bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Non-Coding RNA BCYRN1 Exerts an Oncogenic Rrole in Colorectal Cancer through Regulating miR-204-3p/KRAS Axis
Authors: Yang Liu , Zhang Yinan , Bao Jun , Feng Ji-Feng
Published: June 2020

Background: It has been well documented that long non-coding RNAs (lncRNAs) regulate numerous characteristics of cancer, including proliferation, migration, metastasis, apoptosis, even metabolism. LncRNA BCYRN1 (BCYRN1) is a newly identified brain cytoplasmic lncRNA with 200-nucleotide, which was discovered highly expressed in tumor tissues of cancer, including hepatocellular carcinoma, gastric cancer and lung cancer. However, the roles of BCYRN1 in colorectal cancer (CRC) remain obscure. This study was designed to reveal the acts of BCYRN1 in the occurrence and progression of CRC. Methods: RT-PCR was used to detect the expression level of BCYRN1 in tumor tissues and CRC cell lines. Knock down BCYRN1 in CRC cells, evaluate cell proliferation changes by CCK-8 test, EdU test, and Ki-67 and PCNA expression; evaluate cell migration and invasion changes by wound healing assay, Transwell assay and invasion-related protein expression . Through flow cytometry analysis to assess whether BCYRN1 regulates apoptosis of CRC cells. The dual luciferase reporter gene detects the competitive binding of BCYRN1 to miR-204-3p. In vivo experiments to evaluate the effect of BCYRN1 on tumor development. TargetScan analysis and dual luciferase reporter gene detect the target gene of miR-204-3p. Rescue experiments verified the effect of BCYRN1 on CRC by regulating the effect of miR-204-3p on KRAS.Results: We found that compared with normal tissues and human intestinal epithelial cells (HIECs), BCYRN1 levels were significantly increased in tumor tissues and cell lines of CRC. We further determined that knockdown of BCYRN1 inhibited proliferation, migration, invasion, and promoted apoptosis of CRC cells. In addition, bioinformatics analysis and dual luciferase reporter assay showed that BCYRN1 served as a competitive endogenous RNA (ceRNA) to regulate the development of CRC through competitively binding to miR-204-3p. Further studies proved that overexpression of miR-204-3p reversed the effects of BCYRN1 on CRC. Next, TargetScan analysis and dual luciferase reporter assay indicated that KRAS was a target gene of miR-204-3p and negatively regulated by miR-204-3p. A series of rescue experiments showed that BCYRN1 affected the occurrence and development of CRC by regulating the effects of miR-204-3p on KRAS. In addition, tumorigenic experiments in CRC model mice confirmed that down-regulated BCYRN1 effectively inhibited tumor growth. Conclusions: Our findings suggested that BCYRN1 plays a carcinogenic role in CRC by regulating the miR-204-3p/KRAS axis.
Hill-based Dissimilarity Indices and Null Models for Analysis of Microbial Community Assembly
Authors: Modin Oskar , Liebana Raquel , Saheb-Alam Soroush , Wilén Britt-Marie , Suarez Carolina , Hermansson Malte , Persson Frank
Published: June 2020

Background: High-throughput amplicon sequencing of marker genes, such as the 16S rRNA gene in Bacteria and Archaea, provides a wealth of information about the composition of microbial communities. To quantify differences between samples and draw conclusions about factors affecting community assembly, dissimilarity indices are typically used. However, results are subject to several biases and data interpretation can be challenging. The Jaccard and Bray-Curtis indices, which are often used to quantify taxonomic dissimilarity, are not necessarily the most logical choices. Instead, we argue that Hill-based indices, which make it possible to systematically investigate the impact of relative abundance on dissimilarity, should be used for robust analysis of data. In combination with a null model, mechanisms of microbial community assembly can be analyzed. Here, we also introduce a new software, qdiv, which enables rapid calculations of Hill-based dissimilarity indices in combination with null models.Results: Using amplicon sequencing data from two experimental systems, aerobic granular sludge (AGS) reactors and microbial fuel cells (MFC), we show that the choice of dissimilarity index can have considerable impact on results and conclusions. High dissimilarity between replicates because of random sampling effects make incidence-based indices less suited for identifying differences between groups of samples. Determining a consensus table based on count tables generated with different bioinformatic pipelines reduced the number of low-abundant, potentially spurious amplicon sequence variants (ASVs) in the data sets, which led to lower dissimilarity between replicates. Analysis with a combination of Hill-based indices and a null model allowed us to show that different ecological mechanisms acted on different fractions of the microbial communities in the experimental systems.Conclusions: Hill-based indices provide a rational framework for analysis of dissimilarity between microbial community samples. In combination with a null model, the effects of deterministic and stochastic community assembly factors on taxa of different relative abundances can be systematically investigated. Calculations of Hill-based dissimilarity indices in combination with a null model can be done in qdiv, which is freely available as a Python package (https://github.com/omvatten/qdiv). In qdiv, a consensus table can also be determined from several count tables generated with different bioinformatic pipelines.
Multiple Alu exonizations in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge
Authors: Bhattacharya Aniket , Jha Vineet , Singhal Khushboo , Fatima Mahar , Singh Dayanidhi , Chaturvedi Gaura , Dholakia Dhwani , Kutum Rintu , Pandey Rajesh , Bakken Trygve E. , Seth Pankaj , Pillai Beena , Mukerji Mitali
Published: June 2020

Background: Alu repeats contribute to phylogenetic novelties in conserved regulatory networks in primates. Exaptation of Alus in transcript isoforms could nucleate large-scale mRNA-miRNA interactions and modulate cellular outcomes. Result: Using a functional genomics approach, we report a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) that arise through exonization of 23 Alus in 3’UTR and is expressed in higher primates. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length (9kb) and is expressed in multiple cell lines. Using publicly available datasets, we demonstrate its presence in single nucleus RNA-seq of 15928 human cortical neurons (including rosehip neurons). miRanda predicts ~4700 miRNA recognition elements (MREs; with threshold< -25kcal/mol) for ~1000 miRNAs, which have primarily originated within the 3’UTR-Alus post exonization. CYP20A1_Alu-LT could be a potential multi-miRNA sponge as it harbours ≥10 MREs for 140 miRNAs and has cytosolic localization. In order to test this further, we explored whether expression of CYP20A1_Alu-LT correlates with genome wide mRNAs harboring similar MRE targets. We carried out RNAseq with conjoint miRNA-seq analysis in primary human neurons as we observed CYP20A1_Alu-LT to be downregulated during heat shock response and upregulated in HIV1-Tat treatment. CYP20A1_Alu-LT expression was positively correlated with 380 genes that were significantly downregulated in heat shock and upregulated in Tat and harboured MREs for a set of nine expressed miRNAs that were also enriched in CYP20A1_Alu-LT. The enrichment of MREs in the 380 genes were significant compared to random sets of expressed (p=4.716e-12) as well as differentially expressed genes (p=8.134e-12). Gene ontology suggested involvement of these genes in neuronal development and hemostasis pathways. Conclusion: Our study suggests a potential role for CYP20A1_Alu-LT as miRNA sponge due to significant enrichment of MREs within Alus in a transcript isoform specific manner. This highlights a novel component of Alu-miRNA mediated transcriptional modulation that could govern specific physiological outcomes in higher primates.
The Value of Small Dense Low-Density Lipoprotein Cholesterol in Predicting the Risk and Severity of Coronary Heart Disease in Patients with Type 2 Diabetes Mellitus
Authors: Huang Juan , Gu Jun-Xu , Bao Hui-Zhang , Li Shan-Shan , Yao Xiao-Qin , Yang Ming , Li Yang , Zhang Ai-Min , Yin Yue , Zhang Na , Jia Mei
Published: June 2020

Background: Elevated small density low – density lipoprotein cholesterol (sdLDL-C) particles are hallmarks of atherogenic dyslipidemia in patients with type 2 diabetes mellitus (T2DM), which is hypothesized to drive atherosclerotic risk. The present study aims to investigate the association between serum sdLDL-C level and the presence and severity of coronary heart disease (CHD). Method: A total of 3684 consecutive patients with T2DM who received selective coronary angiography (CAG) were enrolled. The patients were subsequently divided into CHD and non-CHD groups according to results of CAG. The severity of CHD was evaluated by the number of stenotic, and the Gensini Score (GS).The patients were subsequently divided into four groups by the quartiles of sdLDL-C and evaluate the risk and severity of sdLDL-C and CHD.Results: The sdLDL-C levels in CHD group were significantly higher than non-CHD group [0.80 (0.49) mmol/L vs 0.70 (0.30) mmol/L, P < 0.001]. The results from CHD subgroup analysis indicated that the patients with multiple-vessel disease and high GS had higher sdLDL-C levels compared with those in their matched subgroups (P < 0.05). By adjusting the confounding factors and analyzing by the multiple logistic regression, sdLDL-C had independent correlation with the presence and severity of CHD [CHD: OR = 2.757, 95%, CI = 1.662 - 5.364, P = 0.023; multiple-vessel disease: OR = 3.788, 95%, CI = 1.866 - 7.685, P = 0.026; High GS: OR = 3.054, 95%, CI = 1.944 - 5.699, P = 0.022].Conclusion: In T2DM patients, the increase of sdLDL-C is related to the increase the prevalence and the severity of CHD. After adjustment for other risk factors, sdLDL-C was found to be an independent risk factor for CHD. Therefore, measuring sdLDL-C may allow for T2DM patients to predict the presence and severity of CHD.
Views of Cancer Patients, Families, and Providers on Initiating and Engaging in Advance Care Planning: A Qualitative Study
Authors: Toguri James Thomas , Grant-Nunn Lindsay , Urquhart Robin
Published: June 2020

Background: Advance care planning (ACP) is a formal process by which patients reflect upon their goals, values and beliefs to allow them to make decisions about their future medical treatment that align with their goals and values, improving patient-centered care. Despite this, ACP is underutilized and is reported as one of the most difficult processes of oncology. Aims: To 1) explore patients’ and families’ views of ACP and what they need from their physicians during the process; 2) explore physicians’ views of ACP, including their experiences with initiating ACP and views on ACP training; and 3) identify commonalities and differences between patients’ and families’ experiences and those of the physicians who care for them. Design and setting: Qualitative descriptive study in Nova Scotia, Canada.Methods: Semi-structured interviews with advanced cancer patients and their family members (n=8) and oncologists (n=10) were conducted. Data were analyzed using constant comparative analysis, which entailed coding, categorizing, and identifying themes recurrent across the datasets. Results: Themes were identified from the patient / family and oncologist groups, four and five respectively. Themes from patients / families included: 1) positive attitudes towards ACP; 2) healthcare professionals (HCPs) lack an understanding of patients’ and families’ informational needs during the ACP process; 3) limited access to services and supports; and 4) poor communication between HCPs. Themes from oncologists included: 1) initiation of ACP discussions; 2) navigating patient-family dynamics; 3) limited formal training in ACP; 4) ACP requires a team approach; and 5) lack of coordinated systems hinders ACP. Conclusion: Stakeholders believe ACP for advanced cancer patients is important. Patients and families desire earlier and more in-depth discussion of ACP, additional services and supports, and improved communication between their HCPs. In the absence of formal training or guidance, oncologists have used clinical acumen to initiate ACP and a collaborative healthcare team approach.
HDL-proteome enrichment with apolipoprotein A-IV compensates for HDL loss of function in diabetes mellitus kidney disease
Authors: Santana Monique FM , Lira Aécio LA , Pinto Raphael , Minanni Carlos A , Silva Amanda RM , Sawada Maria IBAC , Nakandakare Edna R , Correa-Giannella Maria LC , Ronsein Graziella E , Queiroz Marcia S , Passarelli Marisa
Published: June 2020

Background and aims:Diabetes mellitus kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CV) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CV complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to glomerular filtration rate (GFR) and urinary albumin excretion rate (AER).Methods:DKD individuals were divided in GFR > 60 mL/min/1.73 m2 plus AER stages A1 and A2 (n = 10) and GFR < 60 plus A3 (n = 25) and matched by age with control subjects (GFR > 60; n = 8).Results:Targeted proteomic analyses quantified 29 proteins associated with HDL in all groups, although only 2 were more expressed in GFR < 60 + A3 group in comparison to controls: apolipoprotein D (apo D) and apo A-IV. HDL from GFR < 60 + A3 presented higher levels of total AGEs, pentosidine and carbamoylation (1.2, 1.1 and 4.2 times, respectively) and a reduced ability in removing 14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from GFR < 60 + A3 presented a higher ability in inhibiting the secretion of IL6 and TNF alpha (95%) in LPS-elicited macrophages in comparison to control group.Conclusion:The increment in apo A-IV that presents many antiatherogenic actions seems to counteract the HDL chemical modification by AGE and carbamoylation and its increment in apo D that occurred in well-established DKD.
Human HINT1 Mutant Proteins that Cause Axonal Motor Neuropathy Exhibit Anomalous Interactions with Partner Proteins
Authors: Cortés-Montero Elsa , Rodríguez-Muñoz María , Sánchez-Blázquez Pilar , Garzón-Niño Javier
Published: June 2020

The 14 kDa histidine triad nucleotide-binding protein 1 (HINT1) is critical to maintain the normal function of motor neurons. Thus, a series of human HINT1 mutants cause autosomal recessive axonal neuropathy with neuromyotonia. HINT1 establishes a series of regulatory interactions with signaling proteins, some of which are enriched in motor neurons, such as the type 1 sigma receptor or intracellular domain (ICD) of transmembrane teneurin 1, both of which are also implicated in motor disturbances. In a previous study, we reported the capacity of HINT1 to remove the small ubiquitin-like modiﬁer (SUMO) from a series of substrates and the influence of HINT1 mutants on this activity. We now report how human HINT1 mutations affect the interaction of HINT1 with the regulator of its SUMOylase activity, calcium-activated calmodulin, and its substrate SUMO. Moreover, HINT1 mutants exhibited anomalous interactions with G-protein coupled receptors, such as the mu-opioid, and with glutamate N-methyl-D-aspartate receptors as well. Additionally, these HINT1 mutants showed impaired associations with transcriptional regulators such as the regulator of G protein signaling Z2 protein and the cleaved N-terminal ICD of teneurin 1. Thus, the altered SUMOylase activity of human HINT1 mutants and their anomalous interactions with partner proteins may disrupt signaling pathways essential to the normal function of human motor neurons.
Numerical Study of New Device for Passive Suppression of Vortex-Induced Vibrations in Deep Water Risers
Authors: Abdulaziz Mohammed , Elsaid Emad
Published: June 2020

This paper presents a three dimensional numerical simulation to investigate the effectiveness of a new passive device for vortex-induced vibrations (VIV) suppression of deep water risers based on non-continuous helical strakes in staggered arrangement with two starts. The influence of changing the geometries and design parameters, such as the pitch and shape of strakes, on the VIV was studied. The simulation had been carried out at Reynolds number 104, which satisfies the natural conditions of ocean currents. The presented design has been tested using a numerical solver using OpenFOAM platform, which had been presented and validated using number of published benchmarks. The LES – large-eddy simulation is used for turbulence modeling. The results had been compared with the published numerical and experimental works and other design based on drag coefficient. The comparison shows that the proposed geometry can suppress the VIV, if applied in deep water risers. The drag coefficient of 1.05 is considered a reduced value in the modified strakes shape with two starts and non-continuous helical strakes in staggered arrangement. The addition of strakes to the surface of a flexible cantilever was modeled to give the chance for evaluating the effect of geometry on the VIV.
Quality of Life and associated modifiable social factors in Sri-Lankan children with overweight and obesity: a cross-sectional study
Authors: Gunawardana Shamaali , Gunasinghe Chanduli Binari , Harshani Maddage Samudra , Seneviratne Sumudu Nimali
Published: June 2020

BackgroundData on quality of life (QoL) of children in South Asia affected by overweight and obesity is limited. This study assessed QoL in Sri Lankan children with overweight and obesity from children’s and parents’ perspective and modifiable social factors potentially affecting QoL of these children.Methods Self-reported QoL and parental-perception of QoL were assessed in 8-12 year-old children with overweight and obesity (n=110), referred for obesity management at a tertiary-care children’s hospital in Sri-Lanka, using linguistically validated Pediatric Quality of Life inventory (PedsQLTM) 4.0 (Child-Self Report and Parent-Proxy forms). Social factors affecting QoL were also collected. Data was analyzed by non-parametric tests.ResultsThe median overall QoL was 80.4 (Inter Quartile Range [IQR] 69.6, 89.5). Physical QoL was lower than psychosocial QoL (78.1vs81.7, p=0.032). Parental-perception of children’s QoL correlated with child-reported QoL, but was lower for overall, physical and psychosocial QoL. Obese children had lower overall QoL, and lower QoL in physical and social functioning, compared to overweight children, and body mass index (BMI) was inversely correlated with physical and social functioning. Social factors associated with lower QOL were: being bullied (p=0.005), not getting regular exercise (p=0.017) and having difficulties in finding suitable clothes (p< 0.001).ConclusionsChildren with overweight and obesity from Sri Lanka appeared to have lower QoL than healthy children, with greater impairment of physical QoL than psychosocial QoL. Lower parental-perception of QoL, higher BMI, bullying, lack of regular exercise and lack of suitable clothing, were associated with lower QoL. Potential strategies to improve QoL include promoting regular exercise and a range of children’s clothes to fit larger children, and prevention of bullying.
Stigmatization, discrimination, violation of autonomy and compromised confidentiality: Lived experiences of people living with HIV on the onset of their illness in Turkey
Authors: Senyurek Gamze , Kavas Mustafa Volkan , Ulman Yesim Isil
Published: June 2020

Background: It’s known that people living with HIV (PLWH) are subjected to stigmatization and discrimination while accessing healthcare services. The purpose of this study is to understand the perceptions of PLWH in Turkey, about whom there are limited data on how their lives are affected by such experiences. Methods: Semi-structured interviews were carried out with 20 people, and the obtained data were analyzed thematically.Results: The results highlighted the following themes: problems with patients’ autonomy, failure to protect patients’ confidentiality and personal health data, spouse/partner notification issues, and stigmatizing and discriminatory attitudes intrinsic to healthcare professionals’ approach. The attitudes of healthcare professionals and health institutions negatively influence the utilization of healthcare services by PLWH. Conclusions: We have argued the necessity to raise the healthcare professionals’ and the society’s knowledge and awareness, and develop national policies that would contribute to structure partner notification services and prevent HIV-related discrimination and stigmata.
Nickel Carbon Composite With Carbon Nanotubes for Efficient Electromagnetic Wave Absorption
Authors: Qiu Yun , Yang Haibo , Ma Liang , Lin Ying , Zong Hanwen , Wen Bo , Bai Xiaoyu , Wang Mengqi
Published: June 2020

Nickel carbon composite with carbon nanotubes (Ni-C/CNTs) has been fabricated by pyrolysis the mixture of nickel-based metal organic framework (Ni-MOF) and melamine. The resultant Ni-C/CNTs composite is assembled from one-dimensional (1D) CNTs and three dimensional (3D) spherical Ni-C composite. Besides, the Ni-C/CNTs composite contains abundant nitrogen(N) dopants that contributes to defect dipole polarization. The diameter and length of CNTscan beeffected by changing the mass ratio of Ni-MOF and melamine. The optimizedNi-C/CNTs composite exhibits reflection loss of -55.1 dB at 10.56 GHz, and the effective absorbing bandwidth (reflection loss < -10 dB) is 11.2 GHz (6.0-17.2 GHz)with the thickness range of 1.5-4.0 mm, when the mass ratio of Ni-MOF: melamine is 1: 2. These results indicate that the mixed 1D-3D hierarchical architecture synergistically improves electromagnetic wave absorption properties. This strategy willcontribute for fabricating the carbon hybrid network consisting of metal organic frameworks derived metal/carbon hybrid and CNTs for electromagnetic wave absorption.
Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis
Authors: Yan Feili , Zhong Zhirong , Wang Yao , Li Hui , Mei Zhiqiang , Feng Yue , Chen Xiang , Cai liang , Li Chunhong
Published: June 2020

Backgroud:
Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. To achieve better treatment and reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system.
Results
The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was − 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo pharmacodynamic experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility.
Conclusion
The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.
A Qualitative Study to Explore the Experience of Parents of Newborns Admitted to Neonatal Care Unit in Rural Rwanda
Authors: Byiringiro Samuel , Wong Rex , Logan Jenae , Kaneza Deogratias , Gitera Joseph , Umutesi Sharon , Kirk Catherine M.
Published: June 2020

Background: Neonatal Care Units (NCUs) provide special care for sick and small newborns and can help reduce neonatal mortality. For parents, the experience of having a hospitalized newborn can be traumatic. In LMIC, especially sub-Saharan Africa, there is limited information about the parents’ experience of care in NCUs. Objective: Our study aimed to explore the experience of parents in the NCU of a rural district hospital in Rwanda. Methods: A qualitative study was conducted with parents whose newborns were hospitalized in the Ruli District Hospital NCU from September 2018 to January 2019. In-depth interviews were conducted using a semi-structured guide in the participants homes by trained data collectors. Data were transcribed, translated, and then coded using a structured code book. All data analyses were conducted using Dedoose software. Results: Twenty-one interviews were conducted primarily with mothers (90.5%, n=19) among newborns who were most often discharged home alive (90.5%, n=19). Parents reported stressful and emotional responses to having their newborns admitted particularly when they lacked clear understanding of their newborn’s condition, generally positive communication and interactions with healthcare providers and other parents, policies and procedures in the NCU that contributed to stress and limited access to newborns by fathers and other family members, and stress due to the high financial burden of NCU care. Conclusion: The admission of a newborn into the NCU alone was a source of stress for parents and caregivers in rural Rwanda. However, there were several positive factors of the NCU including involvement of mothers and support from healthcare providers. The experience in the NCU can be improved when healthcare providers communicate and explain the newborn’s status to the parents and actively involve them in the care of their newborn. Expanding the NCU access for families, encouraging peer support, and ensuring financial accessibility for neonatal care services could contribute to improved experiences for families.
Maternal syphilis treatment and pregnancy outcomes: a retrospective study in Jiangxi Province, China
Authors: Wan Zhihua , Zhang Huan , Xu Haigang , Hu Yang , Tan Cai , Tao Yuling
Published: June 2020

Background
Studies investigating the associations of maternal syphilis treatment during pregnancy with pregnancy outcomes mainly concentrated in economically developed areas. Limited data are available in economically underdeveloped areas, such as Jiangxi Province. The study aims to investigate the impact of maternal treatment during pregnancy on pregnancy outcomes in Jiangxi Province, China.
Methods
Data were obtained from the China’s Information System of Prevention of Mother-to-Child Transmission (PMTCT) of syphilis management in Jiangxi Province. All syphilis infected pregnant women who delivered at gestational age of 28 weeks or more and were registered in this system between 1 January 2013 and 31 December 2019 were enrolled. Pregnancy outcomes were evaluated by group-specific analyses according to their treatment status, adequacy and initiation time.
Results
4210 pregnant women with syphilis infection were included in the analyses. Infants born to untreated mothers were at significantly higher risk for stillbirth (adjusted odds ratio (aOR) = 1.74, 95% CI, 1.01-3.00, P = 0.045), preterm birth (aOR = 1.27, 95% CI, 1.02–1.59, P = 0.034) and low birth weight (LBW) (aOR = 1.44; 95% CI, 1.11–1.86, P = 0.006) than those born to treated mothers after adjustment for confounding factors. Moreover, a significantly higher risk of stillbirth (aOR = 3.68; 95% CI, 1.62–8.34, P = 0.002), preterm birth (aOR = 2.26; 95% CI, 1.71-3.00, P < 0.001), LBW (aOR = 2.23; 95% CI, 1.59–3.14, P < 0.001) and congenital syphilis (CS) (aOR = 3.63; 95% CI, 1.80–7.31, P < 0.001) was found in infants exposed to mothers treated inadequately than those treated adequately. In addition, no pregnant women who initiated the treatment in the first trimester delivered a neonatal CS case. Compared with mothers who initiated treatment in the first trimester, those initiated in the third trimester suffered an increased risk of stillbirth (aOR = 4.48; 95% CI, 1.31–15.30, P = 0.017), preterm birth (aOR = 2.34; 95% CI, 1.61–3.40, P < 0.001) and LBW (aOR = 3.25; 95% CI, 1.97–5.37, P < 0.001).
Conclusions
Maternal treatment, especially early and adequate treatment, plays a crucial role in mitigating adverse pregnancy outcomes among syphilis infected women.
Assessment of Novel Lehmann’s Funnel Entry Trap Prototypes Performance to Control Malaria Mosquito Populations
Authors: Sanou Roger , Maïga Hamidou , Bilgo Etienne M. , Sawadogo P. Simon , Sow Bazoumana D. , Ouema Adama , Bayili Koama , Belem Adrien Marie Gaston , Paré Léa Melanie , Dabiré Roch K. , Diabaté Abdoulaye
Published: June 2020

BackgroundThere is a global consensus that new intervention tools are needed to cross the last miles in malaria elimination/eradication. In a recent study in Burkina Faso, the Lehmann Funnel Entry Trap (LFET) have shown excellent promise in mosquito densities reducing even in area of high insecticide resistance up to 80%. It requires no chemicals and is self-operated. However, one of the issues of the LFET is the big size of the funnel occupying lot of space inside houses. Here we compared the performance of three new prototypes of LFET with reduced size that combine screening and killing effect on mosquitoes. MethodsThe study was carried out for three months during the rainy season both in low and high malaria vector density sites, Soumousso and Vallée du Kou respectively. The original LFET was modified and 3 new prototypes were produced locally and tested over 3 months (8 days/month) to evaluate their effectiveness in trapping and killing mosquitoes entering houses through the windows. ResultsIn both sites, an overall of 78,435 culicine mosquitoes collected in both traps and houses and most of them were mainly Anopheles gambiae s.l. n= 76,558 (98%) and other species represented n = 1,877 (2%). Of the culicine caught in the trial, n= 55,256 (72%) were collected in traps. The 3 new LFET prototypes reduced the indoor density of mosquitoes collected in the houses by a range of 36 to 73% and 69 to 70% in low vector density setting, Soumousso and high vector density area, Vallée du Kou respectively. The prototype 1 caught a greater number of mosquitoes than the prototype 2 whereas no difference was observed between other prototypes in VK3. In Soumousso, the prototypes 1 and 2 collected significantly higher number of mosquitoes compared to the prototypes 3 and 4. ConclusionThis study has shown that the new LFET prototypes are promising for malaria vector control and could enter in the malaria vector control toolbox in the coming years. Therefore, a large-scale study with one of the prototypes is needed on the practical ability and community acceptance of the LFET to control malaria vectors.
Prognostic Value of Serum Creatinine in Severe Covid-19 Patients in Wuhan, China: A Retrospective Cohort Study
Authors: Zhang Wei-yun , Xu De-yu , Wang Chang-guo , Liu Ying-ying , Huang Jian-an , Jiang Jun-hong , Zeng Daxiong
Published: June 2020

Objectives: Although the respiratory and immune systems are the major targets of SARS-CoV-2, increasing evidence revealed that kidney injury was not rare in coronavirus disease 2019 (COVID-19). However, the incidences of kidney abnormalities were significantly different, from 0.5 to 75.4% in several reports. The association of kidney injury with prognosis remain controversial.Methods:In this retrospective single center cohort study, laboratory confirmedCOVID-19inpatients with severe type were enrolled. Demographic, clinicaland laboratory data were collected. Association ofserum creatinine (SCr)with 28-days mortality in severe COVID-19 patients was analyzed.Results:18.79% (48/304) patients died during the first 28-days of hospitalization.Non-survivors had a significantly higher SCr levels than survivors (109.27μmol/L vs. 69.99μmol/L, P <0.001). The 28-days mortality in high SCr group (>76μmol/L) was significantly higher than that in low SCr group (31.7% vs. 7.5%, P <0.001). Multivariate logistic regression revealed that the independent risk factors of 28-days outcome included age(OR: 2.95, 95%CI: 1.08-8.05), WBC (OR: 6.09, 95%CI: 2.27-6.39), lymphopenia (OR: 3.49, 95%CI: 1.55-7.92), IL-6 (OR: 4.44, 95%CI: 1.64-11.99) and SCr (OR: 2.69, 95%CI: 1.18-6.11). Kaplan-Meier analysis demonstrated the survival disadvantage in patients with high SCr levels (>76μmol/L). ROC curve showed the SCr cut-off value for predicting 28-days death was 77.5 μmol/L, with the sensitivity of 68.8% and speciality of 74.1%.Conclusion: SCr was associated with poor prognosis and might be an independent risk factor for in-hospital death. The cut-off value of SCr for prognosis prediction was 77.5 μmol/L, with the sensitivity of 68.8% and speciality of 74.1%.
Enhanced Differentiation of Human Pluripotent Stem Cells into Pancreatic Endocrine Cells in 3D Culture by Inhibition of Focal Adhesion Kinase
Authors: Liu Xiaofang , Qin Jinhua , Chang Mingyang , Wang Shuyong , Li Yali , Pei Xuetao , Wang Yunfang
Published: June 2020

Background The generation insulin-producing cells from human pluripotent stem cells (hPSC) in vitro would be useful for drug discovery and cell therapy in diabetes. Three-dimensional (3D) culture is important for the acquisition of mature insulin-producing cells from hPSC, but the mechanism by which 3D culture promoted β cell maturation is poorly understood.Methods We established a stepwise differentiation method to induce human embryonic stem cells (hESC) into mature monohormonal pancreatic endocrine cells (PEC) at high efficiency, with the last maturation stage in 3D culture. To make a comprehensive comparison between 2D culture and 3D culture, we examined gene expression, pancreatic-specific markers and functional characteristics of 2D culture-induced PEC and 3D culture-induced PEC. And the mechanisms was discussed from the perspective of cell-cell and cell-extracellular matrix interactions which are fundamentally different between 2D and 3D culture.Results Expression of pancreatic endocrine-specific transcription factors PDX1, NKX6.1, NGN3, ISL1, PAX6 and hormones INS, GCG, SST were significantly increased in 3D culture-induced PEC. 3D culture gave rise to monohormonal endocrine cells, while 2D culture-induced PEC co-expressed INS and GCG or INS and SST, and some cells even expressed all three hormones. We found that FAK phosphorylation level was significantly downregulated in 3D culture-induced PEC, and treatment with a selective FAK inhibitor PF-537228 could improve the expression of β cell-specific transcription factors. We further demonstrated that 3D culture may promote endocrine commitment by limiting FAK-dependent activation of the Smad2/3 pathway. Moreover, the expression of gap junction protein Connexin 36 is much higher in 3D culture-induce PEC than 2D culture-induced PEC, and inhibition of FAK pathway in 2D culture increased Connexin 36 expression.Conclusion We developed a differentiation strategy to induce monohormonal mature PEC from hPSC and found limited FAK-dependent activation of the Smad2/3 pathway and unregulated expression of Connexin 36 in 3D culture-induced PEC. This study has important implications for the generation of mature, functional β-cells for drug discovery and cell transplantation therapy in diabetes, and sheds new light on the signaling events that regulate endocrine specification.
A Propensity-Score Matched Analysis Comparing Outpatient and Short-Stay Hospitalization to Standard Inpatient Hospitalization Following Total Ankle Arthroplasty
Authors: Plantz Mark A. , Sherman Alain Emil , Kadakia Anish R.
Published: June 2020

Background Given the trend toward value-based care, there has been increased interest in minimizing hospital length of stay (LOS) after orthopaedic procedures. Outpatient total ankle arthroplasty (TAA) has become more popular in recent years; however, research on surgical outcomes of this procedure has been limited. This study sought to emply large sample, propensity-score matched analyses to assess the safety of outpatient and short-stay discharge pathways following TAA. Methods The ACS NSQIP database was used to identify 1,141 patients who underwent primary and revision TAA between 2007 and 2017. Propensity score matching was used to match patients based on several factors, including age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, and several comorbidities. The incidence of various 30-day complications were compared between the short and standard LOS groups to assess for any differences in short-term outcomes. Results A total of 892 patients were included in the final propensity score matched analysis, with 446 patients in each group. The short LOS group had a significantly lower rate of medical complications (0.2% vs. 2.5%, p = 0.006) and non-home discharge (1.3% vs. 12.1%, p < 0.001). There was no significant difference in operative complications (0.4% vs. 1.8%, p = 0.107), unplanned readmission (0.4% vs. 1.1%, p = 0.451), reoperation (0.2% vs. 0.4%, p > 0.999), return to the OR (0.2% vs. 0.9%, p = 0.374), or mortality (0.7% vs. 0.0%, p > 0.249) between the short and standard LOS groups. Conclusions Outpatient and short-stay hospitalization had comparable safety to standard inpatient hospitalization after TAA. Outpatient or short-stay TAA should be considered for patients with low risk of short-term complications.
IRLnc : A Novel Functional Noncoding RNA Contributes to Intramuscular Fat Deposition
Authors: Wang Ligang , Zhou Zhong-Ying , Zhang Tian , Zhang Longchao , Hou Xinhua , Yan Hua , Wang Lixian
Published: June 2020

Background Intramuscular fat (IMF) is associated with meat quality and insulin resistance in animals. Research on genetic mechanism of IMF decomposition has positive meaning to pork quality and diseases such as obesity and type 2 diabetes treatment. In this study, an IMF trait segregation population was used to perform RNA sequencing and to analyze the joint or independent effects of genes and long intergenic non-coding RNAs (lincRNAs) on IMF.ResultsInteresting, one lincRNA gene, namedIMF related LincRNA (IRLnc) not only has a 292-nt conserved region in 100 vertebrates but also has conserved up and down stream genes (<10 kb)in pig and humans. Real-time quantitative polymerase chain reaction (RT-qPCR) validation study indicated thatnuclear receptor subfamily 4 group A member 3 (NR4A3) which located at the downstream of IRLnchas similar expression pattern with IRLnc. RNAi-mediated loss of function screens identified that IRLnc silencing could inhibit both of the RNA and protein expression of NR4A3. And the in-situ hybridization co-expression experiment indicates that IRLnc may directly binding to NR4A3. As the NR4A3 could regulate the catecholamine catabolism, which could affect insulin sensitivity, we inferred that IRLncinfluence IMF decomposition by regulating the expression of NR4A3.ConclusionsIn conclusion, a novel functional noncoding variation named IRLnc have been found contribute to IMF. These finding suggest novel mechanistic approach for treatment of insulin resistance in human beings and meat quality improvement in animal.
Quick BSI Score to Identify Bloodstream Infection at the Emergency Department
Authors: Phungoen Pariwat , Lerdprawat Nunchalit , Sawanyawisuth Kittisak , Chotmongkol Verajit , Ienghong Kamonwon , Sumritrin Sumana , Apiratwarakul Korakot
Published: June 2020

Background
Bloodstream infection (BSI) is a common and urgent condition at the emergency department (ED). In order to diagnose BSI, the current guideline fails to mention the juncture at which blood cultures ought to be taken. The decision whether or not to obtain hemoculture is solely based upon clinical judgment and outcomes pertaining to inappropriately ordered blood culture. This study aimed to develop predictive bloodstream infection scoring at the ED employing only clinical factors presented on ED arrival.
Methods
This study was conducted retrospectively at the ED, Khon Kaen University Hospital, Thailand. Inclusion criteria encompassed adult patients suspected of infection defined by blood culture collection presented at the ED with intravenous antibiotics initiated during ED visits. Independent positive predictors for positive blood culture were used to create the Quick Bloodstream Infection score (qBSI score) through logistic regression analysis.
Results
A total of 169578 patients visited the ED during the study period. Of those, 12556 patients (7.40%) were suspected of infection. 8177 cases met the study criteria and were categorized according to positive blood culture results, i.e. bloodstream infection (741 patients; 9.06%). Probability of positive blood culture was calculated via aged over 55 years + moderate to severe CKD + solid organ tumor + (2 x liver disease) + (2 x history of fever with chills) + (2 x body temperature of over 38.3oC). A score of 1 or over rendered 92.98% sensitivity and negative predictive value of 95.65%.
Conclusions
The qBSI score presented effective sensitivity and negative predictive value amid positive blood culture in patients at the ED suspected of infection. Resultant of employing this score may facilitate in the determining of those exhibiting the need for blood culture at the ED.
Systemic inflammation and chronic kidney injury in a patient due to RNASEH2B defect
Authors: He Tingyan , Xia Yu , Yang Jun
Published: June 2020

Background
Aicardi-Goutières (AGS) is a rare immune dysregulated disease due to mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 or IFIH1. Severe systemic inflammation is not typically persistent in AGS. Chronic kidney injury (CKI) has been never reported in this syndrome. Herein, we report a patient presenting with systemic inflammation and CKI to broaden the clinical phenotype spectrum of RNASEH2B defect.
Methods
Clinical data extracted included medical history, clinical manifestations, laboratory results, radiological findings, management, and prognosis. Whole exome sequencing was performed on whole peripheral blood cells. After exposure to cGAMP in vitro for 24 hours, mRNA expression of twelve IFN-stimulated cytokine genes in PBMCs was assessed. Serum cytokine levels were detected by Milliplex.
Results
A 11-year-old female patient presented with recurrent aseptic fever, arthritis, chilblains, failure to thrive, mild hearing loss, and neurological manifestations. Laboratory and immunologic findings revealed lymphopenia, low complement levels, positive autoantibodies, elevated levels of acute phase reactants and inflammatory cytokines. Renal biopsy showed glomerular sclerosis in three of fourteen glomeruli, infiltration of lymphocytes and other mononuclear cells. Whole exome sequencing (WES) revealed a homozygous and heterozygous mutations in RNASEH2B.Over-expression of IFN-stimulated cytokine genes was observed in the patient, including IFI44, IFI27, IFIT1, IFIT2, IFIT3, ISG15, OAS1, and SIGLEC1.
Conclusions
Systemic autoinflammation and chronic renal injury may expand the clinical phenotype spectrum of RNASEH2B defect.
Trial registration:
Not applicable; this was a retrospective study.
Efficacy of proton pump inhibitor on nighttime reflux symptoms and associated sleep disturbances in patients with gastroesophageal reflux disease: A real-world study in northern China
Authors: Sun Kaidi , Ma Shuang , Hui Yang-Yang , Wang Bin , Yang Bo , Zhu Lan-Ping , Wang Sai-Yu , Li Shu , Zhao Wei , Jiang Kui , Zhao Jing-Wen , Wang Bang-Mao , Chen Xin , Zhang Guo-Liang , Zhou Zheng-Hua , Liu Yan-Di , Ye Qing , Deng Quan-Jun , Liu Gai-Fang , Wang Jun-Min , Chang Li-Li , Zhang Rui-Xing
Published: June 2020

Background

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitors (PPIs) are the main treatment to improve the symptom of GERD. This study was to investigate the efficacy of PPIs on nighttime GERD symptoms and associated sleep disturbances in general Chinese GERD population.
Methods

Adult patients with mild or more serious nighttime GERD symptoms were included. The efficacy was evaluated by the relief rate of nighttime GERD symptoms and GERD-related sleep disturbances after 4 weeks PPIs treatment. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index Score (PSQI).
Results

A total of 750 patients were included in the final analysis. Overall, 51.3% of the patients had achieved a relief of nighttime GERD symptoms after 4 weeks of PPIs treatment. By week 4, the percentages of patients with completely resolved nighttime GERD symptoms and GERD-related sleep disturbances were 32.5% and 51.5%, respectively. PSQI score was significantly improved from 6.82 ± 0.12 at baseline to 4.56 ± 0.09 at 4 weeks (P༜0.001).
Conclusion

PPIs treatment can provide an effective relief of nighttime GERD symptoms and associated sleep disturbances, improving sleep quality of general GERD patients in northern China.
Trial registration:

Trial registration: CHiCTR, ChiCTR1800017652. Registered 08 August 2018, http://chictr.org.cn/index.aspx
NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability
Authors: Guo Hui , Zou Jianping , Zhou Ling , He Yan , Feng Miao , Chen Jun , Li Junhe , Xiong Jianping , Fang Ziling , Xiang Xiaojun
Published: June 2020

Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.