bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of surface roughening and calcite coating of titanium on cell growth and differentiation
Authors: Shi Rui , Hayashi Koichiro , Bang LT , Ishikawa Kunio
Published: October 2019

Medical pure titanium (Ti) exhibits excellent mechanical properties and chemical stability in clinical use, but its initial osteointegration period is often postponed due to the bioinert nature of the Ti surface. Roughening and bioactive material coating of Ti implant surfaces are considered effective to enhance the bioactivity of Ti implants. In this study, we evaluated the effects of surface roughening and calcite (CaCO3) coating of Ti substrates on osteoblastic cell differentiation and growth. We roughened the Ti substrate surface by acid etching, followed by coating with calcite by thermal decomposition of Ca(NO3)2 to CaO followed by thermal carbonation of CaO to CaCO3. The surface topography of roughened Ti substrates (rough Ti) fluctuated, and the arithmetic average of surface roughness (Ra) was 2.2 µm. The rough topography was retained even after calcite coating of rough Ti, and the calcite-coated Ti (calcite-Ti) has an Ra of 2.0 µm. The tensile adhesive and shear adhesive strengths between calcite coating and Ti surface in calcite–Ti were 56.6 ± 16.1 and 10.1 ± 1.39 MPa, respectively. The biological properties and response of calcite–Ti were evaluated in vitro using a pre-osteoblastic cell line (MC3T3-E1). Observation of cell morphology by scanning electron microscopy and immunofluorescence staining revealed that MC3T3-E1 cells attached favorably to the surface with polygonal and filopodial extensions on calcite–Ti. The combination of roughening and calcite coating of the Ti substrate surface significantly increased cell proliferation at 1, 3, and 7 days of incubation. Furthermore, the relative alkaline phosphatase activity of calcite–Ti was higher than that of untreated Ti substrates (smooth Ti) and rough Ti after incubation for 7 days. Thus, the combined surface roughening and calcite coating of Ti substrates promoted MC3T3-E1 differentiation, whereas roughening alone was not effective.
Adaptive fault-tolerant control for active suspension systems based on the terminal sliding mode approach
Authors: Kazemipour Amirhossein , Novinzadeh Alireza B
Published: October 2019

In this paper, a control system is designed for a vehicle active suspension system. In particular, a novel terminal sliding-mode-based fault-tolerant control strategy is presented for the control problem of a nonlinear quarter-car suspension model in the presence of model uncertainties, unknown external disturbances, and actuator failures. The adaptation algorithms are introduced to obviate the need for prior information of the bounds of faults in actuators and uncertainties in the model of the active suspension system. The finite-time convergence of the closed-loop system trajectories is proved by Lyapunov's stability theorem under the suggested control method. Finally, detailed simulations are presented to demonstrate the efficacy and implementation of the developed control strategy.
Performance and noise analysis of vibratory feeder using dynamic rubber spring model
Authors: Singh Chitransh , Chandravanshi Madan Lal
Published: October 2019

In vibratory feeder, material feeding occurs due to the vibration of a trough mounted on helical springs. High vibration amplitude of trough causes the springs to jump and usually results in higher noise level generation and increase in force transmissibility in the support structure of the feeder. Reducing this noise without having significant changes in the dynamics of the feeder unit is a major challenge in the present industries. This paper presents a dynamic rubber spring model for vibratory feeders to reduce the noise level and the force transferred to the support structure of the feeder. Measurement of dynamic parameters such as vibration amplitude and magnitude of force transmitted to support structure, noise level, and conveying speed of particle analyses have been conducted experimentally on vibratory feeder with and without rubber gasket installed at spring support structure. The use of rubber gaskets at spring supports and their implication on force transmissibility and noise level of feeder is established experimentally. The performance analysis of feeder was also conducted using particle conveying speed on trough for different setups of feeder unit. It was found that the introduction of rubber gaskets at spring supports of the feeder increases the system damping, which helps in noise reduction as well as reduced amplitude of vibration and higher acceleration of trough. The increased acceleration leads to higher particle conveying velocity on the feeder trough.
Comparing regional differences in global energy performance
Authors: Ma Liang-Han , Hsieh Jin-Chi , Chiu Yung-Ho
Published: October 2019

This study comprehensively considers any input and output that has a certain physical dimension, utilizes the super slacks-based measure directional distance function data envelopment analysis (DDF-DEA) model to measure global energy performance in the period 2010–2016, and compares regional differences in Americas, Europe and Asia. We employ contained directional, non-directional, and undesirable inputs and outputs, which include population number, fossil fuels energy consumption, gross capital formation, gross domestic product, renewable energy consumption, and carbon dioxide emission. From the full energy efficiency and ranking of the DDF-DEA approach herein, the empirical results show that Trinidad and Tobago exhibits the best efficiency (2.8194) and Uzbekistan has the worst efficiency (0.5734). The best regional energy performance is Americas, and the worst is Asia for 2010–2016, showing that regional energy policies have a significant impact. The Environmental Performance Index is an important sustainable environment index, and most Environmental Performance Index levels are quite consistent with the trend of energy efficiency and ranking with DDF-DEA in this study. The energy efficiencies of the higher Environmental Performance Index group and higher renewable energy consumption group are significantly larger than the lower Environmental Performance Index group and better than the lower renewable energy consumption group, respectively. Therefore, we suggest that all countries should adjust their future energy using a strategy based on annual Environmental Performance Index. Their goals can be to reduce fossil fuels energy consumption, increase renewable energy use, and reduce undesirable output of carbon dioxide. Doing so will help them to develop their economies while taking into account a sustainable environment, thus achieving sustainable economic development.
Current status of global warming potential reduction by cleaner composting
Authors: Liu Tao , Awasthi Sanjeev K , Duan Yumin , Pandey Ashok , Zhang Zengqiang , Awasthi Mukesh K
Published: October 2019

The global living standards are currently undergoing a stage of growth; however, such improvement also brings some challenges. Global warming is the greatest threat to all living things and attracts more and more attention on a global scale due to the rapid development of economy. Carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) are the common components of greenhouse gases, which contribute to the global warming. Mitigation technologies for these gas emissions are urgently needed in every industry for the aim of cleaner production. Traditional agriculture also contributes significantly to enhance the greenhouse gases emission. Composting is a novel and economic greenhouse gases mitigation strategy compared to other technologies in terms of the organic waste disposal. Some of the European countries showed an increase of more than 50% in the composting rate. The microbial respiration, nitrification and denitrification processes, and the generation of anaerobic condition makes the emission of greenhouse gases inevitable during composting. However, although there have been a lot of papers that focused on the reduction of greenhouse gases emission in composting, none of these has summarized the methods of reducing the emission of greenhouse gases during the composting. This review discusses the benefit of composting in greenhouse gases mitigation in the organic waste management and the current methods to improve mitigation efficiency during cleaner composting. Key physical, chemical, and biological parameters related to greenhouse gases mitigation strategies were precisely studied to give a deep understanding about the emission of greenhouse gases during cleaner composting. Furthermore, the mechanism of greenhouse gases emission mitigation strategies for cleaner composting based on various external measures would be helpful for the exploration of novel and effective mitigation strategies.
Treatment with intravenous immunoglobulins in systemic lupus erythematosus: a single-center experience with 63 patients
Authors: Nieto-Aristizábal I , Martínez T , Urbano M -A , Posso-Osorio I , Plata I F , Garcia-Robledo J E , Aragón C C , Santos V A , Tobón G J
Published: October 2019

Background

Intravenous immunoglobulin (IVIG) is prepared using purified human plasma. IVIG therapy has immunomodulatory effects on autoimmune diseases, including severe systemic lupus erythematosus (SLE). However, reports of its effects on large cohorts are scarce.

Methods

This single-center retrospective study included SLE patients treated with at least one IVIG cycle for SLE complications. Demographic data, indications, cycle numbers, and clinical improvement with IVIG were evaluated. SLE Disease Activity Index 2000 (SLEDAI-2K) scores were calculated at admission and after IVIG treatment in order to measure clinical improvement.

Results

Sixty-three SLE patients treated with IVIG (median age: 29 years; interquartile range 21–36 years; 84.13% female) were included, who received 2 g/kg IVIG for two to five days. Main indications were immune thrombocytopenia, hypogammaglobulinemia, infection during a SLE flare, bicytopenia, and immune hemolytic anemia. Seven patients received more than one IVIG cycle without severe adverse effects. Significant differences were found in SLEDAI-2K scores when the indications were immune thrombocytopenia and hypogammaglobulinemia, with a trend for hemolytic anemia. Patients with concomitant infection, myopathy, and gastrointestinal involvement showed a considerable reduction in their last SLEDAI-2K scores. Fourteen patients died during hospitalization, mainly due to septic shock and active SLE.

Conclusions

IVIG showed adequate tolerance and effectiveness in selected severe SLE manifestations, mainly hematological involvement. It was useful for concomitant infection.
Specific and general skills: Concepts, dimensions, and measurements
Authors: Christenko Aleksandr , Martinaitis Žilvinas , Gaušas Simonas
Published: October 2019

A number of academic debates rely on the distinction between general and specific skills as being valuable to a large number or a few firms. However, the meaning attributed to these concepts as well as empirical measurement strategies have significantly varied in the literature. To address the resulting theoretical and empirical confusion, we propose a multidimensional approach for defining skill specificity, which encompasses four distinct concepts: accessibility and similarity of skill sets as well as the portability and replaceability of skills. The former two refer to skills acquired by an individual (i.e. skills are substantively specific), while the latter two depend on the structure of labour demand and supply, institutions and firms’ strategies (i.e. on economic factors) that are time and place dependent. This paper proposes and tests empirical strategies for measuring each concept. The results challenge assumptions in the literature that graduates of vocational training and high-skilled blue-collar occupations have substantively specific skills. The multidimensional conceptualization and empirical results provide a number of theoretical implications. We focus on three conceptual debates regarding firms’ incentives to fund training, workers’ demand for social insurance and types of skills that facilitate or obstruct adjustment to technological and economic shocks.
Testing the boundaries of the consideration doctrine: Can you contract to buy and sell a ghost?
Authors: Giancaspro Mark
Published: October 2019

This article considers whether contracts to purchase ‘haunted’ objects are legally enforceable under Australian contract law. ‘Dybbuk boxes’, and related paraphernalia said to be possessed by spirits, are becoming increasingly popular on online shopping sites and as tourist attractions following recent high-profile incidents involving celebrities such as American rapper and record producer Post Malone. This article suggests that the enforceability of contracts for the sale of haunted items such as dybbuk boxes is dubious at best, and that the countless number of such contracts that have been concluded may be subject to legal challenge.
Analysis of the precision sustainability of the preload double-nut ball screw with consideration of the raceway wear
Authors: Zhao Jiajia , Lin Mingxing , Song Xianchun , Guo Qizhen
Published: October 2019

Ball screws are the driving components used to convert the rotational motion into linear motion in precision equipment. However, the machining accuracy of precision equipment is directly determined by the positioning accuracy of the ball screw. The authors analyze the precision sustainability of preload double-nut ball screws with raceway wear. A new wear model combining the modified Archard theory and the iterative interpolation method is established to analyze the variations in wear depth. A new model considering the coupling relationship between raceway wear and preload loss is proposed to study the precision life of the double-nut ball screw. In addition, a novel running test bench is designed to verify the precision sustainability of ball screws. The precision sustainability of the ball screw is analyzed during its life cycle, and these results match the theoretical values obtained by using the wear model.
‘There’s more to life than money and health’: Family caregivers’ views on the role of Power of Attorney in proxy decisions about research participation for people living with dementia
Authors: Shepherd Victoria , Griffith Richard , Hood Kerenza , Sheehan Mark , Wood Fiona
Published: October 2019

People living with dementia may experience difficulties when making decisions for themselves in the later stages of the condition. While there are mechanisms in England and Wales for appointing an attorney to make decisions about welfare and finances on their behalf, there are no provisions for appointing an attorney to make future decisions about research participation. This is despite a growing focus on Advanced Care Planning and other processes that provide opportunities to discuss future preferences and ensure that decisions are made in line with those preferences. This qualitative study with 15 family caregivers who had acted as research proxies explored the role of Power of Attorney in their decisions about research, and their views about extending current legal arrangements to include research. Five themes were identified: the holistic nature of decision-making; the ‘power’ of attorney; making decisions by putting yourself in their shoes; support for bringing research under the umbrella of attorney arrangements and a unifying theme of trusting relationships. Legal provisions for prospectively appointing a research proxy may encourage discussion about future wishes and so enable decisions about research to be made that are in accordance with the person’s preferences and wishes. However, further consultation with the public including people living with dementia and their families, and a range of stakeholders is needed. Providing guidance to families, people living with dementia and the wider research community may provide greater clarity and improve decision-making in the meantime.
Interaction between CONNEXIN37 and PDE4D gene polymorphisms with susceptibility to ischemic stroke in Chinese population
Authors: Zhang Lixia , Ding Ruohong , Kuang Peng , Wang Leiping , Deng Huixin , Xiong Qingqing , Jiang Hong
Published: October 2019

The objective of this study was to test the relationship of several single nucleotide polymorphisms (SNPs) within phosphodiesterase 4D ( PDE4D) and connexin 37 ( CONNEXIN37) gene additional interactions with ischemic stroke (IS) risk. The online software SNPstats was used for Hardy–Weinberg equilibrium testing. Generalized multifactor dimensionality reduction (GMDR) was employed to detect the potential interactions among CONNEXIN37 gene, PDE4D gene, and smoking. The results indicated that the rs1764391-T and rs966221-G were correlated with higher IS risk, the corresponding ORs (95% CI) were 1.66 (1.21–2.03) and 1.48 (1.11–1.92), respectively. We also found that the first two loci including rs1764391 and rs918592, and the other two-loci including rs1764391 and smoking were significant in the GMDR model. Participants with rs1764391-CT/TT and rs918592-CT/TT genotype have the highest IS risk, compared to subjects with rs1764391-CC and rs918592-CC genotype, OR (95%CI) = 3.16 (1.83–4.45); smokers with rs1764391-CT/TT genotype also have the highest IS risk, compared to never smokers with rs1764391-CC genotype, OR (95%CI) = 2.82 (1.53–4.15), but no significant interaction combinations were found between gene and alcohol drinking. So in this study, the rs1764391-T and rs966221-G, rs1764391–rs918592 interaction, rs1764391–smoking interaction were all associated with higher IS susceptibility.

Impact statement

Till now, no study investigated the interaction between CONNEXIN37 and PDE4D gene, and the gene–environment interaction. Therefore, in the current study, we aimed to evaluate the impact of interactions between CONNEXIN37 and PDE4D gene, and its interaction with environmental risk factors on susceptibility to ischemic stroke (IS).
Living with severe asthma: the role of perceived competence and goal achievement
Authors: Eassey Daniela , Reddel Helen K , Ryan Kath , Smith Lorraine
Published: October 2019

Objective

The overall aim of this study was to examine, among individuals living with severe asthma, the role of perceived competence in achieving their goals.

Methods

Qualitative research methods were used to conduct in-depth semistructured interviews. Interviews were video and/or audio recorded, transcribed and analyzed inductively and deductively, informed by the self-determination theory construct of perceived competence. Thirty-six face-to-face interviews, lasting 1.5–4 h, were conducted across Australia.

Results

Feeling competent to achieve asthma goals played a role in participants’ ability to achieve broader goals. Their desire to achieve their broader goals was strongly driven by their perceived ability to master managing their condition, which at times required more than medical strategies. Two main themes were discerned from the analysis: (1) learning how to look after yourself: self-care is important and (2) reaching an agreement with severe asthma: being at one with the illness.

Discussion

This study highlighted the influence of perceived competence on self-management and goal achievement in severe asthma. Healthcare providers could explore patients’ perceived competence to set and achieve goals, as a self-management strategy. Future research should consider these findings when developing and implementing patient-driven, self-management interventions for those living with severe asthma.
Elevated early lesion water uptake in acute stroke predicts poor outcome despite successful recanalization – When “tissue clock” and “time clock” are desynchronized
Authors: Nawabi Jawed , Flottmann Fabian , Kemmling Andre , Kniep Helge , Leischner Hannes , Sporns Peter , Schön Gerhard , Hanning Uta , Thomalla Götz , Fiehler Jens , Broocks Gabriel
Published: October 2019

Background

Ischemic water uptake in acute stroke is a reliable indicator of lesion age. Nevertheless, inter-individually varying edema progression has been observed and elevated water uptake has recently been described as predictor of malignant infarction.

Aims

We hypothesized that early-elevated lesion water uptake indicates accelerated “tissue clock” desynchronized with “time clock” and therefore predicts poor clinical outcome despite successful recanalization.

Methods

Acute middle cerebral artery stroke patients with multimodal admission-CT who received successful thrombectomy (TICI 2b/3) were analyzed. Net water uptake (NWU), a quantitative imaging biomarker of ischemic edema, was determined in admission-CT and tested as predictor of clinical outcome using modified Rankin Scale (mRS) after 90 days. A binary outcome was defined for mRS 0–4 and mRS 5–6.

Results

Seventy-two patients were included. The mean NWU (SD) in patients with mRS 0–4 was lower compared to patients with mRS 5–6 (5.0% vs. 12.1%; p < 0.001) with similar time from symptom onset to imaging (2.6 h vs. 2.4 h; p = 0.7). Based on receiver operating curve analysis, NWU above 10% identified patients with very poor outcome with high discriminative power (AUC 0.85), followed by Alberta Stroke Program Early CT Score (ASPECTS) (AUC: 0.72) and National Institutes of Health Stroke Scale (NIHSS) (AUC: 0.72).

Conclusions

Quantitative NWU may serve as an indicator of “tissue clock” and pronounced early brain edema with elevated NWU might suggest a desynchronized “tissue clock” with real “time clock” and therefore predict futile recanalization with poor clinical outcome.
Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials
Authors: Lorenzano Svetlana , Vestri Annarita , Lancia Ugo , Bovi Paolo , Cappellari Manuel , Stanzione Paolo , Samà Domenico , Bruscoli Maddalena , Cavazzuti Milena , Zini Andrea , Rasura Maurizia , Beccia Mario , Comi Giancarlo , Sessa Maria , Gandolfo Carlo , Balestrino Maurizio , Agnelli Giancarlo , Caso Valeria , Gerbino Promis Piercarlo , Pozzessere Claudio , Anticoli Sabrina , Perini Francesco , Marcon Michela , Vinattieri Annalisa , Caruso Alba , Magoni Mauro , Furlan Mauro , Orlandi Giovanni , Di Lazzaro Vincenzo , Valente Mariarosaria , Nencini Patrizia , Cordisco Moira , Verna Roberto , Toni Danilo
Published: October 2019

Background

Since its approval, the use of alteplase had been limited to patients aged ≤80 years.

Aims

TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence.

Methods

TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0–2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly.

Results

Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69–2.64, P = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights.

Conclusions

The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.
Cost-effectiveness of exercise therapy in patients with coronary heart disease, chronic heart failure and associated risk factors: A systematic review of economic evaluations of randomized clinical trials
Authors: Oldridge Neil , Taylor Rod S
Published: October 2019

Aims

Prescribed exercise is effective in adults with coronary heart disease (CHD), chronic heart failure (CHF), intermittent claudication, body mass index (BMI) ≥25 kg/m2, hypertension or type 2 diabetes mellitus (T2DM), but the evidence for its cost-effectiveness is limited, shows large variations and is partly contradictory. Using World Health Organization and American Heart Association/American College of Cardiology value for money thresholds, we report the cost-effectiveness of exercise therapy, exercise training and exercise-based cardiac rehabilitation.

Methods

Electronic databases were searched for incremental cost-effectiveness and incremental cost–utility ratios and/or the probability of cost-effectiveness of exercise prescribed as therapy in economic evaluations conducted alongside randomized controlled trials (RCTs) published between 1 July 2008 and 28 October 2018.

Results

Of 19 incremental cost–utility ratios reported in 15 RCTs in patients with CHD, CHF, intermittent claudication or BMI ≥25 kg/m2, 63% met both value for money thresholds as ‘highly cost-effective’ or ‘high value’, with 26% ‘not cost-effective’ or of ‘low value’. The probability of intervention cost-effectiveness ranged from 23 to 100%, probably due to the different populations, interventions and comparators reported in the individual RCTs. Confirmation with the Consolidated Health Economic Evaluation Reporting checklist varied widely across the included studies.

Conclusions

The findings of this review support the cost-effectiveness of exercise therapy in patients with CHD, CHF, BMI ≥25 kg/m2 or intermittent claudication, but, with concerns about reporting standards, need further confirmation. No eligible economic evaluation based on RCTs was identified in patients with hypertension or T2DM.
Diagnostic accuracy of computed tomography perfusion in the prediction of haemorrhagic transformation and patient outcome in acute ischaemic stroke: A systematic review and meta-analysis
Authors: Adebayo Olushola D , Culpan Gary
Published: October 2019

Purpose

The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy of computed tomography brain perfusion in the prediction of haemorrhagic transformation and patient outcome in acute ischaemic stroke.

Method

Electronic databases and grey literature published over the last 10 years related to healthcare and radiology were searched using the key terms: ‘computed tomography perfusion’, ‘haemorrhagic transformation’, ‘acute ischaemic stroke’, ‘functional outcome’ and their synonyms using both UK and American spellings. Inclusion criteria were: sample size at least 30 patients, original research, evaluate ability of computed tomography perfusion to predict haemorrhagic transformation, reports diagnostic accuracy or provide relevant data for a 2 × 2 contingency table, use follow-up non-contrast computed tomography (NCCT) or magnetic resonance imaging as reference standard.

Findings

Twelve studies were included in the review; studies cover a total of 808 patients. Haemorrhagic transformation occurred in 30.2% of patients. Pooled sensitivity and specificity were 85.9% (95% CI; 65–97%), 73.9% (95% CI; 45–92%) and accuracy of 79.1% (95% CI; 57–98%). Pooled NPV was 92.9% with a high false positive rate (19.8%), which could be explained in terms of outcome classification, acquisition artefact and computed tomography perfusion processing algorithms.

Discussion

This review evaluated the importance of using pre-defined threshold measurement for optimal prediction of HT, the relevance of patient pre-treatment clinical parameters to HT occurrence, the CTP parameters and the measurements that are independent predictors of HT, the significance of rtPA rather as an exacerbator of HT and the impact of both minor and major HT/PH on patient 20 functional outcome.

Conclusion

Computed tomography perfusion has a high sensitivity and moderately high specificity for prediction of haemorrhagic transformation in acute ischaemic stroke. Pre-treatment clinical decision making requires consideration of clinical factors in addition to imaging findings. This systematic review and meta-analysis highlights that pre-treatment computed tomography perfusion adds to clinical confidence by predicting potential for haemorrhage, both in thrombolysed and un-thrombolysed patients, and also influences decisions about alternative treatments for acute ischaemic stroke patients.
A multicentre, randomised, sham-controlled trial on REmote iSchemic conditioning In patients with acute STroke (RESIST) – Rationale and study design
Authors: Blauenfeldt Rolf A , Hjort Niels , Gude Martin F , Behrndtz Anne B , Fisher Marc , Valentin Jan B , Kirkegaard Hans , Johnsen Søren P , Hess David C , Andersen Grethe
Published: October 2019

Rationale

Remote ischaemic conditioning, applied in the prehospital setting and continued in-hospital, may improve functional outcome in patients with acute ischaemic stroke and intracerebral haemorrhage.

Aims

To evaluate whether combined remote ischaemic per- and postconditioning can improve long-term functional outcome in acute ischaemic stroke and intracerebral haemorrhage patients.

Methods and design

Danish multicentre, prospective, randomised, patient-assessor blinded, sham-controlled study. Adult patients with a putative stroke identified prehospital with symptom duration <4 h, who are independent in daily activities will be randomised 1:1 to remote ischaemic conditioning or Sham-remote ischaemic conditioning. The treatment protocol will be five cycles, each consisting of 5 min with a blood pressure cuff inflation and 5 min with a deflated cuff placed on the upper extremity. The cuff pressure for remote ischaemic conditioning will be 200 mmHg–285 mmHg according to the individual systolic blood pressure and 20 mmHg sham-remote ischaemic conditioning during inflation. The study is approved as an acute study and consent is waived in the acute phase. Sample size estimation: For a 7% increased odds for a beneficial shift on the modified Rankin Scale at a significance level of 5% and power of 90%, 1000 patients with a target diagnosis of acute ischaemic stroke and intracerebral haemorrhage and a total of 1500 patients with a prehospital presumed stroke will be included. Study outcomes: The primary outcome will be the modified Rankin Scale score measured at three-month follow-up (analysed using ordinal logistic regression). ClinicalTrials.gov Identifier: NCT03481777.
Structure of the intergenic spacers in chicken ribosomal DNA
Authors: Dyomin Alexander , Galkina Svetlana , Fillon Valerie , Cauet Stephane , Lopez-Roques Celine , Rodde Nathalie , Klopp Christophe , Vignal Alain , Sokolovskaya Anastasia , Saifitdinova Alsu , Gaginskaya Elena
Published: October 2019

Background

Ribosomal DNA (rDNA) repeats are situated in the nucleolus organizer regions (NOR) of chromosomes and transcribed into rRNA for ribosome biogenesis. Thus, they are an essential component of eukaryotic genomes. rDNA repeat units consist of rRNA gene clusters that are transcribed into single pre-rRNA molecules, each separated by intergenic spacers (IGS) that contain regulatory elements for rRNA gene cluster transcription. Because of their high repeat content, rDNA sequences are usually absent from genome assemblies. In this work, we used the long-read sequencing technology to describe the chicken IGS and fill the knowledge gap on rDNA sequences of one of the key domesticated animals.

Methods

We used the long-read PacBio RSII technique to sequence the BAC clone WAG137G04 (Wageningen BAC library) known to contain chicken NOR elements and the HGAP workflow software suit to assemble the PacBio RSII reads. Whole-genome sequence contigs homologous to the chicken rDNA repetitive unit were identified based on the Gallus_gallus-5.0 assembly with BLAST. We used the Geneious 9.0.5 and Mega software, maximum likelihood method and Chickspress project for sequence evolution analysis, phylogenetic tree construction and analysis of the raw transcriptome data.

Results

Three complete IGS sequences in the White Leghorn chicken genome and one IGS sequence in the red junglefowl contig AADN04001305.1 (Gallus_gallus-5.0) were detected. They had various lengths and contained three groups of tandem repeats (some of them being very GC rich) that form highly organized arrays. Initiation and termination sites of rDNA transcription were located within small and large unique regions (SUR and LUR), respectively. No functionally significant sites were detected within the tandem repeat sequences.

Conclusions

Due to the highly organized GC-rich repeats, the structure of the chicken IGS differs from that of IGS in human, apes, Xenopus or fish rDNA. However, the chicken IGS shares some molecular organization features with that of the turtles, which are other representatives of the Sauropsida clade that includes birds and reptiles. Our current results on the structure of chicken IGS together with the previously reported ribosomal gene cluster sequence provide sufficient data to consider that the complete chicken rDNA sequence is assembled with confidence in terms of molecular DNA organization.
RACS: rapid analysis of ChIP-Seq data for contig based genomes
Authors: Saettone Alejandro , Ponce Marcelo , Nabeel-Shah Syed , Fillingham Jeffrey
Published: October 2019

Background

Chromatin immunoprecipitation coupled to next generation sequencing (ChIP-Seq) is a widely-used molecular method to investigate the function of chromatin-related proteins by identifying their associated DNA sequences on a genomic scale. ChIP-Seq generates large quantities of data that is difficult to process and analyze, particularly for organisms with a contig-based sequenced genomes that typically have minimal annotation on their associated set of genes other than their associated coordinates primarily predicted by gene finding programs. Poorly annotated genome sequence makes comprehensive analysis of ChIP-Seq data difficult and as such standardized analysis pipelines are lacking.

Results

We present a one-stop computational pipeline, “Rapid Analysis of ChIP-Seq data” (RACS), that utilizes traditional High-Performance Computing (HPC) techniques in association with open source tools for processing and analyzing raw ChIP-Seq data. RACS is an open source computational pipeline available from any of the following repositories https://bitbucket.org/mjponce/RACS or https://gitrepos.scinet.utoronto.ca/public/?a=summary&p=RACS. RACS is particularly useful for ChIP-Seq in organisms with contig-based genomes that have poor gene annotation to aid protein function discovery.To test the performance and efficiency of RACS, we analyzed ChIP-Seq data previously published in a model organism Tetrahymena thermophila which has a contig-based genome. We assessed the generality of RACS by analyzing a previously published data set generated using the model organism Oxytricha trifallax, whose genome sequence is also contig-based with poor annotation.

Conclusions

The RACS computational pipeline presented in this report is an efficient and reliable tool to analyze genome-wide raw ChIP-Seq data generated in model organisms with poorly annotated contig-based genome sequence. Because RACS segregates the found read accumulations between genic and intergenic regions, it is particularly efficient for rapid downstream analyses of proteins involved in gene expression.
SLR: a scaffolding algorithm based on long reads and contig classification
Authors: Luo Junwei , Lyu Mengna , Chen Ranran , Zhang Xiaohong , Luo Huimin , Yan Chaokun
Published: October 2019

Background

Scaffolding is an important step in genome assembly that orders and orients the contigs produced by assemblers. However, repetitive regions in contigs usually prevent scaffolding from producing accurate results. How to solve the problem of repetitive regions has received a great deal of attention. In the past few years, long reads sequenced by third-generation sequencing technologies (Pacific Biosciences and Oxford Nanopore) have been demonstrated to be useful for sequencing repetitive regions in genomes. Although some stand-alone scaffolding algorithms based on long reads have been presented, scaffolding still requires a new strategy to take full advantage of the characteristics of long reads.

Results

Here, we present a new scaffolding algorithm based on long reads and contig classification (SLR). Through the alignment information of long reads and contigs, SLR classifies the contigs into unique contigs and ambiguous contigs for addressing the problem of repetitive regions. Next, SLR uses only unique contigs to produce draft scaffolds. Then, SLR inserts the ambiguous contigs into the draft scaffolds and produces the final scaffolds. We compare SLR to three popular scaffolding tools by using long read datasets sequenced with Pacific Biosciences and Oxford Nanopore technologies. The experimental results show that SLR can produce better results in terms of accuracy and completeness. The open-source code of SLR is available at https://github.com/luojunwei/SLR.

Conclusion

In this paper, we describes SLR, which is designed to scaffold contigs using long reads. We conclude that SLR can improve the completeness of genome assembly.
Comprehensive ensemble in QSAR prediction for drug discovery
Authors: Kwon Sunyoung , Bae Ho , Jo Jeonghee , Yoon Sungroh
Published: October 2019

Background

Quantitative structure-activity relationship (QSAR) is a computational modeling method for revealing relationships between structural properties of chemical compounds and biological activities. QSAR modeling is essential for drug discovery, but it has many constraints. Ensemble-based machine learning approaches have been used to overcome constraints and obtain reliable predictions. Ensemble learning builds a set of diversified models and combines them. However, the most prevalent approach random forest and other ensemble approaches in QSAR prediction limit their model diversity to a single subject.

Results

The proposed ensemble method consistently outperformed thirteen individual models on 19 bioassay datasets and demonstrated superiority over other ensemble approaches that are limited to a single subject. The comprehensive ensemble method is publicly available at http://data.snu.ac.kr/QSAR/.

Conclusions

We propose a comprehensive ensemble method that builds multi-subject diversified models and combines them through second-level meta-learning. In addition, we propose an end-to-end neural network-based individual classifier that can automatically extract sequential features from a simplified molecular-input line-entry system (SMILES). The proposed individual models did not show impressive results as a single model, but it was considered the most important predictor when combined, according to the interpretation of the meta-learning.
Mechanisms of gene rearrangement in 13 bothids based on comparison with a newly completed mitogenome of the threespot flounder, Grammatobothus polyophthalmus (Pleuronectiformes: Bothidae)
Authors: Luo Hairong , Kong Xiaoyu , Chen Shixi , Shi Wei
Published: October 2019

Background

The mitogenomes of 12 teleost fish of the bothid family (order Pleuronectiformes) indicated that the genomic-scale rearrangements characterized in previous work. A novel mechanism of genomic rearrangement called the Dimer-Mitogenome and Non-Random Loss (DMNL) model was used to account for the rearrangement found in one of these bothids, Crossorhombus azureus.

Results

The 18,170 bp mitogenome of G. polyophthalmus contains 37 genes, two control regions (CRs), and the origin of replication of the L-strand (OL). This mitogenome is characterized by genomic-scale rearrangements: genes located on the L-strand are grouped in an 8-gene cluster (Q-A-C-Y-S1-ND6-E-P) that does not include tRNA-N; genes found on the H-strand are grouped together (F-12S … CytB-T) except for tRNA-D that was translocated inside the 8-gene L-strand cluster. Compared to non-rearranged mitogenomes of teleost fishes, gene organization in the mitogenome of G. polyophthalmus and in that of the other 12 bothids characterized thus far is very similar. These rearrangements could be sorted into four types (Type I, II, III and IV), differing in the particular combination of the CR, tRNA-D gene and 8-gene cluster and the shuffling of tRNA-V. The DMNL model was used to account for all but one gene rearrangement found in all 13 bothid mitogenomes. Translocation of tRNA-D most likely occurred after the DMNL process in 10 bothid mitogenomes and could have occurred either before or after DMNL in the three other species. During the DMNL process, the tRNA-N gene was retained rather than the expected tRNA-N′ gene. tRNA-N appears to assist in or act as OL function when the OL secondary structure could not be formed from intergenic sequences. A striking finding was that each of the non-transcribed genes has degenerated to a shorter intergenic spacer during the DMNL process. These findings highlight a rare phenomenon in teleost fish.

Conclusions

This result provides significant evidence to support the existence of dynamic dimeric mitogenomes and the DMNL model as the mechanism of gene rearrangement in bothid mitogenomes, which not only promotes the understanding of mitogenome structural diversity, but also sheds light on mechanisms of mitochondrial genome rearrangement and replication.
PacBio single-molecule long-read sequencing shed new light on the complexity of the Carex breviculmis transcriptome
Authors: Teng Ke , Teng Wenjun , Wen Haifeng , Yue Yuesen , Guo Weier , Wu Juying , Fan Xifeng
Published: October 2019

Background

Carex L., a grass genus commonly known as sedges, is distributed worldwide and contributes constructively to turf management, forage production, and ecological conservation. The development of next-generation sequencing (NGS) technologies has considerably improved our understanding of transcriptome complexity of Carex L. and provided a valuable genetic reference. However, the current transcriptome is not satisfactory mainly because of the enormous difficulty in obtaining full-length transcripts.

Results

In this study, we employed PacBio single-molecule long-read sequencing (SMRT) technology for whole-transcriptome profiling in Carex breviculmis. We generated 60,353 high-confidence non-redundant transcripts with an average length of 2302-bp. A total of 3588 alternative splicing events, and 1273 long non-coding RNAs were identified. Furthermore, 40,347 complete coding sequences were predicted, providing an informative reference transcriptome. In addition, the transcriptional regulation mechanism of C. breviculmis in response to shade stress was further explored by mapping the NGS data to the reference transcriptome constructed by SMRT sequencing.

Conclusions

This study provided a full-length reference transcriptome of C. breviculmis using the SMRT sequencing method for the first time. The transcriptome atlas obtained will not only facilitate future functional genomics studies but also pave the way for further selective and genic engineering breeding projects for C. breviculmis.
Antimicrobial resistance patterns of Uropathogens isolated from adult women with acute uncomplicated cystitis
Authors: Al-Zahrani Jamaan , Al Dossari Khaled , Gabr Ahmed H. , Ahmed Abul-fotouh , Al Shahrani Saad Abdulrahman , Al-Ghamdi Sameer
Published: October 2019

Background

To evaluate the antibiotic resistance patterns of uropathogens isolated from adult women with acute community-acquired (CA) uncomplicated cystitis.

Results

Over a one-year period (May 2015–April 2016), the results of susceptibility testing of outpatient midstream urine samples from 5 different laboratories were prospectively evaluated. The study included only adult women with uncomplicated cystitis. The susceptibility testing in all laboratories was performed using the disk diffusion method with the VITEK-2 Compact system. The isolated uropathogens and their resistance to the tested antibiotics were evaluated. Out of 317 adult women with CA uncomplicated cystitis, 179 had a positive culture. The most commonly isolated organism was Escherichia coli (E. coli) (70.4%), followed by Klebsiella (21.2%). The overall resistance rate was highest for ampicillin (85.6%), followed by cefalotin (56.3%), trimethoprim/sulfamethoxazole (54.7%), pipracillin (51.9%), nitrofurantoin (48.8%) and aztreonam (47.4%). Isolated E. coli strains were commonly resistant to ampicillin (80.5%), trimethoprim/sulfamethoxazole (72.2%) and aztreonam (71.4%), followed by cefalotin (55.9%). The overall ciprofloxacin resistance rate was 17.9%, and the resistent was found only with E. coli (25.4%).

Conclusions

Our results may aid in the selection of proper empiric antibiotic therapy for adult women with acute CA uncomplicated cystitis.
Linkage mapping and quantitative trait loci analysis of sweetness and other fruit quality traits in papaya
Authors: Nantawan Usana , Kanchana-udomkan Chutchamas , Bar Ido , Ford Rebecca
Published: October 2019

Background

The identification and characterisation of quantitative trait loci (QTL) is an important step towards identifying functional sequences underpinning important crop traits and for developing accurate markers for selective breeding strategies. In this study, a genotyping-by-sequencing (GBS) approach detected QTL conditioning desirable fruit quality traits in papaya.

Results

For this, a linkage map was constructed comprising 219 single nucleotide polymorphism (SNP) loci across 10 linkage groups and covering 509 centiMorgan (cM). In total, 21 QTLs were identified for seven key fruit quality traits, including flesh sweetness, fruit weight, fruit length, fruit width skin freckle, flesh thickness and fruit firmness. Several QTL for flesh sweetness, fruit weight, length, width and firmness were stable across harvest years and individually explained up to 19.8% of the phenotypic variance of a particular trait. Where possible, candidate genes were proposed and explored further for their application to marker-assisted breeding.

Conclusions

This study has extended knowledge on the inheritance and genetic control for key papaya physiological and fruit quality traits. Candidate genes together with associated SNP markers represent a valuable resource for the future of strategic selective breeding of elite Australian papaya cultivars.
Tomato glycosyltransferase Twi1 plays a role in flavonoid glycosylation and defence against virus
Authors: Campos Laura , López-Gresa María Pilar , Fuertes Diana , Bellés José María , Rodrigo Ismael , Lisón Purificación
Published: October 2019

Background

Secondary metabolites play an important role in the plant defensive response. They are produced as a defence mechanism against biotic stress by providing plants with antimicrobial and antioxidant weapons. In higher plants, the majority of secondary metabolites accumulate as glycoconjugates. Glycosylation is one of the commonest modifications of secondary metabolites, and is carried out by enzymes called glycosyltransferases.

Results

Here we provide evidence that the previously described tomato wound and pathogen-induced glycosyltransferase Twi1 displays in vitro activity toward the coumarins scopoletin, umbelliferone and esculetin, and the flavonoids quercetin and kaempferol, by uncovering a new role of this gene in plant glycosylation. To test its activity in vivo,Twi1-silenced transgenic tomato plants were generated and infected with Tomato spotted wilt virus. TheTwi1-silenced plants showed a differential accumulation of Twi1 substrates and enhanced susceptibility to the virus.

Conclusions

Biochemical in vitro assays and transgenic plants generation proved to be useful strategies to assign a role of tomato Twi1 in the plant defence response. Twi1 glycosyltransferase showed to regulate quercetin and kaempferol levels in tomato plants, affecting plant resistance to viral infection.