bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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

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

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

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

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

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.
ABC: A Novel Algorithm to Stratify Decompensation Risk in Patients With Compensated Advanced Chronic Liver Disease: an International, Multicenter Cohort Study
Authors: Liu Chuan , Li Jia , Wong Yu Jun , Xie Qing , Hirooka Masashi , Enomoto Hirayuki , Kim Tae Hyung , Hanafy Amr Shaaban , He Ruiling , Koizumi Yohei , Hiasa Yoichi , Nishimura Takashi , Iijima Hiroko , Jung Young Kul , Yim Hyung Joon , Ma Jianzhong , Zeng Qing-Lei Zeng , Sarin Shiv Kumar , Qi Xiaolong
Published: January 2022

Background: Liver-related death is preceded by clinical decompensation; therefore, the risk stratification of decompensation in compensated advanced chronic liver disease (cACLD) is extraordinary significant.Methods: The international, multicenter study included three cohorts from January 2009 to August 2021. In training cohort, the unfavorable Baveno VI criteria patients were used to develop the novel CHESS criteria to stratify decompensation risk. The Algorithm based on Baveno VI criteria plus CHESS criteria (ABC model) was validated in validation cohort, and used to diagnose clinically significant portal hypertension (CSPH) in hepatic venous pressure gradient (HVPG)-performed cohort.Results: A total of 1377 cACLD patients were enrolled. In training cohort, multivariate analysis revealed that liver stiffness measurement (LSM), platelet count (PLT), albumin, alanine aminotransferase (ALT) and varices were the independent risk factors for hepatic decompensation. The novel CHESS criteria was produced, and <-4.4, -4.4 to -3.1 and >-3.1 indicated the low risk, medium risk, and high risk of decompensation, with a 3 year-time-dependent area under the curve (tAUC) of 0.851 (0.800-0.901). In validation cohort, the 3 year-tAUC of ABC model was 0.843 (0.742-0.943). Notably, in HVPG cohort, the high risk group was used to rule in CSPH with a positive predictive value of 0.930.Conclusion: The ABC model can stratify the risk of decompensation in cACLD. HVPG evaluation can be waived in both low risk and high risk cACLD patients as they can be managed by Baveno VI criteria and non-selective β-blockers intervention, respectively, and the remaining medium risk patients need further HVPG evaluation.
Mobilization of Lipids Underpins Honey Bee and Colony Health During Limited Supplementary Feeding
Authors: Castaños Clara , Boyce Mary , Millar Harvey , Lawler Nathan , Bates Tiffane , Grassl Julia
Published: January 2022

Honey bee nutritional health depends on nectar and pollen, which provide the main source of carbohydrate, protein, and lipids to individual bees. During malnutrition the insect metabolism accesses fat body reserves, this process however, is poorly understood, as well as its repercussions at a colony level. Using untargeted lipidomic analysis we examined the effects of different nutritional conditions during larval development followed by recovery and colony productivity. Nutritional stress led to an increase of unsaturation in triacylglycerols and diacylglycerols, as well as a decrease in free fatty acids. Suggesting the bees' metabolism triggers a process that makes lipid reserves rapidly accessible by changing their structure and allowing their mobilization. We also identified the specific lipid desaturase genes in honey bees that are induced in response to starvation. Even though nutritional stress was evident in starving and sugar-fed bees at a colony and physiological level, we found that only starved hives presented long-term effects as honey production.
CASC15 mediated upregulation of SERPINE1 by sponging miR-30c- 5p correlates with poor prognosis and immune infiltration of gastric cancer
Authors: Xie Jun , Liu Kai , Yan Feng
Published: January 2022

Background: As a major regulator of plasminogen activator system (PAs), SERPINE1(PAI-1) is associated with poor prognosis in a variety of cancers, but in Stomach adenocarcinoma (STAD), its mechanism of action is not so clear.Methods：Based on RNA Sequencing dataset and survival data for TCGA-STAD, this study screened out genes of significant difference between the gastric cancer group and the normal group using the R language limma package, and carried out a pan-cancer analysis on their expression in combination with the Genotype-Tissue Expression (GTEx) database at the same time. Subsequently, the miRNA and lncRNA associated with high expression level of PAI-1 significantly were identified through the Starbase database in combination with a series of analyses on expression level, correlation and survival. The correlation of immune cell infiltration, biomarkers of immune cells and immune checkpoints between PAI-1 were investigated via TIMER and GEPIA database.Results：PAI-1 was up-regulated significantly in gastric cancer, and was a risk factor and could indicate the survival of STAD patients. According to analysis results, CASC15/hsa-miR-30c-5p/ PAI-1 axis may be the most potential regulatory network of PAI-1 related to survival in gastric cancer. And the expression level of PAI-1 in gastric cancer had a positive correlation with immune cell infiltration, biomarkers of immune cells and immune checkpoints obviously.Conclusion：Collectively, PAI-1 could accurately indicate prognosis, evaluate the tumor immune infiltration, probability participate in the regulation of gastric cancer through CASC15/miR-30c-5p/ PAI-1 axis, and PAI-1 might exert its oncogenic roles through increasing tumor immune cell infiltration and immune checkpoint expression.
Identification of Necroptosis-related Subtypes, Construction of a Prognosis Model, and Characterization of Immune Infiltration in Colon Cancer.
Authors: Chen Jian-li , Qin Yu-ning , Yang Lei , Jia Xian-gen , Zhang Guo-zhi
Published: January 2022

Background: Necroptosis is a type of programmed necrosis that is participating in the pathology of many diseases. However, the potential mechanisms of action and biological functions of necroptosis-related genes (NRGs) in tumor cells are poorly understood.Methods: We explored alterations in NRGs in 1147 colon cancer samples and assessed their expression from three separate public datasets. Based on the expression of 67 NRGs we divided the patients into two subtypes. Differentially expressed genes (DEGs) associated with prognosis were then screened and the samples were divided into two new gene subtypes based on their expression. The NRG_score was constructed to predict overall survival (OS) and its accuracy in predicting the prognosis of colon cancer patients was tested. Therefore, in order to improve the clinical practice function of NRG_score, a highly accurate multi-factor nomogram was produced.Results: We observed that NRGs expression was associated with patient age, gender, grading, prognosis and immune cell infiltration characteristics. We identified 301 necroptosis subtype-related prognostic genes. In addition, we constructed the NRG_score that can accurately predict the prognosis of colon cancer patients.Conclusion: Our established NRG_score was significantly correlated with immune cell infiltration, somatic cell mutation, cancer stem cell (CSC) index and sensitivity to drugs associated with colon cancer. These researches will contribute to our further understanding of NRGs in colon cancer. More importantly, it provides direction for evaluating the prognosis of colon cancer patients and for exploring more useful immunotherapy options.
Binary Space Partitioning Generates Hierarchical and Rectilinear Neutral Landscape Models Suitable for Human-Dominated Landscapes
Authors: Etherington Thomas , Morgan Fraser , O'Sullivan David
Published: January 2022

Context Neutral landscape models are useful and popular tools for exploring effects of spatial patterns on ecological processes. Most neutral landscape models mimic natural landscape patterns that often consist of curved, complex, and sometimes fractal shapes. However, human-dominated landscapes often have a spatial rectilinear pattern that is highly aligned and dominated by straight lines and right angles.
Objectives As existing rectilinear neutral landscape models lack controls over either the size, position, orientation, and shape of the rectilinear patches, or do not recognise the hierarchical structure of patch formation in human-dominated landscapes, our objective was to create a neutral landscape model capable of meeting these requirements.
Methods We present binary space partitioning as a method that generates hierarchical and rectilinear neutral landscape models. In doing so we explain how to control the size, position, orientation, and shape of the rectilinear patches, as well as generate a tree that records the hierarchical patch structure.
Results Binary space partitioning succeeds in providing a simple, repeatable, process to generate a range of neutral landscape models for human-dominated landscapes. A large variety of landscape patterns can be efficiently produced from only a very small number of parameters.
Conclusions Binary space partitioning based neutral landscape models would be useful in representing many human-dominated landscapes. Their implementation is straightforward and does not require any cognitive or computational requirements that would be beyond landscape ecologists.
Computational Algorithm and Tools of Fuzzy Arithmetic Based on the Principle of Maximum Entropy
Authors: Sveshnikov Sergey , Bocharnikov Victor
Published: January 2022

The standard fuzzy arithmetic introduced by Zadeh is not always suitable for solving applied problems in various fields of science, technology and business. Even in the case of a small sequence of arithmetic operations (for example, when calculating forecast estimates of business profits), the support of the resulting fuzzy number becomes very large. It is difficult to make a decision about investing if the maximum and minimum of the expected profit differ several times. Therefore, the authors developed an algorithm which forms the result of an arithmetic operation as a subset of a fuzzy binary relation and which implements the principle of maximum entropy. This algorithm allows performing arithmetic operations on fuzzy numerical sets with an arbitrary form of the membership function. Compared to standard fuzzy arithmetic, the proposed algorithm provides a much smaller increase in the support of the resulting fuzzy number. We implemented the algorithm in an add-in for Microsoft Excel, which readers can download and use for applied calculations for free.
Numerical Investigation of a Squeezing Flow Between Concentric Cylinders Under the Variable Magnetic Field of Intensity
Authors: Khan Muhammad Sohail , Shabnam Shabnam
Published: January 2022

The theme of the ongoing research is to examine the mass and heat transmission phenomena of squeezing flow between two concentric cylinders under the effect of heat sources and magnetic fields. The impacts of the Lorentz force on the behaviour of the liquid flow is elucidated via a magnetic field which is incorporated in the momentum equation. Moreover, the term Q = Q 0 1−βt has been used as a source/sink within concentric cylinders. The proposed model of PDEs formulates the physical phenomena of time-dependent incompressible two-dimensional squeezing flow via modified Navier-Stokes equation, energy equation and mass transfer equation and variable magnetic field. The proposed model involved a highly nonlinear system of PDEs which has been reduced into a system of ODEs via Lie group of similarity transformation and subsequently solved numerically in MATLAB by Parametric Continuation Method (PCM). The direct impact of the squeezing parameter on the profile of temperature and concentration have been observed. Furthermore, an increment in the heat source indicates a decrement in the liquid temperature profile, while an inverse relationship is observed for the concentration profile. In addition, the declining effect of Soret number on the concentration profile is noticed. Beside this, a direct impact of P r, Ω and Ec on the entropy generation has been noticed, while an opposite impact has been noticed at Bejan number. The numerical outcomes of the proposed model that explain the characteristics of fluid flow are quantitatively elucidated by tables, and displayed graphically.
Protective Ileostomy Increased the Incidence of Rectal Stenosis After Anterior Resection of Rectal Cancer
Authors: Zhang Hui , Li Shanshan , Jin Xin , Wu Xian , Zhang Zhiyuan , Shen Lijun , Wan Juefeng , Wang Yan , Wang Yaqi , Yang Wang , Zhou Menglong , Zhang Jing , Lv Tao , Deng Yun , Xia Fan , Zhang Zhen
Published: January 2022

Background. In most of the views, rectal stenosis results from pelvic radiotherapy. However, patients without receiving radiotherapy also suffer stenosis. In this study, we evaluated the factors associated with rectal stenosis after anterior rectal resection (ARR). Methods. We conducted a retrospective study with ARR patients who underwent neoadjuvant chemoradiotherapy and the patients without radiotherapy. Patients received watch and wait strategy with a clinical complete response after chemoradiotherapy were also included. Patients with colonoscopy follow-up were included for further analyses; 439 patients who underwent neoadjuvant chemoradiotherapy; 545 patients who received ARR without radiotherapy and 33 patients who received watch and wait strategy. Stenosis was defined as cannot pass a 12-mm colonoscopy. Univariate and multivariate logistic regression analyses were performed to identify variables associated with rectal stenosis. Results. According to the multivariate analysis in patients receiving ARR, both protective stoma and preoperative radiotherapy affected the occurrence of stenosis, with the odds ratios (ORs) of 3.375 and 2.251, respectively. According to the multivariate analysis, a preventive ileostomy was the only factor associated with stenosis both in patients receiving preoperative radiotherapy and without radiotherapy. Non-reversal ileostomy and long time between ileostomy and restoration increased the possibility of stenosis. In 33 patients who received watch and wait strategy, only one patient (3%) experienced stenosis. Conclusion. Both surgery and radiotherapy are risk factors for rectal stenosis in rectal cancer patients. Compared to preoperative radiotherapy, a protective ileostomy is a more critical factor associated with rectal stenosis.
Navigating Complexities Towards Sustainable Food Crops Production: Local Practices For Climate Change Adaptation In Rural Ghana
Authors: Dambeebo Daniel , Dakyaga Francis , Derbile Emmanuel K.
Published: January 2022

Globally, food crops production has been challenged by the impacts of climate change. Climate change scholars have argued that rural dwellers, particularly smallholder farmers who engage in food crops production, suffer the most due to their low capacity to adapt. A growing body of knowledge also suggests that local practices serve as safeguards, that enable smallholder farmers to lessen their vulnerability in food crops productions. However, limited scholarly insight has been advanced about sustainable food production via the use of local practices. Through the mixed research approach, our study contributes to local practices and climate adaptation debates by examining the various local practices of smallholder farmers, the challenges they encounter with the use of such practices and the possibility for sustainable food crops production in the future. Our findings suggest that smallholders encounter multiple drawbacks in attempts to utilize local practices to adapt food crops production to climate change including the advent of modern farming inputs/practices. Even when multiple local practices (the planting of crops varieties, switching between crops and livestock rearing, reducing cultivatable land size) are utilized, only the increment in farm size, the use of income/remittances of rural-urban migrants to support food crops production, and early cultivation offered some possibilities of sustaining improvement in food crops production for the future. Therefore, we conclude that local practices are not necessarily panaceas for sustaining food crops production under climate change. We recommend further studies to pay attention to the sustainability of local practices under climate change.
CD90 Is Regulated by NOTCH1 and Hallmarks a More Aggressive Intrahepatic Cholangiocarcinoma Phenotype
Authors: Mancarella Serena , Serino Grazia , Gigante Isabella , Cigliano Antonio , Ribback Silvia , Sanese Paola , Grossi Valentina , Simone Cristiano , Armentano Raffaele , Evert Matthias , Calvisi Diego F. , Giannelli Gianluigi
Published: January 2022

Background.
Intrahepatic Cholangiocarcinoma (iCCA) is characterized by a strong stromal reaction playing a role in tumor progression. Thymus cell antigen 1 (THY1), also called Cluster of Differentiation 90 (CD90), is a key regulator of cell-cell and cell-matrix interaction. In iCCA, CD90 has been reported to be associated with a poor prognosis. In an iCCA PDX model, we recently found that CD90 was downregulated in mice treated with the Notch γ-secretase inhibitor Crenigacestat. The study aims to investigate the role of CD90 in relation to the NOTCH pathway.
Methods.
THY1/CD90 gene and protein expression was evaluated in human iCCA tissues and xenograft models by qRT-PCR, immunohistochemistry, and immunofluorescence. Notch1 inhibition was achieved by siRNA. THY1/CD90 functions were investigated in xenograft models built with HuCCT1 and KKU-M213 cell lines, engineered to overexpress or knockdown THY1, respectively.
Results.
CD90 co-localized with EPCAM, showing its epithelial origin. In vitro, NOTCH1 silencing triggered HES1 and THY1 down-regulation. RBPJ, a critical transcriptional regulator of NOTCH signaling, exhibited putative binding sites on the THY1 promoter and bound to the latter, implying CD90 as a downstream NOTCH pathway effector. In vivo, Crenigacestat suppressed iCCA growth and reduced CD90 expression in the PDX model. In the xenograft model, Crenigacestat inhibited tumor growth of HuCCT1 cells transfected to overexpress CD90 and KKU-M213 cells constitutively expressing high levels of CD90, while not affecting the growth of HuCCT1 control cells and KKU-M213 depleted of CD90. In an iCCA cohort, patients with higher expression levels of NOTCH1/HES1/THY1 displayed a significantly shorter survival.
Conclusions.
iCCA patients with higher NOTCH1/HES1/THY1 expression have the worst prognosis, but they are more likely to benefit from Notch signaling inhibition. These findings represent the scientific rationale for testing NOTCH1 inhibitors in clinical trials, taking the first step toward precision medicine for iCCA.
The breeding effects and genetic mysteries of a milestone variety (Fengbazhan) of modern indica rice in China
Authors: lei Zhao , Shaochuan Zhou , Chongrong Wang , Hong Li , Daoqiang Huang , Zhidong Wang , Degui Zhou , Yibo Chen , Rong Gong , Yangyang Pan
Published: January 2022

Huanghuazhan and Huazhan are the most widely used indica conventional rice and restorer line in China, respectively. In fact, both of them are all derivatives of Fengbazhan (FBZ), and many other FBZ-derived varieties have been widely planted in China, accounting 22% of China’s rice paddy fields. Therefore, evaluating the breeding effects of FBZ and clarifying its genetic mysteries is an effective strategy to interpret the history of modern rice breeding. Here, we report FBZ could be regarded as a milestone for the renewal of China’s modern indica rice. By comparing the variant information of genes that underlie quantitative traits (QTGs), we identified 48 QTGs showing allelic differences among different types of varieties. Further research found that favorable genes were gradually optimized during the breeding of the FBZ-series varieties, while the selection and utilization of Hd1-Pi2-Pid3-Pid2 segment, directly contributed to the breeding of FBZ. Importantly, the application of favorable genes on chromosome 6 solves the problem of ‘high-quality but susceptible to rice blast’, enabling the FBZ-series varieties to achieve high and stable yield, good quality, and wide adaptability in production. We put forward thinking and insights from the perspectives of fertility restoration, defense and growth, germplasm resources, variety replacement and future breeding goals. Our study provides useful gene targets for molecular breeding, as well as a valuable reference for the development of breakthrough varieties.
Distribution of PACAP and PAC1 Receptor in the Human Eye
Authors: Patko Evelin , Szabo Edina , Toth Denes , Tornoczki Tamas , Bosnyak Inez , Vaczy Alexandra , Atlasz Tamas , Reglodi Dora
Published: January 2022

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with widespread distribution and diverse biological functions. Several studies show that PACAP has strong cytoprotective effects mediated mostly through its specific PAC1 receptor (PAC1-R) and it plays important roles in several pathological conditions. Its distribution and altered expression are known in various human tissues, but there is no descriptive data about PACAP and its receptors in the human eyebulb. Since the PACAP38 is the dominant form of the naturally occurring PACAP, our aim was to investigate the distribution of PACAP38-like immunoreactivity in the human eye and to describe the presence of PAC1-R. Semiquantitative evaluation was performed after routine histology and immunohistochemical labeling on human eye sections. Our results showed high level of immunopositivity in the corneal epithelium and endothelium. Within the vascular layer the iris and the ciliary body had strong immunopositivity for both PACAP and the PAC1-R. Several layers of the retina showed immunoreactivity for PACAP and PAC1-R, but the ganglion cell layer had a special pattern in the immunolabeling. Labeling was observed in the neuropil within the optic nerve in both cases and glial cells displayed immunoreactivity for PAC1-R. In summary, our study indicates the widespread occurrence of PACAP and its specific receptor in the human eye, implying that the results from in vitro and animal studies have translational value and most probably are also present in the human eye.
Magnetic confinement of electrons in carbon based materials
Authors: Wang Xuelin
Published: January 2022

A carbon-based topological material which shows anomalous Hall effect at room temperature was found in this study. The topological material with long-range ferromagnetic order was transformed into micro particles with single magnetic domain structure first. Then the micro particles were combined in a special manner to form a micro magnetic mirror, showing the microelectromagnetic confinement of anomalous Hall effect. By controlling the generation and elimination of the confined magnetic field, the electrons can be confined and released. This carbon-based topological material can change the current electricity storage mode of a battery which transforms chemical energy to electric energy and greatly increases the electricity storage density per unit volume.