bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole and placebo on live birth for infertility in women with polycystic ovary syndrome
Authors: Huang Shiya , Hu Min , Ng Ernest Hung Yu , Stener-Victorin Elisabet , Zheng Yanhua , Wen Qidan , Wang Cong , Lai Maohua , Li Juan , Gao Xingcheng , Wang Xinhua , Hu Zhenxing , Xia Tian , Hu Rongkui , Liu Jianping , Wen Xiaohui , Li Shuna , Quan Kewei , Liang Xingyan , Shang Hongcai , Ma Hongxia , Qiao Jie
Published: January 2020

BACKGROUND traditional Chinese Medicine (TCM) usually involves syndrome and disease differentiation, and for acupuncture selection of appropriate points and skillful needling techniques. Many clinical trials on acupuncture used fixed acupuncture protocols without accounting for individual differences. We here design a multicenter randomized controlled trial (RCT) to evaluate whether personalized or fixed acupuncture increases the likelihood of live births for infertility in women with polycystic ovary syndrome (PCOS) compared with letrozole or placebo letrozole. We hypothesis that letrozole is more effective than personalized acupuncture, and personalized acupuncture is more effective than fixed acupuncture, which is more effective than placebo letrozole. Moreover, personalized acupuncture is more likely to reduce miscarriage rate and the risk of pregnancy complications than letrozole.METHODS / DESIGN The study is a randomized assessor-blind controlled trial. A total of 1,100 infertile women with PCOS will be recruited from 28 hospitals and randomly allocated into four groups: A) personalized acupuncture, B) fixed acupuncture, C) letrozole, or D) placebo letrozole. They will receive treatment for 16 weeks and the primary outcome is live birth. Secondary outcomes include ovulation rate, conception rate, pregnancy rate, pregnancy loss rate, changes in hormonal and metabolic parameters, and changes in quality-of-life scores. The adverse events (AEs) will be recorded throughout the trial. All statistical analyses will be performed using the SPSS program V.21.0 (SPSS, Chicago, Illinois, USA) and a p value <0.05 will be considered statistically significant.DISCUSSION This study is the first multicentre RCT to compare personalized or fixed acupuncture, letrozole or placebo letrozole on live birth for infertility in women with PCOS. The findings will inform whether personalized acupuncture therapy could be as an alternative treatment method on live birth for infertile women with PCOS.
Bacillus velezensis LG37: Transcriptome profiling and functional verification of GlnK and NmtA in ammonia (NH4+) assimilation
Authors: Liu Guangxin , V Sarath Babu , Dong Yanjun , Li Xinfeng , A Binda Tembeng , Zhao Lijuan , Tu Jiagang , He Jin , lin li
Published: January 2020

Background
In recent years, interest in Bacillus velezensis has increased significantly due to its role in many industrial water bioremediation processes, including probiotics. In this study, we isolated and assessed the transcriptome of Bacillus velezensis LG37 (isolated from aquaculture pond) under different nitrogen sources. Since Bacillus species exhibit heterogeneity, it is worth to investigate the molecular information of LG37 through ammonia nitrogen assimilation, where ammonia’s nitrogen is considered toxic to aquatics.
Results
Here, a total of 812 differentially expressed genes (DEGs) from the transcriptomic sequencing of LG37 grown minimal medium supplemented with ammonia (treatment) or glutamine (control) were obtained, from which 56 had Fold Change ≥ 2. BLAST NCBI and UniProt databases revealed 27 out of the 56 DEGs were potentially involved in NH 4 + assimilation. Among them, 8 DEGs together with the two-component regulatory system glnK/glnL were randomly selected for validation by quantitative real-time RT-PCR, and the relative expression level showed that glnK/glnL were significantly upregulated that were consistent with the RNA-seq data coupled with six other genes. Moreover, the transcriptome and relative expression analysis showed that the transporter ( amtB ) gene of LG37 was not involved in ammonia transport even in the highest ammonia concentrations. Besides, CRISPR-Cas9 knockout and overexpression LG37 mutants of glnK further evidenced the exclusion of amtB regulation, suggesting involvement of alternative transporter. Additionally, in the transcriptomic data, a novel ammonium transporter nmtA was expressed significantly in increased ammonia concentrations. Subsequently, OE nmtA and Δ nmtA LG37 strains showed a unique expression pattern compared to that of wild-LG37 strain.
Conclusion
Based on the transcriptome data, regulation of nitrogen related genes were promptly screened from the newly isolated LG37 strain to analyse the key regulating factors during ammonia assimilation. The novel NmtA transporter of LG37 became apparent in ammonia transport instead of AmtB, which transport ammonium nitrogen in other Bacillus strains, using the genomic editing tools. Collectively, this study defines the heterogeneity of B. velezensis LG37 all alone through comprehensive transcriptome analysis subsequently by genome editing techniques, sheds light on the enigmatic mechanisms under different nitrogen sources also reveal the need for further research.
Comparative genomics analysis of c-di-GMP metabolism and regulation in Microcystis aeruginosa
Authors: Chen Meng , Xu Chun-Yang , Wang Xu , Ren Chong-Yang , Ding Jiao , Li Li
Published: January 2020

Background: Cyanobacteria are of special concern because they proliferate in eutrophic water bodies worldwide and affect water quality. As an ancient photosynthetic microorganism, cyanobacteria can survive in ecologically diverse habitats because of their capacity to rapidly respond to environmental changes through a web of complex signaling networks, including using second messengers to regulate physiology or metabolism. A ubiquitous second messenger, bis-(3′,5′)-cyclic-dimeric-guanosine monophosphate (c-di-GMP), has been found to regulate essential behaviors in a few cyanobacteria but not Microcystis, which are the most dominant species in cyanobacterial blooms. In this study, comparative genomics analysis was performed to explore the genomic basis of c-di-GMP signaling in Microcystis aeruginosa.
Results: Proteins involved in c-di-GMP metabolism and regulation, such as diguanylate cyclases, phosphodiesterases, and PilZ-containing proteins, were encoded in M. aeruginosa genomes. However, the number of identified protein domains involved in c-di-GMP signaling was not proportional to the size of M. aeruginosa genomes (4.99 Mb in average). Pan-genome analysis showed that genes involved in c-di-GMP metabolism and regulation are conservative in M. aeruginosa strains. Phylogenetic analysis showed good overall congruence between the three types of phylogenetic trees based on 31 highly conserved protein-coding genes, sensor domain-coding genes, and pan-genome matrix. Propensity for gene loss analysis revealed that most of genes involved in c-di-GMP signaling are stable in M. aeruginosa strains. Moreover, bioinformatics and structure analysis of c-di-GMP signal-related GGDEF and EAL domains revealed that they all possess essential conserved amino acid residues that bind the substrate. In addition, it was also found that all selected M. aeruginosa genomes encode PilZ domain containing proteins.
Conclusions: Comparative genomics analysis of c-di-GMP metabolism and regulation in M. aeruginosa strains helped elucidating the genetic basis of c-di-GMP signaling pathways in M. aeruginosa. Knowledge of c-di-GMP metabolism and relevant signal regulatory processes in cyanobacteria can enhance our understanding of their adaptability to various environments and bloom-forming mechanism.
Keywords: Microcystis aeruginosa, Comparative genomics, c-di-GMP, Phylogenetic analysis, GGDEF, EAL, HD-GYP, PilZ
Transcriptome-wide map of m6A circRNAs identified in a rat model of hypoxia mediated pulmonary hypertension
Authors: Su Hua , Wang Guowen , Wu Lingfang , Ma Xiuqing , Ying Kejing , Zhang Ruifeng
Published: January 2020

Background: Hypoxia mediated pulmonary hypertension (HPH) is a lethal disease and lacks effective therapy. CircRNAs play significant roles in physiological process. Recently, circRNAs are found to be m 6 A-modified. The abundance of circRNAs was influenced by m 6 A. Furthermore, the significance of m 6 A circRNAs has not been elucidated in HPH yet. Here we aim to investigate the transcriptome-wide map of m 6 A circRNAs in HPH.
Results: Differentially expressed m 6 A abundance was detected in lungs of HPH rats. M 6 A abundance in circRNAs was significantly reduced in hypoxia in vitro . M 6 A circRNAs were mainly from protein-coding genes spanned single exons in control and HPH groups. Moreover, m 6 A influenced the circRNA–miRNA–mRNA co-expression network in hypoxia. M 6 A circXpo6 and m 6 A circTmtc3 were firstly identified to be downregulated in HPH.
Conclusion: Our study firstly identified the transcriptome-wide map of m 6 A circRNAs in HPH. M 6 A can influence circRNA–miRNA–mRNA network. Furthermore, we firstly identified two HPH-associated m 6 A circRNAs: circXpo6 and circTmtc3. However, the clinical significance of m 6 A circRNAs for HPH should be further validated.
Key words: m 6 A circRNAs; hypoxia mediated pulmonary hypertension; m 6 A circXpo6; m 6 A circTmtc3
Genome-wide identification and expression profiling of SET DOMAIN GROUP family in Dendrobium catenatum
Authors: Chen Dong-Hong , Qiu Han-Lin , Huang Yong , Zhang Lei , Si Jin-Ping
Published: January 2020

Background: Dendrobium catenatum used as a precious Chinese herbal medicine is a kind of epiphytic orchid plant which grows on the trunks and cliffs and often faces up to diverse environmental stresses. SET DOMAIN GROUP (SDG) proteins act as histone lysine methyltransferases which are involved in pleiotropic developmental events and stress responses through modifying chromatin structure and regulating gene transcription, but their roles in D. catenatum are unknown.
Results: In this study, we identified 44 SDG proteins from D. catenatum genome. Subsequently, comprehensive analyses related to gene structure, protein domain organization, and phylogenetic relationship were performed to evaluate these D. catenatum SDG (DcSDG) proteins, along with the well-investigated homologs from the model plants Arabidopsis thaliana and Oryza sativa as well as the newly characterized 42 SDG proteins from a closely related orchid plant Phalaenopsis equestris . We showed DcSDG proteins can be grouped into eight distinct classes (I~VII and M), mostly consistent with the previous description. Based on the catalytic substrates of the reported SDG members mainly in Arabidopsis, Class I (E(z)-Like) is predicted to account for the deposition of H3K27me2/3, Class II (Ash-like) for H3K36me, Class III (Trx/ATX-like) for H3K4me2/3, Class M (ATXR3/7) for H3K4me, Class IV (Su(var)-like) for H3K27me1, Class V (Suv-like) for H3K9me, as well as class VI (S-ET) and class VII (RBCMT) for methylation of both histone and non-histone proteins. RNA-seq derived expression profiling showed that DcSDG proteins usually have wide but distinguished expression in different tissues and organs. Finally, environmental stresses examination showed the expression of DcASHR3, DcSUVR3, DcATXR4, DcATXR5b, and DcSDG49 is closely associated with drought-recovery treatment, the expression of DcSUVH5a , DcATXR5a and DcSUVR14a is significantly influenced by low temperature, and even 61% DcSDG genes are in response to heat shock.
Conclusions: This study systematically identifies and classifies SDG genes in orchid plant D. catenatum , indicates their functional divergence during the evolution, and discovers their broad roles in the developmental programs and stress responses. These results provide constructive clues for further functional investigation and epigenetic mechanism dissection of SET-containing proteins in orchid.
Integrated Care Search: Development and validation of a PubMed search filter for retrieving the integrated care research evidence
Authors: Damarell Raechel A. , Lewis Suzanne , Trenerry Camilla , Tieman Jennifer J.
Published: January 2020

Background Integrated care is an increasingly important principle for organising healthcare. Integrated care models show promise in reducing resource wastage and service fragmentation whilst improving the accessibility, patient-centredness and quality of care for patients. Those needing reliable access to the growing research evidence base for integrated care can be frustrated by search challenges reflective of the topic's complexity. The aim of this study is to report the empirical development and validation of two search filters for rapid and effective retrieval of integrated care evidence in PubMed. One filter is optimised for recall and the other for precision.Methods An Expert Advisory Group comprising international integrated care experts guided the study. A gold standard test set of citations was formed from screening Handbook Integrated Care chapter references for relevance. This set was divided into a Term Identification Set (20%) for determining candidate terms using frequency analysis; a Filter Development Set (40%) for testing performance of term combinations; and a Filter Validation Set (40%) reserved for confirming final filter performance. In developing the high recall filter, recall was steadily increased while maintaining precision at ≥ 50%. Similarly, the high precision filter sought to maximise precision while keeping recall ≥ 50%. For each term combination tested, an approximation of precision was obtained by reviewing the first 100 citations retrieved in Medline for relevance.Results The gold standard set comprised 534 citations. The search filter optimised for recall ('Broad Integrated Care Search') achieved 86.0%-88.3% recall with corresponding low precision (47%-53%). The search filter optimised for precise searching ('Narrow Integrated Care Search') demonstrated precision of 73%-95% with recall reduced to between 55.9% and 59.8%. These filters are now available as one-click URL hyperlinks in the website of International Foundation for Integrated Care.Conclusions The Broad and Narrow Integrated Care Search filters provide potential users, such as policy makers and researchers, seamless, reliable and ongoing access to integrated care evidence for decision making. These filters were developed according to a rigorous and transparent methodology designed to circumvent the challenges of information retrieval posed by this complex, multifaceted topic.
HIV/AIDS treatment failure and associated factors in Ethiopia: Meta-analysis
Authors: Endalamaw Aklilu , Mekonnen Mengistu , Geremw Demeke , Ambaw Fekadu , Tesera Hiwot , Habtewold Tesfa Dejenie
Published: January 2020

Background: The national burden of human immunodeficiency virus treatment failure and associated factors in the Ethiopian context is required to provide evidence towards a renewed ambitious future goal.
Methods: We accessed Ethiopian Universities’ online repository library, Google Scholar, PubMed, Web of Science, and Scopus to get the research articles. We run I-squared statistics to see heterogeneity. Publication bias was checked by using Egger’s regression test. The pooled prevalence was estimated using the DerSimonian-Laird random-effects model. We employed the sensitivity analysis to see the presence of outlier result in the included studies.
Results: The overall human immunodeficiency treatment failure was 15.9% (95% confidence interval: 11.6%-20.1%). Using immunological, virological, and clinical definition, human immunodeficiency treatment failure was 10.2% (95% confidence interval: 6.9%-13.6%), 5.6% (95% confidence interval: 2.9%-8.3%), and 6.3% (95% confidence interval: 4.6%-8.0%), respectively. The pooled effects of World Health Organization clinical stage III/IV (Adjusted Odd Ratio=1.9; 95% CI: 1.3-2.6), presence of opportunistic infections (Adjusted Odd Ratio= 1.8; 95% CI: 1.2-2.4), and poor adherence to highly active antiretroviral therapy (Adjusted Odd Ratio= 8.1; 95% CI: 4.3-11.8) on HIV treatment failure were estimated.
Conclusions: Human immunodeficiency virus treatment failure in Ethiopia found to be high. Being on advanced clinical stage, presence of opportunistic infections, and poor adherence to highly active antiretroviral therapy were the contributing factors of human immunodeficiency virus treatment failure. Human immunodeficiency virus intervention programs need to address the specified contributing factors of human immunodeficiency virus treatment failure. Behavioral intervention to prevent treatment interruption is required to sustain human immunodeficiency virus treatment adherence.
Protocol Registration: It has been registered in the PROSPERO database with a registration number of CRD42018100254.
SERT and BDNF polymorphisms interplay on neuroticism in borderline personality disorder
Authors: Salinas Valeria , Villarroel Juana , Silva Hernán , Herrera Luisa , Jerez Sonia , Zazueta Alejandra , Montes Cristian , Nieto Rodrigo , Bustamante M. Leonor
Published: January 2020

Objective Genetic factors underlying different personality traits are not entirely understood, particularly how genes interact to modulate their effect. We studied 76 patients diagnosed with borderline personality disorder (BPD), characterized by extreme levels of personality traits, especially neuroticism (N), in which we genotyped two polymorphisms, the 5HTTLPR of the Serotonin transporter (SERT) gene, and the Val66Met of the Brain-derived neurotrophic factor (BDNF) gene.Results We found an association with SERT, where S-allele carriers had significantly higher levels of N than L-homozygous. Furthermore, we found that the protective effect of L-homozygosity is only evident on A-allele carriers of the BDNF Val66Met polymorphism. Genetic constitution in SERT and BDNF seems to be important in neuroticism, the most relevant personality trait on BPD.
Reference values of fat mass index and fat-free mass index in healthy Spanish adolescents.
Authors: Durá-Travé Teodoro , Gallinas-Victoriano Fidel , Chueca-Guindulain María , Berrade-Zubiri Sara , Malumbres-Chacón María , Moreno-González Paula
Published: January 2020

Background . Body mass index (BMI) does not allow to discriminate the composition of the different body compartments. The aim of this study is to elaborate reference values ​of the fat mass index (FMI) and fat-free mass index (FFMI) in healthy adolescents using anthropometric techniques in order to be available as reference standards in daily clinical practice.
Whole genome characterization of autochthonous Bos taurus brachyceros and introduced Bos indicus indicus cattle breeds in Cameroon regarding their adaptive phenotypic traits and pathogen resistance
Authors: paguem Archile Eric , Abanda Babette , Achukwi Mbunkah Daniel , Baskaran Praveen , Czemmel Stefan , Renz Alfons , Eisenbarth Albert
Published: January 2020

BackgroundWest African indigenous taurine cattle display unique adaptive traits shaped by husbandry management, regional climate and exposure to endemic pathogens. They are less productive with respect to milk and meat production which has been associated with a number of factors, amongst others small size, traditional beliefs and husbandry practices. This resulted in the severe dwindling of their populations size rendering them vulnerable to extinction. The Namchi (Doayo) taurine cattle breed has documented resistance traits against trypanosome infection and exposure to tick infestation. Nonetheless, the historically later introduced Zebu cattle are the main cattle breeds in Africa today, even though they suffer more from locally prevailing pathogens. By using a reference-based whole genome sequencing approach, we sequenced for the first time the genomes of five cattle breeds from Cameroon: the Namchi (Doayo), an endangered trypanotolerant taurine breed, the Kapsiki, an indigenous trypanosusceptible taurine breed, and three Zebu (Bos indicus indicus) breeds: Ngaoundere Gudali, White Fulani and Red Fulani.ResultsApproximately 167 Giga bases of raw sequencing data were generated and mapped to the cattle reference genome UMD3.1. The coverage was 22 to 30-fold. The single nucleotide polymorphisms (SNPs) were compared with reference genomes of EuropeanBos taurusHolstein and of AsianBos indicusBrahman and the African trypanotolerant N’Dama breeds.Of a total of 50 million SNPs identified, 3.43 million were breed-specific ranging from 0.37 to 0.47 million SNPs in the domestic Cameroonian breeds and approximately 0.58 million constituted of small insertions and deletions. We identified breed specific-non-synonymous variants as genetic traits that could explain certain cattle-breed specific phenotypes such as increased tolerance against trypanosome parasites in the Namchi (Doayo) breed, heat tolerance in the Kapsiki breed, and growth, metabolism and meat quality in the Gudali breeds. Phylogenetic comparison grouped Namchi (Doayo) to the African Zebu clade indicating a hybrid status of the selected animal with a Zebu breed, albeit it showed the Namchi breed’s phenotype.ConclusionsThe findings provide the first comprehensive set of full genome variant data of the most important Cameroonian cattle breeds. The genomic data shall constitute a foundation for breed amelioration whilst exploiting the heritable traits and support conservation efforts for the endangered local cattle breeds.
Lipopolysaccharide regulates thymic stromal lymphopoietin expression via TLR4/MAPK/Akt/NF-κB signaling pathways in nasal fibroblasts: differential inhibitory effects of macrolide and corticosteroid
Authors: Kang Ju-Hyung , Yang Hyun-Woo , Park Joo-Hoo , Shin Jae-Min , Kim Tae-Hoon , Lee Seung Hoon , Lee Heung-Man , Park Il-Ho
Published: January 2020

BackgroundChronic rhinosinusitis (CRS) is inflammatory disease of sinonasal mucosa. Thymic stromal lymphopoietin (TSLP) is associated with Th-2 response and induced by pathogen, allergen, Toll-like receptor (TLR) ligands, and cytokines. Fibroblasts have known to modulators of wound healing, from inflammation to tissue remodeling. We examined effect of lipopolysaccharide (LPS) on TSLP production and underlying mechanisms. We aimed to determine whether effects of commonly used medications in CRS, corticosteroids and macrolides, are related to LPS-induced TSLP in nasal fibroblasts.ResultsFibroblasts were isolated from inferior turbinate tissues of CRS patients. TSLP and TLR4 expression was determined by RT-PCR, western blot, ELISA, and immunofluorescence staining. MAPK, Akt, and NF-κB phosphorylation was determined by western blot and/or luciferase assay. LPS increased TSLP expression in a dose- and time-dependent manner. LPS antagonist and corticosteroids inhibited TLR4 expression in LPS-stimulated fibroblasts. LPS-RS, macrolides, corticosteroids, and specific inhibitors suppressed LPS-induced alterations. Ex vivo culture showed similar results.ConclusionsLPS induces TSLP production via TLR4, MAPK, Akt, and NF-κB pathways. Effects of corticosteroids and macrolides are related to LPS-induced TSLP expression. We would explore new treatment modalities targeting LPS-induced TSLP production that could replace current usage of corticosteroid and macrolides in treatment of CRS.
A Population-Based Survey to Assess Cannabis on Quality of Life among Colorectal Cancer Survivors
Authors: Calcaterra Susan , Burnett-Hartman Andrea N. , Powers J. David , Corley Douglas A , McMullen Carmit M , Pawloski Pamala A. , Feigelson Heather Spencer
Published: January 2020

Background: As more states legalize cannabis for medical and recreational use, people increasingly use cannabis to treat medical conditions and associated symptoms. The prevalence and utility of cannabis for cancer-related symptoms may be clarified by examining cannabis use among patients with a common cancer diagnosis. We aimed to determine the prevalence of cannabis use among colorectal cancer (CRC) survivors and its associations with quality of life (QoL) and cancer-related symptomatology. Methods: A cross-sectional survey of patient-reported QoL outcomes and behaviors, including cannabis use, was conducted within the Patient Outcomes To Advance Learning network’s (PORTAL) CRC Cohort. The cohort included a population-based sample of healthcare system members ≥ 18 years old diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2016. We assessed the association between cannabis use and QoL using the European Organization for Research and Treatment of Cancer QLQ-C30 summary score. Results: Of the 1,784 respondents, 293 (16.4%) reported cannabis use following CRC diagnosis. Current tobacco smokers were more likely to use cannabis compared to former or never tobacco smokers (adjusted odds ratio [aOR] 2.71, 95% CI 1.56 to 4.70). Greater alcohol use (> 4 drinks per month versus ≤ 4 drinks per month) was associated with cannabis use (aOR 2.17, 95% CI 1.65 to 2.85). There was an association between cannabis use and cancer stage at diagnosis, with stage 3 or 4 CRC patients more likely to use cannabis than stage 1 or 2 CRC patients (aOR 1.68, 95% CI 1.25 to 2.25). After adjusting for demographics, medical comorbidities, stage and site of CRC diagnosis, and prescription opioid use, people who used cannabis had significantly lower QoL than people who did not use cannabis (difference of -6.14, 95% CI -8.07 to -4.20). Conclusion: Among CRC survivors, cannabis use was common, associated with more advanced stages of disease, associated with tobacco and alcohol use, and not associated with better QoL. Clinicians should inquire about cannabis use among their patients and provide evidence-based recommendations for cancer-related symptoms.
Surgical intra- and extra-articular anterior cruciate ligament reconstruction: a meta-analysis
Authors: Cheng Xiangyun , Liu Fanxiao , Zhou Dongsheng , Paulus Alexander C.
Published: January 2020

Background: It is still controversial whether the combination of anterior cruciate ligament (ACL) reconstruction and extra-articular reconstruction (EAR) have good clinical efficacy. This meta-analysis aims to compare the clinical effectiveness of ACL reconstruction and combined reconstruction. Methods: Electronic databases, including Medline/PubMed, Embase and the Cochrane Library, were systematically searched to identify targeted studies. A meta-analysis aims to pool the outcome estimates of interest, such as the Lysholm, International Knee Documentation Committee (IKDC) and Tegner scores and the results from the KT-1000/2000 arthrometer test, the Lachman test and the pivot shift test. Results : Twelve studies involving 1146 knees were identified. Compared with single ACL reconstruction, combined reconstruction had better results for a pivot shift of grade 1 (relative ratio [RR] = 0.88, 95% CI: 0.83-0.94) and grade 2 (RR = 0.95, 95% CI: 0.91-0.99) rather than grade 3 (RR = 0.98, 95% CI: 0.90-1.06) and no statistically significant difference for both Lachman grade 1 (RR = 0.96, 95% CI: 0.89-1.05) and grade 2 (RR = 0.96, 95% CI: 0.90-1.03). Combined reconstruction resulted in significant improvements on the instrumented joint laxity test when considering a failure standard of more than 5 mm (a side-to-side arthrometric difference) (RR = 0.94, 95% CI: 0.89-0.98) rather than 3 mm (RR = 0.94, 95% CI: 0.86-1.03). Moreover, combined reconstruction increased the IKDC score at the 12-month (weighted mean difference [WMD] = -6.38, 95% CI: -9.66 to -3.10), 24-month (WMD = -5.60, 95% CI: -8.54 to -2.66) and 36-month follow-ups (WMD = -4.71, 95% CI: -7.59 to -1.83) and the Tegner score at the 36-month follow-up (WMD = -0.53, 95% CI: -0.97 to -0.09), but it did not increase the Lysholm score at the 36-month follow-up (WMD = -0.84, 95% CI: -2.02 to 0.34). Conclusion : With the advances in reconstruction techniques, combined reconstructions were found to be effective in improving rotational stability and to lead to good functional scores. However, obviously, the combined reconstruction technique is more time-consuming and requires an additional incision, which is not suitable for all ACL-deficient patients. Therefore, programs should be personalized and customized for the specific situation of each patient.
Change in Serum Markers Failed to Predict Persistent Infection after Two-stage Exchange ArthroplastyChange in Serum Markers Failed to Predict Persistent Infection after Two-stage Exchange Arthroplasty
Authors: Jiang Qiao , Yang Xue , Xu Chi , Chai Wei , Zhou Yong-gang , Chen Jiying
Published: January 2020

BackgroundTwo-stage exchange arthroplasty is a viable choice for prosthetic joint infection (PJI). After removing the infected prosthesis and implanting an antibiotic-loaded spacer in first stage, the proper timing of reimplantation is crucial for successful treatment. So far, there is no gold reference to determine the eradication of PJI before reimplantation. The combination of serum indicators, synovial white cell count (WBC), culture results, intraoperative histology, and clinical symptoms is used extensively to guide the timing of reimplantation. However, the proper timing of reimplantation was ill defined.PurposeWe wonder: (1) the utility of serum indicators, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen, when predicted failure of reimplantation; (2) correlation between primary culture results and serum markers’ change.MethodA retrospective review of 226 patients treated with a two-stage exchange arthroplasty from 2014 to 2017 was conducted. PJI was diagnosed by using the Musculoskeletal Infection Society (MSIS) criteria. Serum biomarkers and organisms results at the set of PJI diagnosis and reimplantation were reviewed. Treatment success was defined according to the Delphi consensus criteria with a minimum follow-up of 2 year; receiver operator characteristic (ROC) depicted the utility of change in four serum markers when predicted failure.ResultsThe ROC area under the curves (AUC) was 0.543 in CRP, 0.572 in IL-6, 0.621 in ESR, 0.463 in fibrinogen and the combination of them was 0.709 when predicted persistent PJI using value change. The AUC of ROC was 0.521 in CRP, 0.472 in IL-6, 0.413 in ESR, 0.552 in fibrinogen and the combination was 0.630 when determine reimplantation by percent change. No significant association was found between culture results and change in serum markers.ConclusionNeither percent change nor value change in serum makers was proved to be poor markers when predicted persistent PJI, and initial causative organism didn’t influence the normalize of serum markers. Persistent PJI after TJA was still tough to diagnose. The combination of clinical symptom, pathology results, synovial fluid analysis and serum markers may improve the utility.
FBXL6 governs c-MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1
Authors: Shi Weidong , Feng Lanyun , Dong Shu , Ning Zhouyu , Hua Yongqiang , Liu Luming , Chen Zhen , Meng Zhiqiang
Published: January 2020

BackgroundHeat shot protein 90 (HSP90) AA1 functions as an onco-protein to regulate the assembly, manipulation, folding and degradation of its client proteins, including c-MYC. However, the mechanisms underlying the regulation of HSP90AA1 are poorly understood.MethodsTranscriptome RNA-sequencing data of Liver hepatocellular carcinoma (LIHC) samples were used to detect the mRNA expression of FBXL6. Immunoprecipitation/Mass Spectrum (IP/MS) method was used to identify the interacting proteins of FBXL6. The co-immunoprecipitation assay was used to determine the interaction between FBXL6 and HSP90AA1. The in vivo ubiquitination assay was performed to determine the regulation of HSP90AA1 by FBXL6. Luciferase reporter and chromatin immunoprecipitation assays were used to determine the transcriptional regulation of FBXL6 by c-MYC. Cell counting and colony formation assays were implemented to detect the biological effects of FBXL6 on the growth of HCC cells in vitro. The effect of FBXL6 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice. ResultsHere, we identified the orphan F-box protein FBXL6, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the ubiquitin ligase for HSP90AA1. FBXL6 promoted K63-dependent ubiquitination of HSP90AA1 to stabilize it. Through analysis of multiple public liver cancer GEO data, we found that FBXL6 was significantly increased in liver cancer tissues and positively correlated with c-MYC pathway. FBXL6 accumulation in liver cancers causes the stabilization and activation of c-MYC by preventing HSP90AA1 degradation. Activated c-MYC, which in turn directly binds to the promoter region of FBXL6 to induce its mRNA expression.ConclusionCollectively, our data revealed an unknown axis of FBXL6-HSP90AA1-c-MYC which might contribute to the oncogenesis of liver cancer, and we propose that inhibition of FBXL6 might represent an effective therapeutic strategy for liver cancer treatment.
Cultural Adaptation of Health Literacy Measures: Translation Validation of the Newest Vital Sign in Arabic-speaking Parents of Children with Type 1 Diabetes in Kuwait.
Authors: Al-Abdulrazzaq Dalia , Al-Taiar Abdullah , Al-Haddad Muneera , Al-Tararwa Abeer , Al-Zanati Nabeela , Al-Yousef Amna , Davidsson Lena , Al-Kandari Hessa
Published: January 2020

Background Low level of health literacy (HL) has been linked to several adverse health outcomes independently from education, ethnicity and socio-economic status. There is a dire need for a reliable tool to assess HL of patients and general public in Arab countries. This study aimed to assess the feasibility of use and reliability of the Arabic version of the Newest Vital Sign (NVS) in parents of children with type 1 diabetes (T1D).Methods Translation and cross-cultural adaptation of the Arabic version of the NVS (NVS-Ar) was conducted according to established guidelines. In order to investigate the functionality of NVS, the final version of NVS-Ar was administered to 175 adult caregivers of children with T1D, who are native Arabic speakers. We assessed the association between NVS-Ar score for the parents and HbA1C for their children. The internal consistency was evaluated by Cronbach’s Alpha (CA) and reliability was assessed by test retest method.Results The median (interquartile rang IQR) score was 4.0 (3-5). The internal consistency of the NVS-Ar was moderate (CA= 0.58). While the intraclass correlation coefficient (ICC) was 0.61. There was no correlation between NVS-Ar score and HbA1C (Spearman's rho = 0.055; p=0.62). Furthermore, there was significant inverse association between adequate HL and optimal glycemic control among children, which remained evident even after adjusting for the duration of T1D, age or education of the parents/child guardian. However, it lost statistical significance when we adjust for treatment regimen.Conclusion Our findings demonstrate that NVS is unlikely to be a predictive tool for functional HL in Arabic settings and that there is a need to properly translate and validate other tools such as TOFLA or alternatively develop a reliable tool de novo.
Endoscopic Thulium Laser Ablation of Upper Tract Urothelial Carcinoma: a Retrospective Study with Subgroup Analyses
Authors: Hsieh Yu Che , Huang Steven K. , Su Chia-Cheng , Wang Jhih-Cheng , Shen Kun-Hung , Feng I-Jung , Chiu Allen W. , Liu Chien-Liang
Published: January 2020

Introduction The gold standard treatment for upper tract urothelial carcinomas (UTUC) is radical nephroureterectomy with bladder-cuff excision. However, the role of combination of ureterorenoscopy and laser ablation has recently become more essential. This study aimed to investigate the efficacy of Thulium laser ablation of UTUC and estimate clinical outcomes with subgroup analyses. Methods After obtaining informed consent, we retrospectively reviewed all patients who had undergone endoscopic Thulium laser ablation of UTUC as their primary treatment from Jun 2012, to Nov 2018. Sixty-eight patient were enrolled, and thirty-four patients were analyzed after selection by exclusion criteria. Comparisons with bivariate analyses between patients with and without recurrence were examined. Multivariable cox regression model were further applied. Further, Kaplan-Meier survival estimate were presented with comparison of the survival curves, we also combined two of three tumor characteristics (stage, size, and grade of tumor) for subgroup analyses. Results Fifteen patients (44%) had local tumor recurrence. Seven patients (21%) had recurrence at the urinary bladder. Two patients (6%) had lymph node or distal metastasis. A total of 4 patients (12%) had cancer-specific death. In bivariate analyses, statistical significance is noted for age, tumor grade and tumor size with p-values of 0.018, 0.047 and 0.014, respectively. In the multivariable analysis, statistical significance is noted for age and tumor size with p-values of 0.017, and 0.042, respectively. In Kaplan–Meier estimate for subgroup analysis, statistical significance is only noted in the tumor size + tumor grade group but almost achieved in the tumor size + biopsy stage group with p-value of 0.0275 and 0.0518, respectively. Conclusion In our experience, tumor size and tumor grade are influential recurrence factors. However, biopsy stage does not achieve statistical significance in both the recurrence analysis and survival estimate. In the subgroup analyses, tumor size is a more influential factor than tumor grade in the prognosis of local recurrence.
Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex
Authors: Ju Anes , Fernandez-Arroyo Beatriz , Wu Yifan , Jacky Débora , Beyeler Anna
Published: January 2020

The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed six neural populations, including two defined by their fast amino acid transmitter (excitatory or inhibitory), and four defined by their projections to different downstream targets. First, we found that more than 70% of glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, 5-HT1A is highly expressed (~80%) in the insular populations projecting to two sub-nuclei of the amygdala (central and basolateral), as well as in the populations projecting to the rostral and caudal sections of the lateral hypothalamus (LH). Similarly, 70% of insular glutamatergic neurons and only 20% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in most of insula-amygdala and insula-LH projection neurons (>60%). These observations suggest that a majority of glutamatergic neurons can respond to 5-HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.
Serum IgG-indcued microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma
Authors: Ding Xu , Yang Wei , Ren Qinghua , Hu Jiajian , Yang Shen , Han Wei , Wang Jing , Wang Xu , Wang Huanmin
Published: January 2020

BackgroundOpsoclonus-myoclonus syndrome (OMS) is a rare neurological disease. Some children with OMS also have neuroblastoma (NB). We and others have previously documented that serum IgG from children with OMS and NB induces neuronal cytolysis via several signaling pathways. However, mechanisms underlying OMS remain unclear. Here we investigated whether nitric oxide (NO) from activated microglias and its cascade contribute to neuronal cytolysis in pediatric OMS.MethodsThe activation of cultured cerebral cortical and cerebellar microglias incubated with sera or IgG isolated from sera of children with OMS and NB was measured by the expression of the activation marker, cytokines and NO. Neuronal cytolysis was determined after exposing to IgG-treated microglia conditioned media. Using inhibitors and activators, the effects of NO synthesis and its intracellular cascade, namely soluble guanylyl cyclase (sGC) and protein kinase G (PKG), on neuronal cytolysis were evaluated.ResultsIncubation with sera or IgG from children with OMS and NB increased the activation of cerebral cortical and cerebellar microglias, but not the activation of astrocytes or the cytolysis of glial cells. Moreover, the cytolysis of neurons was elevated by conditioned media from microglias incubated with IgG from children with OMS and NB, which was relieved by the inhibitors of NO signaling. By contrast, neuronal cytolysis was exacerbated by the activators of NO signaling but not proinflammatory cytokines. Neuronal cytolysis was suppressed by pretreatment with the microglial inhibitor minocycline, a clinically tested drug. Finally, increased microglial activation did not depend on the Fab fragment of serum IgG.Conclusions﻿Serum IgG from children with OMS and NB potentiates microglial activation, which induces neuronal cytolysis through the NO/sGC/PKG pathway, suggesting an applicability of microglial inhibitor as a therapeutic candidate.
Widespread occurrence of Candidatus Phytoplasma ulmi infecting elm species in Germany
Authors: Schneider Bernd , Kätzel Ralf , Kube Michael
Published: January 2020

Background: Candidatus Phytoplasma ulmi is the causative agent of elm yellows and has been categorised in the European Union as a quarantine pathogen in the past. For central and northern European countries, information on the occurrence and distribution of the pathogen and its impact on elms is scarce, so a survey of native elm trees has been conducted in Germany. Results: About 6,500 samples in total, from Ulmus minor , Ulmus laevis and Ulmus glabra , were collected nationwide. Phytoplasma detection was performed by applying a universal 16Sr DNA-based real-time PCR assay and a novel Ca . P. ulmi species-specific real-time PCR assay targeting the 16S-23S spacer region. Both assays revealed that 28% of the samples were infected by Ca . P. ulmi, but infection rates of the elm species and regional incidences differed. The infection of trees is not correlated to disease-specific symptoms. The survey identified a regional disparity of infection which was high in east, south and central Germany, whereas only a few infected sites were found in the western and northern parts of the country. No correlation was apparent between altitude level and the prevalence of infection. First insights into the monitoring of the seasonal titre of Ca . P. ulmi in an infected tree by real-time PCR revealed high colonisation in all parts of the tree throughout the year. Conclusions: Ca . P. ulmi-infection is widely present in elms in Germany. The rare occurrence of symptoms indicates either a high degree of tolerance in elm populations or a low virulence of pathogen strains enabling high infection rates in a long-living host.
Fenofibrate decreased microalbuminuria in the type 2 diabetes patients with hypertriglyceridemia
Authors: Sun Xiaomeng , Liu Jia , Wang Guang
Published: January 2020

Background: This study was to research the efficacy of fenofibrate in the treatment of microalbuminuria in the patients with type 2 diabetes mellitus (T2DM) and hypertriglyceridemia.Methods: Type 2 diabetic patients (56) with microalbuminuria and hypertriglyceridemia aged 30 to 75 were randomly divided into the fenofibrate treatment group(n=28) and the control group (n=28) for 180 days. Urinary microalbumin /creatinine ratio (UACR) and other metabolic parameters were compared at baseline, during treatment and after treatment.Results: After 180 days, the reduction of levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in two groups were no differences. In treatment group, uric acid (UA) (296.42 ± 56.41 vs 372.46 ± 72.78), triglyceride (TG) [1.51(1.17, 2.06) vs 3.04(2.21, 3.29)], and UACR [36.45 (15.78,102.41) vs 129.00 (53.00, 226.25)] were significantly decreased compared with the baseline. The high-density lipoprotein cholesterol (HDL-C) levels were significantly increased (1.22 ± 0.26 vs 1.09 ± 0.24) compared with the baseline. The decrease in UACR [-44.05(-179.47, -12.16) vs -8.15(-59.69, 41.94)]in treatment group was significantly higher compared with the control group. The decrease in UACR was positively associated with the decreases in TG ( r = 0.447, P = 0.042) and UA ( r = 0.478, P = 0.024) after fenofibrate treatment.Conclusion: In the patients with hypertriglyceridemia and type 2 diabetes mellitus, fenofibrate can improve microalbuminuria and do not increase the deterioration of glomerular filtration rate
Validation of the care providers version of the Rainbow Model of Integrated Care-Measurement Tool in Chinese primary care systems
Authors: Huang Yixiang , Zhu Paiyi , Chen Lijin , Wang Xin , Valentijn Pim
Published: January 2020

Background: The original Rainbow Model of Integrated Care Measurement Tool (RMIC-MT) is based on the Rainbow Model of Integrated Care, which provides a comprehensive theoretical framework for integrated care. To translate and adapt the original care provider version of the Rainbow Model of Integrated Care-Measurement Tool and evaluate its psychometric properties by a pilot study in Chinese primary care systems.Methods: The translation and adaptation process were performed in four steps, forward and back-translation, expert review and pre-testing. We conducted a cross-sectional study with 1610 community care professionals in all 79 community health stations in the Nanshan district. We analyzed the distribution of responses to each item to study the psychometric sensitivity. Exploratory factor analysis with principal axis extraction method and promax rotation was used to assess the construct validity. Pearson’s correlation was used to assess concurrent validity. Cronbach’s alpha was utilized to ascertain the internal consistency reliability. Lastly, confirmation factor analysis was used to evaluate the exploratory factor analysis model fit.Results: During the translation and adaptation process, all 55 items were retained with some detailed modifications. No item was found to have psychometric sensitivity problems. Eight factors were determined by exploratory factor analysis, accounting for 66.41% of the total variance. According to exploratory factor analysis and discussion with all authors, the original ten dimensions were adjusted to nine dimensions in the Chinese version. A standard Cronbach’s alpha of 0.960 and significant correlation among all items in the scale (>0.4) showed good internal consistency reliability of the tool. And, the model passed the majority of goodness-to-fit test by confirmation factor analysis Conclusions: The results showed initial satisfactory psychometric properties for the validation of the RMIC-MT care provider version. Its application in China will promote the development of people-centered integrated primary care. However, further psychometric testing is needed in multiple primary care settings with both public and private community institutes.