bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to Support the In Vitro Culture of Human Ovarian Cells and Follicles? A Preliminary Step for Assembling an Artificial Ovary
Authors: Moshrefi Mojgan , Aflatoonian Abbas , Ghasemi-Esmailabad Saeed , Karimi-Zarchi Mojgan , Sadeghian-Nodoushan Fatemeh , Shahmohamadi Sajad , nikukar Habib 
Published: May 2021

Abstract
BackgroundThe first step in assembling an artificial ovary is supporting the in vitro growth of ovarian cells/follicles. Therefore, proliferation of granulosa or cumulus cells (CCs) is important and due to limited proliferation, improving the mediums for in vitro propagation of these cells is helpful. ObjectiveThis study aimed to characterized the appropriate media and supplements for in vitro culture of ovarian cells (OCs) and CCs. Material & MethodsCortical, medullar and hilar cells of ovary were cultured and their conditioned medium (CMs) collected. The expression of GDF9, as a key factor for ovarian follicular growth, was evaluated. CCs were collected from healthy women, who referred due to male factor infertility. To choose the optimum basal medium, a mixture of OCs was cultured with basal mediums, supplemented with two concentrations of fetal bovine serum (FBS) and human serum albumin (HSA). The cocktails were as follows: [Serum free mediums], [mediums+10%FBS], [mediums+20%FBS], [mediums+1%Alb)], [mediums+2%Alb], [mediums+10%FBS+1%Alb], [mediums+10%FBS+2%Alb], [mediums+20%FBS+1%Alb] & [mediums+20%FBS+2%Alb]. The same process was repeated for CCs. Also, the effect of various concentrations of L-Glutamine, bovine serum albumin (BSA), HSA, insulin transferrin selenium (ITS), Follitropin alfa® and Pregnyl® was evaluated on the growth of CCs. As well, CCs were treated with various concentrations of follicular fluids (FFs) and CMs. CMs were collected from ovarian, testicular, adipose & amniotic derived and ovarian carcinoma cells. FFs were collected from women with poor responders, endometriosis, advanced age, polycystic ovarian syndrome, male factor and unknown infertility. Then, CCs morphology, proliferation capacity and culture duration were evaluated. ResultsAll the ovarian cells expressed GDF9. αMEM+20%FBS and DMEMF12+20%FBS were the most suitable cocktails for OCs and CCs, respectively. 20%FBS was superior to 10% for both OCs and CCs. HSA could not support the growth of OCs and CCs, alone. The cocktail of mediums with 20%FBS superior to the others. The CMs of cortical and (hillar+medullar) cells and FFs from male factor and unknown infertility patients caused higher CCs proliferation. 17 mM/l L-Glutamine, 24 mg/ml BSA, 20 mg/ml HSA, 10 ng/ml ITS, 300 mIU/ml Follitropinα and 3.5 IU/ml Pregnyl led to higher proliferation of CCs. ConclusionCMs, serums and FFs can support the CCs growth alongside with basal mediums, supplemented with hormones, ITS and L-Glutamine, which are cheaper and more accessible.
PremPLI: Predicting the Effects of Missense Mutations on Protein-Ligand Interactions
Authors: Sun Tingting , Chen Yuting , Wen Yuhao , Zhu Zefeng , Li Minghui 
Published: May 2021

Abstract
Protein-ligand interactions trigger a multitude of signal transduction processes and resistance to small-molecule drugs is the main cause of the failure of therapeutic drugs in clinical practice. Missense mutations altering the binding of ligands to proteins are one of the critical mechanisms that result in genetic disease and drug resistance. Computational methods have made a lot of progress for predicting binding affinity changes and identifying resistance mutations, but they are still not satisfied and need to be further improved in both accuracy and speed. To address these issues, we introduced PremPLI, a structure-based machine learning method for quantitatively estimating the effects of single mutations on ligand binding affinity changes. A comprehensive comparison of the predictive performance of PremPLI with other available methods on two benchmark datasets confirms that our approach performs robustly and presents similar or even higher predictive accuracy than the approaches relying on first-principle statistical mechanics and mixed physics- and knowledge-based potentials while requires much less computational resources. PremPLI can be used for guiding the design of ligand-binding proteins, identifying and understanding disease driver mutations, and finding potential resistance mutations for different drugs. PremPLI is freely available at https://lilab.jysw.suda.edu.cn/research/PremPLI/ and allows to do large-scale mutational scanning.
Ionic Homeostasis and Redox Metabolism Upregulated by 24-Epibrassinolide are Crucial for Mitigating Nickel Excess in Soybean Plants, Enhancing Photosystem II Efficiency and Biomass
Authors: Saraiva Marcelo Pires , Maia Camille Ferreira , Batista Bruno Lemos , Lobato Allan Klynger da Silva 
Published: May 2021

Abstract
Nickel (Ni) excess often generates oxidative stress in chloroplasts, causing redox imbalance, membrane damage and negative impacts on biomass. 24-Epibrassinolide (EBR) is a plant growth regulator of great interest in the scientific community because it is a natural molecule extracted from plants that is biodegradable and environmentally friendly. This study aimed to determine whether EBR can induce benefits on ionic homeostasis and antioxidant enzymes and convey possible repercussions on photosystem II efficiency and biomass, more specifically evaluating nutritional, physiological, biochemical and morphological responses in soybean plants subjected to Ni excess. The experiment was randomized with four treatments, including two Ni concentrations (0 and 200 µM Ni, described as – Ni2+ and + Ni2+, respectively) and two concentrations of 24-epibrassinolide (0 and 100 nM EBR, described as – EBR and + EBR, respectively). In general, Ni caused deleterious modulatory effects on chlorophyll fluorescence and gas exchange. In contrast, EBR enhanced the effective quantum yield of PSII photochemistry (15%) and electron transport rate (19%) due to upregulation of superoxide dismutase, catalase, ascorbate peroxidase and peroxidase. Exogenous EBR application promoted significant increases in biomass, and these results were explained by the benefits on nutrient contents and ionic homeostasis, demonstrated by increased Ca2+/Ni2+, Mg2+/Ni+ 2 and Mn2+/Ni2+ ratios.
Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via Cgas-STING Pathway
Authors: Shen Pan , Cheng Zhe , Liu Qiong 
Published: May 2021

Abstract
Background:
Emodin, a natural bioactive compound from traditional Chinese herbs, exerts anti-inflammatory, anti-oxidants, anticancer, hepatoprotective, and neuroprotective effects. However, its protective effects in acetaminophen (APAP)-induced hepatotoxicity still unclear.
Aim:
The study explored the effects of emodin on APAP-induced hepatotoxicity and investigated the potential molecular mechanisms.
Materials and Methods:
C57BL/6 mice with pre-treatment of emodin (15, 30 mg/kg) for consecutive 5 days, then were given APAP (300 mg/kg) to make APAP-induced liver injury model. Mice were sacrificed to detected the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), and the liver tissues levels of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD). Histological assessment, Western blot and ELISA were conducted.
Results:
Emodin pretreatment significantly reduced the levels of ALT, AST, and ALP, increased the levels of ALB, alleviated hepatocellular damage and apoptosis, attenuated the exhaustion of GSH, SOD, and accumulation of MDA, increased the expression of antioxidative enzymes, including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1(NQO1). Additionally, emodin inhibited the expression of NLRP3 and reduced the levels of pro-inflammatory factors, including interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α). Emodin inhibited Cyclic GMP-AMP synthase (cGAS) and its downstream signaling effector stimulator of interferon genes (STING) expression for liver protection against APAP-induced inflammatory responses and apoptosis.
Conclusion:
The above results suggested that emodin protected hepatocytes from APAP induce liver injury via the up-regulation of Nrf2 mediated anti-oxidative stress pathway, the inhibition of NLRP3 inflammasome, and the down-regulation of the cGAS-STING signaling pathway.
Management Costs of Febrile Neutropenia in Oncology Patients in Colombia
Authors: Lema Mauricio , Preciado Beatriz , Quiceno Diana , Mora Sara , Gamboa Natalia Castano , Reyes Juan 
Published: May 2021

Abstract
Purpose: To describe the clinical characteristics, resource utilization, and direct cost of febrile neutropenia (FN) in a healthcare institution in Colombia for patients seen between 2017-2019.Methods: A descriptive and retrospective study of a cohort of patients hospitalized due to FN. Costs were extracted from the review of medical records from diagnosis of FN until discharge or death, and official sources were used to estimate the cost. Results: Forty-four FN episodes were included. Median age was 61 years (IQR: 53-72). Solid tumors accounted for 68.8%. In first-line treatment were 14 (31.8%), same in proportion in adjuvant/neoadjuvant, and 5 (11.4%) in second-line. FN occurred in 15 (34.0%) high-risk patients. Mean LOS per episode was 5.1 ± 2.5 days. All patients were discharged alive. The median overall cost was $925 ± $783 per episode, with hospital stay being the main driver-cost.Conclusion: FN occurred mainly in advanced-stage solid tumors and in low-risk group. Higher costs in this cohort were found in long length of stay and high-risk patients.
Vegetation Shapes Aboveground Invertebrates Communities More Than Soil Properties and Pollution on a Metal Contaminated Site
Authors: Ozaki Shinji , Fritsch Clémentine , Mora Frédéric , Cornier Thierry , Scheifler Renaud , Raoul Francis 
Published: May 2021

Abstract
Pollution with trace metals (TM) has been shown to affect diversity and/or composition of plant and animal communities. While ecotoxicological studies have estimated the impact of TM contamination on plant and animal communities separately, ecological studies have widely demonstrated that vegetation is an important factor shaping invertebrate communities. It is supposed that changes in invertebrate communities under TM contamination would be explained by both direct impact of TM on invertebrate organisms and indirect effects due to changes in plant communities. However, no study has clearly investigated which would more importantly shape invertebrate communities under TM contamination. Here, we hypothesized that invertebrate communities under TM contamination would be affected more importantly by plant communities which constitute their habitat and/or food than by direct impact of TM. Our analysis showed that diversity and community identity of flying invertebrates were explained only by plant diversity which was not affected by TM contamination. Diversity of ground-dwelling (GD) invertebrates in spring was explained more importantly by plant diversity (27% of variation) than by soil characteristics including TM concentrations (8%), whereas their community identity was evenly explained by plant diversity and soil characteristics (2-7%). In autumn, diversity of GD invertebrates was only explained by plant diversity (12%), and their identity was only explained by soil characteristics (8%). We conclude that vegetation shapes invertebrate communities more importantly than direct effects of TM on invertebrates. Vegetation should be taken into account when addressing the impacts of environmental contamination on animal communities.
Comparison of the Tissue Distribution and Metabolism of AN1284, a Potent Anti-Inflammatory Agent, After Subcutaneous and Oral Administration in Mice
Authors: Weitman Michal , Bejar Corina , Melamed Michal , Weill Tehilla , Yanovsky Inessa , Zeeli Shani , Nudelman Avraham , Weinstock Marta 
Published: May 2021

Abstract
Purpose. To establish a liquid chromatography/mass spectrometry method to compare the tissue distribution and metabolism of AN1284 after subcutaneous and oral administration at doses causing maximal reductions in IL-6 in plasma and tissues of mice. Methods. Lipopolysaccharide activated RAW 264.7 macrophages were used to detect the anti-inflammatory activity of AN1284 and its metabolites. Mice were given AN1284 by injection or gavage, 15 min before lipopolysaccharide. The reduction of IL-6 measured after 4h. Results. AN1284 is metabolized to the indole (AN1422), a 7-OH derivative and its glucuronide. AN1422 had weaker anti-inflammatory activity than AN1284 in LPS-activated macrophages and in mice. Maximal reductions in IL-6 in plasma, brain and liver were seen after subcutaneous injection of (0.5 mg/kg). This dose was also most effective in reducing IL-6 in the liver after oral drug administration but 2.5 mg/kg was needed for the same reductions in plasma and brain. Peak concentrations after oral administration of AN1284 (2.5 mg/kg) were 5.5-fold higher in the liver but 7-, 11 and 19-fold lower in plasma, brain and kidneys than after injection of 0.5 mg/kg. Similar concentrations in the liver were achieved by AN1284 (1 mg/kg/day) administered in the drinking fluid, and 2.5 mg/kg/day, via subcutaneously-implanted mini-pumps. Although drug levels were only 12% of the peak seen after acute injection of 0.5 mg/kg, they significantly decreased hepatocellular damage, liver triglycerides and cholesterol in diabetic mice. Conclusion. AN1284 can be given orally to treat chronic liver disease and its preferential concentration in the liver should limit potential adverse effects.
Irinotecan Based Chemotherapy in Extrapulmonary Neuroendocrine Carcinomas: Survival and safety data from a Multicentric Italian Experience
Authors: Bardasi Camilla , Spallanzani Andrea , Benatti Stefania , Spada Francesca , Laffi Alice , Lorenzo Antonuzzo , Lavacchi Daniele , Riccardo Marconcini , Marco Ferrari , Rimini Margherita , Caputo Francesco , Santini Chiara , Cerma Krisida , Casadei-Gardini Andrea , Andrikou Kalliopi , Salati Massimiliano , Bertolini Federica , Fontana Annalisa , Dominici Massimo , Luppi Gabriele , Gelsomino Fabio 
Published: May 2021

Abstract
Purpose: Neuroendocrine carcinomas (NECs) are a rare subgroup of neuroendocrine neoplasms that occasionally originate from gastro-entero-pancreatic (GEP) tract. Evidence of the effectiveness of chemotherapy is scarce. Platinum plus Etoposide regimens are currently the standard treatment in first-line, while little data are available on second-line treatments. The aim of this study is to evaluate the efficacy and safety of Irinotecan (IRI)-based chemotherapy in a series of extrapulmonary NECs. Methods: Patients with NEC diagnosis treated at University Hospitals of Modena, Florence, Pisa, and European Institute of Oncology of Milan with an IRI-based regimen (FOLFIRI or XELIRI) after progression to a first-line platinum-based therapy were enrolled. Objective responses were assessed according to RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were calculated. Results: 34 patients, 16 males, and 18 females, median age of 59 years (range 32-77), with metastatic NEC were included. Twenty-seven pts had Ki-67 ≥ 55% and 4 pts Ki-67 of < 55% (for 3 pts data was not available). The median number of treatment cycles of the IRI-based regimen was 7.5 (range 1-16). Six partial responses (17.6%) and 9 stable diseases (26.5%) were observed, with a disease control rate of 44.1%. Median PFS and OS were 4.4 and 5.9 months, respectively. Neutropenia, anemia, and nausea were the only G3-G4 toxicities reported. Conclusion: Despite the relatively small sample size, IRI-based therapy demonstrated to be a valid option for patients with pre-treated extrapulmonary NEC.
Regional air pollution severity affects the incidence of acute myocardial infarction triggered by short-term pollutant exposure: A time-stratified case-crossover analysis
Authors: Yen Chih-Chien , Chen Ping-Ling 
Published: May 2021

Abstract
Background Long-term exposure to air pollution results in a high incidence of cardiovascular disease. Whether acute myocardial infarction is triggered by short-term exposure to air pollution is related to the average severity of air pollution in the area.DesignCase-crossover analysis.MethodsThis was a retrospective study based on hospital medical records. The study period was 2017-2018. Research data were collected from Taoyuan Hospital, which is located in a low-severity pollution area, and Taichung Hospital, which is in a high-severity pollution area, and the correlation between short-term air pollution exposure and acute myocardial infarction was analyzed.ResultsThe correlation between short-term exposure to ambient air pollutants and acute myocardial infarction was not significant for the cases collected from Taoyuan Hospital (PM2.5 OR: 1.006 & 95% CI: 0.995-1.017; PM10 OR: 0.996 & 95% CI: 0.988-1.003). However, for the cases collected from Taichung Hospital, short-term exposure to ambient PM2.5 (odds ratio: 1.021; 95% confidence interval: 1.002-1.040) and PM10 (odds ratio: 1.010; 95% confidence interval: 1.001-1.020) resulted in high incidence of acute myocardial infarction.ConclusionsShort-term pollutant exposure will increase the incidence of acute myocardial infarction based on the severity of regional air pollution. In addition to addressing traditional cardiovascular disease risk factors, the government must formulate relevant policies for reducing air pollution and thus the hazards to national health.
Bacterial Cellulose Based Facial Mask With Antioxidant Property and High Moisturizing Capacity
Authors: Bilgi Eyup , Gokce Evren Homan , BAYIR ECE , Sendemir Aylin , Ozer Kevser Ozgen , Tuna E. Esin Hames 
Published: May 2021

Abstract
Bacterial cellulose (BC) produced by certain bacteria has the potential to be used in many different areas. Despite its advantageous properties such as high purity, mechanical strength, nanofiber mesh structure, and high-water holding capacity, its production through a biotechnological process prevents it from competing with vegetable cellulose in terms of cost-effectiveness. Therefore, studies associated with BC can be divided in two categories which are development cost effective BC production methods and culture media, and production of high value-added products from BC. In this study, it was aimed to develop a taurine-loaded moisturizing facial mask with antioxidant properties based on BC's high-water retention and chemical retention capacity. BC facial mask samples were characterized by Scanning Electron Microscopy (SEM) imaging, Fourier Transform Infrared (FTIR), Differential Scanning Calorimetry (DSC), Liquid Chromatography–Mass spectrometry (LC-MS), microbial, and mechanical stability tests. According to our results, produced facial mask samples do not show any cytotoxic effect on neither human keratinocyte (HS2) nor mouse fibroblast (L-929) cell lines, it has high thermal stability which making it suitable for different sterilization techniques including sterilization by heat treatment. Taurine release (over 2µg/ml in 5 min) and microbial stability tests (no bacterial growth observed) of packaged products kept at 40 and 25 °C for 6 months have shown that the product preserves its characteristics for a long time. In conclusion “bacterial cellulose-based facial masks" are suitable for use as a facial mask, and they can be used for moisturizing and antioxidant properties by means of taurine.
Evolutionary Game Analysis of Coal Enterprise Resource Integration Under Government Regulation
Authors: Sun Ziyuan , Wang Wei , Zhu Weixing , Ma Lin , Dong Yuting , Lu Jiangwei 
Published: May 2021

Abstract
Based on the perspective of government regulation, this paper discusses how to guide and restrict coal enterprises to conduct resource integration behavior, and whether the government supervises this behavior. First, through empirical research, government regulations of coal enterprises are given practical policy implications. Second, using evolutionary game and simulation technology, from the perspective of government regulation, we explore the complex behavioral interaction mechanism between the dominant and inferior coal enterprises, the mechanism between the government and coal enterprises, and analyze the impact of key factors on the dynamic evolution process. Finally, the sensitivity analysis of the selected parameters is discussed in details, which provides useful decision-making suggestions for the government and enterprises. Results demonstrate that:(1) when the power gap between enterprises is great, government regulations are not effective for inferior enterprises;(2) the combination of government regulation can help to improve the efficiency of coal enterprise strategy selection;(3) excessive government regulations make the strategic choices of the government and coal enterprise tend to swing, failing to achieve effectively resource integration and government supervision.
Differences in the Clinical Presentation, Management, and In-Hospital Outcomes of Acute Aortic Dissection in Patients With and Without End-Stage Renal Disease
Authors: Xie Jiahe , Zeng Shan , Xie Long , Ding Rongming , Hu Jing , Zeng Hong , Lu Weiling , Hu Yuhua , Li Qingrui , Zhong Gaojun , Zhou Shiju , Liu Ziyou , Liao Yulin , Zhong Yiming , Xie Dongming 
Published: May 2021

Abstract
Background
Few studies have evaluated the clinical presentation, management, and outcomes of patients with end-stage renal disease (ESRD) presenting with acute aortic dissection (AAD) in real-world clinical practice. Thus, this study investigated the clinical characteristics, management, and outcomes of AAD patients with ESRD.
Methods
A total of 217 patients were included. We evaluated the differences in the clinical features, management, and in-hospital outcomes of patients with and without a history of ESRD presenting with AAD.
Results
A history of ESRD was present in 71 of 217 patients. Patients with ESRD had atypical clinical manifestations (p < 0.001) and were more likely to be managed medically compared with patients without ESRD (p = 0.002). Hypertension and type B aortic dissection were significantly more common among patients with ESRD. Moreover, patients with ESRD had lower leucocyte and platelet counts than patients without ESRD in laboratory findings (p < 0.001). However, hospitalization days and in-hospital mortality were similar between the two groups (p > 0.05). Multivariate analysis identified Type A aortic dissection as an independent predictor of in-hospital mortality among patients without ESRD (OR, 13.68; 95% CI, 1.92 to 98.90; P = 0.006).
Conclusions
This study highlights differences in the clinical characteristics, management, and outcomes of AAD patients with ESRD. These patients usually have atypical symptoms and more comorbid conditions and are managed more conservatively. However, these patients have no in-hospital survival disadvantage over those without ESRD. Further studies are needed to better understand and optimize care for patients with ESRD presenting with AAD.