bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of leptin and adiponectin with incident type 2 diabetes and interactions among African Americans: the Jackson Heart Study
Authors: Bidulescu Aurelian , Dinh Paul C. , Sarwary Shabir , Forsyth Emily , Luetke Maya C. , King David B. , Liu Jiankang , Davis Sharon K. , Correa Adolfo
Published: February 2020

Background: Growing evidence suggests that leptin is critical for glycemic control. Impaired leptin signaling may also contribute to low adiponectin expression in obese individuals. We assessed the association of leptin and adiponectin with incident type 2 diabetes (T2D), their interactions with sex and obesity status, and mediation by insulin resistance.Methods: Study participants from the Jackson Heart Study, a prospective cohort of adult African Americans in Jackson, Mississippi, included those free of T2D at the baseline Exam 1. Incident T2D was defined as new cases at Exam 2 or Exam 3. We created separate Cox regression models (hazard ratios per log-transformed ng/mL of leptin and adiponectin) with and without insulin resistance, HOMA-IR. Mediation by insulin resistance was analyzed. Several interactions were assessed, including by sex, HbA1c, and obesity.Results: Among 3,363 participants (mean age 53 years, 63% women), 584 developed incident T2D. Leptin was associated with incident T2D when modeled without HOMA-IR (HR=1.29, 95% CI=1.05-1.58). Among men, this positive association between leptin and T2D was significant (HR=1.33, 95% CI=1.05-1.69), but it was nonsignificant among women (HR=1.24, 95% CI=0.94-1.64); statistical interaction with sex was nonsignificant (p=0.65). The associations in all participants and in men were nullified by HOMA-IR (HR=0.99, 95% CI=0.80-1.22; HR=1.00, 95% CI=0.78-1.28, respectively), indicating mediation through insulin resistance (proportion mediated: 1.04), and were not observed in abdominally obese participants. Adiponectin was inversely associated with T2D even after adjustment for HOMA-IR in women (HR=0.68, 95% CI=0.55-0.84), but not in men (HR=0.80, 95% CI=0.62-1.04). The inverse association was present only among abdominally obese participants, and persisted after adjustment for HOMA-IR.Conclusions: Among African Americans in the Jackson Heart Study the association of leptin with incident T2D was explained by HOMA-IR. The association of leptin and incident T2D was mediated by insulin resistance and observed only among abdominally non-obese. Differences by sex appeared: men showed a significant association mediated by insulin resistance. Among abdominally obese participants, adiponectin was inversely associated with incident T2D even after adjustment for HOMA-IR.
Immunogenicity analysis of conserved fragments in Plasmodium ovale species merozoite surface protein 4
Authors: Juliette Uwase , Chu Ruilin , Kassegne Kokouvi , Lei Yao , Shen Feihu , Fu Haitian , Sun Yifan , Xuan Yinghua , Cao Jun , Cheng Yang
Published: February 2020

Background: There is an urgent need for an effective vaccine to control and eradicate malaria, one of the most serious global infectious diseases. Plasmodium merozoite surface protein 4 (MSP4) has been listed as a blood-stage subunit vaccine candidate for malaria. Plasmodium ovale species (spp.) infection is also a source of malaria burden in tropical regions where it is sometimes mixed with other Plasmodium species. However, little is known about P. ovale spp. MSP4.
Methods: The msp4 gene was amplified through polymerase chain reaction using genomic DNA extracted from blood samples of 46 patients infected with P. ovale spp. and amplified products were sequenced. Open reading frames predicted as immunogenic peptides consisting of 119 and 97 amino acids of P. ovale curtisi MSP4 (PocMSP4) and P. ovale wallikeri MSP4 (PowMSP4), respectively, were selected for protein expression. Recombinant proteins (rPoMSP4) were expressed in Escherichia coli, purified, analyzed, and immunized in BALB/c mice. The specificity of anti-MSP4-immunoglubulin (Ig) G antibodies was evaluated by Western blot and enzyme-linked immunosorbent assays, and cellular immune responses were analyzed via lymphocyte proliferation assays.
Results: Full peptide sequences of PocMSP4 and PowMSP4 were completely conserved in all clinical isolates, except in the epidermal growth factor-like domain at the carboxyl terminus where only one mutation was observed in one P. ovale wallikeri isolate. Furthermore, we successfully expressed the truncated pocmsp4 and powmsp4 and purified as ~32 kDa proteins. Our results showed that PocMSP4 and PowMSP4 induced high antibody responses with end-point titers ranging from 1:10,000 to 1:2,560,000 in all immunized mouse groups and with high IgG avidity to PocMSP4 (80.5%) and PowMSP4 (92.3%). Furthermore, rPocMSP4 and rPowMSP4 cross-reacted with anti-PowMSP4-specific or anti-PocMSP4-specific antibodies. Additionally, anti-PoMSP4 IgG antibodies showed broad immuno-specificity in reacting against rPoMSP1 and rPoAMA1. Lastly, PocMSP4- and PowMSP4-immunized mice induced cellular immune responses with PocMSP4 (36%) and PowMSP4 cells (15.8%) as observed through splenocyte proliferation assays.
Conclusion: Our study suggested conservation in PoMSP4 protein sequences and high immunogenicity was observed in rPoMSP4. Furthermore, PocMSP4- and PowMSP4-immunized mice induced cellular immune responses, suggesting that both humoral and cellular immune responses play crucial roles in the protection against any antigen.
Network-based identification of biomarkers for colon adenocarcinoma
Authors: Hu Fuyan , Wang Qing , Yang Zhiyuan , Zhang Zeng , Liu Xiaoping
Published: February 2020

As one of the most common cancers with high mortality in the world, we are still facing a huge challenge in the prevention and treatment of colon cancer. In this study, we firstly constructed a functional network for colon adenocarcinoma (COAD) by using a sample-specific network (SSN) method which can construct individual-specific networks based on gene expression profiles of a single sample. The results of classification and enrichment analysis showed that the identified genes could be used as diagnosis biomarkers. Finally, 12 functional genes and 13 functional interactions in the functional network could serve as prognosis biomarkers since they were associated with the survival rate of COAD.
Collaborative subcellular compartmentalization to improve GPP utilization and boost sabinene accumulation in Saccharomyces cerevisiae
Authors: Jia Hongjie , Chen Tianhua , Qu Junze , Yao Mingdong , Xiao Wenhai , Wang Ying , Li Chun , Yuan Yingjin
Published: February 2020

Background Monoterpenes and their derivatives play an important role as flavorings, perfume additives, pharmaceuticals and advanced biofuels. GPP (geranyl diphosphate) is the direct precursor to biosynthesize this class of products. The present study for monoterpenes synthesis in yeast focused on manipulation of metabolic flux to improve GPP supply. However, if the subcellular distribution of GPP and monoterpene synthase were not coincided with each other, it would be hard to well utilize GPP, leading to a waste of carbon sources.Results Herein, we took sabinene production in Saccharomyces cerevisiae as an instance, and confirmed the location of N-truncated sabinene synthase (t34SabS1) in yeast cytosol (C). We also revealed the existence of GPP pools in organelles [such as lipid monolayer membrane-bound peroxisomes (P) and bilayer membrane-bound mitochondria (M)] beside cytosol. In order to minimize the loss of GPP, an engineering strategy was proposed to coordinated compartmentalization of sabinene synthase. Initially, expression of t34SabS1 in an ERG20-downregulated host only obtained 19.4 mg/L sabinene. Combined targeting t34SabS1 into CM (cytosol and mitochondria) increased sabinene production to 64.6 mg/L. This titer was significantly higher than those generated by harnessing other combinations of subcellular locations ( i.e. CP, PM and even CPM). Further overexpression of the genes involved in mitochondria morphology uncovered four novel molecular targets ( i.e. FIS1 , LSB3 , MBA1 and AIM25 ) associating with sabinene output. Especially, overexpression of AIM25 enhanced the sabinene production to 90.4 mg/L. Eventually, integrating all above engineered genes into host chromosome achieved 154.9 mg/L of sabinene.Conclusions The engineering approaches of this study improve GPP utilization and boost sabinene accumulation almost 60-fold of the original titer. This research highlights the strategy of organelle engineering to improve precursor utilization and to enhance the compartmentalized pathway. It also sets a good reference to synthesize other valuable monoterpenes and their derivatives in eukaryotic hosts.
Information communication texnolgy for monitoring of a prenosological state of the population health 
Authors: Abdumanonov Akhrorjon , Karabaev Muhammadjon
Published: February 2020

Background: The article describes the development of an uninterrupted functioning technology for remote automated monitoring of the prenosological level of individual health, which allows optimizing the medical non-invasive mass examination of the population. Methods:In order to provide their functioning by using information and communication technologies, mobile communications, automated remote exchange methods, accumulation, storage of information, as well as involving medical knowledge, mathematical models and algorithms for their intellectual analysis, the opportunities have been created for the development and implementation of preventive measures that are effective mechanisms to ensure a healthy lifestyle. Results: According to the stated goal, a comprehensive monitoring of the physical, functional and clinical-somatic status of population health indicators is carried out. It provides the implementation of the functions of a comprehensive prenosological examination of citizens and the results of the surveys assess the risk of developing certain diseases; assisting in the implementation of measures to form a healthy lifestyle and reduce the spread of risk factors for noncommunicable diseases among the attached population; dynamic monitoring of the contingent of individuals at increased risk of developing the disease. The practical use of this technology helps to conduct mass prenosological examinations of the population and improve the quality of targeted, personalized prevention of risk factors and improve their health.
Therapeutic effect of acetabular fractures using the Pararectus approach combined with 3D printing technique
Authors: Zou Ruyi , Wu Min , Guan Jianzhong , Xiao Yuzhou , Chen Xiaotian
Published: February 2020

Background To explore the clinical efficacy of pararectus approach combined with 3D printing technique for the surgical treatment of partial complex acetabular fractures. Methods We retrospectively evaluated 18 (11 males and 7 females) patients with complicated acetabular fractures in the period of June 2017 to December 2018; According to judet-letenneal classification: 11 cases were of double column fracture, 6 fractures were of the anterior column with posterior half transverse, and 1 case was of "T" fracture. For all cases, 3D printing is used to print the acetabular model. Pre-bent reconstruction plates from the model were placed to fixate fractures after reduction via the pararectus approach. Results The average time of surgery was 203 min (range:135-245 min)and mean intraoperative blood loss was 1030ml(range:450-1400ml);18 patients were followed up for 12-18 months (average,14 months);One patient (5.6%) developed postoperative wound infection, and the wound completely improved by secretion culture, enhanced dressing and effective antibiotics. One patient (5.6%) developed postoperative ossifying myositis, and there are no obvious symptoms at present; all patients underwent pelvic films and pelvic CT+ three-dimensional reconstruction after surgery, suggesting that fractures reduction as well. All the acetabular fractures united after 12 to 16 weeks(average,13 weeks);According to the modified Merle d’Aubigne and Postel scoring system to assess the hip function: excellent in 13 cases (72.2%), good in 3 cases(16.7%) and fair in 2 cases(11.1%). Conclusions In the treatment of partial complex acetabular fractures, the pararectus approach combined with 3D printing technique can achieve effective reduction and fixation, decrease intraoperative hemorrhage, shorten operation time and the internal fixation position can be properly adjusted during the operation by looking directly at the model.
Preliminary clinical and radiographic outcomes of oblique lateral interbody fusion combined with percutaneous transforaminal endoscopic discectomy for degenerative lumbar disease accompanied by prolapsed disc herniation
Authors: Lou Chao , Liu Shijie , Yu Weiyang , Liu Feijun , Chen Zhenzhong , Gao Jiawei , Pan Bin , He Dengwei
Published: February 2020

Objective: To investigate the preliminary clinical and radiographic outcomes of oblique lateral interbody fusion (OLIF) combined with percutaneous transforaminal endoscopic discectomy (PTED) for the degenerative lumbar disease accompanied by prolapsed disc herniation.Methods: From March 2016 to December 2018, 15 patients with degenerative lumbar spondylolisthesis, lumbar spine instability or lumbar spinal stenosis accompanied by prolapsed disc herniation were underwent OLIF combined with PTED in our spine surgery center, including 6 males and 9 females, the mean age was 61.4±7.1 years. Clinical results, radiological parameters, and related complications were collected and analyzed.Results: All patients firstly received PTED with local anesthesia and then underwent OLIF with general anesthesia. All patients were followed up for an average of 14.6±3.7 months. Mean preoperative visual analog scale scores and Oswestry Disability Index scores were significantly improved postoperatively (P<0.05). The radiographic results include the intervertebral disc height, vertical diameter of intervertebral foramen, spinal canal anteroposterior diameter, segment angle and lumbar lordosis angle were significantly improved postoperatively, respectively (P<0.05). None major implant-related and other severe complications were happened.Conclusions: OLIF combined with PTED can successfully enables direct neural decompression without posterior decompressive procedures and might be an alternative minimally invasive surgical option for properly selected patients.
Identifying the novel key genes in renal cell carcinoma by bioinformatics analysis and cell experiments
Authors: Chen Yeda , Gu Di , Wen Yaoan , Yang Shuxin , Duan Xiaolu , Lai Yongchang , Yang Jianan , Yuan Daozhang , Khan Aisha , Wu Wenqi , Zeng Guohua
Published: February 2020

Background: Although major driver gene have been identified, the complex molecular heterogeneity of renal cell cancer (RCC) remains unclear. Therefore, more relevant genes need to be identified to explain the pathogenesis of renal cancer.Methods: Microarray datasets GSE781, GSE6344, GSE53000 and GSE68417 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by employing GEO2R tool, and function enrichment analyses were performed by using DAVID. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. Survival analysis was performed using GEPIA. Differential expression was verified in Oncomine. Cell experiments (cell viability assays, transwell migration and invasion assays, wound healing assay, flow cytometry) were utilized to verify the roles of the hub genes on the proliferation of kidney cancer cells (A498 and OSRC-2 cell lines). Results: A total of 215 DEGs were identified from four datasets. Six hub gene (SUCLG1, PCK2, GLDC, SLC12A1, ATP1A1, PDHA1) were identified and the overall survival time of patients with RCC were significantly shorter. The expression levels of these six genes were significantly decreased in six RCC cell lines(A498, OSRC-2, 786-O, Caki-1, ACHN, 769-P) compared to 293t cell line. The expression level of both mRNA and protein of these genes were downregulated in RCC samples compared to those in paracancerous normal tissues. Cell viability assays showed that overexpressions of SUCLG1, PCK2, GLDC significantly decreased proliferation of RCC. Transwell migration, invasion, wound healing assay showed overexpression of three genes(SUCLG1, PCK2, GLDC) significantly inhibited the migration, invasion of RCC. Flow cytometry analysis showed that overexpression of three genes(SUCLG1, PCK2, GLDC) induced G1/S/G2 phase arrest of RCC cells. Conclusion: Based on our current findings, it is concluded that SUCLG1, PCK2, GLDC may serve as a potential prognostic marker of RCC.
Identification of genes associated with lymph node metastasis in papillary thyroid carcinoma by weighted gene co-expression network analysis
Authors: Liu Zhen , Guo Mingyue , Wang Lidong , Liu Chenxi , Huang Yonglian
Published: February 2020

Background: Thyroid cancer (TC) is the most common endocrine malignant tumor, in which thyroid papillary carcinoma has the highest incidence of (PTC). However, some patients will relapse or even die because of tumor metastasis. Therefore, for the treatment of PTC, it is extremely important to find gene targets and their potential biomarkers. We obtained the RNA sequence matrix of PTC and the clinical information of the corresponding samples in the TCGA database. Methods: The weighted gene co-expression network analysis was utilized to construct the co-expression network, and the gene modules with high correlation among genes and the relationship between genes and clinical traits were established. Results: We utilized the screened 5271 genes for WGCNA analysis and constructed 19 gene modules. Genes in the magenta module with the highest correlation with lymph node metastasis were selected for enrichment analysis to construct a protein interaction network. After that, we selected 12 hub genes of this module by using the intersection of the differential genes in the data set of cytoscape and GEO database. 12 genes were visualized in GEPIA. After that, the gene expression was verified on the oncomine page, and 8 genes with high correlation with TC lymph metastasis (ARNTL, CDH3, CLDN1, COL8A1, COL8A2, IL1RAP, LPAR5) were screened. Conclusion: In this paper, the differential genes are screened by combining the datasets of TCGA, GEO and Oncomine in TC for the first time, which makes the screened differential genes have more biological significance. These genes may offer new insights for the treatment of PTC lymph node metastasis.
Novel cyclic peptides from lethal Amanita species through a genomic approach, and major peptide toxins in the ectomycorrhizal association
Authors: Luo Hong , Zhou Shengwen , Li Xincan , Li Xuan , Chen Zuo H. , Yang Zhu L. , Li Guohong
Published: February 2020

Background: Most species in the genus Amanita are ectomycorrhizal fungi, and the cyclic peptide toxins that some species produce are notoriously deadly. In total, around 25 of these peptides were found in the fruiting bodies over the past 82 years, and whether any of them are present in the mycorrhizae is unknown. Reportedly, sequenced lethal Amanita genomes harbor a significant number of precursor genes of MSDIN family, indicating there could be a much larger capacity for cyclic peptide production in these mushrooms. However, it is largely unknown that to what extent these genes are transcribed, and further, translated into true cyclic peptides.Method: In this study, three poisonous Amanita species, A. rimosa, A. exitialis and A. subjunquillea, were sequenced through PacBio and Illumina techniques. For expression analysis, one strain of A. subjunquillea was sequenced through RNA-Seq. A genome-guided approach was adopted to identify cyclic peptides by coupling predicted toxin-biosynthetic genes with mass spectrometry (MS and MS/MS). To investigate whether any of the toxins were express in the microbiome, profiling of known major toxins was conducted on A. subjunquillea mycorrhizae via HRMS and gene cloning.Results: The resultant genomes showed significant potential to produce known and unknown cyclic peptides. Together with our 2 previously sequenced genomes, in total 37 unknown MSDIN genes were discovered. Expression of over 90% of the MSDIN genes was demonstrated in two strains of A. subjunquillea. Through the genome-guided approach, 12 MSDIN genes were found to produce true, novel cyclic peptides with no additional posttranslational modifications. When the ectomycorrhizae of A. subjunquillea were analyzed by MS, all major toxins were detected. The corresponding MSDINs for these cyclic peptides were successfully cloned directly from the mycorrhizae.Conclusions: The genome-guided approach provided a speedy method to identify cyclic peptides both in Amanita mushrooms and in the ectomycorrhizae. In this study, a significant number of novel MSDIN genes were discovered, most of which were found to be expressed in the tested species. The identification of the 12 novel cyclic peptides strongly suggests that Amanita species possess a much larger reservoir of these peptides than previously thought. This is the first report to demonstrate that the cyclic peptides in Amanita species are expressed in the mycorrhizal association. All four major toxins, α-amanitin, β-amanitin, phallacidin and phalloidin, are found to be present in the symbiosis, offering new clues to their biological function(s).
E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor
Authors: Wang Qixin , Sundar Isaac , Li Dongmei , Lucas Joseph , Muthumalage Thivanka , McDonough Samantha , Rahman Irfan
Published: February 2020

Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has conducted to understand the mechanism of toxicological and pulmonary effects of e-cigs. We hypothesized that sub-chronic exposure of e-cigs induced inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChR α7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial-cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lungs were collected for determination of inflammatory responses and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased the lung influx of macrophages and T-lymphocytes, and the levels of pro-inflammatory cytokines, while nAChR α7 knockdown blocked the inflammatory responses. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8, and MMP9, in both sex mice were altered at both protein and gene levels when WT mice were exposed to PG alone in a sex-dependent manner. Moreover, MMP12 increased significantly in male mice exposed to PG with or without nicotine in a nAChR α7 dependent manner. Additionally, the abundance of ECM proteins, such as collagen and fibronectin, was significantly altered after sub-chronic e-cig exposure with or without nicotine in a sex-dependent manner, but nAChR α7 independent manner. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChR α7 in a sex-dependent manner.
Construction of miRNA-mRNA regulatory network and prognostic signature in endometrial cancer
Authors: Liu Jinhui , Sun Rui , Nie Sipei , Yang Jing , Li Siyue , Jiang Yi , Cheng wenjun
Published: February 2020

Background: Many studies have well supported the close relationship between miRNA and endometrial cancer (EC). This bioinformatic study, compared with other similar studies, confirmed a new miRNA-mRNA regulatory network to investigate the miRNA-mRNA regulatory network and the prognostic biomarkers in EC. Methods: We downloaded RNA-seq and miRNA-seq data of endometrial cancer from the TCGA database, and then we used EdegR package to screen differentially expressed miRNAs and mRNAs (DE-miRNAs and DE-mRNAs). The differentially expressed genes (DEGs) were identified and their functions were predicted using the functional and pathway enrichment analysis. Protein–protein interaction (PPI) network was established using STRING database, and the hub genes were verified by Gene Expression Proﬁling Interactive Analysis (GEPIA). Then, we constructed a regulatory network of EC-associated miRNAs and hub genes by Cytoscape, and determined the expression of unexplored miRNAs in EC tissues and normal adjacent tissues by quantitative Real-Time PCR (qRT-PCR). A prognostic signature model and a predictive nomogram were constructed. Finally, we explored the association between the prognostic model and the immune cell infiltration. Results: 11531 DE-mRNAs and 236 DE-miRNAs, as well as 275 and 118 candidate DEGs for upregulated and downregulated DE-miRNAs were screened out. These DEGs were significantly concentrated in FOXO signaling pathway, cell cycle and Focal adhesion. Among the 20 hub genes identified, 17 exhibited significantly different expression compared with normal tissues. The miRNA-mRNA network included 5 downregulated and 13 upregulated DE-miRNAs . qRT-PCR proved that the expression levels of miRNA-18a-5p, miRNA-18b-5p, miRNA-449c-5p and miRNA-1224-5p and their target genes, NR3C1, CTGF, MYC, and TNS1 were consistent with our predictions. Univariate and multivariate Cox proportional hazards regression analyses of the hub genes revealed that NR3C1, EZH2, and GATA4 showed a significant prognostic value. We identified the three-gene signature as an independent prognostic indicator for EC ( p =0.022，HR=1.321, 95% CI: 1.041-1.675) and these genes were closely related to eight types of immune infiltration cells. Conclusion: Our study revealed the mechanisms of the carcinogenesis and progression of EC.
Sarcopenic Obesity in Facioscapulohumeral Muscular Dystrophy
Authors: Vera Kathryn , McConville Mary , Kyba Michael , Keller-Ross Manda
Published: February 2020

Background: Sarcopenic obesity has been observed in people with neuromuscular impairment, and is linked to adverse health outcomes.It is unclear, however, if sarcopenia obesity develops in adults with facioscapulohumeral muscular dystrophy (FSHD). Methods: This research was designed to determine if adults with FSHD meet criteria for sarcopenic obesity (appendicular lean mass index (ALMI) scores of <7.26 kg/m2 or 5.45 kg/m2; % body fat of >28% or 40% in men/women). Ten people with FSHD (50±11 years, 2 females) and ten age/sex-matched controls (47±13 years, 2 females) completed one visit, which included a full-body dual-energy x-ray absorptiometry (DXA) scan. Regional and whole body total mass (g), fat mass (FM, (g, %)), and lean mass (LM, (g, %)) were collected; body mass index (BMI, kg/m2) and and sarcopenia measures (appendicular lean mass (sum of arm/leg lean mass, ALM (kg)), ALMI (kg/m2)) were computed. Results: Although total body mass was similar between adults with FSHD and controls (84.5±12.9 vs. 81.8±13.5 kg, respectively; p=0.65), the proportion of mass due to fat was much higher in FSHD, with many individuals having >50% mass due to fat (means: 40.8±7.0 vs. 27.9±7.5%; p=0.001). ALM volume was 23% lower and ALMI was 27% lower in FSHD (p<0.01). Whole body LM trended to be lower in FSHD vs. controls (p=0.05) and arm and leg LM were both lower in FSHD compared with controls (p<0.05). Furthermore, the % LM was 18% lower in FSHD vs. controls (p=0.001). FSHD participants exhibited greater total body FM (p<0.01), total leg fat mass (p<0.001), and but similar total arm fat mass (p=0.09). Conclusions: These data demonstrate that people with FSHD, although similar in total body mass to controls, commonly meet the definition of sarcopenic obesity, with significant consequences for quality of life, and implications for disease management.
Uptake and acceptability of human papillomavirus self-sampling in rural and remote Aboriginal communities: Evaluation of a nurse-led community engagement model
Authors: Dutton Tegan , Marjoram Jo , Burgess Shellie , Campbell Laurinne , Vail Anne , Callan Nichole , Jacob Sunil , Hawkes David , Saville Marion , Bailey Jannine
Published: February 2020

Background Aboriginal women experience disproportionately higher rates of cervical cancer mortality yet are less likely to participate in screening for early detection. This study sought to determine whether a community-based HPV self-sampling service model can effectively recruit never-screened and under-screened Aboriginal women to participate in cervical cancer screening; assess the clinical outcomes; and explore the acceptability of the model from the perspective of the participants. Methods Aboriginal women aged 25-69 years of age were recruited from eight rural and remote communities in New South Wales, Australia to participate in HPV self-sampling via a community-based service model. Outcome measures were: number of women screened by HPV self-sampling, their prior cervical screening status (under-screened or never-screened), clinical outcomes and participation in follow-up pathways of care, and satisfaction with the service model. Results In total, 215 women conducted a HPV self-sampling test and 200 evaluation surveys were completed. One-fifth of participants (n=46) were never-screened and one-third (n=69) were under-screened. Many were unsure of their screening status. Nine women were HPV 16/18 positive and eight had completed all follow up by the conclusion of the study. A further 30 women were HPV other positive of which 14 had completed follow up at the conclusion of the study. Satisfaction with the HPV self-sampling kit, the process of self-sampling and the service model was high (>92% satisfied on all items). Many women had difficulty understanding their official HPV results and placed high importance on the nurse explaining it to them. Conclusions A community-based service model that respects Women’s Business can effectively recruit under-screened and never-screened Aboriginal women to complete cervical cancer screening. Furthermore, this service model supports them to complete recommended follow-up care and engage with their local existing health services.
Cost-Effectiveness Analysis Of Text Messaging To Support Health Advice For Smoking Cessation
Authors: Cobos-Campos Raquel , Mar Javier , Apiñaniz Antxon , de Lafuente Arantza Sáez , Parraza Naiara , Aizpuru Felipe , Orive Gorka
Published: February 2020

Background: Smoking in one of the most serious public health problems. It is well known that it constitutes a major risk factor for chronic diseases and the leading cause of preventable death worldwide.Due to high prevalence of smokers, new cost-effective strategies seeking to increase smoking cessation rates are needed. Methods:We performed a cost-effectiveness analysis comparing two treatments: health advice provided by general practitioners and nurses in primary care, and health advice reinforced by sending motivational text messages to patients’ mobile phones. A Markov model was used in which patients transitioned between three mutually exclusive health states (smoker, former smoker and dead) after 6-month cycles. We calculated the cost-effectiveness ratio associated with the sending of motivational messages throughout a patient’s life. Health care and society perspectives (separately) was adopted. Costs taken into account were direct health care costs and direct health care cost and costsfor lost productivity, respectively.Additionally, deterministic sensitivity analysis was performed modifying the probability of smoking cessation with each option. Results:Sending of text messages as a tool to support health advice was found to be cost-effective as it was associated with increases in costs of €7.4 and €1,327 per QALY gained for men and women respectively from a healthcare perspective, significantly far from the published cost-effectiveness threshold. From a societal perspective, the combined programmed was dominant. Conclusions: Sending text messages is a cost-effective approach. These findings support the implantation of the combined program across primary care health centres.
Genetic testing for the diagnosis and classification of joint hypermobility: a case report of 15 patients
Authors: Zeng Lanlan , Zhang Li , Linpeng Siyuan , Li Zhuo , Liang Desheng , Wu lingqian
Published: February 2020

Background Joint hypermobility (JH) is used to define the capability of a joint moving passively or actively beyond normal limits along physiological axes, which can be influenced by multiple factors (genetic factors, age, gender, weight and training), and the accurate incidence is unclear. In this study, we aimed to identify the genetic cause of JH in 15 patients from seven unrelated Chinese families. Results We identified seven pathogenic/likely-pathogenic variants: two novel mutations, in the COL6A2 and CHST14 genes, and five reported mutations in the COL11A1 , NALCN , GALNS and COL5A1 respectively. Based on the genetic testing, we were able to diagnose the precise condition for each patient: Stickler syndrome in Proband 1, the Ullrich congenital muscular dystrophy in proband 2, CLIFAHDD syndrome in proband 3, Mucopolysaccharidosis IVA in proband 4, Classical Ehlers-Danlos syndrome (EDS) in proband 5, and Musculocontractural EDS in proband 6. Moreover, this is the first time to describe the Musculocontractural EDS caused by CHST14 in China. Though the expression of the mRNA and protein have not significantly changed, we speculated that the mutation of the CHST14 may affect the sulfotransterase activity of the protein. Conclusions The diagnosis in all probands except proband 6 and 7 were corrected following genetic analysis, indicating the importance of the genetic testing in the diagnosis and classification of JH cases. Our findings also offered insight into the genotype-phenotypes relationship and expanded the mutation spectrum of the disease-causing genes in JH.
Association between physical activity and conversion from mild cognitive impairment to dementia
Authors: Kim Yeo Jin , Han Kyung-Do , Baek Min Seok , Cho Hanna , Lyoo Chul Hyoung
Published: February 2020

Background Physical activity has been suggested to prevent the conversion of mild cognitive impairment (MCI) to dementia in patients. We investigated the association between the continuance and regularity of physical activity and the risk of developing dementia in patients with MCI. Methods We analyzed data for 247,149 individuals in the National Health Insurance Service (NHIS) cohort who were enrolled between January 1, 2009 and December 31, 2015. The patients were divided into four groups: those who did not engage in physical activity consistently (Never-PA group), those who initiated physical activity (Initiation-PA group), those who ceased physical activity (Withdrawal-PA group), and those who performed physical activity consistently (Maintenance-PA group). We also divided the patients into two groups: those who engaged in physical activity irregularly (Irregular-PA) and those who undertook physical activity regularly (Regular-PA). Results When the risk for the Never-PA group was set as the benchmark (ref=1), the Maintenance-PA group had the lowest incidence of Alzheimer’s disease (AD) compared to the other groups (HR= 0.82, 95% CI 0.79-0.86). The AD risk of Initiation-PA group (HR = 0.89, 95% CI 0.85-0.93) and Withdrawal-PA group (HR = 1, 95% CI 0.96-1.04) was still lower than the Never-PA group. In addition, compared to the Irregular-PA group, the Regular-PA group had a 15% reduced risk for developing AD. Conclusions Continued regular physical activity in patients with MCI is associated with a protective effect against developing AD. Moreover, ceasing physical activity could halt this protective effect.
Purification and Identification of Surface Active Amphiphilic Candidates Produced by Geotrichum candidum MK880487 Possessing Antifungal Property
Authors: Eldin Ahmed Mohy , Kamel Zeinat , Hossam Nermeen
Published: February 2020

The authors have requested that this preprint be removed from Research Square.
Higher Plasma Cystatin C is associated with Mortality after Acute Respiratory Distress Syndrome: Findings from a Fluid and Catheter Treatment Trial (FACTT) Substudy
Authors: Hendrickson Carolyn M. , Kwong Yuenting Diana , Belzer Annika G , Shlipak Michael G , Matthay Michael A , Liu Kathleen Dori
Published: February 2020

Background: Cystatin C is a well validated marker of glomerular filtration rate in chronic kidney disease. Higher plasma concentrations of cystatin C are associated with worse clinical outcomes in heterogenous populations of critically-ill patients and may be superior to creatinine in identifying kidney injury in critically-ill patients. We hypothesized that elevated levels of plasma cystatin C in patients with Acute Respiratory Distress Syndrome (ARDS) would be associated with mortality risk. Methods: In a retrospective study, cystatin C was measured by nephelometry on plasma obtained at enrollment from 919 patients in the Fluid and Catheter Treatment Trial. Multivariable logistic regression was performed testing the association between quartiles of cystatin C and 60-day mortality. Analyses were stratified by Acute kidney injury (AKI) status identified in the first 7 days after enrollment by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results: Cystatin C was significantly higher among those patients who died compared to those who survived to 60 days [1.2 (0.9 – 1.9) mg/L vs. 0.8 (0.6 – 1.2) mg/L, p <0.001]. Compared to the lower three quartiles, subjects in the highest quartile of cystatin C had a significantly higher odds of death at 60 days [OR 1.8 (1.2-2.6), p=0.003 in adjusted analyses]; the odds of death incrementally rose in higher cystatin C quartiles compared to the lowest quartile (OR 1.1, 1.8, and 2.5). In adjusted analyses stratified by AKI status, compared to subjects in the lower three quartiles, subjects in the highest quartile of cystatin C with AKI had a significantly higher odds of death at 60 days both in participants with AKI [OR 1.6 (1.0-2.4), p=0.048] and those without AKI [OR 2.4 (1.2-5.0), p=0.017]. In adjusted analyses, there was no significant association between sex-stratified baseline creatinine quartiles and mortality. Conclusions: Higher plasma levels of cystatin C on enrollment were strongly associated with mortality at 60-days in patients with ARDS with and without AKI identified by creatinine-based definitions. Compared to creatinine, cystatin C may be a better biomarker of kidney function in patients with ARDS and therefore identify patients with multiple organ failure at higher risk of death.
The Impact of Interval Training on Cardiorespiratory Fitness, Body Composition, Physical Fitness, and Metabolic Parameters in Older Adults: a Systematic Review and Meta-Analysis
Authors: Wu Zhi-Jian , Wang Zhu-Ying , Gao Hao-En , Zhou Xian-Feng , LI Fang Hui
Published: February 2020

Background: This review and meta-analysis aimed to evaluate the effects of high-intensity interval training (HIIT) on cardiorespiratory fitness, body composition, physical fitness, and health-related outcomes in older adults. Methods: Four electronic databases (PubMed, Scopus, Medline, and Web of Science) were searched (until Oct 2019) for randomized trials comparing the effect of HIIT on physical fitness, metabolic parameters, and cardiorespiratory fitness in older adults. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of the included studies; Stata 14.0 software was used for statistical analysis.Results: HIIT significantly improved the maximum rate of oxygen consumption (VO 2max ) compared with a moderate-intensity continuous training (MICT) protocol (HIIT vs. MICT: weighted mean difference = 2.04, 95% confidence interval: 1.01-3.07, p < 0.001). Additional subgroup analyses determined that training periods > 12 wks, training frequencies of 2 sessions/wk, session lengths of 40 min, 6 sets and repetitions, training times per repetition of > 60 s, and rest times of < 90 s are more effective for VO 2max . Conclusions:This systematic review and meta-analysis showed that HIIT induces favorable adaptions in cardiorespiratory fitness, physical fitness, muscle power, cardiac contractile function, and citrate synthase activities in older individuals which may help to maintain aerobic fitness and slow down the process of sarcopenia.
A Scoping Review of Pre-hospital Technology to Assist Ambulance Personnel with Patient Diagnosis or Stratification during the Emergency Assessment of Suspected Stroke
Authors: Lumley Hannah Amanda , Flynn Darren , Shaw Lisa , McClelland Graham , Ford Gary A. , White Phil , Price Christopher
Published: February 2020

Background: Pre-hospital identification of key subgroups within the suspected stroke population could reduce delays to emergency treatment. We aimed to identify and describe technology with existing proof of concept for diagnosis or stratification of patients in the pre-hospital setting. Methods: A systematic electronic search of published literature (from 01/01/2000 to 06/06/2019) was conducted in five bibliographic databases. Two reviewers independently assessed eligibility of studies or study protocols describing direct stratification methods (portable imaging/biomarkers) or facilitative technology (telemedicine) used by ambulance personnel during the assessment of suspected stroke. Eligible descriptions involved use of technology during the actual assessment of suspected stroke to provide information directly to ambulance personnel in the prehospital setting. Due to study, intervention and setting heterogeneity there was no attempt at meta-analysis. Results: 2887 articles were screened for eligibility, 19 of which were retained. Blood biomarker studies (n=2) were protocols of prospective diagnostic accuracy studies, one examining purines and the other a panel of known and novel biomarkers for identifying stroke sub-types (versus mimic). No data were available on diagnostic accuracy or patient health outcomes. Portable imaging studies (n=2) reported that an infrared screening device for detecting haemorrhages yielded moderate sensitivity and poor specificity in a small study, whilst a dry-EEG study to detect large vessel occlusion in ischaemic stroke has not yet reported results. Fifteen evaluations of pre-hospital telemedicine were identified (12 observational and 3 controlled comparisons) which all involved transmission of stroke assessment data from the pre-hospital setting to the hospital. Diagnosis was generally comparable with hospital diagnosis and most telemedicine systems reduced time-to-treatment; however, it is unknown whether this time saving translated into more favourable clinical outcomes. Telemedicine systems were deemed acceptable by clinicians. Conclusions: Pre-hospital technologies to stratify suspected stroke into clinically important subgroups may be feasible but insufficient evidence precludes recommendations on their routine use in the pre-hospital setting. Multi-centre diagnostic accuracy studies and clinical utility trials combining promising technologies are warranted. Keywords: Stroke; pre-hospital; stratification; diagnosis; technology; biomarkers; imaging; telemedicine; ambulance; paramedic.
Treatment outcomes and prognostic factors for non- malignancy associated secondary hemophagocytic lymphohistiocytosis in children
Authors: Pan Hua , Wang Gaoyan , Guan Enben , Song Liang , Song Aiqin , Liu Xiaodan , Yi Zhi , Sun Li-rong
Published: February 2020

Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome that requires prompt diagnosis and appropriate treatment. A risk-stratification model that could be used to identify high-risk pediatric patients with HLH who should be considered for second-line therapies, including salvage regimens and allogeneic hematopoietic cell transplantation (HCT), was developed.Methods: The medical records of 88 pediatric patients (median age 1.4 years, range 0.2-15 years) with non-malignancy associated secondary HLH were retrospectively reviewed. Treatment strategies included dexamethasone, etoposide, and cyclosporine. Results:Survival analysis showed patients with Epstein-Barr virus(EBV)-HLH experienced better 5-year overall survival (OS) than patients with HLH due to other infections and unknown causes, autoimmune disease, or immunodeficiency (80% vs. 77%, 65%, 11%, p<0.001). On multivariate analysis, among all patients, non-response at 8 weeks was the most powerful predictor of poor OS. When treatment response was excluded, hemoglobin <60g/L and albumin <25g/L at diagnosis were associated with poor OS. In patients with EBV-HLH, hemoglobin <60g/L at diagnosis was associated with poor OS. A prognostic risk score was established and weighted based on hazard ratios calculated for three parameters measured at diagnosis: hemoglobin <60g/L (2 points), platelets <30x109/L (1 point), albumin < 25g/L (2 points). Five-year OS of low-risk (score 0-1), intermediate-risk (score 2), and poor-risk (score ≥3) patients were 88%, 38%, and 22%, respectively (p<0.001).Conclusions: These findings indicate that clinicians should be aware of predictive factors at diagnosis and consider 8-week treatment response to identify patients with high-risk of disease progression and the need for second-line therapy and allogeneic HCT.
Serum miR-27a is a biomarker for prognosis of non-small cell lung cancer patients receiving chemotherapy
Authors: Xie Erfu , Ji Yazhou , Lin Mingxin , Jin Yuexinzi , Zhang Shichang , Huang Lei , Sun Ruihong , Wang Fang , Pan Shiyang
Published: February 2020

Background: Previous studies suggest that miR-27a may be involved in cancer development and progression. The purpose of this article was to investigate the clinical value of miR-27a in evaluating the prognosis of chemotherapy in NSCLC patients.Methods: The apoptosis rates of the SPC-A1 cells treated with optical cisplatin were determined by flow cytometry in different time. Simultaneously, the expression of miR-27a in supernatants and cells were detected. Fifty-two newly diagnosed cases of NSCLC patients were recruited. All patients received the Gemcitabine and Cisplatin as the first-line chemotherapy and Docetaxel as the second-line chemotherapy. At the end of every chemotherapy cycle, a therapeutic evaluation was performed according to the RECIST criteria. The expression of serum miR-27a was detected in each cycle.Results: After treated with cisplatin of 2.5μg/mL, the apoptosis rates of the SPC-A1 cells were significantly greater than the paired untreated control groups in 12, 24, 48 and 72 h, the expression of miR-27a in supernatants and cells also showed consistent changes with the apoptosis and displayed a time-dependent change. The chi-square test showed the elevation of miR-27a after chemotherapy was more common in patients with PR compared with the patients who achieved NR (61.5% vs 30.8%, P=0.026). Kaplan-Meier survival analysis indicated that patients with decreased miR-27a have poor outcome compared with those with increased miR-27a patients (P=0.0051). Furthermore, dynamic changes with serum miR-27a with gradual increasing trend during chemotherapy predicted a good prognosis.Conclusions: Serum miR-27a may be an independent predictor for prognosis of NSCLC.