bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 3-Week Dynamic Differences of Immunological Parameters in Severe and Non-severe COVID-19
Authors: Li Qiang , Xu Wei , Li Weixia , Huang Chenglu , Chen Liang 
Published: June 2020

Abstract
Objective We aimed to compare the dynamic differences of immunological parameters in severe and non-severe COVID-19. Methods In this study, the cytokine profiles and lymphocyte subsets of 70 patients (31 severe COVID-19 and 39 non-severe COVID-19) were longitudinally analyzed. Results Compared with non-severe cases, severe cases had higher age (64 vs 36 years, p<0.001), more common comorbidities (74.2% vs 15.4%, p<0.001), and more frequently lymphopenia (0.7 vs 1.6×109/L, p<0.001). Severe cases had markedly higher levels of IL-6, IL-8, and IL-10 than non-severe cases from baseline to 3 weeks after admission (p<0.001). No significant differences were observed in the levels of IL-1β, IL-2, IL-4, IL-5, IL-12P70, IL-17, TNF-α, IFN-α, and IFN-γ between the two groups during the follow-up (p > 0.05). The absolute numbers of CD3+, CD4+, CD8+, and CD45+ T cells were markedly lower in severe cases compared with that in non-severe cases from baseline to 3 weeks after admission (p<0.001). The decrease of T lymphocyte subsets reached its peak from day 1 to 3 after admission, and gradually increased from day 4 to 21 in the non-severe group; however, reached its peak from day 4 to 7 after admission, and sustained at a low levels in the severe group. Conclusion The dynamic changes of cytokine profiles and T lymphocyte subsets are related with the disease severity of patients with COVID-19.
Potential causes and consequences of rapid mitochondrial genome evolution in thermoacidophilic Galdieria (Rhodophyta)
Authors: Cho Chung Hyun , Park Seung In , Ciniglia Claudia , Yang Eun Chan , Graf Louis , Bhattacharya Debashish , Yoon Hwan Su 
Published: June 2020

Abstract
The Cyanidiophyceae is an early-diverged red algal class that thrives in extreme conditions around acidic hot springs. Although this lineage has been highlighted as a model for understanding the biology of extremophilic eukaryotes, little is known about the evolutionary history of their mitochondrial genomes. To fill this knowledge gap, we sequenced five mitogenomes from representative clades of Cyanidiophyceae and identified two major groups, here referred to as Galdieria-type (G-type) and Cyanidium-type (C-type). G-type mitogenomes exhibit the following three features: (i) reduction in genome size and gene inventory, (ii) evolution of unique protein properties including charge, hydropathy, stability, amino acid composition, and protein size, and (iii) distinctive GC-content and skewness of nucleotides. Based on GC-skew-associated characteristics, we postulate that unidirectional DNA replication may have resulted in the rapid evolution of G-type mitogenomes. This high divergence was likely driven by natural selection in the multiple extreme environments Galdieria species inhabit, their highly flexible heterotrophic metabolism, and the impacts of population size reduction. We speculate that the interplay between mitogenome divergence and adaptation may help explain the dominance of Galdieria species in diverse extreme habitats.
Global Optimization of a Numerical Two-layer Model Using Observed Data: A Case Study of the 2018 Sunda Strait Tsunami
Authors: Pakoksung Kwanchai , Suppasri Anawat , Abdul Muhari , Syamsidik Syamsidik , Imamura Fumihiko 
Published: June 2020

Abstract
Following the eruption of Anak Krakatoa, aconsiderable landslide occurred on the southwestern part of the volcano and, upon entering the sea, generated a large tsunami within the Sunda Strait, Indonesia, on 22 December 2018. This tsunami traveled ~5 km across the strait basin and inundated the shorelines of Sumatra and Java with a vertical runupreaching 13 m. Following the event, observed field data, GPS measurements of the inundation, and multibeam echo soundings of the bathymetry within the strait were collected and publicly provided. Using this dataset, numerical modeling of the tsunami was conducted using the two-layer (soil and water) TUNAMI-N2 model based on a combination of landslidesources and bathymetry data. The two-layer model was implemented to nest the grid system using a finest grid size of 20 m. To constrain the unknown landslide parameters, the differential evolution (DE) global optimization algorithm was applied, which resulted in a parameter set that minimized the deviation from the measured bathymetry after the event. The DE global optimization procedure was effective at determining the landslide parameters for the model with the minimum deviation from the measured seafloor. The lowest deviation from the measured bathymetry was obtained for the best-fitting parameters:a maximum landslide thickness of 301.2 m and a landslide time of 10.8 minutes. The landslide volume of 0.182 km3 estimated by the best-fitting parameters shows that the tsunami flow depth could have reached 3-10 m along the shore with a K value of0.89, although thesimulated flow depths were underestimatedin comparison with the observation data. According to the waveforms, the general wave pattern was well reproduced at tide gauges during the event. A large number of objective function evaluations were necessary to locate the minimum with the DE procedure to fix the grid cell size to 20 m;this limited the accuracy of the obtained parameter values for the two-layer model. Moreover, considering the generalizations in the modeling of landslide movements, the impact landslide time and thickness must be carefully calculated to obtain a suitable accuracy.
Attenuation of The Protective Effect of Honey On Alcohol Induced Hepatotoxicity By Kolanut In Male Albino Rats
Authors: Saka Adeoye Waheed , Kehinde Busuyi David , Akintola Adebola Olayemi , Oyekanmi Samuel Seyi , Oyewande Ajoke Esther , Ogwumu Murphy Dumbiri 
Published: June 2020

Abstract
Background: The excessive use of alcohol can lead to alcohol liver damage. However, natural compounds such as honey and kolanut have been investigated to have hepatoprotective activities against liver damage. Objectives: The possible protective effects of aqueous extract of kolanut and honey and the combination of both on alcohol induced hepatotoxicity of male rats were investigated.Materials and Methods: The rats were randomly divided into five equal groups (n=6). Group A was allowed access to water; Group B received ethanol (45% at 3g/kg) once for 21 days, Group C, D and E received alcohol an hour before treated with 50mg/kg of Cola nitida, 2.5g/kg of honey and combination of both respectively. Histopathological analysis and measurement of serum alanine aminotransferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), malondialdehyde (MDA) and catalase (CAT).Results: Administration of ethanol (45%) at 3g/kg to rats resulted in significant (P < 0.05) increase in the activities of hepatic markers enzymes (ALT, AST, ALP) as compared with control. Pretreatment of rats with kolanut (50 mg/kg) and honey (2.5g/kg) separately caused significant reduction in ALT, AST and ALP activities while pretreatment with combination of both was not better than the decrease observed when pretreated separately as compared to alcohol-induced group. Conversely, the results of oxidative stress and histological findings took a different pattern in all the pretreated groups.Conclusion: The result showed that the combination of honey and kolanut does not work synergistically in alcohol-induced hepatic damage.
Inhibition of the Mammalian Target of Rapamycin Pathway Stimulates Osteoblast Proliferation and Differentiation Through Autophagy in MC3T3-E1 Cells
Authors: Li Xining , Li Xi-Ning , Zhao Yu , Zhou Zhi-Gang , Zhou Hong-Chang , Min Ji-Kang 
Published: June 2020

Abstract
Background: OP(Osteoporosis) is a common bone metabolic disorder in the elderly characterized by loss of bone mass and a tendency to fracture. The mammalian target of rapamycin (mTOR) pathway in autophagy plays an indispensable role in maintaining the stability of the intracellular environment and ensuring the normal physiological functions of cells. Methods: In this study, different concentrations(20, 40, 60, 80, 100, 120, 140, 160, 180 and 200nM) of rapamycin were used to act on MC3T3-E1 osteoblasts for different time lengths(6, 12, 24, 36 and 48 hours). CCK8 was used to detect the proliferative activity of cells and screen suitable rapamycin concentration for subsequent experiments. Western blot and real-time quantitative PCR were used to detect the expression changes of phosphorylated mTOR, upstream and downstream mTOR pathway, autophagy and osteogenic differentiation markers. The expression of LC3 was observed by immunofluorescence. The differentiation ability of osteoblasts was observed by alizarin red and alkaline phosphatase staining.Results: The results showed that the induction of proliferation activity of osteoblasts from 20 nM to 200 nM presented a parabolic feature. After the action time of 50 μM rapamycin exceeded 12 hours, the proportion of S stage cells was significantly increased. The results of gene and protein analysis showed that rapamycin significantly inhibited the phosphorylation of mTOR, and the phosphorylation of the downstream factors of mTOR, 4E-BP1(eIF4E-binding protein 1) and S6K1(p70 ribosomal S6 kinase 1) also decreased. Rapamycin significantly increased the expression of LC3 II (microtubule associated protein 1 light chain 3-α), significantly increased the ratio of LC3II/LC3I, and significantly decreased the expression of p62(sequestosome-1). Rapamycin significantly induced the expression of ALP(Alkaline phosphatase), Runx2(Runt-related transcription factor 2) and osterix. Conclusions: This study confirmed that rapamycin stimulates the autophagy of osteoblasts by inhibiting mTOR and promotes their proliferation and differentiation, suggesting that mTOR may be a potential therapeutic target for osteoporosis.
Phosphorylation of Pit-1 by Cyclin-Dependent Kinase 5 at Serine 126 is Associated with Cell Proliferation and Poor Prognosis in Prolactinomas
Authors: Fang Qiuyue , Li Chuzhong , Gong Lei , Guo Jing , Xie Weiyan , Zhang Yazhuo 
Published: June 2020

Abstract
Background Pit-1 is a POU-homeodomain transcription factor, and cyclin-dependent kinase 5 (CDK5) is a protein kinase that can phosphorylate many key transcription factors, but the mechanism by which CDK5 phosphorylates Pit-1 is unclear.Methods We generated an antibody that specifically recognizes phosphorylated the serine at position 126 of Pit-1 (Ser126-Pit-1); we used western blotting to detect the level of Pit-1 phosphorylation and observed the proliferation and apoptosis of GH3 cells with different levels of Pit-1 phosphorylation by clone formation experiments, cell viability assays, and flow cytometry. ELISA was used to measure the level of prolactin (PRL) in the supernatant of GH3 cells. Tissue microarrays and immunohistochemistry (IHC) were used to evaluate the expression of the phosphorylation level of Ser126-Pit-1 (pSer126-Pit-1) in prolactinomas. Results Our data indicated that Ser126-Pit-1 is specifically phosphorylated by CDK5. pSer-126-Pit-1 can promote cell proliferation and PRL secretion. Besides, a higher level of pSer-126-Pit-1 correlates with a worse prognosis in patients with prolactinoma. Conclusions CDK5 mediated Ser126-Pit-1 phosphorylation regulates prolactinoma progression and PRL secretion.
Necessity for Detection of SARS-CoV-2 RNA in Multiple Types of Specimens for the Discharge of the Patients with COVID-19
Authors: Tong Yongqing , Bao Anyu , Chen Hongbing , Huang Jingtao , Lv Zhihua , Feng Lina , Cheng Yun , Wang Youna , Bai Li , Rao Wenlong , Zheng Hongyun , Wu Zegang , Qiao Bin , Zhao Zhijun , Wang Huiming , Li Yan 
Published: June 2020

Abstract
Background The SARS-CoV-2 RNA was detected positive again after discharged from hospital in some COVID-19 patients, with or without clinical symptoms such as fever or dry cough. Methods 1008 severe COVID-19 patients, with SARS-CoV-2 RNA positive detected with the mixed specimen of nasopharyngeal swab and oropharyngeal swab by real-time fluorescence quantitative PCR (RT-qPCR), were selected to monitor SARS-CoV-2 RNA with the 12 types of specimens by RT-qPCR during hospitalization. All of 20 discharged cases with COVID-19 were selected to detect SARS-CoV-2 RNA in isolation period with 7 types of specimens by RT-qPCR before releasing the isolation period.Results Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn’t be detected in other types of specimen in this study. Of the 20 discharged cases, the positive rate of SARS-CoV-2 RNA was 30% (6/20); 2 cases were positive in sputum at day 8 and day 9, 1 case was positive in nasopharynx swab at day 6, 1 case was positive in anal swab at day 8, and 1 case was positive in 3 specimens (nasopharynx swab, oropharynx swab and sputum) simultaneously at day4; no positive SARS-CoV-2 RNA was detected in other specimens including stool, urine and blood at the discharged patients.Conclusions SARS-CoV-2 RNA should be detected in multiple specimens, such as nasopharynx swab, oropharynx swab, sputum, and if necessary, stool and anal anal swab specimens should be performed simultaneously at discharge when the patients were considered for clinical cure and before releasing the isolation period.
IL-6R protective variant rs7529229 reduces interleukin-6 signaling and contributes to decreased ischemic stroke risk
Authors: Zhang Haihua , Zhao Wenbo , Liu Bian , Wang Tao , Han Zhifa , Ji Xunming , Liu Guiyou 
Published: June 2020

Abstract
BackgroundInterleukin-6 (IL-6) signaling is associated with the increased risk of coronary artery disease (CAD) and ischemic stroke (IS). Growing evidence shows that the minor allele of IL-6R rs7529229 variant could significantly increase the soluble IL-6 receptor levels and reduce CAD risk. However, it is largely unknown about the role of rs7529229 in IS, which promotes us to perform a comprehensive analysis. MethodsIn stage 1, we performed a meta-analysis of three GWAS datasets from MEGASTROKE, UK Biobank, and Million Veteran Program to evaluate the association of rs7529229 with IS. In stage 2, we conducted an expression quantitative trait loci analysis to examine the effects of rs7529229 on IL-6R expression in neuropathologically normal individuals from UK Brain Expression Consortium, GTEx project and eQTLGen Consortium. In stage 3, a tissue-specific gene expression analysis is used to evaluate the potential difference of IL-6R expression across the human tissues using gene expression data from GTEx. In stage 4, a case-control gene expression analysis is used to explore the potentially differential expression of IL-6R in IS and healthy controls in whole blood. ResultsOur results show that (1) rs7529229 minor allele could significantly reduce the risk of IS (OR=0.97, 95% CI 0.95-0.99, P=2.30E-03); (2) rs7529229 minor allele could significantly reduce IL-6R expression in relevant tissues especially in blood vessels and whole blood; (3) IL-6R is mainly expressed in skeletal muscle and whole blood; (4) expression of IL-6R is significantly reduced in healthy controls compared with IS cases in whole blood. Importantly, the biological senses in stage 1-4 are all convergent. ConclusionsCollectively, these findings indicate that rs7529229 minor allele may first reduce IL-6R expression in relevant tissues, further reduce IL-6 signaling, and eventually reduce the IS risk. Hence, IL-6R may be a potential therapeutic target, and blocking IL-6 signaling might be effective in treatment of IS.
The role of water in host-guest interaction
Authors: Rizzi Valerio , Bonati Luigi , Ansari Narjes , Parrinello Michele 
Published: June 2020

Abstract
One of the main applications of atomistic computer simulations is the calculation of ligand binding energies. The accuracy of these calculations depends on the force field quality and on the thoroughness of configuration sampling. Sampling is an obstacle in modern simulations due to the frequent appearance of kinetic bottlenecks in the free energy landscape. Very often this difficulty is circumvented by enhanced sampling techniques. Typically, these techniques depend on the introduction of appropriate collective variables that are meant to capture the system's degrees of freedom. In ligand binding, water has long been known to play a key role, but its complex behaviour has proven difficult to fully capture. In this paper we combine machine learning with physical intuition to build a non-local and highly efficient water-describing collective variable. We use it to study a set of of host-guest systems from the SAMPL5 challenge. We obtain highly accurate binding energies and good agreement with experiments. The role of water during the binding process is then analysed in some detail.
Myeloid-Derived Suppressor Cells Therapy Enhance Immunoregulatory Properties in Acute Graft Versus Host Diseas with Combination of Regulatory T Cells
Authors: Park Min-Jung , Baek Jin-Ah , Kim Se-Young , Jung Kyung-Ah , Choi Jeong Won , Park Sung-Hwan , Kwok Seung‐Ki , Cho Mi-La 
Published: June 2020

Abstract
Background: Myeloid-derived suppressor cells (MDSCs) play a critical role in modulating the immune response and suppressing autoimmunity and transplantation. Regulatory T cells (Tregs) exert therapeutic potential due to their immunomodulatory properties, which have been demonstrated both in vitro and in clinical trials. Cell-based therapy for acute Graft-versus-host disease (aGVHD) may enable induction of donor-specific tolerance in the preclinical setting. Methods: We investigated whether the immunoregulatory activity of the combination of MDSCs and Tregs on T cell and B cell subset and alloreactive T cell response. We evaluated the therapeutic effects of combined cell therapy for aGVHD following MHC-mismatched bone marrow transplantation. We compared histologic analysis from the target tissues of each groups were and immune cell population by flow cytometric analysisResults: We report a novel approach to inducing immune tolerance using a combination of donor-derived MDSCs and Tregs. The combined cell-therapy modulated in vitro the proliferation of alloreactive T cells and the Treg/Th17 balance in mice system. Systemic infusion of MDSCs and Tregs ameliorated serverity and inflammation of aGVHD by reducing the populations of proinflammatory Th1/Th17 cells and the expression of proinflammatory cytokines in target tissue. The combined therapy promoted the differentiation of allogeneic T cells toward Foxp3+Tregs and IL-10-producing regulatory B cells. The combination treatment control also activated human T and B cell subset.Conclusions: Therefore, the combination of MDSCs and Tregs has immunomodulatory activity and induces immune tolerance to prevent of aGVHD severity. This could lead to the development of new clinical approaches to the prevent aGVHD.
Prognostic Impact of Remnant-like Particle Cholesterol in Patients with Differing Glucose Metabolic Status: an Observational Cohort Study from China
Authors: Zhao Qi , Zhang Ting-yu , Cheng Yu-jing , Ma Yue , Xu Ying-kai , Yang Jia-qi , Zhou Yu-jie 
Published: June 2020

Abstract
Background: It is uncertain whether remnant-like particle cholesterol (RLP-C) could predict residual risk in patients under different glucose metabolic status. This study aimed to evaluate the relationship between RLP-C and adverse prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) and identify the potential impact of glucose metabolism on the predictive value of RLP-C.Methods: The study enrolled 2419 patients with NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. RLP-C was calculated as follows: total cholesterol (TC) minus low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The primary endpoint was a composite of events as follows: all-cause death, non-fatal myocardial infarction (MI), and ischemia-driven revascularization.Results: RLP-C was significantly associated with adverse prognosis in the total population [hazard ratio (HR) 1.291 per 1-SD increase of RLP-C, 95% confidence interval (CI) 1.119-1.490, P < 0.001], independent of confounding risk factors. However, subgroup analysis showed that increasing RLP-C was shown to be associated with a higher risk of adverse events in the diabetic population only [HR 1.385 per 1-SD increase of RLP-C, 95% CI 1.183-1.620, P < 0.001]. RLP-C failed to be a significant determinant of adverse prognosis in the pre-diabetic and non-diabetic population. The addition of RLP-C to the baseline model significantly enhanced the predictive value for adverse events both in the total and diabetic populations.Conclusions: Higher RLP-C level is a significant and independent predictor of adverse prognosis in diabetic patients with NSTE-ACS who underwent PCI.
Effect of Crown to Implant Ratio and Implantoplasty on The Fracture Resistance of Narrow Dental Implants with Marginal Bone Loss. An In Vitro Study.
Authors: Almeida Bruno Leitão , Font Octavi Camps , Correia André , Mari Javier Mir , Figueiredo Rui , Castellón Eduard Valmaseda 
Published: June 2020

Abstract
Background: Perimplantitis is a biological complication that affects soft and hard tissue around dental implants. Implantoplasty polishes exposed implant surface aiming to decontaminate it and make it less prone to bacterial colonization. This study aims to analyze macroscopic changes after implantoplasty (IP), whether a higher crown-to-implant-ratio (CIR) reduces implant fracture resistance and if implants are more fracture-prone after IP and in the presence of 50% vertical bone loss.Methods: Narrow platform (3.5mm) 15mm long titanium dental implants with a rough surface and hexagonal external connection were placed in standardized bone-like resin casts leaving 7.5mm exposed. Half were selected for IP. Macroscopic changes were observed using plain standardized x-rays and ImageJ software. The IP and control groups were each divided into 3 subgroups with different clinical CIR (2:1, 2.5:1 and 3:1). A static load test was performed and scanning electron microscopy (SEM) was used to evaluate failure loads and implant fractures. Results: IP effect was similar across the sample in all reference points and no perforations were observed. Only 2.5:1 group showed a significant reduction in fracture resistance between the IP and control implants. Significant reductions in mechanical resistance in the 2.5:1 and 2:1 group, compared to 3:1 group, were found.Conclusions: Our results suggest that implants with higher CIR are more prone to fracture in the presence of 50% vertical bone loss; Fracture resistance does not differ significantly between IP and intact implants and CIR seems more relevant than IP considering implant fracture resistance.