The resulting carbon dots exhibited a distinct blue fluorescence upon exposure to ultraviolet radiation with a 366 nm wavelength. The photoluminescence spectrum of carbon dots displayed a fluorescence peak around 470 nm when excited with a 325 nm wavelength. The synthesized carbon dots demonstrated thermal stability and maintained photoluminescence intensity under different pH conditions, including neutral and alkaline mediums, and good salt resistance ability. Raman spectroscopy confirmed the presence of structural defects within the carbon dots, which are associated with the presence of hybrid groups on their surface. Fourier-transform infrared analysis detected various carbon-bonded, nitrogen-bonded, and oxygen-bonded units. The quantum yield was around 8.9%. These findings from our experiments indicate that the manufactured carbon dots possess substantial promise for a wide range of applications within the biotechnology field.
Achieving quantitative reproducibility in label-free multisite DIA experiments through multirun alignment
Authors: Gupta Shubham , Sing Justin C. , Röst Hannes L. 
Published: October 2023

AbstractDIA is a mainstream method for quantitative proteomics, but consistent quantification across multiple LC-MS/MS instruments remains a bottleneck in parallelizing data acquisition. One reason for this inconsistency and missing quantification is the retention time shift which current software does not adequately address for runs from multiple sites. We present multirun chromatogram alignment strategies to map peaks across columns, including the traditional reference-based Star method, and two novel approaches: MST and Progressive alignment. These reference-free strategies produce a quantitatively accurate data-matrix, even from heterogeneous multi-column studies. Progressive alignment also generates merged chromatograms from all runs which has not been previously achieved for LC-MS/MS data. First, we demonstrate the effectiveness of multirun alignment strategies on a gold-standard annotated dataset, resulting in a threefold reduction in quantitation error-rate compared to non-aligned DIA results. Subsequently, on a multi-species dataset that DIAlignR effectively controls the quantitative error rate, improves precision in protein measurements, and exhibits conservative peak alignment. We next show that the MST alignment reduces cross-site CV by 50% for highly abundant proteins when applied to a dataset from 11 different LC-MS/MS setups. Finally, the reanalysis of 949 plasma runs with multirun alignment revealed a more than 50% increase in insulin resistance (IR) and respiratory viral infection (RVI) proteins, identifying 11 and 13 proteins respectively, compared to prior analysis without it. The three strategies are implemented in our DIAlignR workflow (>2.3) and can be combined with linear, non-linear, or hybrid pairwise alignment.
PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy
Authors: Dou Xuefeng , Fu Qiang , Long Qilai , Liu Shuning , Zou Yejun , Fu Da , Xu Qixia , Jiang Zhirui , Ren Xiaohui , Zhang Guilong , Wei Xiaoling , Li Qingfeng , Campisi Judith , Zhao Yuzheng , Sun Yu 
Published: October 2023

AbstractSenescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. Senescent cells display a PDK4-dependent increase in aerobic glycolysis and enhanced lactate production but maintain mitochondrial respiration and redox activity, thus adopting a special form of metabolic reprogramming. Medium from PDK4+ stromal cells promotes the malignancy of recipient cancer cells in vitro, whereas inhibition of PDK4 causes tumor regression in vivo. We find that lactate promotes reactive oxygen species production via NOX1 to drive the senescence-associated secretory phenotype, whereas PDK4 suppression reduces DNA damage severity and restrains the senescence-associated secretory phenotype. In preclinical trials, PDK4 inhibition alleviates physical dysfunction and prevents age-associated frailty. Together, our study confirms the hypercatabolic nature of senescent cells and reveals a metabolic link between cellular senescence, lactate production, and possibly, age-related pathologies, including but not limited to cancer.
Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia
Authors: Bruedigam Claudia , Porter Amy H. , Song Axia , Vroeg in de Wei Gerjanne , Stoll Thomas , Straube Jasmin , Cooper Leanne , Cheng Guidan , Kahl Vivian F. S. , Sobinoff Alexander P. , Ling Victoria Y. , Jebaraj Billy Michael Chelliah , Janardhanan Yashaswini , Haldar Rohit , Bray Laura J. , Bullinger Lars , Heidel Florian H. , Kennedy Glen A. , Hill Michelle M. , Pickett Hilda A. , Abdel-Wahab Omar , Hartel Gunter , Lane Steven W. 
Published: October 2023

AbstractTelomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft resource and perform integrated genomics, transcriptomics and lipidomics analyses combined with functional genetics to identify key mediators of imetelstat efficacy. In a randomized phase II-like preclinical trial in patient-derived xenografts, imetelstat effectively diminishes AML burden and preferentially targets subgroups containing mutant NRAS and oxidative stress-associated gene expression signatures. Unbiased, genome-wide CRISPR/Cas9 editing identifies ferroptosis regulators as key mediators of imetelstat efficacy. Imetelstat promotes the formation of polyunsaturated fatty acid-containing phospholipids, causing excessive levels of lipid peroxidation and oxidative stress. Pharmacological inhibition of ferroptosis diminishes imetelstat efficacy. We leverage these mechanistic insights to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patient samples to imetelstat causing substantial disease control in AML.