bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of peri-implant submucosal microbiota in arches with zirconia or titanium implant-supported fixed complete dental prostheses: a study protocol for a randomized controlled trial
Authors: Jia Pingyi , Yang Jingwen , Yue Zhaoguo , Liu Jianzhang , Liu Qi , Liu Zhongning , Tang Lin , Hou Jianxia 
Published: November 2020

Abstract
Background
The success rate of implant-supported prostheses for edentulous patients is relatively high. However, the incidence of biological complications, especially peri-implant mucositis and peri-implantitis, increases yearly after the placement of prostheses. The accumulation of pathogenic bacteria adjacent to a prosthesis is the main cause of biological complications. Titanium, one of the classical materials for implant-supported prostheses, performs well in terms of biocompatibility and ease of maintenance, but is still susceptible to biofilm formation. Zirconia, which has emerged as an appealing substitute, not only has comparable properties, but presents different surface properties that influence the adherence of oral bacteria. However, evidence of a direct effect on oral flora is limited. Therefore, the aim of the present study was to assess the effects of material properties on biofilm formation and composition.

Methods
The proposed study is designed as a 5-year randomized controlled trial. We plan to enroll 44 edentulous (mandible) patients seeking full-arch, fixed, implant-supported prostheses. The participants will be randomly allocated to one of two groups: group 1, in which the participants will receive zirconia frameworks with ceramic veneering, or group 2, in which the participants will receive titanium frameworks with acrylic resin veneering. Ten follow-up examinations will be completed by the end of this 5-year trial. Mucosal conditions around the implants will be recorded every 6 months after restoration. Peri-implant submucosal plaque will be collected at each reexamination, and bacteria flora analysis will be performed with 16S rRNA gene sequencing technology in order to compare differences in microbial diversity between groups. One week before each visit, periodontal maintenance will be arranged. Each participant will receive an X-ray examination every 12 months as a key index to evaluate the marginal bone level around the implants.

Discussion
The current study aims to explore the oral microbiology of patients following dental restoration with zirconia ceramic frameworks or titanium frameworks. The features of the microbiota and the mucosal condition around the two different materials will be evaluated and compared to determine whether zirconia is an appropriate material for fixed implant-supported prostheses for edentulous patients.

Trial registration
International Clinical Trials Registry Platform (ICTRP) ChiCTR2000029470. Registered on 2 February 2020. http://www.chictr.org.cn/searchproj.aspx?
Platelet-rich plasma versus corticosteroid injection for treatment of trigger finger: study protocol for a prospective randomized triple-blind placebo-controlled trial
Authors: Aspinen Samuli , Nordback Panu H. , Anttila Turkka , Stjernberg-Salmela Susanna , Ryhänen Jorma , Kosola Jussi 
Published: November 2020

AbstractBackgroundTrigger finger is a common hand disorder that limits finger range of motion and causes pain and snapping of the affected finger. Trigger finger is caused by an imbalance of the tendon sheath and the flexor tendon. The initial treatment is generally a local corticosteroid injection around the first annular (A1) pulley. However, it is not unusual that surgical release of the A1 pulley is required. Moreover, adverse events after local corticosteroid injection or operative treatment may occur. Platelet-rich plasma (PRP) has been shown to be safe and to reduce symptoms in different tendon pathologies, such as DeQuervain’s disease. However, the effects of PRP on trigger finger have not been studied. The aim of this single-center triple-blind randomized controlled trial is to study whether PRP is non-inferior to corticosteroid injection in treating trigger finger. The secondary outcome is to assess the safety and efficacy of PRP in comparison to placebo.MethodsThe trial is designed as a randomized, controlled, patient-, investigator-, and outcome assessor-blinded, single-center, three-armed 1:1:1 non-inferiority trial. The patients with clinical symptoms of trigger finger will be randomly assigned to treatment with PRP, corticosteroid, or normal saline injection. The primary outcome is Patient-Rated Wrist Evaluation and symptom resolution. Secondary outcomes include Quick-Disabilities of the Arm, Shoulder and Hand; pain; grip strength; finger active range of motion; and complications. Appropriate statistical methods will be applied.DiscussionWe present a novel RCT study design on the use of PRP for the treatment of trigger finger compared to corticosteroid and normal saline injection. The results of the trial will indicate if PRP is appropriate for the treatment of trigger finger.Trial registrationClinicalTrials.govNCT04167098. Registered on November 18, 2019.
Hydroxyurea Optimization through Precision Study (HOPS): study protocol for a randomized, multicenter trial in children with sickle cell anemia
Authors: Meier Emily R. , Creary Susan E. , Heeney Matthew M. , Dong Min , Appiah-Kubi Abena O. , Nelson Stephen C. , Niss Omar , Piccone Connie , Quarmyne Maa-Ohui , Quinn Charles T. , Saving Kay L. , Scott John P. , Talati Ravi , Latham Teresa S. , Pfeiffer Amanda , Shook Lisa M. , Vinks Alexander A. , Lane Adam , McGann Patrick T. 
Published: November 2020

AbstractBackgroundSickle cell disease (SCD) is a severe and devastating hematological disorder that affects over 100,000 persons in the USA and millions worldwide. Hydroxyurea is the primary disease-modifying therapy for the SCD, with proven benefits to reduce both short-term and long-term complications. Despite the well-described inter-patient variability in pharmacokinetics (PK), pharmacodynamics, and optimal dose, hydroxyurea is traditionally initiated at a weight-based dose with a subsequent conservative dose escalation strategy to avoid myelosuppression. Because the dose escalation process is time consuming and requires frequent laboratory checks, many providers default to a fixed dose, resulting in inadequate hydroxyurea exposure and suboptimal benefits for many patients. Results from a single-center trial of individualized, PK-guided dosing of hydroxyurea for children with SCD suggest that individualized dosing achieves the optimal dose more rapidly and provides superior clinical and laboratory benefits than traditional dosing strategies. However, it is not clear whether these results were due to individualized dosing, the young age that hydroxyurea treatment was initiated in the study, or both. The Hydroxyurea Optimization through Precision Study (HOPS) aims to validate the feasibility and benefits of this PK-guided dosing approach in a multi-center trial.MethodsHOPS is a randomized, multicenter trial comparing standard vs. PK-guided dosing for children with SCD as they initiate hydroxyurea therapy. Participants (ages 6 months through 21 years), recruited from 11 pediatric sickle cell centers across the USA, are randomized to receive hydroxyurea either using a starting dose of 20 mg/kg/day (Standard Arm) or a PK-guided dose (Alternative Arm). PK data will be collected using a novel sparse microsampling approach requiring only 10 μL of blood collected at 3 time-points over 3 h. A protocol-guided strategy more aggressive protocols is then used to guide dose escalations and reductions in both arms following initiation of hydroxyurea. The primary endpoint is the mean %HbF after 6 months of hydroxyurea.DiscussionHOPS will answer important questions about the clinical feasibility, benefits, and safety of PK-guided dosing of hydroxyurea for children with SCD with potential to change the treatment paradigm from a standard weight-based approach to one that safely and effectively optimize the laboratory and clinical response.Trial registrationClinicalTrials.govNCT03789591. Registered on 28 December 2018.
Major SCP/TAPS protein expansion in Lucilia cuprina is associated with novel tandem array organisation and domain architecture
Authors: Prawer Yair D. J. , Stroehlein Andreas J. , Young Neil D. , Kapoor Shilpa , Hall Ross S. , Ghazali Razi , Batterham Phillip , Gasser Robin B. , Perry Trent , Anstead Clare A. 
Published: November 2020

Abstract
Background
Larvae of the Australian sheep blowfly, Lucilia cuprina, parasitise sheep by feeding on skin excretions, dermal tissue and blood, causing severe damage known as flystrike or myiasis. Recent advances in -omic technologies and bioinformatic data analyses have led to a greater understanding of blowfly biology and should allow the identification of protein families involved in host-parasite interactions and disease. Current literature suggests that proteins of the SCP (Sperm-Coating Protein)/TAPS (Tpx-1/Ag5/PR-1/Sc7) (SCP/TAPS) superfamily play key roles in immune modulation, cross-talk between parasite and host as well as developmental and reproductive processes in parasites.

Methods
Here, we employed a bioinformatics workflow to curate the SCP/TAPS protein gene family in L. cuprina. Protein sequence, the presence and number of conserved CAP-domains and phylogeny were used to group identified SCP/TAPS proteins; these were compared to those found in Drosophila melanogaster to make functional predictions. In addition, transcription levels of SCP/TAPS protein-encoding genes were explored in different developmental stages.

Results
A total of 27 genes were identified as belonging to the SCP/TAPS gene family: encoding 26 single-domain proteins each with a single CAP domain and a solitary double-domain protein containing two conserved cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) domains. Surprisingly, 16 SCP/TAPS predicted proteins formed an extended tandem array spanning a 53 kb region of one genomic region, which was confirmed by MinION long-read sequencing. RNA-seq data indicated that these 16 genes are highly transcribed in all developmental stages (excluding the embryo).

Conclusions
Future work should assess the potential of selected SCP/TAPS proteins as novel targets for the control of L. cuprina and related parasitic flies of major socioeconomic importance.

Graphical Abstract
IRF-1 expressed in the inner cell mass of the porcine early blastocyst enhances the pluripotency of induced pluripotent stem cells
Authors: Shi Bingbo , Gao Dengfeng , Zhong Liang , Zhi Minglei , Weng Xiaogang , Xu Junjun , Li Junhong , Du Xuguang , Xin Yanli , Gao Jie , Zhu Qianqian , Cao Suying , Liu Zhonghua , Han Jianyong 
Published: November 2020

Abstract
Background
Despite years of research, porcine-induced pluripotent stem cells (piPSCs) with germline chimeric capacity have not been established. Furthermore, the key transcription factors (TFs) defining the naïve state in piPSCs also remain elusive, even though TFs in the inner cell mass (ICM) are believed to be key molecular determinants of naïve pluripotency. In this study, interferon regulatory factor 1 (IRF-1) was screened to express higher in ICM than trophectoderm (TE). But the impact of IRF-1 on maintenance of pluripotency in piPSCs was not determined.

Methods
Transcriptome profiles of the early ICM were analyzed to determine highly interconnected TFs. Cells carrying these TFs’ reporter were used to as donor cells for somatic cell nuclear transfer to detect expression patterns in blastocysts. Next, IRF1-Flag was overexpressed in DOX-hLIF-2i piPSCs and AP staining, qRT-PCR, and RNA-seq were conducted to examine the effect of IRF-1 on pluripotency. Then, the expression of IRF-1 in DOX-hLIF-2i piPSCs was labeled by GFP and qRT-PCR was conducted to determine the difference between GFP-positive and GFP-negative cells. Next, ChIP-Seq was conducted to identify genes target by IRF-1. Treatment with IL7 in wild-type piPSCs and STAT3 phosphorylation inhibitor in IRF-1 overexpressing piPSCs was conducted to confirm the roles of JAK-STAT3 signaling pathway in IRF-1’s regulation of pluripotency. Moreover, during reprogramming, IRF-1 was overexpressed and knocked down to determine the change of reprogramming efficiency.

Results
IRF-1 was screened to be expressed higher in porcine ICM than TE of d6~7 SCNT blastocysts. First, overexpression of IRF-1 in the piPSCs was observed to promote the morphology, AP staining, and expression profiles of pluripotency genes as would be expected when cells approach the naïve state. Genes, KEGG pathways, and GO terms related to the process of differentiation were also downregulated. Next, in the wild-type piPSCs, high-level fluorescence activated by the IRF-1 promoter was associated with higher expression of naïve related genes in piPSCs. Analysis by ChIP-Seq indicated that genes related to the JAK-STAT pathway, and expression of IL7 and STAT3 were activated by IRF-1. The inhibitor of STAT3 phosphorylation was observed could revert the expression of primed genes in IRF-1 overexpressing cells, but the addition of IL7 in culture medium had no apparent change in the cell morphology, AP staining results, or expression of pluripotency related genes. In addition, knockdown of IRF-1 during reprogramming appeared to reduce reprogramming efficiency, whereas overexpression exerted the converse effect.

Conclusion
The IRF-1 expressed in the ICM of pigs’ early blastocyst enhances the pluripotency of piPSCs, in part through promoting the JAK-STAT pathway.
Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages
Authors: Liu Jin , Qiu Xinyu , Lv Yajie , Zheng Chenxi , Dong Yan , Dou Geng , Zhu Bin , Liu Anqi , Wang Wei , Zhou Jun , Liu Siying , Liu Shiyu , Gao Bo , Jin Yan 
Published: November 2020

Abstract
Background
As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects.

Methods
ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro.

Results
We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process.

Conclusions
Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.
Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells
Authors: Wang Zheng-gang , He Zhi-yi , Liang Shuang , Yang Qing , Cheng Peng , Chen An-min 
Published: November 2020

Abstract
Background
Mesenchymal stem cell (MSC)-derived exosomes have shown comprehensive application prospects over the years. Despite performing similar functions, exosomes from different origins present heterogeneous characteristics and components; however, the relative study remains scarce. Lacking of a valuable reference, researchers select source cells for exosome studies mainly based on accessibility and personal preference.

Methods
In this study, exosomes secreted by MSCs derived from different tissues were isolated, by ultracentrifugation, and proteomics analysis was performed. A total of 1014 proteins were detected using a label-free method.

Results
Bioinformatics analysis revealed their shared function in the extracellular matrix receptor. Bone marrow MSC-derived exosomes showed superior regeneration ability, and adipose tissue MSC-derived exosomes played a significant role in immune regulation, whereas umbilical cord MSC-derived exosomes were more prominent in tissue damage repair.

Conclusions
This study systematically and comprehensively analyzes the human MSC-derived exosomes via proteomics, which reveals their potential applications in different fields, so as to provide a reference for researchers to select optimal source cells in future exosome-related studies.
KLHL18 inhibits the proliferation, migration, and invasion of non-small cell lung cancer by inhibiting PI3K/PD-L1 axis activity
Authors: Jiang Xizi , XU Yitong , Ren Hongjiu , Jiang Jun , Wudu Muli , Wang Qiongzi , Guan Jingqian , Su Hongbo , Zhang Yao , Zhang Bo , Guo Yuanzi , Hu Yujiao , Jiang Lihong , Liu Zongang , Wang Huanxi , Cheng Yu , Sun Limei , Qiu Xueshan 
Published: November 2020

Abstract
Background
The expression of Kelch-like protein 18 (KLHL18) in non-small cell lung cancer (NSCLC) is lower than that in normal lung tissue according to the Gene Expression Profiling Interactive Analysis database. KLHL18 is a BTB domain protein and binds cullin 3 (CUL3). However, whether this complex participates in ubiquitination-mediated protein degradation in NSCLC is unclear. Therefore, we aimed to investigate the role of KLHL18 in human NSCLC cells.

Results
We found that KLHL18 is downregulated in cancer cells and is associated with poor prognosis. Further, its expression was significantly associated with tumor node metastasis (TNM) stage, lymph node metastasis, and tumor size. In vitro analysis of NSCLC cells showed that overexpressing KLHL18 inhibited cell proliferation, migration, and invasion. We found that the tumor-inhibitory effect of the KLHL18 protein was achieved by promoting the ubiquitination and degradation of phosphatidylinositol 3-kinase (PI3K) p85α and inhibiting the expression of PD-L1 protein, ultimately preventing tumor cell immune escape.

Conclusions
Our results identified the tumor-suppressive mechanism of KLHL18 and suggested that it is closely related to NSCLC occurrence and development. Further investigation of the underlying mechanism may provide new targets for NSCLC treatment.
Hereditary angioedema caused by a premature stop codon mutation in the SERPING1 gene
Authors: Xu Ying-Yang , Gu Jian-Qing , Zhi Yu-Xiang 
Published: November 2020

Abstract
Background
Hereditary angioedema with deficient and dysfunctional C1 inhibitor (C1-INH-HAE) is a rare genetic disorder. The majority of the cases with this disease are caused by mutations in the C1-inbitor gene SERPING1 and are classified as type 1 and type 2. We aimed to detect mutations in the SERPING1 gene and evaluate its expression in nine probands with hereditary angioedema from nine different families.

Methods
Nine probands with hereditary angioedema from nine different families and 53 healthy controls were recruited in this study. All eight exons and intron–exon boundaries in the SERPING1 gene were amplified by PCR and then sequenced. Mutations were identified by alignment with reference sequences. mRNA expression was measured by real-time PCR.

Results
All probands were diagnosed with HAE type 1. Nine mutations were found in nine patients: c.44delT, c.289C<T, c.296_303delCCATCCAA, c.538C<T, c.786_787insT, c.794 G < A, c.939delT, c.1214_1223delCCAGCCAGGA, and c.1279delC. All mutations formed a premature stop codon that might lead to the impaired synthesis of C1 inhibitor and result in the deficiency of this protein. None of the detected mutations were observed in the controls. In the C1-INH-HAE group, SERPING1 mRNA expression was significantly reduced (20% of the normal average level) compared to controls.

Conclusions
Three known and six novel mutations in the SERPING1 gene were identified, and they produced a truncated nonfunctional C1 inhibitor without a reactive central loop. All the mutations led to reduced expression of SERPING1 mRNA in peripheral blood and low antigenic C1 inhibitor levels.
The stochastic θ method for stationary distribution of stochastic differential equations with Markovian switching
Authors: Jiang Yanan , Hu Liangjian , Lu Jianqiu 
Published: November 2020

AbstractIn this paper, stationary distribution of stochastic differential equations (SDEs) with Markovian switching is approximated by numerical solutions generated by the stochastic θ method. We prove the existence and uniqueness of stationary distribution of the numerical solutions firstly. Then, the convergence of numerical stationary distribution to the underlying one is discussed. Numerical simulations are conducted to support the theoretical results.
A trend prevalence of visceral Leishmaniasis in West Armachiho District, Amhara Region, Northwest Ethiopia
Authors: Gize Addisu , Workineh Addisu , Hailu Taddesse 
Published: November 2020

Abstract
Background
Visceral leishmaniasis (VL) is a disease caused by an obligate intracellular protozoan parasite that affects animals and humans. An estimated 3.2 million people are at risk of VL, and 3700–7400 cases occur annually in Ethiopia. The highest numbers of VL cases have been previously reported from the North Western parts of the country, especially in West Armachiho District. The aim of this study was to determine the trend prevalence of VL at the study area.

Methods
Health center based retrospective data were collected to determine the trend prevalence of VL among patients who had blood examination from January 2010 to August 2015. The blood samples were collected by finger pricking and the infections were confirmed by using rK39 antibody test.

Result
Of the 9299 VL suspected cases, 1948 (21%) were positive for rK39 antibody test. Of these, 1757 (90.2%) were primary kala-azar cases, 167 (8.6%) were relapse and the remaining 24 (1.2%) were post kala-azar dermal leishmaniasis cases.

Conclusions
The prevalence of VL is still high in the study area. Therefore, early case detection, diagnosis, treatment, and timely analysis are essential.