bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoral reciprocal expression of monocarboxylate transporter 4 and glypican-3 in hepatocellular carcinomas
Authors: Yorita Kenji , Ohno Akinobu , Nishida Takahiro , Kondo Kazuhiro , Ohtomo Toshihiko , Kataoka Hiroaki 
Published: October 2019

Abstract
Objective: We previously reported the identification of monocarboxylate transporter 4 (MCT4) and glypican-3 (GPC3) as prognostic factors for hepatocellular carcinoma (HCC), which are now considered significant poor prognostic factors for the disease. This study aimed to clarify the detailed interaction of these two factors in HCC t o improve our understanding of aggressive HCC phenotype s. A total of 225 Japanese patients with HCC from our previous study were subjected to immunohistochemical analyses. Results: The number of MCT4-positive (MCT4+) HCC cases was 47 (21%), and most MCT4+ HCC showed high GPC3 expression (94%, 44/47 cases). In 44 MCT4+/GPC3+ HCC cases, intratumoral heterogeneity of GPC3 or MCT4 expression was further evaluated. We observed reciprocal (inverse), synergistic, mixed reciprocal and synergistic, or irrelevant interaction of MCT4 and GPC3 expression in 29 (66%), 5 (11%), 1 (2%), and 9 cases (21%), respectively. The cases exhibiting reciprocal expression of both markers tended to have cirrhosis without a history of neoadjuvant therapy. In summary, although MCT4+ HCC cases are mostly GPC3+, intratumoral expression patterns of MCT4 and GPC3 are frequently reciprocal each other, suggesting that dual targeting of MCT4 and GPC3 may achieve a better antitumor effect for MCT4+ HCC cases.
MetaCNV - a consensus approach to infer accurate copy numbers from low coverage data
Authors: Friedrich Stefanie , Barbulescu Remus , Helleday Thomas , Sonnhammer Erik LL 
Published: October 2019

Abstract
Background : The majority of copy number callers requires high read coverage data that is often achieved with elevated material input, which increases the heterogeneity of tissue samples. However, to gain insights into smaller areas within a tissue sample, e.g a cancerous area in a heterogeneous tissue sample, less material is used for sequencing, which results in lower read coverage. Therefore, more focus needs to be put on copy number calling that is sensitive enough for low coverage data. Results : We present MetaCNV, a copy number caller that infers reliable copy numbers for human genomes with a consensus approach. MetaCNV specializes in low coverage data, but also performs well on normal and high coverage data. MetaCNV integrates the results of multiple copy number callers and infers absolute and unbiased copy numbers for the entire genome. MetaCNV is based on a meta-model that bypasses the weaknesses of current calling models while combining the strengths of existing approaches. Here we apply MetaCNV based on ReadDepth, SVDetect, and CNVnator to five datasets in order to demonstrate how the approach improves copy number calling. Conclusions : MetaCNV, available at https://bitbucket.org/sonnhammergroup/metacnv , provides accurate copy number prediction on low coverage data and performs well on high coverage data.
Blood signatures for second stage Human African Trypanosomiasis: A transcriptomic approach.
Authors: Mulindwa Julius , Matovu Enock , Enyaru John , Clayton Christine 
Published: October 2019

Abstract
Background
Rhodesiense sleeping sickness is caused by infection with T. b rhodesiense parasites resulting in an acute disease that is fatal if not treated in time. The global impact of active T. b rhodesiense infection on the patient’s immune response in the early and late stages of the disease is not known.

Results
We previously described the transcriptomes of T. b rhodesiense from infected early stage blood (n=3) and late stage CSF (n=3) samples from Eastern Uganda. We here identify human transcripts that were differentially expressed (padj < 0.05) in the early stage blood versus healthy controls (n=3) and early stage blood versus late stage CSF. Differential expression in infected blood showed an enrichment of innate immune response genes whereas that of the CSF showed enrichment for anti-inflammatory and neuro-degeneration signalling pathways. We also identified genes (C1QC, MARCO, IGHD3-10) that were up-regulated (log 2 FC > 2.5) in both the blood and CSF.

Conclusion
The data yields insights into the host’s response to T. b rhodesiense parasites in the blood and central nervous system. We identified key pathways and signalling molecules for the predominant innate immune response in the early stage infection; and anti-inflammatory and neuro-degeneration pathways associated with sleep disorders in second stage infection. We further identified potential blood biomarkers that can be used for diagnosis of late stage disease without the need for lumbar puncture.
The effects of age, cigarette smoking, sex and race on the qualitative characteristics of lung transcriptome
Authors: Guan Qingzhou , Zhang Juan , Guo You , Xia Jie , Zhang Jiahui , Xie Jiajing , Cai Hao , Yan Haidan , Wang Xianlong , Guo Zheng 
Published: October 2019

Abstract
Background: Methods based on within-sample relative expression orderings (REOs) comparisons have been proposed for identifying differentially expressed genes (DEGs) at the individual level and for detecting disease-associated genes based on one-phenotype disease data by reusing data of normal samples from other sources. However, the common potential confounding factors, including age, cigarette smoking, sex and race whether could affect the REOs of gene pairs is still unclear. Methods: For one confounding factor, based on the numbers of related gene pairs or DEGs, we evaluated the effect of this confounding factor on the REOs of gene pairs within normal lung tissues transcriptome.
Results: Our results showed that age has little effect on REOs within lung tissues. We found that about 0.23% of the significantly stable REOs of gene pairs in non-smokers’ lung tissues are reversed in smokers’ lung tissues, introduced by 344 DEGs between the two groups of samples (RankCompV2, FDR < 0.05), which are enriched in metabolism of xenobiotics by cytochrome P450, glutathione metabolism and other pathways (hypergeometric test, FDR < 0.05). Comparison between the normal lung tissue samples of males and females revealed fewer reversal REOs introduced by 24 DEGs between the sex groups, among which 19 DEGs are located on sex chromosomes and 5 DEGs involving in spermatogenesis and regulation of oocyte are located on autosomes. Between the normal lung tissue samples of white and black people, we identified 22 DEGs (RankCompV2, FDR < 0.05) which introduced a few reversal REOs between the two races.
Conclusions: In summary, the REO-based study should take into account the confounding factors of cigarette smoking, sex and race.
Asthma in children treated with paracetamol versus ibuprofen: A systematic review and meta-analysis of randomised controlled trials
Authors: Sherbash Mohamed , Furuya-Kanamori Luis , Nader Joanne Daghfal , Thalib Lukman 
Published: October 2019

Abstract
Background:
Paracetamol and ibuprofen are the most commonly used medications for fever and pain management in children. While the efficacy appears similar with both drugs, there are contradictory findings related to adverse events. In particular, incidence of asthma among children taking paracetamol compared to ibuprofen, remain unsettled.
Methods:
We conducted a meta-analysis of randomized controlled trials (RCTs) that compared asthma in children taking paracetamol versus ibuprofen. A comprehensive search was conducted in five databases. RCTs reporting on cases of asthma in infants or children after the administration of paracetamol or ibuprofen were included. The pooled effect size was estimated using the inverse variance heterogeneity model.
Results:
Five RCTs with 85095 children were included in the analysis. The pooled estimate (RR 1.04; 95%CI 0.84-1.29) revealed no difference in the risk of developing asthma or presenting an exacerbation of asthma in children who received paracetamol compared to ibuprofen. When the analysis was restricted to RCTs that examined the incidence of asthma, the pooled estimate remained similar (RR 1.03; 95%CI 0.64-1.67). Additional bias adjusted quality effect sensitivity model yielded similar results (RR 1.03; 95%CI 0.84-1.28).
Conclusion:
Ibuprofen and paracetamol have similar tolerance and safety profiles in terms of incidence of asthma in children.
Comparison Of Clinical Characteristics Between Two Non-Cystic Fibrosis Bronchiectasis Children Cohorts Followed Up From A Single Tertiary Center At Different Time Intervals
Authors: Erdem Ela , Gokdemir Yasemin , Atag Emine , Ikizoglu Nilay Bas , Ergenekon Pinar , Yilmaz Cansu Yegit , Kut Arif , Ersu Refika , Karakoc Fazilet , Karadag Bulent 
Published: October 2019

Abstract
Background
The diagnosis of non-cystic fibrosis (CF) bronchiectasis is increasing in both developed and nondeveloped countries in recent years. Although the main features are similar, etiologies seem to change. Our aim was to evaluate the clinical and laboratory characteristics of non-CF bronchiectasis patients and to compare these data with our previous cohort in 2001.
Methods
104 children with non-CF bronchiectasis being followed-up between 2002 and 2019 were enrolled. Age of diagnosis, underlying etiology and distribution of microorganisms in sputum culture were recorded. Clinical outcomes were evaluated in terms of lung function tests and annual pulmonary exacerbation rates at presentation and within the last 12 months of the follow-up.
Results
Mean FEV1 and FVC % of predicted at presentation were improved compared with previous study (76.6±17.1 vs. 63.3±22.1 and 76.6±15.1 vs. 67.3±23.1, respectively; p<0.001). There was a significant decrase in pulmonary exacerbation rate from 6.05±2.88 at presentation to 3.23±2.08 during follow-up (p<0.0001). In 80.8% of patients, an underlying etiology was identified. There was an increase in primary ciliary dyskinesia (PCD) (32.7% vs. 6.3%;p:0.001), decrease in idiopathic cases (19.2% vs. 37.8%;p: 0.03) with no change in postinfectious and immunodeficiencies. Sputum cultures were positive in 77.9% of patients which was 46.9% in the previous study (p=0.001).
Conclusion
Baseline pulmonary function tests were better and distribution of underlying etiology had changed with a remarkable increase in diagnosis of PCD. Recent advances in diagnosis also makes it easier to evaluate the patients in a better way, still awaiting for international consensus and guidelines on non-CF bronchiectasis in children.
Clinical Results of Intraductal Meibomian Gland Probing Combined with Intense Pulsed Light in Treating Patients with Refractory Obstructive Meibomian Gland Dysfunction: A Randomized Controlled Trial
Authors: Huang Xiaodan , Qin Qiyu , Wang Linping , Zheng Jiao , Lin Lin , Jin Xiuming 
Published: October 2019

Abstract
Background: This study aims to optimize the therapeutic regimen for refractory obstructive meibomian gland dysfunction (o-MGD) patients by combining intraductal meibomian gland probing (MGP) and intense pulsed light (IPL) to enhance their positive effects and reduce their limitations. Methods: This randomized, assessor blind study includes 45 patients (90 eyes) with refractory o-MGD who were divided into 3 groups via allocation concealment: IPL (group I, received an IPL treatment course: 3 times at 3-week intervals), MGP (group II, received MGP one time), and combined MGP-IPL (group III, MGP first followed by an IPL treatment course). Standard Patient Evaluation of Eye Dryness score (SPEED), tear break-up time (TBUT), corneal fluorescein staining (CFS), meibum grade, and lid margin finding results were assessed at baseline, 3 weeks after final treatment for groups I and III, 3 and 12 weeks after MGP for group II. Six months after final treatment, the SPEED and willingness to receive any treatment again were also collected for all groups. Paired Wilcoxon, Mann-Whitney U with Bonferroni correction, and Kruskal-Wallis tests were used for data analysis. Results: For all 3 groups, all previously mentioned indexes improved significantly following treatment (P＜0.01). MGP-IPL was better than IPL and MGP in terms of post-treatment SPEED, TBUT, meibum grade, and lid telangiectasia (P＜0.05/3). Furthermore, the MGP-IPL was better than IPL in terms of lid tenderness and better than MGP in terms of orifice abnormality (P＜ 0.05/3). Six months later, the SPEED for the MGP-IPL was also significantly lower than other groups (P＜0.05/3). Moreover, no patients in the MGP-IPL group expressed the need to be treated again compared to 35.7% or 20% of patients in the IPL or MGP groups, respectively. Conclusions: Compared with IPL or MGP alone, the combination MGP-IPL produced best results in relieving all signs and symptoms and helping patients attain long-lasting symptom relief. Trial registration: http://clinicaltrials.gov, ChiCTR1900021273 (retrospectively registered February 9, 2019).
Structural and functional insights into the Diabrotica virgifera virgifera ATP-binding cassette transporter gene family
Authors: Adedipe Folukemi , Grubbs Nathaniel , Coates Brad , Wiegmman Brian , Lorenzen Marce 
Published: October 2019

Abstract
Background

The western corn rootworm, Diabrotica virgifera virgifera , is a pervasive pest of cultivated maize in North America and Europe, which has adapted to survive exposure to multiple insecticidal agents. Due to their role in insecticide transport, we sought to identify members of the ATP-binding cassette (ABC) transporter family in D. v. virgifera using a transcriptomics approach.Results

In this study, 65 putative D. v. virgifera ABC ( Dvv ABC) transporters were identified within a combined transcriptome assembly generated from embryonic, larval, adult male, and adult female RNA-sequence libraries. Phylogenetic analysis placed the deduced amino-acid sequences of the Dvv ABC transporters into eight subfamilies (A to H). Of these, eight shared structural and functional conservation with Tribolium castaneum ABC transporter orthologs known to exhibit overt RNA interference (RNAi) knockdown phenotypes. Interestingly, depletion of DvvABCB_19147 and DvvABCG_3712 transcripts in adult females produced detrimental reproductive and developmental phenotypes (egg-laying or -hatching defects), demonstrating the potential of these genes as targets for RNAi-mediated insect control tactics.Conclusions

By combining sequence data from four libraries covering three distinct life stages, we have produced a relatively comprehensive de novo transcriptome assembly for D. v. virgifera . Moreover, we have identified 65 members of the ABC transporter family, and provided the first insights into the developmental and physiological roles of ABC transporters in this pest species.
The Effect of An Educational Program for Pregnant Women to Prevent Allergic Diseases In Infants: study protocol for a randomized controlled trial
Authors: Ito Rie , Nezu Yoko , Ishiguro Nao , Nakade Masato , Ishitsuka Yukiko , Naru Eiji 
Published: October 2019

Abstract
Background Allergic diseases in infants have dramatically increased in developed countries during the past few decades. To date, extensive research has been done on risk factors for allergies in infancy, and preventive measures against it. However, the effect of the primary approach to preventing infants' allergy still remains limited. The aim of this trial is to evaluate whether prenatal education interventions, including the latest public research results on allergic diseases, prevent the infant allergies onset. Methods/Design We designed a randomized, controlled, two-arm (standard prenatal education vs our education), parallel-group, assessor-blind, trial. A sample of 120 pregnant women will be recruited at Chiba Aiyukai Kinen hospital and allocation is by computer-generated randomization. Pregnant women in the intervention arm participate in the childbirth education program established by the specialist and a pediatric allergy educator. The program was developed based on evidences supporting interventions on primary prevention, which are suggested to be beneficial to infant’s allergies in recent studies. The primary objective of the study is to determine whether it is possible to establish effective behaviors for allergy prevention during early infancy in pregnant women who participate in an educational program developed by pediatric allergy specialists. Four months after birth, their behaviors will be compared against those of pregnant women who did not participate in the program. Discussion Allergies are common in many individuals worldwide, and can be present from babyhood through the person’s lifetime. One of the strong points of this study is that it will provide pregnant women with accumulated information on preventive knowledge against allergy that can be effective in some cases, and women can apply a combination of these behavior before and after pregnancy. The results of our program will be publicized to help change the behaviors of mothers, and if the program is effective for preventing allergies in infants, it will be disclosed worldwide as a new preventive measure for allergy in infants.
Targeting Bacterial Antioxidant Systems for Antibiotics Development
Authors: Ren Xiaoyuan , Zou Lili , Holmgren Arne 
Published: October 2019

:The emergence of multidrug-resistant bacteria has become an urgent issue in modern medicine which requires novel strategies to develop antibiotics. Recent studies have supported the hypothesis that antibiotic-induced bacterial cell death is mediated by Reactive Oxygen Species (ROS). The hypothesis also highlighted the importance of antioxidant systems, the defense mechanism which contributes to antibiotic resistance. Thioredoxin and glutathione systems are the two major thiol-dependent systems which not only provide antioxidant capacity but also participate in various biological events in bacteria, such as DNA synthesis and protein folding. The biological importance makes them promising targets for novel antibiotics development. Based on the idea, ebselen and auranofin, two bacterial thioredoxin reductase inhibitors, have been found to inhibit the growth of bacteria lacking the GSH efficiently. A recent study combining ebselen and silver exhibited a strong synergistic effect against Multidrug-Resistant (MDR) Gram-negative bacteria which possess both thioredoxin and glutathione systems. These drug-repurposing studies are promising for quick clinical usage due to their well-known profile.
A Preliminary Study for Quantitative Assessment with HFUS (High- Frequency Ultrasound) of Nodular Skin Melanoma Breslow Thickness in Adults Before Surgery: Interdisciplinary Team Experience
Authors: Reginelli Alfonso , Belfiore Maria P. , Russo Anna , Turriziani Fabrizio , Moscarella Elvira , Troiani Teresa , Brancaccio Gabriella , Ronchi Andrea , Giunta Emilio , Sica Antonello , Iovino Francesco , Ciardiello Fortunato , Franco Renato , Argenziano Giuseppe , Grassi Roberto , Cappabianca Salvatore 
Published: October 2019

Background:Cutaneous melanoma is one of the most severe skin diseases. Nodular melanoma is the second melanoma subtype in order of frequency. The prognosis of skin melanoma depends on the vertical growth of the tumor (Breslow index). For this measurement, excisional biopsy is strongly recommended. This is, however, an invasive procedure and may cause damage to the lymphatic drainage system. The HFUS system, , can be extremely useful for determining tumor thickness in the preoperative phase, given its high resolution capacity. The aim of this preliminary study is to define the role of HFUS for the nodular skin melanoma Breslow thickness in adults before surgery by making a comparison with histological features.Methods:In this study, 14 melanocytic lesions (8 male and 6 female) were evaluated with dermatoscopic clinical features strongly indicative of nodular melanoma. Out of these, excisional biopsy of 7 lesions was requested. The ultrasounds were performed preoperatively. The images were acquired through the first ultrasound scanner with ultra-high frequency probes (range from 50MHz to 70 MHz) available on the market under the EEC mark (Vevo "MD, FUJIFILM Visual Sonics, Amsterdam, the Netherlands) equipped with a linear probe of 50-70 MHz.Results:From the ultrasonographic analysis of 14 nodular melanoma thickness was determined for the presence of two hyperechogenic laminae, separated by a hypo / anechoic space. The twelve lesions were in situ while the other two lesions showed ultrasonography for example; the satellite lesions (less than two centimeters from the primary lesion) and in transit (localizable to more than two centimeters from the primary lesion). Four of these lesions were ulcerated. A comparsion was made the 7 lesions on between the thickness calculated with this method, and that obtained on the bioptic piece. The presence of a positive concordance has been evident in all of the cases.Conclusions:If further studies are needed to support its widespread clinical use, its is believed that, in expert hands and with an interdisciplinary team, HFUS is already capable to reliably calculate a Breslow index in a large majority of patients with cutaneous melanoma.
EXPLORING LEGAL BORDERLANDS: INTRODUCING THE THEME
Authors: Fortes Pedro Rubim Borges , Kampourakis Ioannis 
Published: October 2019

The theme Exploring Legal Borderlands has been used as an inspiration for contemporary research at the Centre for Socio-Legal Studies (CSLS) at the University of Oxford since 2015, when Naomi Creutzfeldt and Petra Mahy organised a stream at the Socio-Legal Studies Association (SLSA) Conference at the University of Warwick. Importantly, this research agenda remains relevant and a series of papers have been presented at the subsequent annual SLSA conferences in Lancaster (2016), Newcastle (2017), Bristol (2018), and more recently in Leeds (2019). In the last five years, various scholars presented their innovative interdisciplinary research at this stream and it remained organized by junior scholars affiliated with CSLS and the University of Oxford. However, the definition of legal borderlands was not provided in a clear statement. Legal borderlands, as understood in this issue, are about this ambiguity inherent in a world of multiple normative orders. The following issue’s originality consists in the conceptual exploration of the idea of legal borderlands. In an increasingly interconnected world of diverse and often conflicting normative orders, such research is particularly relevant. As far as it concerns this article, in addition to this introduction, Section II briefly examines the legal boundaries and the dichotomy between (il)legality and a-legality. Section III focuses on normative pluralism and the development of juridical orders. Section IV discusses global regulation as an expansion of legal borderlands. Section V brings concluding remarks and summarizes the articles that follow.