bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dromedary camel CD14high MHCIIhigh monocytes display inflammatory properties and are reduced in newborn camel calves
Authors: Hussen Jamal , Shawaf Turke , Al-Mubarak Abdullah I. A. , Al Humam Naser Abdallah , Almathen Faisal , Schuberth Hans-Joachim 
Published: February 2020

Abstract
Background
In human and different animal species, blood monocytes are classified based on their expression pattern of different monocytic markers into phenotypically and functionally different subsets. In the current study, we used flow cytometry and monoclonal antibodies to CD172a, CD14, CD163 and MHCII to identify monocyte subsets in peripheral blood of dromedary camels.

Results
Based on CD14, CD163 and MHCII expression, camel CD172a + monocytes were divided into three subsets: The major subpopulation of camel monocytes (mo-I) showed high expression of CD14 and CD163, but low expression of MHCII. A second subset of monocytes (mo-II) expressed highly all three markers, CD14, CD163 and MHCII. A third monocyte subset (mo-III) displayed low expression of CD14 and CD163 with high MHCII expression. While the two MHCIIhigh subsets (mo-II and mo-III) showed higher expression of CD11a in comparison to the MHCIIlow subset (mo-I), CD18 and CD11b were highest expressed on the two CD14high subsets (mo-I and mo-II). Bacterial stimulation of camel leukocytes identified mo-II cells as an antimicrobial monocyte subset with the highest phagocytic and ROS production capacity. The comparison of monocyte counts and phenotype between newborn calves and adult camels revealed significantly reduced numbers of mo-II cells in newborn animals. Monocytes of newborns expressed significantly more CD172a and CD163 molecules but less CD14 and MHCII molecules than monocytes of adult camels.

Conclusions
Camel monocyte subsets, mo-I, mo-II and mo-III are counterparts of bovine classical, intermediate and non-classical monocytes respectively. The distribution of camel monocyte subsets is influenced by age.
Exploring and analysing single cell multi-omics data with VDJView
Authors: Samir Jerome , Rizzetto Simone , Gupta Money , Luciani Fabio 
Published: February 2020

AbstractBackgroundSingle cell RNA sequencing provides unprecedented opportunity to simultaneously explore the transcriptomic and immune receptor diversity of T and B cells. However, there are limited tools available that simultaneously analyse large multi-omics datasets integrated with metadata such as patient and clinical information.ResultsWe developed VDJView, which permits the simultaneous or independent analysis and visualisation of gene expression, immune receptors, and clinical metadata of both T and B cells. This tool is implemented as an easy-to-use R shiny web-application, which integrates numerous gene expression and TCR analysis tools, and accepts data from plate-based sorted or high-throughput single cell platforms. We utilised VDJView to analyse several 10X scRNA-seq datasets, including a recent dataset of 150,000 CD8+T cells with available gene expression, TCR sequences, quantification of 15 surface proteins, and 44 antigen specificities (across viruses, cancer, and self-antigens). We performed quality control, filtering of tetramer non-specific cells, clustering, random sampling and hypothesis testing to discover antigen specific gene signatures which were associated with immune cell differentiation states and clonal expansion across the pathogen specific T cells. We also analysed 563 single cells (plate-based sorted) obtained from 11 subjects, revealing clonally expanded T and B cells across primary cancer tissues and metastatic lymph-node. These immune cells clustered with distinct gene signatures according to the breast cancer molecular subtype. VDJView has been tested in lab meetings and peer-to-peer discussions, showing effective data generation and discussion without the need to consult bioinformaticians.ConclusionsVDJView enables researchers without profound bioinformatics skills to analyse immune scRNA-seq data, integrating and visualising this with clonality and metadata profiles, thus accelerating the process of hypothesis testing, data interpretation and discovery of cellular heterogeneity. VDJView is freely available athttps://bitbucket.org/kirbyvisp/vdjview.
Prevalence and distribution patterns of allergens among children with asthma and asthma-like symptoms in Shanghai, China
Authors: Mao Song , Wu Liangxia , Shi Wenjing 
Published: February 2020

Abstract
Objective
We aimed to identify the prevalence and distribution patterns of allergens among Chinese children with asthma/asthma-like symptoms (ALS).

Methods
A total of 3479 children with asthma/ALS were enrolled. Skin prick test (SPT) was used to test the allergen-specific IgE. We analysed allergens prevalence and distribution, and its relationship with demographic characteristics.

Results
Aeroallergens prevalence was higher than that of food allergens (p < 10− 4). Boys had higher aeroallergens prevalence than that in girls (p < 10− 4). Significant difference of aeroallergens prevalence among cases with different parental allergy history was observed (p < 10− 4). Age was positively associated with aeroallergens prevalence before the age of 11.5 (P < 10− 4), particularly before the age of 2.42 (P < 10− 4). Age was negatively associated with aeroallergens prevalence after the age of 11.5 (P = 0.021). Age was negatively associated with food allergens prevalence before the age of 3.42 (P < 10− 4). Age was associated with the intensity of dermatophagoides farinae (DF)/house dust mite (HDM) allergens (P < 10− 4). Age was negatively associated with the intensity of shrimp, and crab allergens before the age of 3.3 and 3.3, respectively (P = 0.012, < 10− 4). Boys had higher intensity of DF and HDM allergens than that in girls (P < 10− 4, P < 10− 4). Significant differences of the intensity of DF and HDM allergens among groups with different parental allergy history were noted (P < 10− 4, P < 10− 4).

Conclusions
Boys and parental allergy history were associated with higher prevalence and intenstity of aeroallergens. Age was positively and negatively associated with aeroallergens prevalence before and after the age of 11.5, respectively. Age was negatively associated with food allergens prevalence before the age of 3.42.
Increased risk of cardiovascular mortality by strict glycemic control (pre-procedural HbA1c < 6.5%) in Japanese medically-treated diabetic patients following percutaneous coronary intervention: a 10-year follow-up study
Authors: Funamizu Takehiro , Iwata Hiroshi , Nishida Yuya , Miyosawa Katsutoshi , Doi Shinichiro , Chikata Yuichi , Shitara Jun , Endo Hirohisa , Wada Hideki , Naito Ryo , Ogita Manabu , Dohi Tomotaka , Kasai Takatoshi , Okazaki Shinya , Isoda Kikuo , Miyauchi Katsumi , Daida Hiroyuki 
Published: February 2020

Abstract
Background
In the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabetic patients undergoing percutaneous coronary intervention (PCI).

Methods
This is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: < 6.5% (n = 267), 6.5–7.0% (n = 268), 7.0–7.5% (n = 262), 7.5–8.5% (n = 287) and ≥ 8.5% (n = 244), and 7.0% > and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years.

Results
In the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan–Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c < 6.5% compared with those with 7.0–7.5% (P = 0.042). Multivariate Cox hazard analysis revealed a U-shaped relationship between preprocedural HbA1c level and risk of CV death, and the lowest risk was in the HbA1c 7.0–7.5% group (Hazard ratio of HbA1c < 6.5% compared to 7.0–7.5%: 2.97, 95% confidence interval: 1.33–7.25, P = 0.007). Similarly, univariate analysis revealed the lowest risk of sudden death was in the HbA1c 7.0–7.5% group.

Conclusion
The findings indicate an increased risk of CV mortality by strict glycemic control (HbA1c < 6.5%) in the secondary prevention of CV disease in Japanese patients with medically-treated diabetes.
Trial registration This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry UMIN-CTR 000035587).
Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis
Authors: Zheng Wei , Li Hui , Zhang Hui , Zhang Chao , Zhu Zhonglin , Liang Hong , Zhou Yifeng 
Published: February 2020

Abstract
Background
Rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) is a newly discovered oncogene in several diseases, such as breast cancer, non-small cell lung cancer and uveal melanoma. Nevertheless, its molecular role in colorectal cancer (CRC) remains unknown. This paper explored the role of RHPN1-AS1 in CRC progression.

Methods
qRT-PCR was used to detect relevant RNAs expression. CCK-8, EdU, flow cytometry, Transwell and western blot assays were performed to investigate the function of RHPN1-AS1 in CRC cells. Xenograft model was constructed to evaluate the effects of RHPN1-AS1 on tumor growth in vivo. Mechanical experiments were performed to investigate the relationship between relative genes.

Results
RHPN1-AS1 was significantly overexpressed in CRC cell lines. Knockdown of RHPN1-AS1 could inhibit cell proliferation, while stimulating cell apoptosis in vitro. Cell migration and invasion abilities were greatly suppressed after silencing RHPN1-AS1. Besides, signal transducer and activator of transcription 3 (STAT3) served as transcription factor of RHPN1-AS1. Moreover, miR-7-5p was identified as a target of RHPN1-AS1 and was negatively regulated by RHPN1-AS1 in CRC. MiR-7-5p inhibition rescued the oncogenic function of RHPN1-AS1. Additionally, O-GlcNAcylation transferase (OGT) was the downstream target of miR-7-5p. OGT overexpression could abrogate the anti-tumor effects of RHPN1-AS1 knockdown on CRC.

Conclusion
RHPN1-AS1 regulates CRC by mediating OGT through sponging miR-7-5p, suggesting that RHPN1-AS1 might be a potential therapeutic target for CRC.
Caveolin-2 is regulated by BRD4 and contributes to cell growth in pancreatic cancer
Authors: Jiao Feng , Han Ting , Yuan Cuncun , Liang Yiyi , Cui Jiujie , Zhuo Meng , Wang Liwei 
Published: February 2020

AbstractBackgroundThe bromodomain and extra-terminal domain (BET) family of proteins, especially BRD4 play an important role in epigenetic regulation, and are essential for cell survival and also are promising anticancer targets. This study aims to analyze the effect of BRD4 on the cell growth and progression of pancreatic cancer and novel mechanisms involved.MethodsExpression of BRD4 in pancreatic cancer and paired adjacent noncancerous tissues from 76 patients was analyzed by western blotting, immunohistochemistry, and real time PCR. Its correlation with the clinicopathological characteristics and prognosis of pancreatic cancer patients was analyzed. The effects of BRD4 on the cell proliferation were detected by colony formation assay and sulforhodamine B assay. Migration and invasion were determined by Transwell assays, and the effect of BRD4 on subcutaneous tumor formation was verified in nude mice. Cell cycle analysis was detected by flow cytometry. The potential downstream targets of BRD4 and related molecular mechanisms were clarified by RNA sequencing, chromatin immunoprecipitation and dual luciferase reporter assay.ResultsBRD4 was overexpressed in pancreatic cancer. Biological results showed that BRD4 functioned as tumor promoter, facilitated cell proliferation, migration and invasion in vitro and in vivo. Further, caveolin-2 was selected as the downstream gene of BRD4 by RNA sequencing. Caveolin-2 overexpression can partially reverse the decreased cell growth ability caused by BRD4 knockdown, but did not affect cell migration and invasion. Chromatin immunoprecipitation assay and dual luciferase reporter assay revealed BRD4 could bind to the promoter region of caveolin-2 and upregulate caveolin-2 expression. Clinical data further indicated a positive correlation between BRD4 and caveolin-2 expression. BRD4 (high)/caveolin-2 (high) correlated with shorter overall survival of patients with pancreatic cancer. Multivariate analysis revealed that both BRD4 and caveolin-2 were independent factors.ConclusionsOur findings reveal the oncogenic effects of BRD4 in pancreatic cancer and elucidate a possible mechanism by which BRD4 and caveolin-2 act to enhance cell growth. Targeting the BRD4-caveolin-2 interaction by development of BET inhibitors will be a therapeutic strategy for pancreatic cancer.
Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer
Authors: Peng Qiliang , Cheng Ming , Li Ting , Chen Xiangying , Shen Yi , Zhu Yaqun , Xu Bo 
Published: February 2020

Abstract
Background
Accumulating evidence has demonstrated that microRNA-200s (miR-200a, miR-200b and miR-200c) could serve as promising molecular biomarkers for cancer prognosis. Nevertheless, the associations between miR-200s expression and colorectal cancer (CRC) prognosis remain controversial.

Methods
We applied two mainstream approaches combining meta-analysis and bioinformatics analysis to answer whether miR-200s were associated with the prognosis of CRC patients and why miR-200s could be used as prognostic biomarkers for CRC.

Results
Consequently, low expression of miR-200s was associated with unfavorable overall survival (OS) in CRC patients (HR: 1.09; 95% CI 1.01–1.17; P = 0.025). According to the subgroup analysis, the prognostic role of miR-200s was more significant for tissue samples, large samples, American patients and miR-200a subgroups. Then the target genes of miR-200s were predicted and applied for functional enrichment analyses. The results showed that the target genes of miR-200s were mainly enriched into some vital ontology subjects such as regulation ability, key cell structures and binding function. Moreover, a series of important signaling pathways were identified, which were significantly linked with the initiation and progression of CRC. Additionally, a protein‑protein interaction (PPI) network of miR-200s targets was constructed to screen hub genes and modules. The identified hub genes and modules were validated to be highly involved in the occurrence and development of CRC.

Conclusions
Current evidences revealed that miR-200s could be promising biomarkers for CRC prognosis. However, the findings still need to be validated with more larger-scale prospective studies and biological experiments before miR-200s could be applied into clinical application.
Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda
Authors: Balikagala Betty , Sakurai-Yatsushiro Miki , Tachibana Shin-Ichiro , Ikeda Mie , Yamauchi Masato , Katuro Osbert T. , Ntege Edward H. , Sekihara Makoto , Fukuda Naoyuki , Takahashi Nobuyuki , Yatsushiro Shouki , Mori Toshiyuki , Hirai Makoto , Opio Walter , Obwoya Paul S. , Anywar Denis A. , Auma Mary A. , Palacpac Nirianne M. Q. , Tsuboi Takafumi , Odongo-Aginya Emmanuel I. , Kimura Eisaku , Ogwang Martin , Horii Toshihiro , Mita Toshihiro 
Published: February 2020

Abstract
Background
Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods.

Methods
Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed.

Results
Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC50 values for chloroquine were persistently low throughout the study period (17.4–24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower IC50s to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10−8). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018.

Conclusion
This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.
Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan
Authors: Mohamed Abdelrahim O. , Hussien Maazza , Mohamed Amal , Suliman Abdelmaroof , Elkando Nuha S. , Abdelbagi Hanadi , Malik Elfatih M. , Abdelraheem Mohammed H. , Hamid Muzamil Mahdi Abdel 
Published: February 2020

Abstract
Background
Plasmodium falciparum malaria is a public health problem worldwide. Malaria treatment policy has faced periodic changes due to emergence of drug resistant parasites. In Sudan chloroquine has been replaced by artesunate and sulfadoxine/pyrimethamine (AS/SP) in 2005 and to artemether–lumefantrine (AL) in 2017, due to the development of drug resistance. Different molecular markers have been used to monitor the status of drug resistant P. falciparum. This study aimed to determine the frequency of malaria drug resistance molecular markers in Southeast Sudan.

Methods
The samples of this study were day zero dried blood spot samples collected from efficacy studies in the Blue Nile State from November 2015 to January 2016. A total of 130 samples were amplified and sequenced using illumina Miseq platform. The molecular markers included were Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfk13, exonuclease and artemisinin resistant (ART‐R) genetic background (Pfmdr2, ferroredoxine, Pfcrt and Pfarps10).

Results
Resistance markers for chloroquine were detected in 25.8% of the samples as mutant haplotype Pfcrt 72-76 CVIET and 21.7% Pfmdr1 86Y. Pfdhfr mutations were detected in codons 51, 59 and 108. The ICNI double-mutant haplotype was the most prevalent (69%). Pfdhps mutations were detected in codons 436, 437, 540, 581 and 613. The SGEGA triple-mutant haplotype was the most prevalent (43%). In Pfdhfr/Pfdhps combined mutation, quintuple mutation ICNI/SGEGA is the most frequent one (29%). Six of the seven treatment failure samples had quintuple mutation and the seventh was quadruple. This was significantly higher from the adequately responsive group (P < 0.01). Pfk13 novel mutations were found in 7 (8.8%) samples, which were not linked to artemisinin resistance. Mutations in ART‐R genetic background genes ranged from zero to 7%. Exonuclease mutation was not detected.

Conclusion
In this study, moderate resistance to chloroquine and high resistance to SP was observed. Novel mutations of Pfk13 gene not linked to treatment failure were described. There was no resistance to piperaquine the partner drug of dihydroartemisinin/piperaquine (DHA-PPQ).
Determinants for early introduction of complementary foods in Australian infants: findings from the HSHK birth cohort study
Authors: Arora Amit , Manohar Narendar , Hector Debra , Bhole Sameer , Hayen Andrew , Eastwood John , Scott Jane Anne 
Published: February 2020

Abstract
Objective
The purpose of this study was to examine the timing of introduction of complementary (solid) foods among infants in South Western Sydney, Australia, and describe the maternal and infant characteristics associated with very early introduction of solids.

Methods
Mother-infant dyads (n = 1035) were recruited into the “Healthy Smiles Healthy Kids” study by Child and Family Health Nurses at the first post-natal home visit. Data collected via telephone interviews at 8, 17, 34 and 52 weeks postpartum included timing of introduction of solids and a variety of maternal and infant characteristics (n = 934). Multiple logistic regression was used to identify factors independently associated with the risk of introducing solids very early, which for the purpose of this study was defined as being before 17 weeks.

Results
The median age of introduction of solids was 22 weeks. In total, 13.6% (n = 127) of infants had received solids before 17 weeks and 76.9% (n = 719) before 26 weeks of age. The practice of introducing solids early decreased with older age of the mother. Compared to women < 25 years of age, those who were 35 years or older were 72% less likely to introduce solids very early (OR = 0.28, CI95 0.14–0.58). Single mothers had more than twice the odds of introducing solids before the age of 17 weeks compared to married women (OR = 2.35, CI95 1.33–4.16). Women who had returned to work between 6 to 12 months postpartum were 46% less likely to introduce solids very early compared with those who were not working at the child’s first birthday (OR = 0.54, CI95 0.30–0.97). Women born in Vietnam and Indian sub-continent had lower odds of introducing solids very early compared to Australian born women (OR = 0.42, CI95 0.21–0.84 and OR = 0.30, CI95 0.12–0.79, respectively). Infants who were exclusively formula-fed at 4 weeks postpartum had more than twice the odds of receiving solids very early (OR = 2.34, CI95 1.49–3.66).

Conclusions
Women who are younger, single mothers, those not working by the time of child’s first birthday, those born in Australia, and those who exclusively formula-feed their babies at 4 weeks postpartum should be targeted for health promotion programs that aim to delay the introduction of solids in infants to the recommended time.
Data anomalies and apparent reporting errors in ‘Randomized controlled trial testing weight loss and abdominal obesity outcomes of moxibustion’
Authors: Mestre Luis M. , Dickinson Stephanie L. , Golzarri-Arroyo Lilian , Brown Andrew W. , Allison David B. 
Published: February 2020

AbstractRandomized Controlled Trials (RCTs) are the best method to determine causal effects for treatments if they are well done and well reported. Good evidence about proposed treatments for obesity is needed, and Hsieh et al. (Biomed Eng Online 17:149, 2018) are to be commended for putting moxibustion to the test. However, careful evaluation of the paper reveals inconsistencies and apparent reporting errors, which raise doubts about conclusions from the study.