bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of Capecitabine and its Metabolites in Plasma of Egyptian Colorectal Cancer Patients
Authors: Shams Sara , Samir Liza , Abdelmaksoud Sahar , Gad Mohamed Zakaria , Hanafi Rasha 
Published: February 2023

Abstract
The incidence of Colorectal cancer (CRC) is increasing worldwide. It has variable signs and symptoms starting from change in bowel habit to nausea and vomiting. Chemotherapeutic agents are often prescribed in CRC such as Capecitabine (CCB) and 5-Fluorouracil (FU). CCB is the prodrug of FU in oral dosage form, which makes it preferable by physicians, since no hospitalization is needed for drug administration. CCB is activated to FU in a 3-steps reaction producing 5'-deoxy-5-fluorocytidine (DFCR) (by carboxylesterase (CES) enzyme), then 5'-deoxy-5-fluorouridine (DFUR) (by cytidine deaminase (CDD) enzyme) and finally FU (by thymidine phosphorylase (TYMP) enzyme), the active form, which is later deactivated to give 5,6-dihydro-5-fluorouracil (DHFU). Different patients exhibit variable drug responses and adverse in response to CCB therapy, despite being treated by the same dose, which could be attributed tothe occurrence of different possible enzyme single nucleotide polymorphisms (SNPs) along the activation and deactivation pathways of CCB. The most commonly occurring toxicities in CCB therapy are Hand-Foot syndrome and diarrhea. This study aims at developing and validating a new method for simultaneous determination of CCB and its metabolites by HPLC-UV, followed by a correlation study with the toxicities occurring during therapy, where predictions of toxicity could be based on metabolites level instead ofthe tedious process of genotyping. A new superior analytical method was optimized by a Quality by Design approach using DryLab® software achieving baseline resolution of the 6 analytes within the least possible gradient time of 10 min. The method also showed linearity (in a range from 1 to 500 µg/ml), accuracy, precision and robustness upon validation. LOD was found to be 3 ng/mL for DHFU and CCB, and 0.3 ng/mL for DFUR, DFCR and FU. The LOQ was found to be 10 ng/mL for DHFU and CCB, and 1 ng/mL for DFUR, DFCR and FU. Clinical results showed a positive correlation between the concentration of DFCR and mucositis and between the concentration of DFUR and Hand-Foot Syndrome, confirming that this technique could be used for predicting such toxicities.
Stoichiometry of litter decomposition under the effects of global change: A meta-analysis.
Authors: Casa Javier de la , Sardans Jordi , Galindo-Díaz Marta , Peñuelas Josep 
Published: February 2023

Abstract
The cycling of nutrients from plant litter has relevant implications on the functioning of terrestrial ecosystems by controlling the availability of nutrients and net primary production. The effects of global change have been widely studied for most aspects of ecosystem functioning, but the direct implications on the stoichiometry and nutrient dynamics of litter decomposition are still poorly understood. We conducted a meta-analysis to determine how warming, changes of water availability, and enrichments of N and P interfere with the immobilisation/mineralisation of nutrients and the stoichiometric relationships during litter decomposition. Our database consisted of 194 experiments from 43 studies that experimentally simulated (i) warming, (ii) drought, (iii) irrigation, (iv) N enrichment, (v) P enrichment, and (vi) combined N and P (N + P) enrichment. We compared the early stages (approximately half a year) and late stages (approximately one year) of decomposition; and the specific effects taking into account the climate, the species used and the ecosystem type. We explored the different effects of all treatments and highlight three of them. (i) Warming and nutrient enrichment induce a faster release of C during decomposition, prominent in grassland and coniferous forests of continental climates, and with a potential feedback loop to climate change. (ii) C:P and overall C:N ratios generally decreased in most of the scenarios of global change analyzed at short- and long-term during litter decomposition, while the N:P ratios are more resilient to change. (iii) P limitation might be exacerbated in in warming continental climates; arid environments experiencing droughts; temperate environments with increasing water availability; and temperate broadleaved forest experiencing N and P enrichment. Our results provide information about the fate of litter decomposition and its nutrient and stoichiometric dynamics in response to drivers of global change. However, further experimentation and analysis considering all interacting drivers are warranted.
MMP9 in Pan-Cancer and Computational Study to Screen MMP9 Inhibitors
Authors: Wu Bo , Wang Xinyu , Chen Chunzheng , Yang Qifan , Zhou Pengcheng , Lu Shiyuan , Lin Liangxin , Liu Yanwei , Li Ming , Zhu Dong 
Published: February 2023

Abstract
Purpose Stromal metalloproteinase 9 (MMP9) is a stromal cell protein associated with extracellular matrix (ECM) degradation and remodeling, which promotes tumor invasion and metastasis and regulates the activity of cell adhesion molecules and cytokines. This study aims to evaluate the MMP9 in pan-cancer and to screen out new major compounds and drug candidates that can inhibit MMP9.
Methods The pan-cancer dataset was downloaded from UCSC database. The MMP9 expression in pan-cancer was evaluated and the correlation of MMP9 with tumor microenvironment (TME), RNA Modification Genes and tumor mutation burden (TMB) in pan-cancer. Then, MMP9 crystal structures was download and a ligand-based pharmacophore model was constructed. machine learning model was also constructed for further screen. The identify compounds were pooled into Discovery Studio 4.5 for ADME (absorption, distribution, metabolism, excretion) and toxicity prediction. Molecular docking was performed using the Glide module of the Schrödinger kit to demonstrate the binding affinity and mechanism between compounds and MMP9. To assess whether the ligand-receptor complex is stable, Molecular Dynamics Simulation of Discovery Studio 4.5 was used.
Results The results of our pan-cancer analysis showed difference expression of MMP9 in tumor tissues. Prognostic analysis showed that higher MMP9 expression means both worse survival rate and tumor progression in GMBLGG, KIPAN, UVM, LGG, ACC, and LIHC. MMP9 expression in GMBLGG, KIPAN, UVM, LGG, ACC, and LIHC was significantly positively correlated with TME. After screened by ligand-based pharmacophore model and machine learning model, 49 small molecules were identified. ADME and toxicity prediction results indicated that CEMBL82047 and CEMBL381163 were identified as potential MMP9 inhibitor. CEMBL82047 and CEMBL381163 showed robust binding affinity with MMP9, and the complex can exist stably in the natural environment.
Conclusion CHEMBL82047 and CHEMBL381163 are ideal potential leading compounds for inhibiting MMP9. The findings of this study and these selected drug candidates have greatly contributed to the design and improvement of novel MMP9-targeted drugs.
Asymptotic Log-harnack Inequality for the 2d Stochastic Cahn-hilliard-navier-stokes System With Degenerate Noise
Authors: Medjo T. Tachim 
Published: February 2023

Abstract
In this article, we consider a Cahn-Hilliard-Navier-Stokes equations in a two dimensional bounded domain and examine some asymptotic behaviors of the strong solution. More precisely, we establish the asymptotic log-Harnack inequality for the transition semigroup associated with the Cahn-Hilliard-Navier-Stokes system driven by an additive degenerate noise via the asymptotic coupling method. As consequences of the asymptotic log-Harnack inequality, we derive the gradient estimate, the asymptotic irreducibility, the asymptotic strong Feller property, the asymptotic heat kernel estimate and the ergodicity.
Mathematics Subject Classification. 35R60,35Q35,60H15,76M35,86A05.
Recent Change in Sea Level Along the Coast of New Zealand Using Tide Gauge and XTRACK Coastal Altimetry Data
Authors: Erkoç Muharrem Hilmi 
Published: February 2023

Abstract
The rise in sea level along the coasts of New Zealand has accelerated in recent decades due to the impact of climate change. Determining the effects of these changes on the coastal regions is critical for their sustainability. In order to gain insight into these impacts, the present study aimed to analyze sea level changes using satellite altimetry and tide gauge data from 11 tide gauge stations along the New Zealand coast between 1993 and 2022, as well as XTRACK data processed with the coastal altimetry approach to minimize the effects of classical altimetry near coasts. The least-squares parameter estimation method was used to analyze the data and determine annual and semi-annual seasonal effects. The results showed that the sea level trend is rising in both methods; for instance, 4.2 ± 0.6 mm/yr from the tide gauge data and 3.6 ± 0.8 mm/yr from the XTRACK data at the WELLINGTON HARBOUR tide gauge. The results of this study demonstrate the importance of closely monitoring the impacts of sea level rise on the coastal regions of New Zealand to ensure their long-term sustainability. The results also highlight the utility of using multiple data sources and methods to provide a comprehensive understanding of these changes.
18 F-PSMA-1007 and 18 F-FDG PET/CT in patients with prostate cancer
Authors: Liu Fucen , Jiang Yiyi , Li Boliang , Wang Yichao , Zhou Wenyao , Ruan Yashi , Wang Jiangping , Zhang Hao , Zhang Jun 
Published: February 2023

Abstract
Purpose To explore the value of 18F-PSMA-1007 and 18F-FDG PET/CT in prostate cancer （PCa） patients, this study compared the performance of the two tracers to detect PCa and then analyzed the correlation between the metabolic parameters and serum PSA value. Finally, we evaluated the application of both tracers in the auxiliary staging of PCa patients.
Methods Thirty patients diagnosed with PCa who underwent both 18F-PSMA-1007 and 18F-FDG PET/CT were enrolled. The detection rate, number, location of lesions, and metabolic parameters SUVs (SUVmax, SUVmean), PSMA-TV, MTV, TL-PSMA, TLG, and tumor-to-background ratio (TBR) were recorded and compared. The correlation between metabolic parameters and serum PSA was analyzed. Finally, the differences and consistency of both tracers for the same patient’s NM stage and clinical stage were compared.
Results Patient analysis showed that 18F-PSMA-1007 PET/CT had a similar ability to identify the primary tumor and local recurrence (p=1.000) as 18F-FDG PET/CT but identified more patients with metastases (p=0.016), especially bone metastases (p=0.004). Lesion analysis showed that 18F-PSMA-1007 PET/CT identified more primary lesions, local recurrences, and metastases. It also had higher diagnostic efficacy for lymph nodes and bone metastases (both p<0.05). For lesions with positive uptake, the median SUVs and TBR of 18F-PSMA-1007 PET/CT were significantly higher than 18F-FDG PET/CT (all p<0.05). The median PSMA-TV was higher than the median MTV. Still, the difference was not statistically significant (p>0.05), while the median TL-PSMA was significantly higher than the median TLG (p<0.05). Volume-based metabolic parameters PSMA-TV, TL-PSMA, MTV, and TLG, were significantly and positively correlated with PSA (all p<0.05). In contrast, SUVs and TBR for the primary tumor or local recurrence were not associated with PSA. 18F-PSMA-1007 PET/CT identified more M1 patients and higher clinical stage, and it had higher diagnostic efficacy than 18F-FDG PET/CT (p<0.05).
Conclusions 18F-PSMA-1007 PET/CT was a valuable imaging modality for PCa. It had better diagnostic efficacy, lesions detection, and a higher median value for metabolic parameters than 18F-FDG PET/CT. Volume-based metabolic parameters reflecting the total tumor burden were positively correlated with serum PSA levels. 18F-PSMA-1007 PET/CT had a higher clinical application value than 18F-FDG PET/CT for PCa patients.
Deep learning-driven automatic reconstruction of genome-scale metabolic networks
Authors: Liu Xiaoyi , Yang Hongpeng , Ai Chengwei , Ding Yijie , Tang Jijun , Guo Fei 
Published: February 2023

Abstract
Incomplete knowledge of metabolic processes impairs the accuracy of GEnome-scale Metabolic models (GEMs), hindering advancements in systems biology and metabolic engineering. To close this critical gap, we present CLOSEgaps, a machine learning-based algorithm that considers the hypergraph topology of metabolic networks and hypothetical reactions to predict missing reactions and identify gaps in GEMs. Extensive results show that CLOSEgaps accurately gap-filled metabolic networks, filling over 96% of artificially introduced gaps, and enhances the predictability of fermentation products in 24 wild-type GEMs. Furthermore, we integrate CLOSEgaps into a generalized workflow for automated metabolic network reconstruction, hereby named NICEgame, and found a notable improvement in producing four crucial metabolites (Lactate, Ethanol, Propionate, and Succinate) in two organisms. As a broadly applicable solution for any GEM or reaction, CLOSEgaps promises to enhance biotechnological and biomedical applications by improving GEM-based predictions and automating the NICEgame workflow.
Innate Immune Cells Activating Receptors Are Crucial Factors Regulating Inflammation and Cell Death in Traumatic Brain Injury
Authors: Zhou Xudong , He Jingjing , Yue Aochun , Song Huiping , Liu Xuhan , Han Wei , Li Qin 
Published: February 2023

Abstract
After traumatic brain injury (TBI), excessive or persisting inflammatory responses often lead to neuronal death and chronic traumatic encephalopathy. However, effective targeted drugs for this mechanism are lacking. Therefore, comprehensive understanding of neuroinflammatory response mechanisms and search for new therapeutic targets are particularly important for neurological function recovery after brain trauma. In this study, we collated and analyzed multiple RNA expression profiling microarray, bulk RNA high throughput sequencing and single-cell sequencing data. The results revealed that after TBI, there was an infiltration of innate immune cells into brain tissue, with a significantly higher proportion of macrophages in the cortex and hippocampus compared to the thalamus and hypothalamus. The inflammatory response was strongest within one week, then gradually decreased in the following month, and aggravated again three months later. After brain trauma, CD86, CCR5, PTPRC, ITGB2, FCGR2B, TLR2, and TYROBP were identified as the seven key nodes that trigger inflammation. Interestingly, all these proteins are activating receptors or cofactors on the surface of innate immune cells. Clustering analysis revealed that these immune activating receptors can collectively regulate the occurrence of TBI-induced cell death. Among them, ferroptosis, necrosis and apoptosis were most strongly correlated with these activating receptors, while autophagy was negatively correlated with them. In single-cell analysis, microglia, monocytes and dendritic cells were found to be the main subjects expressing these immune node genes. Cell-cell communication of chemokine-related pathways such as CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) dominate the immune response after brain trauma, and tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF) and transforming growth factor b (TGF-b) are also involved in the process of inflammation.
The clinical-stage drug BTZ-043 accumulates in tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis
Authors: Treu Axel , Hölscher Christoph , Kokesch-Himmelreich Julia , Marwitz Franziska , Dreisbach Julia , Converse Paul , Tyagi Sandeep , Gerbach Sina , Gyr Luzia , Lemm Ann-Kathrin , Volz Johanna , Hölscher Alexandra , Heinrich Norbert , Kloss Florian , Nuermberger Eric , Schwudke Dominik , Hoelscher Michael , Römpp Andreas , Walter Kerstin 
Published: February 2023

Abstract

Centrally necrotizing granulomas that harbor Mycobacterium tuberculosis (Mtb) are the hallmark of human tuberculosis (TB). New anti-TB therapies will need to effectively penetrate the cellular and necrotic, non-vascularized compartments of these lesions and reach sufficient concentrations to eliminate Mtb. BTZ‑043 is a novel antibiotic showing good bactericidal activity in humans in a phase IIa trial. Here, we report on the substantial efficacy of BTZ‑043 in the advanced pre-clinical model of interleukin-13-overexpressing mice, which mimic human TB pathology of pulmonary central granuloma necrosis. Accordingly, pulmonary BTZ‑043 concentrations were severalfold above the minimal inhibitory concentration in these mice. The detailed histological characterization of lung granulomas in combination with high resolution MALDI imaging revealed that BTZ‑043 diffuses and accumulates in the cellular compartment, and fully penetrates the necrotic center. In summary, this study is the first visualizing an efficient penetration, accumulation, and retention of a clinical-stage TB drug in human-like centrally necrotizing granulomas.
Subcontractor Networks and Affiliated Private Costs: Evidence forom Oklahoma Bridge Contracts
Authors: Press Robert 
Published: February 2023

Abstract
This paper offers a theoretical framework associating subcontractor networks in procurement auctions to affiliated costs among bidders. Building on the methodology by Li and Zhang (2010), we construct a model that allows for cost affiliation depending on firm-pair observables. The extension is used to test for entry affiliation caused by overlapping subcontractor networks in a sample of Oklahoma bridge building contracts from 2004 to 2016. The empirical analysis finds statistically significant evidence of affiliation, driven by subcontracting networks, affecting firms’ decisions to bid on projects.
JEL Codes: D44, D85, L14, H57
Analysis of elastoplastic solution of tunnel surrounding rock pressure considering intermediate principal stress and rock dilatancy under groundwater seepage
Authors: Yu Bingxin , Zhou Xiaojun , Zhang Yujin , Cai Pengli , Qiu Jutao , Zhou Hang 
Published: February 2023

Abstract
When calculating the surrounding rock pressure of a deep tunnel in watery strata, the effect of seepage pressure caused by ground water is usually underestimated, this occasionally results in poor tunnel lining design and durability. In order to study the interaction between surrounding rock and deep tunnel support under groundwater seepage, the intermediate principal stress is introduced in Drucker-Prager yield criterion, and non-associated flow rule is adopted as well as the dilatancy effect of surrounding rock is also considered. The elastoplastic pressure and deformation laws of surrounding rock and tunnel support at greater depth are analyzed using theoretical derivation and numerical simulation. In addition, the influence of the important parameters involved in the theoretical analysis on the plastic zone of surrounding rock is discussed. The results show that the analytical solution is strongly consistent with the results obtained from numerical simulation; Considering groundwater seepage, the calculation method in which intermediate principal stress is considered has a non-negligible influence on the elastoplastic solution of the surrounding rock pressure; Three important factors including permeability coefficient, internal friction angle as well as seepage pressure reduction factor play a dominant role in determining rock pressure and plastic zone around deep tunnel due to groundwater seepage. The work presented in the paper enriches the elastoplastic theory to analyze surrounding rock pressure applied to deep tunnel under seepage conditions in watery strata, and is beneficial to further explore the interaction between surrounding rock and tunnel support in water-rich strata.
“Prevalence of Chronic Food Insecurity, Policies, and Redressal Patterns among the PVTGs: A Case Study of Sahariya Tribe from India”
Authors: Patel Praveen Kumar , Mitra R. P. 
Published: February 2023

Abstract
Zero hunger and good health are two main goals for sustainable development, but when it comes to vulnerable sections of society, they struggle to meet their basic needs. In the Global Hunger Index 2021, India has been placed under a severe category with a score of 27.5. Sahariyas are a Particularly Vulnerable Tribal Group that faces numerous challenges in obtaining food security and adequate nutrition. The current study seeks to comprehend the complexities of food and nutrition among the Sahariya tribe. It also aims to determine the coping mechanisms used by households to mitigate food insecurity. This study is based on empirical data collected through fieldwork among 68 households in the Shivpuri district of Madhya Pradesh. Interviews, participant observation, and focus group discussions were used as methods of data collection. Their food patterns have been observed through household-level food analysis and narratives related to food insecurity. The study discussed the relationship between food insecurity and socioeconomic variables found in the studied area. The study revealed that Sahariyas are found to be mainly landless laborers (72.05%), Begging and rag-picking (39.71%), and forest dwellers (57.35%). Most of them have been found to struggle with their day-to-day food and life. To envision a new policy environment that can help in resolving food insecurity issues, a more in-depth understanding of the evolution of the food system is necessary.
Same same, but different: exploring the enigmatic role of the pituitary adenylate cyclase- activating polypeptide (PACAP) in invertebrate physiology
Authors: Pirger Zsolt , Urbán Péter , Gálik Bence , Márk László , Tóth Gábor K. , Koene Joris M. , Kemenes György , Reglődi Dóra , Kiss Tibor , Fodor István 
Published: February 2023

Abstract
There is a long-standing debate about the presence and functionality of the pituitary adenylate cyclase-activating polypeptide (PACAP) in non-bilaterians, protostomes, and invertebrate deuterostomes. Evidence has been accumulating that homologous sequences to genes encoding PACAP peptides and their receptors in vertebrates are missing in invertebrate genomes. This is at odds, however, with the partial sequence-, immunohistochemical-, and physiological evidence in the literature. In this study, we first sequenced the neural transcriptome of the widely used invertebrate model species, the great pond snail (Lymnaea stagnalis), and then screened it for sequences homologous to the elements of the vertebrate PACAP system. Further, we performed in vitro and in vivo studies on the heart of L. stagnalis to explore the enigmatic role of vertebrate PACAP in invertebrate physiology. Our thorough screening failed to identify putative transcripts (or genes) to the vertebrate PACAP prepropeptides, active peptides, and their receptors. Despite the lack of the relevant sequences, our immunohistochemical investigations with an anti-human PAC1 receptor antibody yielded a positive signal in the neuronal elements in the heart. Although gel electrophoretic separation, followed by immunostaining, of proteins extracted from the central nervous system found a relevant band for the vertebrate PACAP-38, mass spectrometric analysis of the band did not find any corresponding peptide sequences. Similarly to the effects reported in vertebrates, 10 µM synthetic PACAP-38 significantly increased the cAMP synthesis in the homogenate of the heart and had a positive ionotropic effect on isolated heart preparations. Moreover, it modulated significantly the effects of serotonin and acetylcholine. Our findings support the idea that elements of the PACAP system are absent in mollusks and emerged after the protostome-deuterostome divergence. The physiological effects of vertebrate PACAP peptides in protostomes, no matter how similar they are to those in vertebrates, should be considered non-specific. Further studies should be aimed at investigating the cellular and molecular underpinnings including the identification of the receptors to which the vertebrate PACAP peptides may bind non-specifically.