bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maximum Daily Dose of G-CSF is a Critical Factor for Preventing Recurrence of Febrile Neutropenia in Patients with Gynecologic Cancer: A Case-Control Study
Authors: Kim Nam Kyeong , Suh Dong Hoon , Kim Kidong , No Jae Hong , Kim Yong Beom 
Published: January 2022

Abstract
Background
To optimize and to identify the use of granulocyte-colony stimulating factor (G-CSF) and identify critical factors for preventing recurrence of febrile neutropenia (FN) in women undergoing chemotherapy for the treatment of gynecologic cancer.
Methods
The medical records of consecutive patients who underwent chemotherapy for the treatment of gynecologic cancer and experienced FN at least once at Seoul National University Bundang Hospital from 2003 to 2021 were retrospectively reviewed. Student’s t-test, χ2-test, and multivariate forward conditional Cox regression analysis were used to identify the optimal usage of G-CSF and the clinico-laboratory factors that can affect the recurrence of FN.
Results
A total of 157 patients who met the inclusion criteria were included. Of the 157 patients, 49 (31.2%) experienced recurrence of FN. Age≥55 years (p=0.043), previous lines of chemotherapy≤1 (p=0.002), thrombocytopenia (p=0.025), total dose (p=0.003), and maximum daily dose (p=0.009) of G-CSF were significantly associated with recurrence of FN. However, anemia, septic shock at initial FN, concurrent chemoradiation, maximal target of absolute neutrophil count, and total duration of G-CSF administration were not associated with recurrence of FN. Multiple regression analysis showed that age≥55 years (HR, 2.42; 95% CI, 1.14-5.14; p=0.022), previous chemotherapy≤1 (HR, 4.01; 95% CI, 1.40-11.55; p=0.010), and maximum daily dose of G-CSF≤600 µg (HR, 5.18; 95% CI, 1.12-24.02; p=0.036) were independent risk factors for recurrent FN. Multivariate Cox regression analysis showed that a maximum daily dose of G-CSF≤600 µg was the only independent risk factor for short recurrence-free survival of FN (HR, 4.75; 95% CI, 1.15-19.56; p=0.031). There was no difference in the side effects of G-CSF (bone pain, diarrhea, and deep vein thrombosis) and recovery time from recurrence of FN between maximum daily dose of G-CSF≤600 µg and >600 µg.
Conclusions
Dose-dense administration of G-CSF>600 µg /day could prevent recurrence of FN in women who undergo chemotherapy for the treatment of gynecologic cancer and FN. Old age and FN at early lines of chemotherapy seem to be associated with FN recurrence.
Synthesis, Spectral, and X-ray Structural Characterization of Mixed Tetraamine-Barbitone Nickel (II) Complex Grafted g-C3N4 for Oxidative Stress and Cytotoxic Activities
Authors: Ibrahim Mohamed M. , Meral Gaber A. M. , Abdou Safaa N. , Mohamed Mahmoud A. , Soliman Mohamed Mohamed , Al-Juaid Salih , Taleb Manal F. Abou , Amin Mohamed A. 
Published: January 2022

Abstract
A new mixed ligand complex, viz., [Ni(Tren)(Barb)(H2O)](Barb)(Barb-H)•2H2O (NiC) {Tren = tris(2-aminoethyl)amine and Barb = 5,5-diethlybarbiturate} has been synthesized and characterized. The nickel(II) complex was grafted to g-C3N4, forming NiC@g-C3N4. The obtained NiC complex and its hybrid material NiC@g-C3N4 were characterized by means of FT-IR, TGA-DSC, UV-vis., SEM-EDX, and XRD. Single crystal X-ray crystallography suggests that NiC exhibits NiN5O octahedral geometry. The results also show that the complex molecules are connected via N–H××××O hydrogen bonds. The complex NiC and its NiC@g-C3N4 composite showed cytotoxic effects on in vivo experiments. They also showed an increase in tissue damage markers that are represented by the increase in tissue levels of malondialdehyde (MDA) in brain, liver, kidney and heart. In parallel, both materials showed inhibitory activity for examined antioxidants such as glutathione-S-transferase (GST), superozide dismutase (SOD), glutathione (GSH), glutathione reductase (GSH-R). The destructive effects were clearer for the NiC@g-C3N4 composite compared to in liver, brain and kidney, respectively. The grafting of NiC complex in g-C3N4 is responsible for improving the catalytic activity, which is due to the synergistic effect of both components and facile recovery, as well recycling of the catalyst.
Predicting the Number of COVID-19 Infections and Deaths in USA
Authors: Ebubeogu Amarachukwu Felix , Ozigbu Chamberline Ekene , Conserve Donaldson F. , Seixas Azizi , Ofem Paulinus , Maswadi Kholoud 
Published: January 2022

Abstract
Background: Uncertainties surrounding the 2019 novel coronavirus (COVID-19) remain a major global health challenge and requires attention. Researchers and medical experts have made remarkable efforts to reduce the number of cases and prevent future outbreaks through vaccines and other measures. However, there is little evidence on how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection entropy can be applied in predicting the possible number of infections and deaths. In addition, more studies on how the COVID-19 infection density contributes to the rise in infections are needed. This study demonstrates how the SARS-COV-2 daily infection entropy can be applied in predicting the number of infections within a given period. In addition, the infection density within a given population attributes to an increase in the number of COVID-19 cases and, consequently, the new variants. Result: Using the COVID-19 initial data reported by Johns Hopkins University, World Health Organization and Global Initiative on Sharing All Influenza Data, the result shows that the original SAR-COV-2 strain has R0<1 with an initial infection growth rate entropy of 9.11 bits for the United States. At close proximity the average infection time for an infected individual to infect others within a susceptible population is approximately 7 minutes. Assuming no vaccines were available, in the United States, the number of infections could range between 41,220,199 and 82,440,398 in late March 2022 with approximately, 1,211,036 deaths. However, with the available vaccines, nearly 48 Million COVID-19 cases and 706, 437 deaths have been prevented. Conclusion: The proposed technique will contribute to the ongoing investigation of the COVID-19 pandemic and a blueprint to address the uncertainties surrounding the pandemic.
Synergistically Degradation of Cellulose by Anlpmo14g, A Fungal Lytic Polysaccharide Monooxygenase from Aspergillus Niger
Authors: Ma Lijuan , Wang Yaqi , Liu Yining , Fan Linlin , Cao Yuying , Wang Shuang , Li Hongxuan , Du Liping , Huang Jihong , Wang Hong 
Published: January 2022

Abstract
The auxiliary active family 9 (AA9) of fungal lytic polysaccharide monooxygenases (LPMOs) can improve the lignocellulosic hydrolysis through an oxidative mechanism. Aspergillus niger is an important industrial producer of glycoside hydrolases, but little research on LPMOs in A. niger have been reported. This study aimed to research the biochemical characteristics of LPMOs from A. niger and the synergy with cellulase on cellulose hydrolysis. Reducing sugar produced when An LPMO14g acted on Carboxyl Methyl Cellulose (CMC), Avicel ® , xylan, filter paper, straw and corn cobs, and MALDI-TOF/TOF mass spectrometry analysis indicated that it oxidatively cleaved the glycosidic bonds of Avicel ® at C1 position. The addition of An LPMO14g into the hydrolysis systems of Avicel® and straw catalyzed by cellulase could increase the yields of reducing sugar by 92.66% and 141.42%, respectively. Homology modeling displayed that the residues H1, H86, Y175, Y24, P83 and Y212 of An LPMO14g played an important role in the catalytic process of cellulose. This study enriches the AA9 LPMO family and provides a promising candidate for the high-efficient enzyme cocktails for lignocellulose degradation.
TITTLE: Cardioprotective Effect of New NIL10 Nanoparticles Through IL10 Receptor/STAT3 Activation in Mice and Pigs Subjected Acute Myocardial Infarction
Authors: Tesoro Laura , Botana Laura , Ramírez-Carracedo Rafael , Hernández Ignacio , Díez-Mata Javier , Alcharani Nunzio , Saura Marta , Jiménez-Guirado Beatriz , Ovejero-Paredes Karina , Filice Marco , Zamorano Jose Luis , Zaragoza Carlos 
Published: January 2022

Abstract
Rationale: Early response after acute myocardial infarction (AMI) is crucial to prevent extensive cardiac necrosis. Interleukin-10 (IL-10) is a key antiinflammatory cytokine, whose expression is closely associated with macrophage polarization towards inflammation resolution. Results: We synthesized NIL10, a micelle-based nanoparticle conjugated to IT9302, a peptide homologue to IL-10 functional domain, with the aim of targeting IL-10 receptor in mice and pigs subjected to AMI. Intravenous administration of 1 mg/kg NIL10 improved the cardiac function of mice and pigs subjected to AMI, as shown by a significant recovery of the left ventricle ejection fraction (LVEF) by days 3 and 7 after AMI, when compared to the levels found in animals injected with NIL10SC, a nanoparticle conjugated with the peptide in a scrambled orientation, in which inflammatory foci and fibrosis were strongly elevated. In IL-10 null mice subjected to AMI, NIL10 also improved heart contractility, while in IL10 receptor deficient animals, NIL10 had no effect. To test whether NIL10 may induce macrophage polarization, M2 macrophage populations were increased after day 3 of reperfusion, in which anti-inflammatory cytokines, including IL4, IL7, IL10, IL13, IL16 and IL27 were also elevated in mice and pigs injected with NIL10. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of pro-inflammatory NF-kB transcription factor nuclear translocation, as evidenced by inhibition of nuclear p65 in macrophages stimulated with 500 mM LPS in response to incubation with NIL10, and prevented by co-incubation with the STAT-3 pharmacological inhibitor STATTIC, as also evidenced by testing the NF-kB -dependent readout iNOS gene expression with same results. Conclusions: Our findings propose NIL10 nanoparticles as a novel compound to improve cardiac function after myocardial infarction, to preventing cardiac necrosis by inducing polarization toward M2-resolving macrophages, through inhibition of STAT3-induced nuclear translocation of NF-kB.
A Single Point Mutation in the Plasmodium Falciparum 3´-5´Exonuclease Does Not Alter Piperaquine Susceptibility
Authors: Boonyalai Nonlawat , Kirativanich Kirakarn , Thamnurak Chatchadaporn , Praditpol Chantida , Vesely Brian A. , Wojnarski Mariusz , Greisenbeck John S. , Waters Norman C. 
Published: January 2022

Abstract
Background

The rise in Plasmodium falciparum resistance to dihydroartemisinin-piperaquine (DHA-PPQ) treatment has been documented in the Greater Mekong Subregion with associations with mutations in the P. falciparum chloroquine resistance transporter (pfcrt) and plasmepsin 2 (pfpm2) genes. However, it is unclear whether other genes also play a role with PPQ resistance, such as the E415G mutation in the exonuclease (pfexo) gene. The aim of this study was to investigate the role of this mutation in PPQ resistance by generating transgenic parasites expressing the pfexo-E415G mutant allele.
Methods

Transgenic parasite clones carrying the E415G mutation in pfexo of the B5 isolate were derived by CRISPR-Cas9 gene editing and verified using PCR and gene sequencing. Polymorphisms of pfkelch-13, pfcrt, and pfexo were examined by PCR while the copy number variations of pfpm2 were examined by both relative quantitative real-time PCR and the duplication breakpoint assay. Drug sensitivity against a panel of antimalarials, the ring-stage survival assay (RSA), the PPQ survival assay (PSA), and bimodal dose-response curves were used to evaluate antimalarial susceptibility.
Results

The transgenic line, B5-rexo-E415G-B8, was successfully generated. The PPQ-IC90, %PPQ survival, and the bimodal dose-response clearly showed that E415G mutation in PfEXO of B5 isolate remained fully susceptible to PPQ. Furthermore, growth assays demonstrated that the engineered parasites grew slightly faster than the unmodified parental isolates whereas P. falciparum isolates harbouring pfkelch-13, pfcrt, and pfexo mutations with multiple copies of pfpm2 grew much more slowly.
Conclusions

Insertion of the E415G mutation in PfEXO did not lead to increased PPQ-IC90 and % PPQ survival, suggesting that this mutation is not associated with PPQ resistance and unsuitable to be used as a molecular marker for monitoring PPQ-resistant parasites. The results also highlight the importance of monitoring and evaluating suspected genetic mutations with regard to parasite fitness and resistance.
WITHDRAWN: Temperature-dependent IL6-STAT3-HSP90 signaling mediates viral entry
Authors: Hou Guoli , lv Zhao , Liu Wenzhi , Xiong Shuting , Hu Liang , Ding Chunhua , Song Rui , Wang Hongquan , Zhang Yongan , Xiao Tiaoyi , li Junhua 
Published: January 2022

Abstract
IL6-STAT3 signaling is a canonical pro-inflammatory pathway that is evolutionarily conserved and plays important roles in both temperature stress and virus infection. However, our understanding of the molecular mechanisms underpinning the temperature-dependent pathogenesis of viral infection in ectotherms remains rudimentary. Here we report that Grass carp reovirus (GCRV) hijacks the temperature-dependent IL6-STAT3-HSP90 signaling axis to promote viral entry. Exploring the temperature-dependent phenotype of GCRV infection, we discovered that the activation of the IL6-STAT3 signaling facilitated viral entry by increasing the expression of heat shock proteins (HSPs). Further biochemical, transcriptomic, and microscopic analyses revealed that major capsid protein VP7 of GCRV interacted with HSP90 and relevant cytoskeleton proteins to enable viral entry. Accordingly, exogenous expression of either IL6, HSP90, or VP7 in cells engendered an increased viral entry in a dose dependent manner. Interestingly, other viruses infecting invertebrate insects, ectothermic vertebrates (e.g., fish, amphibians), and endothermic mammals (e.g., swine, mouse, human) have evolved similar mechanism to promote their infection. Altogether, our work delineates a pivotal role of the IL6-STAT3-HSP90 signaling axis in the temperature-dependency of viral entry, pinpointing the feasibility of developing targeted therapies for viral diseases in the future.
Benchmarking causal reasoning algorithms for gene expression-based compound mechanism of action analysis
Authors: Hosseini-Gerami Layla , Collier David A. , Laing Emma , Evans David , Broughton Howard , Bender Andreas 
Published: January 2022

Abstract
Background
Elucidating compound mechanism of action (MoA) is beneficial to drug discovery, but in practice often represents a significant challenge. Causal Reasoning approaches aim to address this situation by inferring dysregulated signalling proteins using transcriptomics data and biological networks; however, a comprehensive benchmarking of such approaches has not yet been reported. Here we benchmarked four causal reasoning algorithms (SigNet, CausalR, CausalR ScanR and CARNIVAL) with four networks (the smaller Omnipath network vs. 3 larger MetaBase™ networks), using LINCS L1000 and CMap microarray data, and assessed to what extent each factor dictated the successful recovery of direct targets and compound-associated signalling pathways in a benchmark dataset comprising 269 compounds. We additionally examined impact on performance in terms of the functions and roles of protein targets and their connectivity bias in the prior knowledge networks.
Results
According to ANOVA analysis, the combination of algorithm and network most significantly dictated the performance of causal reasoning algorithms, with the SigNet recovering the greatest number of direct targets. With respect to the recovery of signalling pathways, CARNIVAL with the Omnipath network was able to recover the most informative pathways containing compound targets, based on the Reactome pathway hierarchy. We found no significant difference in performance between L1000 data or microarray data, even when limited to just 978 ‘landmark’ genes. Notably, all causal reasoning algorithms also outperformed pathway recovery based on input DEGs, despite these often being used for pathway enrichment. Causal reasoning methods performance was somewhat correlated with connectivity and biological role of the targets.
Conclusions
Overall, we conclude that causal reasoning performs well at recovering compound MoA upstream from gene expression changes by leveraging prior knowledge networks, and that the choice of network and algorithm has a profound impact on the performance of causal reasoning algorithms. Based on the analyses presented here this is true for both microarray-based gene expression data as well as those based on the L1000 platform.
The Effect of Exposing High Yielding Dairy Cows To Short Wavelength LED Illumination During The Night On Fatty Acid Profile
Authors: Asher Aviv , Fialko Matan , Fares Florin , Moallem Uzi , Yaacoby Shamai , Gutman Roee 
Published: January 2022

Abstract
Fatty acid levels vary between day and night milking. Many dairy cows are kept under whole light at night (LAN) illumination using a white light-emitting diode (W-LED) suspected of disrupting circadian rhythms. We investigated the effect of W-LED LAN and same lux level red LED (R-LED) LAN, which is known not to disrupt circadian rhythms in other mammals, on milk yield and circadian composition, compared to a natural light-dark (LD)-cycle of 10-11 h light. Cows under the natural LD-cycle showed circadian variation in milk-fat composition, characterized by higher health-promoting monounsaturated fatty acid (MUFA) and lower saturated fatty acid (SFA) levels in 13:30-h (day milk, DM) than 03:30-h (night milk, NM). W-LED did not affect milk and milk-fat yields, yet abolished the circadian pattern of milk-fat composition towards a less healthy fatty acid profile by lowering MUFA levels of DM. Switching W-LED to R-LED reversed these circadian disruptions. Therefore, R-LED and W-LED have no commercial advantage over the tested LD-cycle, while W-LED is disadvantageous, showing a circadian disruption. Accordingly, if the illumination is indispensable, the R-LED regime is preferable over W-LED for cow’s wellbeing and for preserving the natural milk-fat profile; while differentiating DM from NM from a commercial-health-promoting perspective.
Exploring The Molecular Mechanisms Underpinning H2O2-Induced Oxidative Stress Hypersensitivity in D-Erythroascorbic Acid-deficient Yeast Cells
Authors: Kim Il-Sup 
Published: January 2022

Abstract
Yeast is predominantly composed of the ascorbate (AsA; vitamin C) analog D-erythroascorbic acid (eAsA), a major antioxidant molecule. In contrast to AsA, little information exists on the mechanisms underpinning eAsA responses to cellular stress. Therefore, we performed transcriptome-based gene expression profiling to demonstrate whether eAsA deficiency in ara2Δ cells affects the cellular response to oxidative stress. Mutant ara2Δ cells promoted stress sensitivity to H2O2-induced oxidative stress by triggering redox homeostasis imbalances in the cytosol and mitochondria. Transcriptomic analysis showed that 644 genes in the oxidative stress-exposed ara2Δ cells had two-fold changes in expression; approximately 370 genes, including 111 encoding unknown proteins, and 274 genes, including 64 encoding for hypothetical proteins were up- and downregulated, respectively. Furthermore, oxidative stress-exposed ara2Δ cells upregulated the transcription factors (TFs) involved in zinc-finger DNA-binding (RGM1 and HAL9), while downregulating the stress-responsive TFs (CRZ1, SMP1, MSN2, and SKN7) and those regulating ribosomal proteins and biogenesis genes (MSS11 and SFP1). Signal network-related genes, excluding SNF3, were also downregulated. For protein kinases, ara2Δ cells activated the expression of genes involved in Ser/Thr protein kinase, meiosis, sporulation, gluconeogenesis, autophagy, DNA replication, DNA repair, and telomere maintenance., while downregulating those associated with the stress-activated protein kinase C (PKC)-mitogen-activated protein kinase (MAPK) signaling pathway, glycolysis, gluconeogenesis, vacuolar membrane kinase, cyclin-dependent kinase activator, and prospore closure. Gene ontology analysis of down-stream regions revealed that genes whose expression increased in the absence of eAsA included those associated with tRNA metabolism, transposable elements, and small nuclear ribonucleoprotein complexes. Downregulated genes were largely involved in sister chromatid segregation coupled to the spindle pole body and microtubule cytoskeleton, telomere organization, purine metabolism, redox and protein homeostasis. In addition, ara2Δ cells showed a decreased synthesis of secondary metabolites and metabolic molecules, including NAD, pyrimidine, and heme. Taken together, these results suggest that eAsA deficiency plays a key role in regulating the expression of genes associated with a variety of specific functions in oxidative stress-exposed yeast cells; indicating that eAsA is vital for adaptive responses to oxidative stress. Furthermore, these data provide new insights into the eAsA-deficient molecular mechanisms underpinning H2O2-induced oxidative stress.
Antimutagenic and Cytotoxic Potential of Punica Granatum L. And Opuntia Ficus-indica L. Peels
Authors: elbatanony marwa , elsawi salma , El-Feky Amal , Farghaly Ayman 
Published: January 2022

Abstract
Introduction: This study pointed to validate the phytochemistry, antioxidant and antimutagenic activities of two common plant peels; Punica granatum L. and Opuntia ficus-indica L.Material and methods: HPLC analysis was performed for identification of phenolics and flavonoids, beside to isolation of some triterpenes and phenolics from both plant peels.Results: P. granatum peels composed of 16 flavonoids and 18 phenolics, while O. ficus-indica comprised of 18 flavonoids and 10 phenolics. α-Amyrin acetate (1), friedelin (2), lup-20(29)-en-3β-ol (3), quercetin-3,4'-dimethyl ether-7-O-α-Larabinofuranosyl β-D-glucopyranoside (4), punicaflavanol (5), and two hydrolyzabl tannins (6&7) were isolated from P. granatum peels, while friedelin (8), 24-Methylene-ergosta-5-en-3β-ol (9), apigenin-7-O-glucoside (10), isorhamnetin 3-O-β-D-glucopyranoside (11), and betanin pigment (12) were isolated from O. ficus-indica peels. Compounds (1-5 and 8, 10, 11, 12) were isolated for the first time from both plant peels. P. granatum and O. ficus-indica peel extracts have relatively significant antioxidant, cytotoxic and antimutagenic effects.Discussion and conclusion: The tested plant peel extracts could be a reliable source as natural antioxidant, antimutagenic and cytotoxic agents with a high level of safety. The novelty of this study is the comparison of such activities of the peels under study.
Modelling Sustainable Supply Chain Process Considering Cost-Sharing and Stock-Dependence Demand Under Uncertain Environment.
Authors: Jena Sarat Kumar , Behera Chinmaya 
Published: January 2022

Abstract
Greenhouse gas is one of the major concerns for policymakers and academicians in the modern era. Renewable energy helps to reduce emissions if the industry supply chain is used optimally. Further, there is little understanding of how renewable energy implementation cost and stock dependence simultaneously impact supply chain (SC) profit. Thus, we propose a duopoly sustainable supply chain considering renewable implementation and stock-dependence demand under uncertain environments. A mathematical model is developed for a sustainable supply chain under three scenarios: (i) Renewable energy effort by manufacturer and cost-shared by the retailer (Model M) (ii) Renewable energy effort by retailer and cost-shared by the manufacturer (Model R), and (iii) Renewable energy effort by both retailer and manufacturer and cost-shared by the manufacturer and retailer (Model C). Nash equilibrium was used to find optimal strategies for players under different integrated channels. The result finds that Model M is comparatively better than the other two models as cost-sharing increases. The result additionally establishes that the total profit decreases as the cost of sharing increases in Model C and Model R, whereas it increases in Model M.