bluuebunny/crossref_metadata_2025_split huggingface dataset:
In search of the mRNA modification landscape in plants
Authors: Chmielowska-Bąk Jagna , Arasimowicz-Jelonek Magdalena , Deckert Joanna 
Published: October 2019

AbstractBackgroundPrecise regulation of gene expression is indispensable for the proper functioning of organisms in both optimal and challenging conditions. The most commonly known regulative mechanisms include the modulation of transcription, translation and adjustment of the transcript, and protein half-life. New players have recently emerged in the arena of gene expression regulators – chemical modifications of mRNAs.Main textThe latest studies show that modified ribonucleotides affect transcript splicing, localization, secondary structures, interaction with other molecules and translation efficiency. Thus far, attention has been focused mostly on the most widespread mRNA modification – adenosine methylation at the N6position (m6A). However, initial reports on the formation and possible functions of other modified ribonucleotides, such as cytosine methylated at the 5′ position (m5C), 8-hydroxyguanosine (8-OHG) and 8-nitroguanosine (8-NO2G), have started to appear in the literature. Additionally, some reports indicate that pseudouridine (Ψ) is present in mRNAs and might perform important regulatory functions in eukaryotic cells. The present review summarizes current knowledge regarding the above-mentioned modified ribonucleotides (m6A, m5C, 8-OHG, 8-NO2G) in transcripts across various plant species, including Arabidopsis, rice, sunflower, wheat, soybean and potato.ConclusionsChemical modifications of ribonucleotides affect mRNA stability and translation efficiency. They thus constitute a newly discovered layer of gene expression regulation and have a profound effect on the development and functioning of various organisms, including plants.
Treatment and outcome of the patients with rhabdomyosarcoma of the biliary tree: Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS)
Authors: Urla Cristian , Warmann Steven W. , Sparber-Sauer Monika , Schuck Andreas , Leuschner Ivo , Klingebiel Thomas , Blumenstock Gunnar , Seitz Guido , Koscielniak Ewa , Fuchs Jörg 
Published: October 2019

Abstract

Background
Biliary rhabdomyosarcoma (RMS) is the most common biliary tumor in children. The management of affected patients contains unique challenges because of the rarity of this tumor entity and its critical location at the porta hepatis, which can make achievement of a radical resection very difficult.

Methods
In a retrospective chart analysis we analysed children suffering from biliary RMS who were registered in three different CWS trials (CWS-96, CWS-2002P, and SoTiSaR registry).

Results
Seventeen patients (12 female, 5 male) with a median age of 4.3 years were assessed. The median follow-up was 42.2 months (10.7–202.5). The 5-year overall (OS) and event free survival (EFS) rates were 58% (45–71) and 47% (34–50), respectively. Patients > 10 years of age and those with alveolar histology had the worst prognosis (OS 0%). Patients with botryoid histology had an excellent survival (OS 100%) compared to those with non-botryoid histology (OS 38%, 22–54, p = 0.047). Microscopic complete tumor resection was achieved in almost all patients who received initial tumor biopsy followed by chemotherapy and delayed surgery.

Conclusion
Positive predictive factors for survival of children with biliary RMS are age ≤ 10 years and botryoid tumor histology. Primary surgery with intention of tumor resection should be avoided.
Legal medicine implications in fibrinolytic therapy of acute ischemic stroke
Authors: Sabau Monica , Bungau Simona , Buhas Camelia Liana , Carp Gheorghe , Daina Lucia-Georgeta , Judea-Pusta Claudia Teodora , Buhas Bogdan Adrian , Jurca Claudia Maria , Daina Cristian Marius , Tit Delia Mirela 
Published: October 2019

Abstract

Background
Before the advent of fibrinolytic therapy as a gold standard method of care for cases of acute ischemic stroke in Romania, issues regarding legal medicine aspects involved in this area of medical expertise were already presented and, in the majority of cases, the doctors seem to be unprepared for these situations.

Main text
The present research illustrates some of the cases in which these aspects were involved, that adressed a clinical center having 6 years of professional experience in the application of fibrinolytic treatment for stroke. The following cases report either situations in which the afore mentioned therapy was not rightfully administrated or legal aspects regarding the obtainment of informed consent.

Conclusion
Obtaining informed consent is a mandatory procedure, which takes time, to the detriment of application of fibrinolytic treatment.
(−)-Epigallocatechin-3-gallate derivatives combined with cisplatin exhibit synergistic inhibitory effects on non-small-cell lung cancer cells
Authors: Wang Jing , Sun Peiyuan , Wang Qi , Zhang Pan , Wang Yuna , Zi Chengting , Wang Xuanjun , Sheng Jun 
Published: October 2019

Abstract

Background
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The inhibition of epidermal growth factor receptor (EGFR) signaling by tyrosine kinase inhibitors or monoclonal antibodies plays a key role in NSCLC treatment. Unfortunately, these treatment strategies are limited by eventual resistance and cell lines with differential EGFR status. Therefore, new therapeutic strategies for NSCLC are urgently required.

Methods
To improve the stability and absorption of (−)-epigallocatechin-3-gallate (EGCG), we synthesized a series of EGCG derivatives. The antitumor activities of EGCG derivatives with or without cisplatin were investigated in vitro and vivo. Cell proliferation, cell cycle distribution and apoptosis were measured in NSCLC cell lines and in vivo in a NCI-H441 xenograft model.

Results
We found that the EGCG derivatives inhibited cell viability and colony formation, caused cell cycle redistribution, and induced apoptosis. More importantly, the combination of the EGCG derivative and cisplatin led to increased growth inhibition, caused cell cycle redistribution, and enhanced the apoptosis rate compared to either compound alone. Consistent with the experiments in vitro, EGCG derivatives plus cisplatin significantly reduced tumor growth.

Conclusions
The combination treatment was found to inhibit the EGFR signaling pathway and decrease the expression of p-EGFR, p-AKT, and p-ERK in vitro and vivo. Our results suggest that compound 3 is a novel potential compound for NSCLC patients.
Conventional versus hypofractionated postmastectomy radiotherapy: a report on long-term outcomes and late toxicity
Authors: Chitapanarux Imjai , Klunklin Pitchayaponne , Pinitpatcharalert Attapol , Sripan Patumrat , Tharavichitkul Ekkasit , Nobnop Wannapha , Onchan Wimrak , Chakrabandhu Somvilai , Jia-Mahasap Bongkot , Euathrongchit Juntima , Wannasopha Yutthaphan , Srisuwan Tanop 
Published: October 2019

AbstractObjectiveWe evaluated the long-term outcomes and late toxicity of conventional fractionated (CF) and hypofractionated (HF) postmastectomy radiotherapy (PMRT) in terms of locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and late toxicity.MethodsA cohort of 1640 of breast cancer patients receiving PMRT between January 2004 and December 2014 were enrolled. Nine hundred eighty patients were treated with HF-PMRT: 2.65 Gy/fraction to a total of 42.4–53 Gy and 660 patients were treated with CF-PMRT: 2 Gy/fraction to a total of 50–60 Gy.ResultsThe median follow-up time was 71.8 months (range 41.5–115.9 months). No significant difference was found in the rates of 5-year LRRFS, DFS, and OS of HF-PMRT vs CF-PMRT; 96% vs. 94% (p = 0.373), 70% vs. 72% (p = 0.849), and 73% vs. 74% (p = 0.463), respectively. We identified a cohort of 937 eligible breast cancer patients who could receive late toxicities assessment. With a median follow-up time of this patient cohort of 106.3 months (range 76–134 months), there was a significant higher incidence of grade 2 or more late skin (4% vs 1%) and subcutaneous (7% vs 2%) toxicity in patients treated with HF-PMRT vs CF-PMRT. Patients who received additional radiation boost were significantly higher in the HF-PMRT group. Grade 2 or more late RTOG/EORTC lung toxicity was significant lesser in HF-PMRT vs CF-PMRT (9% vs 16%). Grade 1 brachial plexopathy was also significant lesser in HF-PMRT vs CF-PMRT (2% vs 8%). Heart toxicity and lymphedema were similar in both groups.ConclusionsHF-PMRT is feasible to deliver with comparable long-term efficacy to CF-PMRT. HF-PMRT had higher grade 2 or more skin and subcutaneous toxicity but less lung and brachial plexus toxicity.
Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production
Authors: Kong De-Long , Kong Fan-Yun , Liu Xiang-Ye , Yan Chao , Cui Jie , Tang Ren-Xian , Zheng Kui-Yang 
Published: October 2019

Abstract

Background
Inflammation-induced dysfunction of hepatic stellate cells (HSCs) is involved in schistosomiasis-associated liver fibrosis, and soluble egg antigen (SEA) is a crucial pathogen-associated molecular pattern associated with liver injury in schistosomiasis. In addition, numerous studies have shown that caspase-1-mediated pyroptosis participates in the development of multiple inflammation-related diseases. However, whether pyroptotic cell death of HSCs is involved in SEA-mediated liver damage is not well understood.

Methods
Primary cultured HSCs and Schistosoma japonicum-infected mouse liver tissue were analysed for histological changes and caspase-1 activation, and the role of pyroptosis in the mechanisms underlying SEA-induced HSC death was investigated. Accumulation of reactive oxygen species (ROS) in infected livers and SEA-stimulated HSCs was measured by flow cytometry and immunofluorescence.

Results
Caspase-1 activity was elevated in both liver tissues and HSCs of S. japonicum-infected mice. Furthermore, SEA stimulation increased the proportion of pyroptotic HSCs, as shown by lactate dehydrogenase (LDH) release assays and by flow cytometric analysis of propidium iodide (PI) and caspase-1 double staining in cells. In addition, ROS generation was elevated in infected liver tissues and SEA-stimulated HSCs, and ROS inhibition downregulated SEA-induced caspase-1 activation and pyroptosis in HSCs.

Conclusions
Our present study demonstrates that pyroptotic cell death in HSCs induced by SEA via ROS-mediated caspase-1 activation may serve as a significant mechanism to initiate the inflammatory response and thereby exacerbate liver injury during S. japonicum infection.
Correction to: Aedes vittatus in Spain: current distribution, barcoding characterization and potential role as vectors of human diseases
Authors: Díez-Fernández Alazne , Martínez-de la Puente Josué , Ruiz Santiago , Gutiérrez-López Rafael , Soriguer Ramón , Figuerola Jordi 
Published: October 2019

Unfortunately, the original version of this article [1] contained an error. In the distribution map in Fig. 3, the presence of the mosquito Aedes vittatus was incorrectly indicated for Libya and Egypt.
Population genetics of Aedes albopictus (Diptera: Culicidae) in its native range in Lao People’s Democratic Republic
Authors: Motoki Maysa Tiemi , Fonseca Dina Madera , Miot Elliott Frederic , Demari-Silva Bruna , Thammavong Phoutmany , Chonephetsarath Somsanith , Phommavanh Nothasine , Hertz Jeffrey Conrad , Kittayapong Pattamaporn , Brey Paul Trevor , Marcombe Sebastien 
Published: October 2019

AbstractBackgroundThe Asian tiger mosquito,Aedes(Stegomyia)albopictus(Skuse) is an important worldwide invasive species and can be a locally important vector of chikungunya, dengue and, potentially, Zika. This species is native to Southeast Asia where populations thrive in both temperate and tropical climates. A better understanding of the population structure ofAe. albopictusin Lao PDR is very important in order to support the implementation of strategies for diseases prevention and vector control. In the present study, we investigated the genetic variability ofAe. albopictusacross a north-south transect in Lao PDR.MethodsWe used variability in a 1337-bp fragment of the mitochondrial cytochromecoxidase subunit 1 gene (cox1), to assess the population structure ofAe. albopictusin Lao PDR. For context, we also examined variability at the same genetic locus in samples ofAe. albopictusfrom Thailand, China, Taiwan, Japan, Singapore, Italy and the USA.ResultsWe observed very high levels of genetic polymorphism with 46 novel haplotypes inAe. albopictusfrom 9 localities in Lao PDR and Thailand populations. Significant differences were observed between the Luangnamtha population and other locations in Lao PDR. However, we found no evidence of isolation by distance. There was overall little genetic structure indicating ongoing and frequent gene flow among populations or a recent population expansion. Indeed, the neutrality test supported population expansion in LaotianAe. albopictusand mismatch distribution analyses showed a lack of low frequency alleles, a pattern often seen in bottlenecked populations. When samples from Lao PDR were analyzed together with samples from Thailand, China, Taiwan, Japan, Singapore, Italy and the USA, phylogenetic network and Bayesian cluster analysis showed that most populations from tropical/subtropical regions are more genetically related to each other, than populations from temperate regions. Similarly, most populations from temperate regions are more genetically related to each other, than those from tropical/subtropical regions.ConclusionsAedes albopictusin Lao PDR are genetically related to populations from tropical/subtropical regions (i.e. Thailand, Singapore, and California and Texas in the USA). The extensive gene flow among locations in Lao PDR indicates that local control is undermined by repeated introductions from untreated sites.
Effect of chemical amendments on reduction of bioavailable heavy metals and ecotoxicity in soil
Authors: Yoon Dong-Hyun , Choi Won Seok , Hong Young Kyu , Lee Young Bok , Kim Sung Chul 
Published: October 2019

AbstractHeavy metal pollution in soil has been concerned because of toxicity in ecosystem and adverse effect on human health. Main objective of this study was to examine reduction of bioavailable heavy metals and consequently, decrease of ecotoxicity to biota when chemical amendments were applied in soil. Three chemical amendments, acid mine drainage sludge (AMDS), lime stone (LS), and steel slag (SS) were applied with varied application ratio (1, 3, 5%) in heavy metal polluted soil and bioavailable fraction of heavy metal was monitored. In addition, ecotoxicity test using earthworm (Eisenia fetida) was conducted for 28 days examining mortality, weight increase, and bioaccumulation of heavy metal in the earthworm. Result showed that AMDS was the most efficient amendment for reducing bioavailable heavy metals in soil while SS showed the least efficiency. Reduction ratio of bioavailable-As, Cd, and Pb was ranged 39.0–92.0% depending on application ratio and heavy metal species for AMDS application. However, only bioavailable-Pb was reduced at the range between 39.1% and 56.5% when SS was applied in soil. In contrast, the lowest concentration of As, Cd, and Pb and ecotoxicity effect in the earthworm was observed in SS treatment indicating that exposure route of heavy metals or particle size of amendments might effect on uptake of heavy metals to the earthworm. Overall, ecotoxicity test in combination with chemical concentration monitoring is a useful tool for evaluating remediation efficiency of heavy metal polluted soil.
Effect of the Incretin Hormones on the Endocrine Pancreas in End-Stage Renal Disease
Authors: Jørgensen Morten B , Idorn Thomas , Rydahl Casper , Hansen Henrik P , Bressendorff Iain , Brandi Lisbet , Wewer Albrechtsen Nicolai J , van Hall Gerrit , Hartmann Bolette , Holst Jens J , Knop Filip K , Hornum Mads , Feldt-Rasmussen Bo 
Published: October 2019

Abstract

Context
The insulin-stimulating and glucagon-regulating effects of the 2 incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), contribute to maintain normal glucose homeostasis. Impaired glucose tolerance occurs with high prevalence among patients with end-stage renal disease (ESRD).

Objective
To evaluate the effect of the incretin hormones on endocrine pancreatic function in patients with ESRD.

Design and Setting
Twelve ESRD patients on chronic hemodialysis and 12 matched healthy controls, all with normal oral glucose tolerance test, were included. On 3 separate days, a 2-hour euglycemic clamp followed by a 2-hour hyperglycemic clamp (3 mM above fasting level) was performed with concomitant infusion of GLP-1 (1 pmol/kg/min), GIP (2 pmol/kg/min), or saline administered in a randomized, double-blinded fashion. A 30% lower infusion rate was used in the ESRD group to obtain comparable incretin hormone plasma levels.

Results
During clamps, comparable plasma glucose and intact incretin hormone concentrations were achieved. The effect of GLP-1 to increase insulin concentrations relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (50 [8–72]%, P = 0.03). Similarly, the effect of GIP relative to placebo levels tended to be lower during euglycemia in ESRD and was significantly reduced during hyperglycemia (34 [13–50]%, P = 0.005). Glucagon was suppressed in both groups, with controls reaching lower concentrations than ESRD patients.

Conclusions
The effect of incretin hormones to increase insulin release is reduced in ESRD, which, together with elevated glucagon levels, could contribute to the high prevalence of impaired glucose tolerance among ESRD patients.
Evaluation of methods to assign cell type labels to cell clusters from single-cell RNA-sequencing data
Authors: Diaz-Mejia J. Javier , Meng Elaine C. , Pico Alexander R. , MacParland Sonya A. , Ketela Troy , Pugh Trevor J. , Bader Gary D. , Morris John H. 
Published: October 2019

Background: Identification of cell type subpopulations from complex cell mixtures using single-cell RNA-sequencing (scRNA-seq) data includes automated steps from normalization to cell clustering. However, assigning cell type labels to cell clusters is often conducted manually, resulting in limited documentation, low reproducibility and uncontrolled vocabularies. This is partially due to the scarcity of reference cell type signatures and because some methods support limited cell type signatures. Methods: In this study, we benchmarked five methods representing first-generation enrichment analysis (ORA), second-generation approaches (GSEA and GSVA), machine learning tools (CIBERSORT) and network-based neighbor voting (METANEIGHBOR), for the task of assigning cell type labels to cell clusters from scRNA-seq data. We used five scRNA-seq datasets: human liver, 11 Tabula Muris mouse tissues, two human peripheral blood mononuclear cell datasets, and mouse retinal neurons, for which reference cell type signatures were available. The datasets span Drop-seq, 10X Chromium and Seq-Well technologies and range in size from ~3,700 to ~68,000 cells. Results: Our results show that, in general, all five methods perform well in the task as evaluated by receiver operating characteristic curve analysis (average area under the curve (AUC) = 0.91, sd = 0.06), whereas precision-recall analyses show a wide variation depending on the method and dataset (average AUC = 0.53, sd = 0.24). We observed an influence of the number of genes in cell type signatures on performance, with smaller signatures leading more frequently to incorrect results. Conclusions: GSVA was the overall top performer and was more robust in cell type signature subsampling simulations, although different methods performed well using different datasets. METANEIGHBOR and GSVA were the fastest methods. CIBERSORT and METANEIGHBOR were more influenced than the other methods by analyses including only expected cell types. We provide an extensible framework that can be used to evaluate other methods and datasets at https://github.com/jdime/scRNAseq_cell_cluster_labeling.
Pragmatic Home-Based Exercise after Total Hip Arthroplasty - Silkeborg: Protocol for a prospective cohort study (PHETHAS-1)
Authors: Mikkelsen Lone Ramer , Madsen Merete Nørgaard , Rathleff Michael Skovdal , Thorborg Kristian , Rossen Camilla Blach , Kallemose Thomas , Bandholm Thomas 
Published: October 2019

Introduction: Rehabilitation exercises are offered to patients after total hip arthroplasty (THA); however, the effectiveness and optimal type and dose of exercise remains unknown. The primary objective of this trial is to indicate the preliminary efficacy of home-based rehabilitation using elastic band exercise on performance-based function after THA, based on the relationship between the performed exercise dose and the change in performance-based function (gait speed) from 3 (start of intervention) to 10 weeks (end of intervention) after surgery. The secondary objective is to investigate if a dose-response relationship exists between the performed exercise dose and changes in: hip-related disability, lower-extremity functional performance, and hip muscle strength Methods: In this prospective cohort study, patients scheduled for THA will be consecutively included until 88 have completed the intervention period from 3 to 10 weeks postoperatively. Participants perform the standard rehabilitation program with elastic band exercises. Exercise dose (exposure) will be objectively quantified using a sensor attached to the elastic band. The primary outcome is gait speed measured by the 40-m fast-paced walk test. Secondary outcomes include: patient reported hip disability (Hip disability and Osteoarthritis Outcome Score (HOOS)), hip muscle strength (hand-held dynamometry) and lower extremity function (30-s chair stand test). Discussion: This trial will add knowledge concerning the relationship between performed exercise dose and post-operative outcomes after THA. The protocol paper describes the study design and methods in detail, including the statistical analysis plan. Trial registration: Pre-registered on March 27, 2017 at ClinicalTrails.gov (ID: NCT03109821).