bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relatives of patients with metastatic lung cancer’s views on the achievement of treatment goals and the choice to start treatment: an interview study
Authors: Mieras Adinda , Onwuteaka-Philipsen Bregje D. , Becker-Commissaris Annemarie , Bos Jose C.M. , Pasman H.Roeline W. 
Published: March 2020

Abstract
Purpose. Lung cancer has a high impact on both patients and relatives. Previous studies looked into treatment goals patients have before starting a treatment. However, studies on relatives’ perceptions of treatment at the end of life are scarce. Therefore, we studied the perspectives of relatives in hindsight on the achievement of treatment goals and the choice to start treatment for metastatic lung cancer of their loved one.Methods. We conducted a semi-structured telephone interview study in six hospitals across the Netherlands, one academic and five non-academic hospitals between February 2017 and November 2019. We included 118 relatives of deceased patients diagnosed with metastatic lung cancer who started a systemic treatment and who completed a questionnaire on their treatment goals before start of the treatment and when treatment was finished. We asked the relatives about the achievement of patients’ treatment goals and relatives’ satisfaction with the choice to start treatment.Results. Relatives reported the goals ‘quality of life’, ‘decrease tumour size’ and ‘life prolongation’ as achieved in 21%, 37% and 41% respectively. Most of the relatives (78%) were satisfied with the choice to start a treatment. Also, when none of the goals were achieved, 70% of the relatives were satisfied. About one in two relatives who were satisfied with the patient’s choice did mention negative aspects of the treatment choice, such as that the treatment did not work, that there were side effects or that it would not have been the relatives choice. This was four in five for relatives who were not satisfied. Most mentioned positive aspects were that they tried everything and that it was the patient’s choice. Conclusion. Relatives reported patients’ treatment goals as not achieved in a majority of cases. They were, however, in majority of the cases satisfied about the treatment choice. Being satisfied does not provide a full picture of their experience with the treatment decision as a majority mentions negative aspects of this decision. At the time of making the treatment decision it is important to manage expectations about chance of success and possible side effects of the treatment.
A Serological Survey of Brucellosis in Wildlife in Four Major National Parks of Uganda
Authors: Aruho Robert , MacLeod Ewan T. , Manirakiza Leonard , Rwego Innocent Bidason 
Published: March 2020

Abstract
Background: Brucellosis is a contagious zoonotic disease of great public health and economic significance especially in developing countries. The disease affects humans and several species of livestock and wildlife. Studies on Brucellosis in wildlife in Uganda have been limited to single populations particularly in Queen Elizabeth National Park. This study aimed at estimating the seroprevalence of Brucella spp. in wildlife in four major national parks of Uganda. This was a retrospective survey which utilized archived samples collected from wildlife during the annual disease surveillance activities between 2013 and 2017. Results: A total of 241 samples from seven species namely African buffalo (Syncerus caffer, n = 109), African elephant (Loxodonta africana, n = 20), giraffe (Giraffa camelopardalis rothschildi, n = 41), Ugandan kob (Kobus kob thomasi, n = 36), lion (Panthera leo, n = 6), plain zebra (Equus quagga, n = 25), and bushbuck (Tragelaphus scriptus, n = 2), were tested for antibodies using the Rose Bengal Plate Test. The overall seroprevalence in the four national parks was 31.1% (75/241; 95% CI: 25.6 - 37.2). Kidepo Valley National Park had a significantly higher seroprevalence of 55.9% (19/34; 95% CI: 39.5 - 71.1) compared to other sampled national parks (p < 0.05). Lions had the highest seroprevalence at 66.7% (4/6; 95% Confidence Interval [CI]: 30.00 – 90.3), followed by African buffalo with 48.6% (53/109; 95% CI: 39.5 - 57.9). There were no antibodies for Brucella spp. detected in African elephant and bushbuck. Conclusion: This study shows variations in prevalence of brucellosis between species and across national parks and notably a high prevalence of brucellosis in wildlife in Uganda than that recorded elsewhere in sub-Saharan region of Africa. Potential for transmission to other wildlife and spill over to livestock is high especially in national parks with high livestock-wildlife interaction.
Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis
Authors: Guo Mengzhou , Yuan Feifei , Qi Feng , Sun Jialei , Rao Qianwen , Zhao Zhiying , Huang Peixin , Fang Tingting , Yang Biwei , jinglin xia 
Published: March 2020

Abstract
Background FGL1-LAG-3 pathway is a promising immunotherapeutic target and has synergistic effect with PD-1/PD-L1. However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unkonwn. Method The distributions, associations, and clinical significances of LAG-3, FGL1, PD-L1 and CD8 protein expression in 143 HCC patients were assessed by multiplex immunofluorescence. Results We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3 + cells but not PD-L1. CD8 + T cells densities had positive correlation with PD-L1 levels and negative asscociation with FGL1 expression. Elevated densities of LAG-3 + cells and low levels of CD8 + T cells were correlated with poor disease outcome.Moreover,LAG-3 + cells deteriorated patient stratification based on the abundance of CD8 + T cells. Paitents with positive PD-L1 expression on tumor cells (PD-L1TC + ) tended to have a improved survival than that with negative PD-L1 expression on tumor cells (PD-L1TC - ). Futhermore, PD-L1TC - in combination with high densities of LAG-3 + cells showed the worst prognosis, and PD-L1TC + patients with low densities of LAG-3 + cells had the best prognosis. Conclusions LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3 + cells and CD8 + T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively. Levels of LAG-3 + cells in combination with PD-L1 status on tumor cells have potential to identify patients who may benefit from immune checkpoints blockade combination strategies.
Dysregulation of HULC promotes contrast-induced nephropathy (CIN) via regulating signaling pathway of micorRNA-512 and prostaglandin E1 (PGE1)
Authors: Zhang Liang , Li Pan , Zhang Bi-li , Yu Man-li , Xu Rong-liang , Wu Hong , Chen Shao-ping 
Published: March 2020

Abstract
Background It has been shown that contrast-induced nephropathy (CIN) could be attenuated by the administration of PGE1. As an enzyme responsible for the production of PGE1, PTGS1 is confirmed in this study as a miR-512 target. Meanwhile, HULC has been identified as a competing endogenous RNA of miR-512. Therefore, in this study, we tested the diagnostic value of HULC and miR-512 in subjects with or without CIN. In addition, we evaluated the regulatory relationship among HULC, miR-512, PTGS1 and PGE1 in vitro. Methods We enrolled 320 patients with coronary heart disease and divided them into a CIN group and a non-CIN group. Subsequently, we detected the differential expression of miR-512, HULC and PGE1 in the two groups. We also used a dual luciferase reporter assay to evaluate the regulatory relationship among HULC, miR-512, PTGS1 and PGE1 in THP-1 cells. Results In patients with CIN, the expression levels of HULC and PGE1 were lower, but the expression level of miR-512 was higher. MiR-512 could directly bind to and negatively regulate the expression of PTGS1 and HULC. The expression of HULC is positively correlated with the expression of PTGS1 and PGE1, while negatively correlated with the expression of miR-512. Conclusions MiR-512 is highly expressed in patients with CIN and promotes the progression of CIN by negatively regulating the expression of PTGS1 and HULC.
Human fetal skin-derived stem cell secretome reduce liver fibrosis by regulating TGF-β/Smad signal pathway
Authors: Yao Xia , Wang Jing , Zhu Jiajing , Rong Xiaoli 
Published: March 2020

Abstract
Background: Liver fibrosis resulting from chronic liver injury is one of the major causes of mortality worldwide. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease, while maintaining its advantages. Methods: In this study, we investigated the effect of human fetal skin-derived stem cells (hFFSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFFSCs secretome in liver fibrosis, we established the CCl4-induced rat liver fibrosis model, and administered hFFSCs secretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFFSCs secretome in hepatic stellate cells (HSCs). Results: Our results showed that hFFSCs secretom effectively reduced collagen content in liver, improved the liver function and promoted liver regeneration. In addition, we found that hFSSC secretom inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, however, increased Smad7 expression. Conclusions: In conclusions, our results suggest that hFFSCs secretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.
A novel β-N-acetyl glucosaminidase from Chitinolyticbacter meiyuanensis possessing transglycosylation activity and its use in generating long-chain N-acetyl chitooligosaccharides
Authors: Zhang Alei , Mo Xiaofang , Zhou Ning , Wang Yingying , Wei Guoguang , Chen Jie , Chen Kequan , Ouyang Pingkai 
Published: March 2020

Abstract
Background: N-acetyl glucosamine (GlcNAc) and N-acetyl chitooligosaccharides (N-acetyl COSs) exhibit antitumor and antimicrobial activities, and have been widely used in the pharmaceutical, agriculture, food, and chemical industries. Thus, it is crucial to discover a NAGase that can both synthesize GlcNAc and N-acetyl COSs. Results: The gene encoding the novel β-N-acetyl glucosaminidase, designated CmNAGase, was cloned from Chitinolyticbacter meiyuanensis SYBC-H1. The deduced amino acid sequence of CmNAGase contains a glycoside hydrolase family 20 catalytic module that shows low identity with the corresponding domain of the well-characterized NAGases. CmNAGase gene was highly expressed with soluble form in Escherichia coli BL21 (DE3) cells, whereupon it had a specific activity of 4,878.6 U/mg of protein toward p-nitrophenyl-N-acetyl glucosaminide. CmNAGase had a molecular mass of 92 kDa, and its optimum activity was at pH 5.4 and 40ºC. The Vmax, Km, and Kcat of CmNAGase were 833.33 μmol·L-1 ·min-1, 10.9 mmol, and 6.37 ´ 108 mM·mg-1, respectively. Analysis of the hydrolysis products of N-acetyl chitooligosaccharides and colloidal chitin revealed that CmNAGase exhibits exo-acting activities. Particularly, it possesses transglycosylation activity, which can synthesize (GlcNAc)n+1 from (GlcNAc)n (n=1−6), respectively. In addition, CmNAGase also can catalyze GlcNAc to its dimers with various linked forms. Conclusions: The observations recorded in this study that CmNAGase is an exo NAGase with unique transglycosylation activity, suggests a possible application in the production of long-chain N-acetyl CHOs. This is first report of a bacterial NAGase, which can produce long-chain N-acetyl COSs via transglycosylation activity.
WITHDRAWN: Targeting exosomal miR-488 inhibits head and neck squamous cell carcinoma growth by mediating RAB25
Authors: Wang Xueping , Zhu Xiaoyuan , Zhao Yulin 
Published: March 2020

Abstract
Background: Cancer cell-derived exosomes and its packaged miRNAs have been identified to regulate tumor growth and progression. However, its role in head and neck squamous cell carcinoma (HNSCC) and the potential mechanism still need to be further investigated. Methods: RNA sequencing was conducted to select the dysregulated genes in HNSCC. Gene ontology (GO) analysis and TCGA database were performed to analyze the potential candidate genes for HNSCC progression. Cell viability was analyzed using MTT, and colony formation was visualized using crystal violet staining. Luciferase reporter assay was employed to identify the interaction between miR-488 and RAB25. The role of miR-488 and RAB25 in tumor growth and drug response were investigated in vivo and in vitro. Results: The dysregulated genes in HNSCC captured the signaling of exosomes biogenesis dysfunction. Compared with the normal cells NP69, HNSCC cells had enriched exosomes and its packaged miRNAs, including miR-488. Luciferase reporter assay showed that RAB25 is a downstream target of miR-488. RAB25 was downregulated in HNSCC patients and predicted a poor prognosis. MiR-488/RAB25 signaling controlled cancer cell viability and colony formation ability in vitro and growth in vivo. Importantly, targeting miR-488 significantly inhibited tumor growth and promoted drug response to chemotherapy, suggesting a potential therapeutic promising for HNSCC. Conclusion These findings demonstrate a tumor-cell derived exosomal miR-488 promotes tumor growth by targeting RAB25 that could be targeted for HNSCC treatment.
Assessment of Right Ventricular Function in Children with Sickle Cell Anaemia Seen in Enugu, Nigeria.
Authors: Chinawa Josephat Maduabuchi , Chukwu Bartholomew F , Chinawa Awoere T , Ossai Ndudi , Ikefuna Anthony N , Aronu Ann E , Obidike Egbuna O 
Published: March 2020

Abstract
Background: Sickle cell anaemia (SCA) is characterized by attendant ischemia-reperfusion injury especially to the heart. Objectives: To compare the right ventricular function of children with SCA in steady state (subjects) with those with haemoglobin AA genotype (controls), using echocardiography. Methods: The cross-sectional study utilized echocardiographic measurements to assess right ventricular function among children with SCA and their controls. Results: The mean trans annular plane systolic excursion (TAPSE) in subjects, 28.24±5.23 (Z score: 0.258±1.10) was higher than that in control, 25.82±3.59 (Z score: - 0.263±0.80), and the difference in mean was statistically significant, (t=2.703, p=0.008). Significantly higher proportion of subjects with sickle cell anaemia had right ventricular dysfunction (Abnormal TAPSE), 25 (50.0% when compared with those in control, 11 (22.0%, (χ 2 =8.5, p=0.0035). A higher proportion of subjects with sickle cell anaemia (25.5%) had Pulmonary hypertension (RVP) when compared with control (2.0%) and the difference in proportions was found to be statistically significant, (χ 2 =11.668, p=0.001). The prevalence of right ventricular diastolic dysfunction in subjects was 9.8 % while control was 0%. Conclusion Children with sickle cell anaemia present with right ventricular dysfunction. Prevalence of right ventricular systolic and diastolic dysfunction were higher in subjects. More children with genotype SS group, (25.5%) had pulmonary hypertension (RVP). Key words: Anaemia; children; Enugu; sickle cell anaemia; right ventricular function
Investigation into the reproducibility of the association of cord blood magnesium concentration and cerebral palsy or death in children
Authors: Dixon Christopher Luke , Liu Xiaoxi , Balch Alfred , Costantine Maged , Sherwin Catherine M. 
Published: March 2020

Abstract
Objective: To evaluate the association of cord blood magnesium concentrations at the time of birth with cerebral palsy (CP) and neonatal death. Study Design: A secondary analysis of a randomized controlled trial that randomized women at imminent risk of delivery between 24 and 31 weeks of gestation to receive magnesium sulfate or placebo. This ‘study’s primary outcome was a composite of either moderate to severe CP or death. Secondary outcomes included CP, moderate to severe CP, neonatal death, and neonatal head ultrasound findings. We used a logistic regression model to evaluate the relationship between the concentration of magnesium in cord blood and study outcomes. Results: A total of 668 women were included in this analysis and were randomized to magnesium sulfate at 28 ± 2.5 ‘weeks’ gestation. Cord blood magnesium concentrations were not associated with the primary outcome of infant death by 1 year of age or moderate or severe cerebral palsy, as assessed at or beyond 2 years of age (aOR 0.95 (0.67, 1.36), p = 0.79). Cord blood magnesium concentrations were not associated with any of the secondary outcome measurements. Conclusion: Cord blood magnesium concentrations were not associated with moderate to severe cerebral palsy or death, or other neurodevelopmental or sonographic outcomes.
Preterm birth determinants among newborns at six public hospitals in Northeast Amhara, Ethiopia: unmatched case-control study
Authors: Shiferaw Mesfin , Tebeje Nigusie Birhan , Mekonnen Habtamu Sewunet 
Published: March 2020

Abstract
Background Preterm birth is a global public health problem. Worldwide, every year about 15 million newborns are born preterm and about 1.1 million of them die due to complications related to prematurity. More than 81% of preterm births were in Asia and Sub-Saharan Africa. Nowadays, preterm birth is the first leading cause of under-five mortality and is one of the limiting factors for achieving a reduction in under-five mortality rate. Therefore, the aim of this study was to identify the determinants of preterm birth at public hospitals in the Northeast Amhara, Ethiopia, 2019. Method Hospital-based unmatched case-control study was conducted at public hospitals in Northeast Amhara, Ethiopia from March 15 th to April 25 th , 2019. Data were collected using interviewer-administered structured pre-tested tool and document review for cases and controls. Data were entered in to Epi Info version 7.2.2.6 and exported to SPSS version 23 software for data analysis. Bi-variable and multivariable binary logistic regression were used to measure the association between preterm birth and risk factors. Adjusted Odds ratio (AOR) at 95% confidence interval (CI) was calculated and P value ≤0.05 declared statistically significant. Result The study identified that ANC follow up less than four visits [AOR 2.267, Cl (1.205, 4.264)], pregnancy-induced hypertension [AOR 4.453, Cl (1.276, 15.536)], no iron/folic acid supplementation during pregnancy [AOR 4.175, Cl (1.632, 10.680)], anemia during pregnancy [AOR 4.776, Cl (1.492, 15.285)], and birth defect [AOR 6.160, Cl (l.896, 20.013)] were significantly associated determinants of preterm birth. Conclusion Antenatal care follow up fewer than four visits, pregnancy induced hypertension, no iron/folic acid supplementation during pregnancy, being anemic during pregnancy, and birth defect were important determinants of preterm birth.
Analysis of KIF2C, 4A, 10, 11, 14, 18B, 20A, and 23 in HCC and their clinical significance as new-born prognostic markers of HCC
Authors: Qiu Meng-jun , Wang Qiu-shuang , He Xiao-xiao , Li Qiu-ting , Jiang Xin , Xiong Zhi-fan , Yang Sheng-li 
Published: March 2020

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. However, the molecular mechanism of its pathogenesis remains to be studied. This study aimed to identify potential KIF genes associated with HCC progression. Methods: We used bioinformatics to initially analyze the expression level and prognostic significance of KIF factors in HCC. Results: We found that compared with the normal control group, KIF2C, 4A, 10, 11, 14, 18B, 20A, and 23 mRNA expression levels increased significantly in HCC. 8 KIF factors had different levels of gene amplification, depth to delete, and missense mutation, and were closely related to the clinical-pathologic stage. Gene set enrichment analysis showed that high mRNA expression of 8 KIF factors in HCC patients were associated with cell cycle, mismatch repair, homologous recombination, and DNA replication. Conclusions: This study expands our understanding of KIF factors in HCC and can provide a theoretical basis for further basic and clinical research in HCC.
Allogeneic hematopoietic stem cell transplantation can improve the prognosis of high-risk pediatric t (8;21) acute myeloid leukemia in first remission based on MRD-guided treatment
Authors: Hu Guan-hua , Cheng Yi-fei , Lu Ai-dong , Wang Yu , Zuo Ying-xi , Yan Chen-hua , Wu Jun , Sun Yu-qian , Suo Pan , Chen Yu-hong , Chen Huan , Jia Yue-ping , Liu Kai-yan , Han Wei , Xu Lan-ping , Zhang Leping , Huang Xiao-jun 
Published: March 2020

Abstract
Background Pediatric acute myeloid leukemia (AML) with t (8;21) (q22;q22) or RUNX1-RUNX1T1 rearrangement is classified as a low-risk group. However, relapse is still the main factor affecting survival. The purpose of this study was to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t (8;21) AML based on MRD-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and define who will benefit from allo-HSCT. Methods Overall, 129 newly diagnosed pediatric patients with AML with t (8;21) were included in this study. The patients were divided into a high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after two cycles of consolidation chemotherapy. We recommended allo-HSCT for the high-risk group and chemotherapy for the low-risk group. The characteristics and outcomes of 125 patients were analyzed.Results For the high-risk patients, allo-HSCT improved event-free survival (EFS) compared to chemotherapy (87.4% [95% CI, 86%–108.7%]) vs. 61.9% [95% CI, 51.96%–80.41%]; P = 0.026). Overall survival (OS) of the high-risk HSCT group was better than that of the high-risk-chemo group but the difference was not statistically significant (82.8% [95% CI, 78.6%–101.7%]) vs. 71.4% [95% CI, 62.09%–87.6%]; P = 0.26). The EFS of the C-KIT+ high-risk-HSCT group was better than that of the C-KIT+ high-risk-chemo group but the difference was not statistically significant (82.9% [95% CI, 59.3%–84.8%]) vs. 75% [95% CI, 49.3%–85.6%]; P = 0.4). Extramedullary infiltration (EI) at diagnosis was associated with high cumulative incidence of relapse for high-risk patients (50% [95% CI, 17.2%–66.5%]) vs. 18.4% [95% CI, 3.0%–18.9%]; P = 0.004); allo-HSCT can improve survival (P = 0.009). Conclusions allo-HSCT can improve the prognosis of high-risk pediatric t (8;21) AML based on MRD-guided treatment. Patients with KIT mutation may benefit from allo-HSCT, but this result was not statistically significant. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.