bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uremia causes dysbiosis-mediated periodontal disease
Authors: Randall David , Alsam Asil , Kieswich Julius , Joseph Susan , Aduse-Opoku Joseph , Davis Graham , Mills David , Boyde Alan , Swann Jonathan , Thiemermann Christoph , McCafferty Kieran , Curtis Mike , Yaqoob Magdi 
Published: January 2021

Abstract
It is presently unclear why there is a high prevalence of periodontal disease (PD) in individuals living with chronic kidney disease (CKD). By employing three different models in rats and mice, we demonstrate that experimental uremia causes periodontal bone loss. Uremia alters the biochemical composition of saliva and induces progressive dysbiosis of the oral microbiota, with microbial samples from uremic animals displaying reduced overall bacterial growth, increased alpha diversity, reduced abundance of key components of the healthy oral microbiota such as Streptococcus and Rothia, and an increase in minor taxa including those from gram-negative phyla Proteobacteria and Bacteroidetes. We show that transfer of oral microbiota from uremic mice induces PD in germ-free animals, whilst co-housing with healthy animals ameliorates the PD phenotype in rats. Thus, we advocate that periodontal disease should be regarded as a bacterially mediated complication of chronic uremia.
CASTELO: Clustered Atom Subtypes Aided Lead Optimization - A Combined Machine Learning and Molecular Modeling Method
Authors: Zhang Leili , Domeniconi Giacomo , Yang Chih-Chieh , Kang Seung-gu , Zhou Ruhong , Cong Guojing 
Published: January 2021

Abstract
Background: Drug discovery is a multi-stage process that comprises two costly major steps: pre-clinical research and clinical trials. Among its stages, lead optimization easily consumes more than half of the pre-clinical budget. We propose a combined machine learning and molecular modeling approach that partially automates lead optimization workflow in silico, providing suggestions for modification hot spots.Results: The initial data collection is achieved with physics-based molecular dynamics (MD) simulation. Contact matrices are calculated as the preliminary features extracted from the simulations. To take advantage of the temporal information from the simulations, we enhanced contact matrices data with temporal dynamism representation, which are then modeled with unsupervised convolutional variational autoencoder (CVAE). Finally, conventional and CVAE-based clustering methods are compared with metrics to rank the submolecular structures and propose potential candidates for lead optimization.Conclusion: With no need for extensive structure-activity data, our method provides new hints for drug modification hotspots which can be used to improve drug potency and reduce the lead optimization time. It can potentially become a valuable tool for medicinal chemists.
Fetal Growth Restriction as the Initial Finding of Preeclampsia is a Clinical Predictor of Maternal and Neonatal Prognoses: A Single-center Retrospective Study
Authors: Takahashi Masaya , Makino Shintaro , Oguma Kyoko , Imai Haruka , Takamizu Ai , Koizumi Akari , Yoshida Koyo 
Published: January 2021

Abstract
Background: Preeclampsia (PE) is a hypertensive disorder specific to pregnancy, which sometimes causes severe maternal-neonatal complications. The International Society for the Study of Hypertension in Pregnancy revised their criteria for PE in 2018; a PE diagnosis can be established in the absence of proteinuria when other specific symptoms exist, such as other organ dysfunction or uteroplacental dysfunction. Therefore, the initial findings of PE (IFsPE) at the first diagnosis can vary considerably across patients. However, there are no reports on patients with PE based on different IFsPE and their impact on patients’ clinical outcomes. Thus, we aimed to investigate the predictors of maternal and neonatal outcomes based on IFsPE according to the new criteria.Methods: This was a retrospective study involving 3729 women who delivered at our hospital between 2015 and 2019. All women were reclassified based on the new criteria. They were divided into three groups based on the IFsPE: Classification 1 (C-1), proteinuria (classical criteria); Classification 2 (C-2), damage to other maternal organs; and Classification 3 (C-3), uteroplacental dysfunction. Maternal and fetal conditions and perinatal outcomes were assessed in the three groups.Results: In total, 104 women with PE were included. Of those, 42 (40.4%), 28 (26.9%), and 34 (32.7%) were assigned to C-1, C-2, and C-3 groups, respectively. All women in C-3 showed fetal growth restriction (FGR). The number of gestational weeks at PE diagnosis and delivery was significantly lower in the C-3 group (C-1, 35.5±3.0 weeks; C-2, 35.2±3.6 weeks; C-3, 31.6±4.6 weeks, P < 0.01; and C-1, 36.8±2.8 weeks; C-2, 36.3±3.2 weeks; C-3, 33.4±4.4 weeks, P < 0.01, respectively). The rates of preterm delivery at < 34 weeks (odds ratio [OR]=4.58 [1.74-12.10] and OR=2.83 [1.01-7.97]), cesarean delivery (OR=4.35 [1.41-13.45] and OR=5.03 [1.51-16.78]), Apgar scores < 7 at 1 min (OR=6.58 [2.08-20.80] and OR=4.09 [1.26-13.29]), neonatal intensive care unit admission (OR=12.19 [3.62-41.08], OR=7.50 [2.09-26.96]), and composite neonatal complications (OR=6.58 [2.08-20.80] and OR=5.33 [1.52-18.70]) were significantly higher in the C-3 group than in the C-1 and C-2 groups.Conclusions: PE patients with FGR had the most unfavorable prognosis for both maternal and neonatal outcomes.
Genome-wide Identification and Expression Analysis of the GRAS Transcription Factor Family and its Response to Abiotic Stress in Sorghum [Sorghum bicolor (L.) Moench]
Authors: Fan Yu , Yan Jun , Lai Dili , Yang Hao , Xue Guoxing , He Ailing , Feng Liang , Chen Long , Cheng Xiao-bin , Ruan Jingjun , Cheng Jianping 
Published: January 2021

Abstract
Background: GRAS is a very important family of transcription factors that are unique to plants, playing important roles in plant development and their response to abiotic stress. Since the sequencing of the sorghum genome, a large number of genetic studies based on this genomic information have been carried out. Nevertheless, no detailed identification or genome-wide analysis of GRAS family genes in Sorghum bicolor has been published.Results: A total of 81 SbGRAS genes were identified based on the S. bicolor genome. They were named SbGRAS01 to SbGRAS81 and grouped into 13 subfamilies (LISCL, DLT, OS19, SCL4/7, PAT1, SHR, SCL3, HAM-1, SCR, DELLA, HAM-2, LAS and OS4). SbGRAS genes are not evenly distributed on the chromosomes, and we found tandem duplication events and segmental duplications of SbGRAS genes on S. bicolor chromosomes. According to the results of the gene and motif composition, SbGRAS members located in the same group contained analogous intron/exon and motif organizations. By quantitative (q) RT-PCR, we quantified the expression of SbGRAS members in different plant tissues and in plants exposed to six abiotic stresses at the seedling stage. We also measured gibberellin content under the different abiotic stresses.Conclusions: We identified 81 SbGRAS genes and further analyzed their structural composition, and evolution and expression patterns of SbGRAS proteins. The latter analysis indicated that SbGRAS is important in the course of plant development and its response to abiotic stress. Collectively, this systematic analysis lays the foundation for further study of the functional characteristics of GRAS genes of S. bicolor.
Efficacy And Dose Effect Of Intradiscal Injection Of Sustained-Release Simvastatin Hydrogel For Treatment Of Discogenic Low Back Pain In Rabbitsintradiscal&nbsp;
Authors: Huang Xiaodong , Wang Weiheng , Ye Xiaojian , Lin Chia- Ying , Wu Zenghui 
Published: January 2021

Abstract
Purpose: The aim of this study was to explore the efficacy and dose effect of intradiscal injection of simvastatin sustained release hydrogel in the treatment of discogenic low back pain in rabbits.Methods: 36 female rabbits were randomly divided into G1 and G2 groups. In group G1, L1/2 was disc degeneration (group DDD), L2/3 was normal group (control group), L3/4 was medium dose treatment group (1mg/ml, DDD+ medium group), L4/5 was normal group, L5/6 was intervertebral disc degeneration + hydrogel segment (medium group). In group G2, L1 / 2 was degenerative segment, L2 / 3 was normal group, L3 / 4 was low-dose treatment segment (0.3mg/ml, DDD + low-dose group), L4 / 5 was normal group, L5 / 6 was high-dose treatment segment (3mg / ml, DDD + high-dose group). The intervertebral disc was evaluated by X-ray, MRI, water content, and hematoxylin-eosin.Result: At 12 and 24 weeks after treatment, the% DHI of control group and DDD + high were higher than those of DDD group and DDD + gel group (P <0.05); T2 image signal of the DDD+High group and Control group is better than DDD group, DDD+GEL group, DDD+ Medium and DDD +Low group (P <0.05). Intradiscal injection of simvastatin can delay disc degeneration and has a dose effect. At 4 and 12 weeks after treatment, the water content of intervertebral disc in control group and DDD + high group in control group were higher than DDD group, DDD + gel group and DDD + low group(P <0.05). Conclution：we verified the therapeutic efficacy and dose effect of simvastatin sustained-release system in rabbit DLBP model. The optimal treatment concentration was further optimized based on the dose gradient.
Latrine coverage and associated factors among urban communities found in Ambo town, West Shoa Zone, Ethiopia
Authors: Samuel Fikresilasie , Demissew Assalif , Alem Yonas , Hailesilassie Yonas 
Published: January 2021

Abstract
Background: Latrine is one of many emergency responses essential for people’s dignity, safety, health and well-beings. It is a major priority, and the coverage needs to be addressed with as much speed and effort as possible. This study is intended to find out the latrine coverage and associated risk factors which hinders the coverage in Ambo town, Ethiopia.Methods: A survey was conducted from December 2015 to April 2016 among the community found in Ambo town. About 321 households were recruited in the study. Data on latrine coverage and associated risk factors like socio-demographic characteristics, behavioral and environmental factors were collected using pretested questionnaire. Risk factors related to latrine coverage were tested to determine the potential of these factors to limit latrine availability in Ambo town.Results: This study results showed that 265(82.3%) of subjects had a latrine. Among these majority of latrines 194(60.2%) were traditional pit latrines. About 123 (38.2%) of latrines found in this study, had a hand washing facility whereas, 142 (44.1%) had not these facilities. Factors like: religion, family size, and educational level of respondents were significantly associated with availability of latrines (P<0.05).Conclusions: Based on this study finding, the latrine coverage in ambo town is very good though the coverage of improved latrines still needs attention at all level of stakeholders. Most of latrines were traditional pit latrines. Enhancing the awareness level of the community about sanitation and its benefit would facilitate the coverage and the quality of latrines.
Comparing the efficacy and safety of Dexmedetomidine/Ketamine with Propofol/Fentanyl for sedation in colonoscopy patients: A double-blinded randomized clinical trial
Authors: Aminnejad Reza , Hormati Ahmad , Shafiee Hamed , Alemi Faezeh , Hormati Maryam , Saeidi Mohammad , Ahmadpour Sajjad , Sabouri Seyed Mahdi , Aghaali Mohammad 
Published: January 2021

Abstract
BackgroundIn this double-blinded randomized clinical trial, we aimed to compare safety and efficacy of combination of dexmedetomidine and ketamine (DK) with propofol and fentanyl (PF) for sedation in colonoscopy patients.MethodsIn this study, 64 patients undergoing colonoscopy were randomized in two groups, A, receiving PF, and B receiving DK for sedation. Among 64 patients, 31 patients included in PF and 33 patients included in DK group. Both groups were similar in terms of demographics. Patients’ sedation score (based on Ramsy scale) and vital signs recorded at the times of 2, 5, 10 and 15 minutes. Complications including apnea, hypotension, hypoxia, nausea and vomiting along with gastroenterologist satisfaction and patients’ pain score (based on Wong Baker faces pain assessment scale) recorded by a checklist. Data were analyzed by SPSS V.18, using chi-square, independent t-tests and repeated measure analysis with a p value < 0.05 significance level.ResultsThe mean score of sedation was 4.82 ± 0.49 in DK group and 5.22 ± 0.45 in PF group (p value = 0.001). Serious complications, including hypotension (p value = 0.005) and apnea (p value = 0.10) were significantly higher in PF group. Satisfaction of gastroenterologist (p value = 0.400) and patients’ pain score (p value = 0.900) were similar among groups.ConclusionCombination of DK provides sufficient sedation with less complications in compare with PF in colonoscopy patients.Trial registrationThe study protocol designed on the basis of Helsinki declaration for ethical consideration and was approved by the Ethics Committee of Qom University of Medical Sciences (ethics code: IR.MUQ.REC.1397.149); the study was also registered at the Iranian Center for Clinical Trials (No. IRCT20161205031252N11).
Cardiopulmonary protection of modified remote ischemic preconditioning in mitral valve replacement surgery: A randomized controlled trial
Authors: Zhou Kang , Zhang Lianqin , Gu Tianzhu , Xu Jingjing , Shi Mengzhu , Zhu Jiang , Liu Jindong 
Published: January 2021

Abstract
BackgroundRemote ischemic preconditioning (RIPC) is reported to have early-phase and delayed-phase organ-protective effects. Whether the modified RIPC (mRIPC) protocol performed repeatedly provides cardiopulmonary protection is still uncertain.MethodsIn this single-center, randomized, controlled trial, 86 patients undergoing elective mitral valve replacement (MVR) surgery were randomized 1:1 to receive either mRIPC or no ischemic preconditioning (control). Three cycles of 5 min ischemia and 5 min reperfusion induced by a blood pressure cuff served as the RIPC stimulus. Modified RIPC was induced at the following three time points: 24 h, 12 h and 1 h before surgery. Blood samples were withdrawn at 10 min after intubation (T0), at 1 h after aortic declamping (T1), and at 6 h (T2), 12 h (T3), and 24 h (T4) after surgery to measure the serum concentrations of myocardial enzymes and other biomarkers, including cardiac troponin I (cTnI), which was the primary end point of this study. Creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), inotropic score (IS) and inflammatory mediators were also measured. Blood gas analysis was conducted to calculate the PaO2/FiO2 ratio and A-aDO2, and the incidence of acute lung injury (ALI) was also recorded.ResultsModified RIPC significantly decreased the serum concentrations of cTnI, CK-MB and LDH at T2, T3 and T4 (P < 0.01), and the IS decreased compared with that in the control group (11.96 ± 0.92 vs. 14.20 ± 1.09, P < 0.01). In addition, the incidence of ALI in the mRIPC group was decreased (18.60% vs. 34.88%, P = 0.046), and the PaO2/FiO2 was higher at T4 (P < 0.05). Compared with those in the control group, the levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were decreased at T1, T2, T3 and T4 (P < 0.05) in the mRIPC group, and the level of IL-10 increased at the same time.ConclusionsModified RIPC decreased the incidence of myocardial and lung injury in MVR surgery, providing new evidence for the clinical application of RIPC in valve surgery.Trial registrationThis study was registered in ClinicalTrials.gov (NCT03010839). Date of Registration on November 5th, 2016.
The Effect of Yoga on the Delivery and Neonatal Outcomes in Nulliparous Pregnant Women in Iran: a Clinical Trial Study
Authors: Yekefallah Leili , Namdar Peyman , dehghankar Leila , Golestaneh4 Fereshteh , Taheri Soghra , Mohammadkhaniha Frahnaz 
Published: January 2021

Abstract
Background: yoga can reduce the risk of preterm delivery, cesarean section (CS), and fetal death. The aim of the present study was to investigate the effects of yoga on pregnancy, delivery, and neonatal outcomes. Methods: the random allocation method was used among 70 nulliparous women. The data collection tool was a questionnaire pregnancy, delivery, and neonatal outcomes. The intervention in this study was practicing hate yoga. Results: The results showed that yoga reduced the induction of labor, the episiotomy rupture, duration of labor, also had a significant effect on normal birth weight and delivery at the appropriate gestational age. There were significant differences between the first and second Apgar scores of the infants.Conclusion: The results of the present study showed that yoga can improve the outcomes of pregnancy and childbirth. they can be used as part of the care protocol along with childbirth preparation classes to reduce the complications of pregnancy and childbirth.Trial registration: IRCT20180623040197N2
Standardization of the Laser Notching Method for Measuring Fracture Toughness in Structural Ceramics
Authors: Wang Anzhe , Zhao Xinyuan , Huang Mingxu , Cheng Yehong , Zhang Dongyang 
Published: January 2021

Abstract
The single-edge V-notched beam (SEVNB) method based on the laser notching approach can effectively overcome the shortcoming of time-consuming and avoid large errors in traditional fracture toughness measurement ways, nevertheless the laser notching method has not yet been standardized. Taking oxide (ZrO2 and Al2O3), carbide (SiC), nitride (Si3N4) and boride (ZrB2-based) ceramics as the research objects, this paper systematically discussed the effects of notch tip sharpness, notch depth and equivalent notch angle on the measured value of fracture toughness, thereby clearly defined the range of these parameters that required for measuring the fracture toughness accurately. Furthermore, in order to give full play to the advantages of the laser notching method, the feasibility of sample miniaturization was also discussed. This study could provide important data reference and theoretical basis for the standardization of laser method in the near future.
CXCR2 As a Novel Target for Overcoming Resistance to Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukemia Cells
Authors: Kim Ji-Hea , Lee Seung-Jin , Kang Ka-Won , Lee Byung-Hyun , Park Yong , Kim Byung Soo 
Published: January 2021

Abstract
Background: Chronic myeloid leukemia (CML) is a reciprocal translocation disorder driven by a breakpoint cluster region (BCR)-Abelson leukemia virus (ABL) fusion gene that stimulates abnormal tyrosine kinase activity. Tyrosine kinase inhibitors (TKIs) are effective in the treatment of Philadelphia chromosome (Ph)+ CML patients. However, the appearance of TKI-resistant CML cells is a hurdle in CML treatment. Therefore, it is necessary to identify novel treatments that could target a different mechanism than that of tyrosine kinases.Methods: The study was designed to verify whether C-X-C chemokine receptor 2 (CXCR2) could be a novel target for TKI-resistant CML treatment. We examined CXCR2 ligands from CML patient samples and TKI-resistant CML cell lines. Then, we inhibited CXCR2 and examined the effects on cell proliferation and apoptosis using immunoblotting and flow cytometry. The CXCR2 inhibition effect was also confirmed using a mouse xenograft model with TKI-sensitive and -resistant CML cells.Results: Interleukin 8 (IL-8), a CXCR2 ligand, was significantly increased in the bone marrow serum of initially diagnosed CML patients. CML cell lines expressed CXCR2, regardless of their sensitivity to TKIs. IL-8 stimulated CXCR2, mTOR, and c-Myc mRNA expression in CML cell lines. CXCR2 antagonists suppressed the proliferation of CML cells via cell cycle arrest in the G2/M phase. In addition, CXCR2 inhibition attenuated mTOR, c-Myc, and BCR-ABL expression, leading to CML cell apoptosis, irrespective of TKI responsiveness. Moreover, SB225002, a CXCR2 antagonist, caused higher cell death in CML cells than TKIs. Using a mouse xenograft model, we confirmed that SB225002 suppresses CML cells, with a prominent effect on TKI-resistant CML cells.Conclusions: Taken together, our findings demonstrate that IL-8 is a prognostic factor to the progress of CML. Inhibiting the CXCR2-mTOR-c-Myc cascade is a promising therapeutic strategy to overcome TKI-sensitive and -insensitive CML. Thus, CXCR2 blockade is a novel therapeutic strategy to treat CML, and SB225002, a commercially available CXCR2 antagonist, might be a drug candidate to treat TKI-resistant CML.
SUMOylation of IGF2BP2 Promotes Vasculogenic Mimicry of Glioma Via Regulating OIP5-AS1/miR-495-3p
Authors: Li Hao , Wang Di , Yi Bolong , Cai Heng , Wang Yipeng , Lou Xin , Xi Zhuo , Li Zhen 
Published: January 2021

Abstract
Background: Glioma is the most common primary malignant tumor of human central nervous system, and its rich vascular characteristics make anti-angiogenic therapy become a therapeutic hotspot. However, the existence of glioma VM makes the anti-angiogenic therapy ineffective. SUMOylation is a post-translational modification that affects cell tumorigenicity by regulating the expression and activity of substrate proteins.Methods: The binding and modification of IGF2BP2 and SUMO1were identified using Ni2+-NTA agarose bead pull-down assays, CO-IP and western blot; and in vitro SUMOylation assays combined with immunoprecipitation and Immunofluorescence staining were performed to explore the detail affects and regulations of the SUMOylation on IGF2BP2. RT-PCR and western blot were used to detect the expression levels of IGF2BP2, OIP5-AS1, and miR-495-3p in glioma tissues and cell lines. CCK-8 assays, cell transwell assays, and three-dimensional cell culture methods were used for evaluating the function of IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14 in biological behaviors of glioma cells. Meantime, RIP and luciferase reporter assays were used forinquiring into the interactions among IGF2BP2, OIP5-AS1, miR-495-3p, HIF1A and MMP14. Eventually, the tumor xenografts in nude mice further ascertained the effects of IGF2BP2 SUMOylation on glioma cells.Results: This study proved that IGF2BP2 mainly binds to SUMO1 and was SUMOylated at the lysine residues K497, K505 and K509 sites, which can be reduced by SENP1. SUMOylation increased IGF2BP2 protein expression and blocked its degradation through ubiquitin-proteasome pathway, thereby increasing its stability. The expressions of IGF2BP2 and OIP5-AS1 were up-regulated and the expression of miR-495-3p was down-regulated in both glioma tissues and cells. IGF2BP2 enhances the stability of OIP5-AS1, thereby increasing the binding of OIP5-AS1 to miR-495-3p, weakening the binding of miR-495-3p to the 3’UTR of HIF1A and MMP14 mRNA, and ultimately promoting the formation of VM in glioma.Conclusions: This study first revealed that SUMOylation of IGF2BP2 regulated OIP5-AS1/miR-495-3p to promote VM formation in glioma cells and xenografts growth in nude mice, providing a new idea for molecular targeted therapy of glioma.