bluuebunny/crossref_metadata_2025_split huggingface dataset:
High throughput genotyping of structural variations in a complex plant genome using an original Affymetrix® axiom® array
Authors: Mabire Clément , Duarte Jorge , Darracq Aude , Pirani Ali , Rimbert Hélène , Madur Delphine , Combes Valérie , Vitte Clémentine , Praud Sébastien , Rivière Nathalie , Joets Johann , Pichon Jean-Philippe , Nicolas Stéphane D. 
Published: November 2019

Abstract

Background
Insertions/deletions (InDels) and more specifically presence/absence variations (PAVs) are pervasive in several species and have strong functional and phenotypic effect by removing or drastically modifying genes. Genotyping of such variants on large panels remains poorly addressed, while necessary for approaches such as association mapping or genomic selection.

Results
We have developed, as a proof of concept, a new high-throughput and affordable approach to genotype InDels. We first identified 141,000 InDels by aligning reads from the B73 line against the genome of three temperate maize inbred lines (F2, PH207, and C103) and reciprocally. Next, we designed an Affymetrix® Axiom® array to target these InDels, with a combination of probes selected at breakpoint sites (13%) or within the InDel sequence, either at polymorphic (25%) or non-polymorphic sites (63%) sites. The final array design is composed of 662,772 probes and targets 105,927 InDels, including PAVs ranging from 35 bp to 129kbp. After Affymetrix® quality control, we successfully genotyped 86,648 polymorphic InDels (82% of all InDels interrogated by the array) on 445 maize DNA samples with 422,369 probes. Genotyping InDels using this approach produced a highly reliable dataset, with low genotyping error (~ 3%), high call rate (~ 98%), and high reproducibility (> 95%). This reliability can be further increased by combining genotyping of several probes calling the same InDels (< 0.1% error rate and > 99.9% of call rate for 5 probes). This “proof of concept” tool was used to estimate the kinship matrix between 362 maize lines with 57,824 polymorphic InDels. This InDels kinship matrix was highly correlated with kinship estimated using SNPs from Illumina 50 K SNP arrays.

Conclusions
We efficiently genotyped thousands of small to large InDels on a sizeable number of individuals using a new Affymetrix® Axiom® array. This powerful approach opens the way to studying the contribution of InDels to trait variation and heterosis in maize. The approach is easily extendable to other species and should contribute to decipher the biological impact of InDels at a larger scale.
Molecular dissection of the replication system of plasmid pIGRK encoding two in-frame Rep proteins with antagonistic functions
Authors: Wawrzyniak Paweł , Sobolewska-Ruta Agnieszka , Zaleski Piotr , Łukasiewicz Natalia , Kabaj Paulina , Kierył Piotr , Gościk Agata , Bierczyńska-Krzysik Anna , Baran Piotr , Mazurkiewicz-Pisarek Anna , Płucienniczak Andrzej , Bartosik Dariusz 
Published: November 2019

AbstractBackgroundGene overlapping is a frequent phenomenon in microbial genomes. Excluding so-called “trivial overlapping”, there are significant implications of such genetic arrangements, including regulation of gene expression and modification of protein activity. It is also postulated that, besides gene duplication, the appearance of overlapping genes (OGs) is one of the most important factors promoting a genome’s novelty and evolution. OGs coding for in-frame proteins with different functions are a particularly interesting case. In this study we identified and characterized two in-frame proteins encoded by OGs on plasmid pIGRK fromKlebsiella pneumoniae, a representative of the newly distinguished pHW126 plasmid family.ResultsA singlerepRlocus located within the replication system of plasmid pIGRK encodes, in the same frame, two functional polypeptides: a full-length RepR protein and a RepR’ protein (withN-terminal truncation) translated from an internal START codon. Both proteins form homodimers, and interact with diverse DNA regions within the plasmid replication origin andrepRpromoter operator. Interestingly, RepR and RepR’ have opposing functions – RepR is crucial for initiation of pIGRK replication, while RepR’ is a negative regulator of this process. Nevertheless, both proteins act cooperatively as negative transcriptional regulators of their own expression.ConclusionsRegulation of the initiation of pIGRK replication is a complex process in which a major role is played by two in-frame proteins with antagonistic functions. In-frame encoded Rep proteins are uncommon, having been described in only a few plasmids. This is the first description of such proteins in a plasmid of the pHW126 family.
Prediction mapping of human leptospirosis using ANN, GWR, SVM and GLM approaches
Authors: Mohammadinia Ali , Saeidian Bahram , Pradhan Biswajeet , Ghaemi Zeinab 
Published: November 2019

AbstractBackgroundRecent reports of the National Ministry of Health and Treatment of Iran (NMHT) show that Gilan has a higher annual incidence rate of leptospirosis than other provinces across the country. Despite several efforts of the government and NMHT to eradicate leptospirosis, it remains a public health problem in this province. Modelling and Prediction of this disease may play an important role in reduction of the prevalence.MethodsThis study aims to model and predict the spatial distribution of leptospirosis utilizing Geographically Weighted Regression (GWR), Generalized Linear Model (GLM), Support Vector Machine (SVM) and Artificial Neural Network (ANN) as capable approaches. Five environmental parameters of precipitation, temperature, humidity, elevation and vegetation are used for modelling and predicting of the disease. Data of 2009 and 2010 are used for training, and 2011 for testing and evaluating the models.ResultsResults indicate that utilized approaches in this study can model and predict leptospirosis with high significance level. To evaluate the efficiency of the approaches, MSE (GWR = 0.050, SVM = 0.137, GLM = 0.118 and ANN = 0.137), MAE (0.012, 0.063, 0.052 and 0.063), MRE (0.011, 0.018, 0.017 and 0.018) and R2(0.85, 0.80, 0.78 and 0.75) are used.ConclusionResults indicate the practical usefulness of approaches for spatial modelling and predicting leptospirosis. The efficiency of models is as follow: GWR > SVM > GLM > ANN. In addition, temperature and humidity are investigated as the most influential parameters. Moreover, the suitable habitat of leptospirosis is mostly within the central rural districts of the province.
Capsular warning syndrome: clinical analysis and treatment
Authors: He Lanying , Xu Ronghua , Wang Jian , Zhang Lili , Zhang Lijuan , Zhou Fangfang , Dong Weiwei 
Published: November 2019

Abstract

Background
Capsular warning syndrome (CWS) is a rare clinical syndrome, which is defined as a recurrent transient lacunar syndrome. The mechanism and clinical management of CWS remain unclear. The aim of the study was to discuss the clinical characteristics of CWS and evaluate the different outcome between rt-PA and no rt-PA therapy.

Methods
The present multicenter retrospective study involved three medical centers, and the clinical data were collected from patients with CWS between January 2013 and December 2018. The clinical characteristics of CWS were analyzed. Patients were divided into two groups: rt-PA and no rt-PA groups. The therapeutic effects and prognosis of these two groups were analyzed. A good prognosis was defined as 3-month modified Rankin Scale (mRS) ≤ 2.

Results
Our study included 72 patients, 27 patients were assigned to rt-PA group, 45 in no rt-PA group. Hypertension and dyslipidemia were the most common risk factors. The mean number of episodes before irreversible neurological impairment or the symptoms completely disappeared was five times (range: 3–11 times). A total of 58 (80.55%) patients had acute infarction lesions on the diffusion weighted imaging (DWI). The most common infarct location was the internal capsule (41,70.69%), followed by the thalamus and pons. The difference in therapeutic effects between the rt-PA, single and double antiplatelet groups was not statistically significant (P > 0.05). A good prognosis was observed in 61 (84.72%) patients after 3 months, in which 23 (23/27, 85.19%) patients were from the rt-PA group and 38 (38/45,84.44%) patients were from the no rt-PA group (P > 0.05). After 3 months of follow-up, two patients had recurrent ischemic stroke.

Conclusion
The most effective treatment of CWS remains unclear. Intravenous thrombolysis is safe for CWS patients. Regardless of the high frequency of infarction in CWS patients, more than 80% patients had a favorable functional prognosis.
Impact of the intervention program “JolinchenKids – fit and healthy in daycare” on energy balance related-behaviors: results of a cluster controlled trial
Authors: Steenbock Berit , Buck Christoph , Zeeb Hajo , Rach Stefan , Pischke Claudia R. 
Published: November 2019

Abstract

Background
The purpose of this study was to evaluate the multi-component health promotion program, JolinchenKids – fit and healthy in daycare, designed to promote physical activity (PA), healthy eating, and mental wellbeing among 3- to 6-year-old preschoolers.

Methods
For this cluster controlled trial, 62 daycare facilities (DFs) from thirteen different federal states in Germany were recruited (31 intervention, 31 control DFs). Outcome measures were children’s habitual PA, fruits and vegetable consumption, consumption of unsweetened beverages and snacks with parents as raters. Study nurses assessed children’s body composition and motor skills. Data was collected at baseline and 12 months later. To track adherence to the implementation of intervention modules at individual DF groups, an implementation calendar was used from baseline to follow-up. Linear mixed models were used to investigate effects for survey, group and their interaction at the individual level while accounting for clustering.

Results
Samples of 831 (baseline) and 641 (follow-up) children aged 4.3 ± 0.8 and 5.2 ± 0.8 years were analysed. More than half of the intervention DFs chose the nutrition or PA module for the first year of implementation while an implementation level of > 50% was only achieved in less than a third. A significant intervention effect (survey × group interaction) was found for the standing long jump favouring children at intervention DFs (β = 3.08; 95% Confidence interval [CI]: (0.09; 6.07)). No significant intervention effects were found for time spent on PA, total screen time, dietary habits, and body composition, i.e. body-mass-index and percentage of body fat.

Conclusions
Participation in JolinchenKids – fit and healthy in daycare led to improvements in some indicators for motor skills. However, other health outcomes and behaviours were not affected by program participation over the course of 1 year.

Trial registration
German Clinical Trials Register DRKS00011065 (Date of registration 16-09-2016).
Non-inferior comparative study comparing one or two day antimicrobial prophylaxis after clean orthopaedic surgery (NOCOTA study): a study protocol for a cluster pseudo-randomized controlled trial comparing duration of antibiotic prophylaxis
Authors: Nagata Kosei , Yamada Koji , Shinozaki Tomohiro , Miyazaki Tsuyoshi , Tokimura Fumiaki , Oka Hiroyuki , Tajiri Yasuhito , Tanaka Sakae , Okazaki Hiroshi 
Published: November 2019

Abstract

Background
Antimicrobial prophylaxis (AMP) is one of the most important measures for preventing surgical site infections (SSIs); however, controversies remain regarding its adequate duration. Although the World Health Organization and the Center for Disease Control and Prevention do not recommend additional AMP after closure, the American Society of Health-System Pharmacists and the Musculoskeletal Infection Society permit the use of postoperative AMP, but recommend discontinuation within 24 h. Similarly, the Japanese Society of Chemotherapy and the Japan Society for Surgical Infection also permit AMP within 24–48 h after various orthopaedic procedures. In these guidelines, recommendations regarding AMP duration were weak due to a relative lack of evidence, and currently, there is no high-quality evidence comparing AMP use within 24 h versus 24–48 h regarding orthopaedic procedures. Urinary tract infection (UTI) and respiratory tract infection (RTI) are also important health care-associated infections (HAIs) faced after surgery. Although AMP duration may affect these HAIs, its effects have not been well evaluated.

Methods
We have organized a multicenter, prospective, cluster pseudo-randomized controlled trial to examine the non-inferiority of shorter AMP duration (within 24 h) against longer duration (24–48 h) in preventing postoperative HAIs. Participating facilities will be divided into two groups. In Group 24, AMP will be discontinued within 24 h after surgery. In Group 48, AMP will be discontinued within 24–48 h after surgery. The group allocation will be switched every 2 months until the targeted recruitment (500 participants per group) is met.
The primary outcome will be the cumulative incidence of all HAIs (SSI, UTI, RTI, and other infectious diseases), which require antibiotic therapies within 30 days after surgery. In addition to mortality and cardiovascular events, prolonged hospitalization (> 30 days) and the rate of antibiotic resistance rate of SSI pathogens will also be evaluated. Outcomes will be evaluated within 30–180 days after surgery in person by the surgeon, by mail, or by telephone survey. Data will be analyzed by a statistician not engaged in data collection.

Discussion
This study may provide valuable information for developing future recommendations for adequate AMP duration after clean orthopaedic surgery.

Trial registration
UMIN000030929, registered January 22, 2018.
Feet deformities and their close association with postural stability deficits in children aged 10–15 years
Authors: Szczepanowska-Wolowiec Beata , Sztandera Paulina , Kotela Ireneusz , Zak Marek 
Published: November 2019

Abstract

Background
Children and young people make up an age group most vulnerable to falls. Various stability disorders may become instrumental in sustaining more frequent falls and resultant fractures. Correct morphological structure impacts overall efficiency of the foot, as well as offers significant diagnostic potential. Even minor foot disorders may affect the entire bio kinematic chain, also impacting the foot’s motility. Structural alterations within a foot may also impair balance in the standing position, and contribute to more frequent injuries. The study aimed to assess the relationship between feet deformities and postural stability deficits in schoolchildren prone to sustain accidental falls.

Methods
The study involved 200 children (101 girls and 99 boys) aged 10–15 years,
randomly selected from primary schools. A 2D podoscan was used to assess the plantar part of the foot, while stabilometric examination was aided by the FreeMed dynamometric platform.

Results
Correlation between respective variables was reflected by Spearman’s rank coefficient. The subjects’ age negatively correlated with the COP range of movement along the Y axis, and the COP surface area, while their BMI negatively correlated with the COP trajectory’s length. Step regression analysis indicated that the width of the left foot, the left foot Wejsflog index, the left foot Clark’s angle, the hallux valgus angle were the essential predictors of stabilometric variables in girls. In boys, though, predictive value was associated with Clarke’s angle of the left and right foot, Wejsflog index of the right foot, and the width of both the left and right foot.

Conclusions
There is a statistically significant correlation between morphological variables of the foot and postural stability. When assessing the key variables of the foot and their interrelationship with postural stability, the Clarke’s angle, Wejsflog index, hallux valgus angle, and foot width, should be granted due prominence in the girls. As regards the boys, the following variables were established as predictive in assessing postural stability: Clarke’s angle, Wejsflog index, and foot width.
Integrative molecular analysis of metastatic hepatocellular carcinoma
Authors: Wang Dongfang , Zhu Yanjing , Tang Jing , Lian Qiuyu , Luo Guijuan , Wen Wen , Zhang Michael Q. , Wang Hongyang , Chen Lei , Gu Jin 
Published: November 2019

Abstract

Background
Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Intrahepatic metastasis, such as portal vein tumor thrombosis (PVTT), strongly indicates poor prognosis of HCC. But now, there are limited understandings of the molecular features and mechanisms of those metastatic HCCs.

Methods
To characterize the molecular alterations of the metastatic HCCs, we implemented an integrative analysis of the copy number variations (CNVs), DNA methylations and transcriptomes of matched adjacent normal, primary tumor and PVTT samples from 19 HCC patients.

Results
CNV analysis identified a frequently amplified focal region chr11q13.3 and a novel deletion peak chr19q13.41 containing three miRNAs. The integrative analysis with RNA-seq data suggests that CNVs and differential promoter methylations regulate distinct oncogenic processes. Then, we used individualized differential analysis to identify the differentially expressed genes between matched primary tumor and PVTT of each patient. Results show that 5 out of 19 studied patients acquire evidential progressive alterations of gene expressions (more than 1000 differentially expressed genes were identified in each patient). While, another subset of eight patients have nearly identical gene expressions between the corresponding matched primary tumor and PVTT. Twenty genes were found to be recurrently and progressively differentially expressed in multiple patients. These genes are mainly associated with focal adhesion, xenobiotics metabolism by cytochrome P450 and amino acid metabolism. For several differentially expressed genes in metabolic pathways, their expressions are significantly associated with overall survivals and vascular invasions of HCC patients. The following transwell assay experiments validate that they can regulate invasive phenotypes of HCC cells.

Conclusions
The metastatic HCCs with PVTTs have significant molecular alterations comparing with adjacent normal tissues. The recurrent alteration patterns are similar to several previously published general HCC cohorts, but usually with higher severity. By an individualized differential analysis strategy, the progressively differentially expressed genes between the primary tumor and PVTT were identified for each patient. A few patients aquire evidential progressive alterations of gene expressions. And, experiments show that several recurrently differentially expressed genes can strongly regulate HCC cell invasions.
Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies
Authors: Razquin Cristina , Ruiz-Canela Miguel , Clish Clary B. , Li Jun , Toledo Estefania , Dennis Courtney , Liang Liming , Salas-Huetos Albert , Pierce Kerry A. , Guasch-Ferré Marta , Corella Dolores , Ros Emilio , Estruch Ramon , Gómez-Gracia Enrique , Fitó Montse , Lapetra Jose , Romaguera Dora , Alonso-Gómez Angel , Serra-Majem Lluis , Salas-Salvadó Jordi , Hu Frank B. , Martínez-González Miguel A. 
Published: November 2019

Abstract
Background
The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk.

Methods
Two unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography–tandem mass spectrometry, at baseline and after 1-year of intervention.

Results
In weighted Cox regression models, we found that baseline lysine (HR+1 SD increase = 1.26; 95% CI 1.06–1.51) and 2-AAA (HR+1 SD increase = 1.28; 95% CI 1.05–1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites.

Conclusions
Our results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found.
Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003
Salinomycin effectively eliminates cancer stem-like cells and obviates hepatic metastasis in uveal melanoma
Authors: Zhou Jingfeng , Liu Shenglan , Wang Yun , Dai Wei , Zou Hailin , Wang Shubo , Zhang Jing , Pan Jingxuan 
Published: November 2019

Abstract
Background
Uveal melanoma (UM) is the most common primary intraocular tumor. Hepatic metastasis is the major and direct death-related reason in UM patients. Given that cancer stem-like cells (CSCs) are roots of metastasis, targeting CSCs may be a promising strategy to overcome hepatic metastasis in UM. Salinomycin, which has been identified as a selective inhibitor of CSCs in multiple types of cancer, may be an attractive agent against CSCs thereby restrain hepatic metastasis in UM. The objective of the study is to explore the antitumor activity of salinomycin against UM and clarify its underlying mechanism.

Methods
UM cells were treated with salinomycin, and its effects on cell proliferation, apoptosis, migration, invasion, CSCs population, and the related signal transduction pathways were determined. The in vivo antitumor activity of salinomycin was evaluated in the NOD/SCID UM xenograft model and intrasplenic transplantation liver metastasis mouse model.

Results
We found that salinomycin remarkably obviated growth and survival in UM cell lines and in a UM xenograft mouse model. Meanwhile, salinomycin significantly eliminated CSCs and efficiently hampered hepatic metastasis in UM liver metastasis mouse model. Mechanistically, Twist1 was fundamental for the salinomycin-enabled CSCs elimination and migration/invasion blockage in UM cells.

Conclusions
Our findings suggest that targeting UM CSCs by salinomycin is a promising therapeutic strategy to hamper hepatic metastasis in UM. These results provide the first pre-clinical evidence for further testing of salinomycin for its antitumor efficacy in UM patients with hepatic metastasis.