bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of technology for public health surveillance reporting: opportunities, challenges and lessons learnt from Kenya
Authors: Njeru Ian , Kareko David , Kisangau Ngina , Langat Daniel , Liku Nzisa , Owiso George , Dolan Samantha , Rabinowitz Peter , Macharia Daniel , Ekechi Chinyere , Widdowson Marc-Alain 
Published: July 2020

Abstract
Background: Effective public health surveillance systems are crucial for early detection and response to outbreaks. In 2016, Kenya transitioned its surveillance system from a standalone web-based surveillance system to the more sustainable and integrated District Health Information System 2 (DHIS2). As part of Global Health Security Agenda (GHSA) initiatives in Kenya, training on use of the new system was conducted among surveillance officers. We evaluated the surveillance indicators during the transition period in order to assess the impact of this training on surveillance metrics and identify challenges affecting reporting rates. Methods: From February to May 2017, we analysed surveillance data for 13 intervention and 13 comparison counties. An intervention county was defined as one that had received refresher training on DHIS2 while a comparison county was one that had not received training. We evaluated the impact of the training by analysing completeness and timeliness of reporting 15 weeks before and 12 weeks after the training. A chi-square test of independence was used to compare the reporting rates between the two groups. A structured questionnaire was administered to the training participants to assess the challenges affecting surveillance reporting. Results: The average completeness of reporting for the intervention counties increased from 45% to 62%, i.e. by 17 percentage points (95% CI 16.14 -17.86) compared to an increase from 49% to 52% for the comparison group, i.e. by 3 percentage points (95% CI 2.23 -3.77). The timeliness of reporting increased from 30% to 51%, i.e. by 21 percentage points (95% CI 20.16 - 21.84) for the intervention group, compared to an increase from 31% to 38% for the comparison group, i.e.by 7 percentage points (95% CI 6.27-7.73). Major challenges for the low reporting rates included lack of budget support from government, lack of airtime for reporting, health workers strike, health facilities not sending surveillance data, use of wrong denominator to calculate reporting rates and surveillance officers having other competing tasks. Conclusions: Training plays an important role in improving public health surveillance reporting. However, to improve surveillance reporting rates to the desired national targets, other challenges affecting reporting must be identified and addressed accordingly.
MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4
Authors: Lin Ji , Huang Huijuan , Lin Liheng , Li Weiwei , Huang Jianfen 
Published: July 2020

Abstract
Background: MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells. Results: Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions: In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.
Mouse skeletal muscles infected with Plasmodium berghei and Plasmodium chabaudi reveal a crosstalk between lipid mediators and gene expression
Authors: Marrelli Mauro Toledo , Wang Zhiying , Huang Jian , Brotto Marco 
Published: July 2020

Abstract
Background Malaria is one of the most prevalent infectious disease in the world with 3.2 billion humans at risk. Malaria causes splenomegaly and damage in other organs including skeletal muscles. Skeletal muscles comprise nearly 50% of the human body and are largely responsible for the regulation and modulation of overall metabolism. It is essential to understand how malaria damages muscles in order to develop effective preventive measures and/or treatments. Using a pre-clinical animal model, the potential molecular mechanisms of Plasmodium infection affecting skeletal muscles of mice were investigated. Methods Mouse Signal Transduction Pathway Finder PCR Array was used to monitor gene expression changes of 10 essential signaling pathways in skeletal muscles from mice infected with Plasmodium berghei and Plasmodium chabaudi. Then, a new targeted-lipidomic approach using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to profile 158 lipid signalling mediators (LMs), mostly eicosanoids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), was applied. Finally, 16 key LMs directly associated with inflammation, oxidative stress, and tissue healing in skeletal muscles, were quantified. Results The results showed that the expression of key genes altered by Plasmodium infection is associated with inflammation, oxidative stress, and atrophy. In support to gene profiling results, lipidomics revealed higher concentrations of LMs in skeletal muscles directly related to inflammatory responses, while on the levels of LMs crucial in resolving inflammation and tissue repair reduced significantly. Conclusion The results provide new insights into the molecular mechanisms of malaria-induced muscle damage and revealed a potential mechanism modulating inflammation in malarial muscles. These pre-clinical studies should help with future clinical studies in humans aimed at monitoring of disease progression and development of specific interventions for the prevention and mitigation of long-term chronic effects on skeletal muscle function.
Reclassification of tumor size for solitary HBV-related hepatocellular carcinoma by minimum p value method: a large retrospective study
Authors: Liu Hongzhi , Yang Yuan , Chen Chuanchun , Wang Lei , Huang Qizhen , Zeng Jianxing , Lin Kongying , Zeng Yongyi , Guo Pengfei , Zhou Weiping , Liu Jingfeng 
Published: July 2020

Abstract
Background and Objectives Tumor size is one of the most important issues for hepatocellular carcinoma (HCC) treatment and prognosis but the classification of it still controversial. The aim of this study was to screen appropriate cutoffs for size of solitary hepatitis B virus (HBV) related HCC.Methods A cohort of 1760 patients with solitary HBV-related HCC undergoing curative liver resection were divided into 11 groups based on tumor size in 1-cm interval. The minimum p value method was used to screen the appropriate size cutoff according to overall survival (OS). If multiple cutoffs meet the above standard, univariate analysis will be performed by using the Cox proportional hazards regression model, and hazard ratio (HR) will be considered as a criterion to assess the difference in survival.Results There are 8 dichotomy, 8 trichotomy and no inquartation cutoffs were screened when classifying tumor sizes in accordance with OS. The HR values of tumor size at these trichotomy cutoffs for OS were compared, the highest HR value is 2.79 when size cutoff is 3/9cm. Then, we reclassified patients into three new classifications: ≤ 3cm (n = 422), > 3 and ≤ 9cm (n = 1072), and > 9cm (n = 266). The comparison of clinicopathologic characteristics among these three classifications showed that the increase of tumor size was associated with the increase of α-fetoprotein (AFP), microvascular invasion (MVI), tumor differentiation, and liver cirrhosis. And the comparison of the OS among three classifications showed statistical differences. Conclusions This study suggested that size criteria of 3cm and 9cm in solitary HBV-related HCC patients were appropriate based on biological characteristics and prognostic significance.
Aspects of the development of Ixodes anatis under different environmental conditions in the laboratory and in the field
Authors: Bansal Natasha , Pomroy William , Heath Allen C , Castro Isabel 
Published: July 2020

Abstract
Background Numerous laboratory and few field-based studies have explored the influence of microclimates on developmental times of different stages of various species of ixodid ticks and found that most of these species develop quicker and survive better at temperatures between 18 and 26°C and relative humidity between 75% and 94%. Ixodes anatis Chilton, 1904, or kiwi tick, is an endophilic, nidicolous species endemic to North Island brown kiwi (Apteryx mantelli, NIBK) and the tokoeka (Apteryx australis). Little is known about the environmental conditions that are ideal for the development of the kiwi tick. Our aims in this study were to determine and compare the conditions of temperature and RH that ensured the best survival, and the shortest interstadial periods for the kiwi tick, in the laboratory and outdoors inside artificial kiwi burrows.Methods We collected free walking engorged ticks off wild kiwi hosts and placed them in the laboratory at various fixed temperature and humidity regimes. We also placed sets of different stages of these ticks in artificial kiwi burrows and in both cases, recorded the times taken for the ticks to moult to the next stage.Results We found that larvae and nymphs both showed optimum development between 10-20°C, which is lower than many other species of ixodid ticks. However, larvae moulted quicker and survived better when saturation deficits were <1-2 mmHg (RH>94%) while for nymphs the optimum saturation deficits were 1-10 mmHg.Conclusions We believe that the kiwi tick has adapted to stable, but relatively cool and humid conditions in the burrows reflecting the evolutionary consequences of its association with the kiwi.
Inter-scanner reproducibility of brain volumetry: influence of automated brain segmentation software
Authors: Liu Sirui , Hou Bou , Zhang Yiwei , Lin Tianye , Fan Xiaoyuan , You Hui , Feng Feng 
Published: July 2020

Abstract
Background: The inter-scanner reproducibility of brain volumetry is important in multi-site neuroimaging studies, where the reliability of automated brain segmentation (ABS) tools plays an important role. This study aimed to evaluate the influence of ABS tools on the consistency and reproducibility of the quantified brain volumetry from different scanners. Methods: We included fifteen healthy volunteers who were scanned with 3D isotropic brain T1-weighted sequence on three different 3.0 Tesla MRI scanners (GE, Siemens and Philips). For each individual, the time span between image acquisitions on different scanners was limited to one hour. All the T1-weighted images were processed with FreeSurfer v6.0, FSL v5.0 and AccuBrain ® with default settings to obtain volumetry of brain tissues (e.g. gray matter) and substructures (e.g. basal ganglia structures) if available. Cofficient of variation (CV) was calculated to test inter-scanner variability in brain volumetry of various structures as quantified by these ABS tools. Results: The mean inter-scanner CV values per brain structure among three MRI scanners ranged from 6.946% to 12.29% (mean, 9.577%) for FreeSurfer, 7.245% to 20.98% (mean, 12.60%) for FSL and 1.348% to 8.800% (mean value, 3.546%) for AccuBrain @ . In addition, AccuBrain ® and FreeSurfer achieved the lowest mean values of region-specific CV between GE and Siemens scanners (from 0.818% to 5.958% for AccuBrain ® , and from 0.903% to 7.977% for FreeSurfer), while FSL-FIRST had the lowest mean values of region-specific CV between GE and Philips scanners (from 2.603% to 16.310%). AccuBrain ® also had the lowest mean values of region-specific CV between Siemens and Philips (from 1.138% to 6.615%). Conclusion: There is a large discrepancy in the inter-scanner reproducibility of brain volumetry when using different processing software. Image acquisition protocols and selection of ABS tool for brain volumetry quantification have impact on the robustness of results in multi-site studies.
Pericardial fat and its influence on cardiac diastolic function
Authors: de Wit-Verheggen Vera , Altintas Sibel , Spee Romy , Mihl Casper , Kuijk Sander van , Wildberger Joachim , Schrauwen-Hinderling Vera , Kietselaer Bas , de Weijer Tineke van 
Published: July 2020

Abstract
Background Pericardial fat (PF) has been suggested to directly act on cardiomyocytes, leading to diastolic dysfunction. The aim of this study was to investigate whether a higher PF volume is associated with a lower diastolic function in healthy subjects.Methods 254 adults (40-70 years, BMI 18-35 kg/m2, normal left ventricular ejection fraction), with (a)typical chest pain (otherwise healthy) from the cardiology outpatient clinic were retrospectively included in this study. All patients underwent a coronary computed tomographic angiography for the measurement of pericardial fat volume, as well as a transthoracic echocardiography for the assessment of diastolic function parameters. To assess the independent association of PF and diastolic function parameters, multivariable linear regression analysis was performed. To maximize differences in PF volume, the group was divided in low (lowest quartile of both sexes) and high (highest quartile of both sexes) PF volume. Multivariable binary logistic analysis was used to study the associations within the groups between PF and diastolic function, adjusted for age, BMI, and sex.Results Significant associations for all four diastolic parameters with the PF volume were found after adjusting for BMI, age, and sex. In addition, subjects with high pericardial fat had a reduced left atrial volume index (p=0.02), lower E/e (p<0.01) and E/A (p=0.01), reduced e’ lateral (p<0.01), reduced e’ septal p=0.03), compared to subjects with low pericardial fat.Conclusion These findings confirm that pericardial fat volume, even in healthy subjects with normal cardiac function, is associated with diastolic function. Our results suggest that the mechanical effects of PF may limit the distensibility of the heart and thereby directly contribute to diastolic dysfunction.Trial registration NCT01671930
The role of the Oncostatin M/ OSM receptor β axis in activating dermal microvascular endothelial cells in Systemic Sclerosis
Authors: Marden Grace , Wan Qianqian , Wilks James , Nevin Katherine , Feeney Maria , Wisniacki Nicolas , Trojanowski Marcin , Bujor Andreea , Stawski Lukasz , Trojanowska Maria 
Published: July 2020

Abstract
Background: Scleroderma (SSc) is a rare autoimmune disease characterized by vascular impairment and progressive fibrosis of the skin and other organs. Oncostatin M, a member of the IL-6 family, is elevated in SSc serum and was recognized as a significant player in various stages of fibrosis. The goal of this study was to assess the contribution of the OSM/OSMRβ pathway to endothelial cell (EC) injury and activation in SSc. Methods: IHC and IF were used to assess the distribution of OSM and OSMRβ in SSc (n=14) and healthy control (n=7) skin biopsies. Cell culture experiments were performed in human dermal microvascular endothelial cells (HDMECs) and included mRNA and protein analysis, and cell migration and proliferation assays. Ex vivo skin organoid culture was used to evaluate the effect of OSM on perivascular fibrosis.Results: OSMRβ protein was elevated in dermal ECs and in fibroblasts of SSc patients. Treatments of HDMECs with OSM or IL-6 +sIL-6R have demonstrated that both cytokines similarly stimulated proinflammatory genes and genes related to endothelial-to mesenchymal transition ((EndMT). OSM was more effective than IL-6+sIL-6R in inducing cell migration, while both treatments similarly induced cell proliferation. The effects of OSM were mediated via OSMRβ and STAT3, while the LIFR did not contribute to these responses. Both, OSM and IL-6+sIL-6R induced profibrotic gene expression in HDMECs, as well as expansion of the perivascular PDGFRβ+ cells in the ex vivo human skin culture system. Additional studies in HDMECs showed that siRNA-mediated downregulation of FLI1 and its close homolog ERG resulted in increased expression of OSMRβ in HDMECs.Conclusions: This work provides new insights into the role of the OSM/OSMRβ axis in activation/injury of dermal ECs and supports the involvement of this pathway in SSc vascular disease.
Determinants of deranged thyroid function parameters in children admitted for management of diabetic ketoacidosis/diabetic ketosis
Authors: Shao Peng , Guo Shujuan , Li Guimei , Qin Daogang , Li Sen , Ying Luan 
Published: July 2020

Abstract
Background: Sick euthyroid syndrome is frequent in children admitted with diabetic ketoacidosis/diabetic ketosis (DKA/DK). This study evaluates the interplay of various metabolic factors with occurrence of deranged thyroid function tests in children admitted for management of DKA/DK.Methods: 98 DKA and 96 DK children patients were selected from hospital records, among which individuals on thyroxine replacement, with overt hypothyroidism or positive anti-thyroperoxidase (TPO) antibody were excluded. Tests for liver function, renal function, lipid profile, serum osmolarity, thyroid function, c-peptide levels, and glycosylated hemoglobin were done for all. Children were divided into euthyroid (n=88) and euthyroid sick syndrome（ESS）groups (n=106).Results: The ESS group had a higher level of white blood cell count (WBC), plasma glucose (PG), beta-hydroxybutyric acid (β-HB), triglyceride (TG), anion gap (AG), glycosylated hemoglobin (HbA1c) and a lower level of HCO3-, prealbumin (PA), and albumin (ALB) compared with the euthyroid group (P<0.05). Free T3 (FT3) levels were significantly correlated to β-HB, HCO3-, AG, PA, and HbA1c (r=-0.642, 0.681, -0.377, 0.581, -0.309, respectively; P<0.01). Free T4 （FT4） levels were significantly correlated to β-HB, HCO3-, and ALB levels (r=-0.489, 0.338, 0.529, respectively; P<0.01). TSH levels were significantly affected by HCO3– only (r=-0.28; P<0.01). HCO3– level was the most important factor deciding euthyroid or ESS on logistic regression analysis (OR=0.844, P=0.004, 95%CI=0.751­-0.948).Conclusions: Lower levels of free thyroid hormones and occurrence of ESS were associated with a higher degree of acidosis in children with DKA/DK.
Ferritin modifies the relationship between inflammation and arterial stiffness in hypertensive patients with different glucose tolerance
Authors: Sciacqua Angela , Ventura Ettore , Tripepi Giovanni , Cassano Velia , D'Arrigo Graziella , Roumeliotis Stefanos , Maio Raffaele , Miceli Sofia , Perticone Maria , Andreozzi Francesco , Sesti Giorgio , Perticone Francesco 
Published: July 2020

Abstract
Backgroud: Ferritin, a crucial element for iron homeostasis, is associated with chronic diseases characterized by subclinical inflammation such as essential arterial hypertension and type 2 diabetes mellitus (T2DM), showing a prognostic value in different clinical settings. We investigated whether ferritin is associated with arterial stiffness (AS), an early indicator of atherosclerosis, and if it could act as effect modifier on the relationship between inflammation and AS in hypertensive patients with different glucose tolerance.Methods: We enrolled 462 newly diagnosed untreated hypertensive (HT) patients. All subjects underwent an oral glucose tolerance test. Insulin sensitivity was assessed by MATSUDA index and ferritin levels were estimated by immunoradiometric assay. AS was defined by carotid-femoral pulse wave velocity (PWV). Results: Out of 462 patients, 271 showed normal glucose tolerance (HT/NGT), 146 impaired glucose tolerance (HT/IGT) and 45 were diabetic (HT/T2DM). Iron levels significantly decreased and transferrin and ferritin significantly increased from the first to the third group. PWV values were significantly higher in HT/IGT and HT/T2DM patients. PWV was related directly with ferritin, high sensitivity C reactive protein (hs-CRP), transferrin, and inversely with MATSUDA index. Ferritin resulted the strongest determinant of PWV explaining a 14.9% of its variation; moreover it was a strong modifier of the relationship between hs-CRP and PWV. The estimated augmentation in PWV portended by a fixed increase in hs-CRP, was higher across increasing values of ferritin.Conclusion: Ferritin represents an independent risk factor of arterial stiffness in our study population and a strong effect modifier on the relationship between inflammation and PWV. However, further studies are needed to fully elucidate the potential role of this biomarker in human atherosclerosis.
Identification of a 4-lncRNA Signature Predicting Prognosis of Patients with Non-Small Cell Lung Cancer: a Multicenter Study in China
Authors: Wang Rui-Qi , Long Xiao-Ran , Ge Chun-Lei , Zhang Mei-Yin , Huang Long , Zhou Ning-Ning , Hu Yi , Li Rui-Lei , Li Zhen , Chen Dong-Ni , Zhang Lan-Jun , Wen Zhe-Sheng , Mai Shi-Juan , WANG HUI-YUN 
Published: July 2020

Abstract
Background: Previous findings have indicated that the tumor, nodes, and metastases (TNM) staging system is sub-optimal in terms of predicting survival outcomes in patients with non-small lung carcinoma (NSCLC).Thus, the aims to identify a long non-coding RNA (lncRNA) signature for predicting survival in patients with NSCLC and to provide additional prognostic information in combination with the TNM system.Methods: Patients with NSCLC were recruited from a hospital and divided into a discovery cohort (n=194) and validation cohort (n=172), and detected using a custom lncRNA microarray. Lung tissues obtained from patients at a different hospital (n = 73, independent validation cohort) were examined via qRT-PCR. Differentially expressed lncRNAs were determined with the Significance Analysis of Microarrays program and used to identify those associated with survival in the discovery cohort. These prognostic lncRNAs were employed to construct a prognostic signature with a risk-score method. Then, the utility of the prognostic signature was confirmed using the validation cohort and the independent cohort. Results: In the discovery cohort, we identified 305 lncRNAs that were differentially expressed between the NSCLC tissues and matched, adjacent normal lung tissues, of which 15 are associated with survival; a 4-lncRNA prognostic signature was identified from the 15 survival lncRNAs, which was significantly correlated with survivals of NSCLC patients. This signature was further validated in the validation cohort and independent cohort. Moreover, multivariate Cox analysis demonstrates that the 4-LncRNA signature is an independent survival predictor. Then we established a new risk-score model by combining 4-lncRNA signature and TNM stage. The receiver operating characteristics (ROC) curve indicates that the prognostic value of the combined model is significantly higher than that of the TNM stage alone, in all the cohorts. Conclusions: In this study, we identified a 4-lncRNA signature that can potentially serve as a powerful prognosis biomarker and can provide additional survival information to the traditional TNM staging system.