bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrupted Time-Series Analysis to Evaluate the Impact of a National Antimicrobial Stewardship Campaign on Antibiotic Prescribing: A Typical Practice in China’s Primary Care
Authors: Li Hui , Gong Yanhong , Han Jing , Zhang Shengchao , Chen Shanquan , Xu Xing , Lu Zuxun , Yin Xiaoxv 
Published: July 2020

Abstract

Background
After implementing the 2011 national antimicrobial stewardship campaign, few studies focused on evaluating its effect in China’s primary care facilities.

Methods
We randomly selected 11 community health centers in Shenzhen, China, and collected all outpatient prescriptions of these centers from 2010 to 2015. To evaluate the impact of local interventions on antibiotic prescribing, we used a segmented regression model of interrupted time series to analyze 7 outcomes (ie, percentage of prescriptions with antibiotics, and percentages of prescriptions with broad-spectrum antibiotics, with parenteral antibiotics, and with 2 or more antibiotics in all prescriptions or antibiotic-containing prescriptions).

Results
Overall, 1 482 223 outpatient prescriptions were obtained. The intervention was associated with a significant immediate change (–5.2%, P = .04) and change in slope (–3.1% per month, P &lt; .01) for the percentage of prescriptions with antibiotics, and its relative cumulative effect at the end of the study was –74.0% (95% confidence interval, –79.0 to –69.1). After the intervention, the percentage of prescriptions with broad-spectrum and with parenteral antibiotics decreased dramatically by 36.7% and 77.3%, respectively, but their percentages in antibiotic-containing prescriptions decreased insignificantly. Percentage of prescriptions with two or more antibiotics in all prescriptions or antibiotic-containing prescriptions only showed immediate changes, but significant changes in slope were not observed.

Conclusions
A typical practice in Shenzhen, China, showed that strict enforcement of the antimicrobial stewardship campaign could effectively reduce antibiotic prescribing in primary care with a stable long-term effect. However, prescribing of broad-spectrum and parenteral antibiotics was still prevalent. More targeted interventions are required to promote appropriate antibiotic use.
Context sensitivity and economic-geographic (re)theorising
Authors: Gong Huiwen , Hassink Robert 
Published: July 2020

AbstractDrawing upon critical realism and the literature on theorising in social sciences, this article contributes to the understanding of theorising in economic geography by highlighting the role of context throughout the theory development process. By critically reviewing two key concepts in economic geography—related variety and knowledge bases—from a critical realist theory development perspective, scholars’ sensitivity to local context through the whole theorising process is examined. We argue that the particular strength of economic geography with regard to advancing theory lies in the continuous application of concepts and theories (that is, generalities) within new contexts (that is, confrontation with new particularities).
Ultrasensitive DNA Immune Repertoire Sequencing Using Unique Molecular Identifiers
Authors: Johansson Gustav , Kaltak Melita , Rîmniceanu Cristiana , Singh Avadhesh K , Lycke Jan , Malmeström Clas , Hühn Michael , Vaarala Outi , Cardell Susanna , Ståhlberg Anders 
Published: July 2020

Abstract

Background
Immune repertoire sequencing of the T-cell receptor can identify clonotypes that have expanded as a result of antigen recognition or hematological malignancies. However, current sequencing protocols display limitations with nonuniform amplification and polymerase-induced errors during sequencing. Here, we developed a sequencing method that overcame these issues and applied it to γδ T cells, a cell type that plays a unique role in immunity, autoimmunity, homeostasis of intestine, skin, adipose tissue, and cancer biology.

Methods
The ultrasensitive immune repertoire sequencing method used PCR-introduced unique molecular identifiers. We constructed a 32-panel assay that captured the full diversity of the recombined T-cell receptor delta loci in γδ T cells. The protocol was validated on synthetic reference molecules and blood samples of healthy individuals.

Results
The 32-panel assay displayed wide dynamic range, high reproducibility, and analytical sensitivity with single-nucleotide resolution. The method corrected for sequencing-depended quantification bias and polymerase-induced errors and could be applied to both enriched and nonenriched cells. Healthy donors displayed oligoclonal expansion of γδ T cells and similar frequencies of clonotypes were detected in both enrichment and nonenriched samples.

Conclusions
Ultrasensitive immune repertoire sequencing strategy enables quantification of individual and specific clonotypes in a background that can be applied to clinical as well as basic application areas. Our approach is simple, flexible, and can easily be implemented in any molecular laboratory.
Angiopoietin-1 enhanced myocyte mitosis, engraftment, and the reparability of hiPSC-CMs for treatment of myocardial infarction
Authors: Tao Zhonghao , Loo Szejie , Su Liping , Tan Shihua , Tee Guizhen , Gan Shu Uin , Zhang Jianyi , Chen Xin , Ye Lei 
Published: July 2020

Abstract

Aims
To examine whether transient over-expression of angiopoietin-1 (Ang-1) increases the potency of hiPSC-CMs for treatment of heart failure.

Methods and results
Atrial hiPSC-CMs (hiPSC-aCMs) were differentiated from hiPSCs and purified by lactic acid and were transfected with Ang-1 (Ang-1-hiPSC-aCMs) plasmid using lipoSTEM. Ang-1 gene transfection efficiency was characterized in vitro. Gene transfected CMs (1×106) were seeded into a fibrin/thrombin patch and implanted on the rat-infarcted left ventricular (LV) anterior wall after myocardial infarction (MI). Echo function was determined at 1- and 6 weeks post-MI. Immunohistochemistry study was performed at 6 weeks post-MI. Ang-1 (20 and 40 ng/mL) protected hiPSC-aCMs from hypoxia through up-regulating pERK1/2 and inhibiting Bax protein expressions. Ang-1-hiPSC-aCMs transiently secreted Ang-1 protein up to 14 days, with peak level on day-2 post-transfection (24.39 ± 13.02 ng/mL) in vitro. Animal study showed that transplantation of Ang-1-hiPSC-aCM seeded patch more effectively limited rat heart apoptosis at 1 day post-MI as compared with LipoSTEM-Ang-1 or hiPSC-aCMs transplantation. Ang-1-hiPSC-aCMs transplantation induced host (rat) and donor (human) CM mitosis and arteriole formation, improved cell engraftment rate, more effectively limited LV dilation (EDV = 460.7 ± 96.1 μL and ESV = 219.8 ± 72.9 μL) and improved LV global pump function (EF = 53.1 ± 9%) as compared with the MI (EDV = 570.9 ± 91.8 μL, P = 0.033; ESV = 331.6 ± 71.2 μL, P = 0.011; EF = 42.3 ± 4.1%, P = 0.02) or the LipoSTEM-Ang-1 injected (EDV = 491.4 ± 100.4 μL, P = 0.854; ESV = 280.9 ± 71.5 μL, P = 0.287; EF = 43.2 ± 4.6, P = 0.039) or hiPSC-CM transplanted (EDV = 547.9 ± 55.5 μL, P = 0.095; ESV = 300.2 ± 88.4 μL, P = 0.075; EF = 46 ± 10.9%, P = 0.166) animal groups at 6 weeks post-MI and treatment.

Conclusion
Transient over-expression of Ang-1 enhanced hiPSC-aCM mitosis and engraftment and increased the reparability potency of hiPSC-aCMs for treatment of MI.
A novel method for measuring absolute coronary blood flow and microvascular resistance in patients with ischaemic heart disease
Authors: Morris Paul D , Gosling Rebecca , Zwierzak Iwona , Evans Holli , Aubiniere-Robb Louise , Czechowicz Krzysztof , Evans Paul C , Hose D Rodney , Lawford Patricia V , Narracott Andrew J , Gunn Julian P 
Published: July 2020

Abstract

Aims
Ischaemic heart disease is the reduction of myocardial blood flow, caused by epicardial and/or microvascular disease. Both are common and prognostically important conditions, with distinct guideline-indicated management. Fractional flow reserve (FFR) is the current gold-standard assessment of epicardial coronary disease but is only a surrogate of flow and only predicts percentage flow changes. It cannot assess absolute (volumetric) flow or microvascular disease. The aim of this study was to develop and validate a novel method that predicts absolute coronary blood flow and microvascular resistance (MVR) in the catheter laboratory.

Methods and results
A computational fluid dynamics (CFD) model was used to predict absolute coronary flow (QCFD) and coronary MVR using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, three-dimensional printed coronary arteries; and then in vivo, in patients with coronary disease. In vitro, QCFD agreed closely with the experimental flow over all flow rates [bias +2.08 mL/min; 95% confidence interval (error range) −4.7 to +8.8 mL/min; R2 = 0.999, P &lt; 0.001; variability coefficient &lt;1%]. In vivo, QCFD and MVR were successfully computed in all 40 patients under baseline and hyperaemic conditions, from which coronary flow reserve (CFR) was also calculated. QCFD-derived CFR correlated closely with pressure-derived CFR (R2 = 0.92, P &lt; 0.001). This novel method was significantly more accurate than Doppler-wire-derived flow both in vitro (±6.7 vs. ±34 mL/min) and in vivo (±0.9 vs. ±24.4 mmHg).

Conclusions
Absolute coronary flow and MVR can be determined alongside FFR, in absolute units, during routine catheter laboratory assessment, without the need for additional catheters, wires or drug infusions. Using this novel method, epicardial and microvascular disease can be discriminated and quantified. This comprehensive coronary physiological assessment may enable a new level of patient stratification and management.
Agricultural bankers’ farmland price expectations
Authors: Kuethe Todd H , Oppedahl David 
Published: July 2020

Abstract
Previous studies provide conflicting evidence on the degree to which Federal Reserve surveys of agricultural bankers provide useful information on the future direction of farm real estate values. We use unbalanced panel of responses from the Federal Reserve Bank of Chicago’s Land Values and Credit Conditions Survey between 1993Q1 and 2019Q2 to empirically test adaptive, rational and extrapolative expectations. We find that respondents extrapolate recent farmland price experiences but are overly cautious, as observed farmland price changes tend to be greater than expected. This is the first study of individual farmland price expectations collected by Federal Reserve surveys of agricultural bankers.
Assessing health systems’ preparedness for providing care for refugees, asylum seekers and migrants: a scoping review
Authors: Kocot Ewa , Szetela Anna 
Published: July 2020

Abstract

Background
Health care systems and care professionals often face the challenge of providing adequate health care for migrant groups. The objective of this study is to answer the question of whether and how meeting the special health system requirements regarding refugees (R), asylum seekers (AS) and migrants (M) (RASM) is checked and evaluated.

Methods
A scoping review was used as a methodology of the research, with four electronic databases, websites of relevant organizations and European projects searched, using a strictly defined search strategy. Finally, 66 studies were included in the analysis.

Results
The included studies presented assessment of different types, aspects and facilities of health care, as well as various methods of analysis. In the vast majority of the studies (n = 52, 78%) interviews or questionnaires were used to collect data. The studies were mostly declared to be qualitative. The main issues assessed in the studies can be categorized into three groups: (i) legal aspects, (ii) before receiving health care and (iii) during health care usage.

Conclusions
RASM inflow is a big challenge for health care system in many countries. The first step to guarantee adequate health care for RASM is assessing how the system is functioning. This makes it possible to find gaps, indicate the directions of activities needed and monitor progress. Further work on the development of a comprehensive tool, checked in terms of validity and reliability assessment, and enabling examination of many aspects of health care for RASM should be carried out.
Altered bone development with impaired cartilage formation precedes neuromuscular symptoms in spinal muscular atrophy
Authors: Hensel Niko , Brickwedde Hermann , Tsaknakis Konstantinos , Grages Antonia , Braunschweig Lena , Lüders Katja A , Lorenz Heiko M , Lippross Sebastian , Walter Lisa M , Tavassol Frank , Lienenklaus Stefan , Neunaber Claudia , Claus Peter , Hell Anna K 
Published: July 2020

AbstractSpinal muscular atrophy (SMA) is a fatal neurodegenerative disease of newborns and children caused by mutations or deletions of the survival of motoneuron gene 1 resulting in low levels of the SMN protein. While neuromuscular degeneration is the cardinal symptom of the disease, the reduction of the ubiquitously expressed SMN additionally elicits non-motoneuron symptoms. Impaired bone development is a key feature of SMA, but it is yet unknown whether this is an indirect functional consequence of muscle weakness or caused by bone-intrinsic mechanisms. Therefore, we radiologically examined SMA patients in a prospective, non-randomized cohort study characterizing bone size and bone mineral density (BMD) and performed equivalent measurements in pre-symptomatic SMA mice. BMD as well as lumbar vertebral body size were significantly reduced in SMA patients. This growth defect but not BMD reduction was confirmed in SMA mice by μCT before the onset of neuromuscular symptoms indicating that it is at least partially independent of neuromuscular degeneration. Interestingly, the number of chondroblasts in the hypertrophic zone of the growth plate was significantly reduced. This was underlined by RNAseq and expression data from developing SMA mice vertebral bodies, which revealed molecular changes related to cell division and cartilage remodeling. Together, these findings suggest a bone intrinsic defect in SMA. This phenotype may not be rescued by novel drugs that enhance SMN levels in the central nervous system only.
Introducing a Human Rights-based Disability Research Methodology
Authors: Arstein-Kerslake Anna , Maker Yvette , Flynn Eilionóir , Ward Olympia , Bell Ruby , Degener Theresia 
Published: July 2020

Abstract
Research has the potential to be a powerful tool for the realisation of the rights of disabled people. However, antiquated research practices continue to marginalise disabled people by excluding them from research; inadequately remunerating them for participation in research; undertaking research that assumes difference; and not including their voice in the leadership design or implementation of research. This article builds on emancipatory, participatory and inclusive research methodologies to introduce a new human rights-based disability research methodology that presents a roadmap to overcome these problems and transform research into a means of rights realisation. It presents a protocol for the methodology that was created by the international Disability Human Rights Research Network. Finally, it explores many challenges that researchers may face when endeavouring to implement the methodology.
Association of Myeloid Liver Kinase B1 Depletion With a Reduction in Alveolar Macrophage Numbers and an Impaired Host Defense During Gram-Negative Pneumonia
Authors: Otto Natasja A , de Vos Alex F , van Heijst Jeroen W J , Roelofs Joris J T H , van der Poll Tom 
Published: July 2020

AbstractBackgroundLiver kinase B1 (LKB1) has been studied extensively as a tumor suppressor gene (Stk11) in the context of cancer. We hypothesized that myeloid LKB1 plays a role in innate immunity during pneumonia.MethodsMice deficient for LKB1 in myeloid cells (LysM-cre × Stk11fl/fl) or neutrophils (Mrp8-cre × Stk11fl/fl) were infected with Klebsiella pneumoniae via the airways. LysM-cre × Stk11fl/fl mice were also intranasally challenged with lipopolysaccharide (LPS).ResultsMice with myeloid LKB1 deficiency, but not those with neutrophil LKB1 deficiency, had increased bacterial loads in lungs 6–40 hours after infection, compared with control mice, pointing to a role for LKB1 in macrophages. Myeloid LKB1 deficiency was associated with reduced cytokine release into the airways on local LPS instillation. The number of classic (SiglecFhighCD11bneg) alveolar macrophages (AMs) was reduced by approximately 50% in the lungs of myeloid LKB1–deficient mice, which was not caused by increased cell death or reduced proliferation. Instead, these mice had AMs with a “nonclassic” (SiglecFlowCD11bpos) phenotype. AMs did not up-regulate glycolysis in response to LPS, irrespective of LKB1 presence.ConclusionMyeloid LKB1 is important for local host defense during Klebsiella pneumonia by maintaining adequate AM numbers in the lung.
Induction of the Coxsackievirus and Adenovirus Receptor in Macrophages During the Formation of Atherosclerotic Plaques
Authors: Nilchian Azadeh , Plant Estelle , Parniewska Malgorzata M , Santiago Ana , Rossignoli Aránzazu , Skogsberg Josefin , Hedin Ulf , Matic Ljubica , Fuxe Jonas 
Published: July 2020

Abstract
Multiple viruses are implicated in atherosclerosis, but the mechanisms by which they infect cells and contribute to plaque formation in arterial walls are not well understood. Based on reports showing the presence of enterovirus in atherosclerotic plaques we hypothesized that the coxsackievirus and adenovirus receptor (CXADR/CAR), although absent in normal arteries, could be induced during plaque formation. Large-scale microarray and mass spectrometric analyses revealed significant up-regulation of CXADR messenger RNA and protein levels in plaque-invested carotid arteries compared with control arteries. Macrophages were identified as a previously unknown cellular source of CXADR in human plaques and plaques from Ldr−/−Apob100/100 mice. CXADR was specifically associated with M1-polarized macrophages and foam cells and was experimentally induced during macrophage differentiation. Furthermore, it was significantly correlated with receptors for other viruses linked to atherosclerosis. The results show that CXADR is induced in macrophages during plaque formation, suggesting a mechanism by which enterovirus infect cells in atherosclerotic plaques.
Trialstreamer: A living, automatically updated database of clinical trial reports
Authors: Marshall Iain J , Nye Benjamin , Kuiper Joël , Noel-Storr Anna , Marshall Rachel , Maclean Rory , Soboczenski Frank , Nenkova Ani , Thomas James , Wallace Byron C 
Published: July 2020

Abstract

Objective
Randomized controlled trials (RCTs) are the gold standard method for evaluating whether a treatment works in health care but can be difficult to find and make use of. We describe the development and evaluation of a system to automatically find and categorize all new RCT reports.

Materials and Methods
Trialstreamer continuously monitors PubMed and the World Health Organization International Clinical Trials Registry Platform, looking for new RCTs in humans using a validated classifier. We combine machine learning and rule-based methods to extract information from the RCT abstracts, including free-text descriptions of trial PICO (populations, interventions/comparators, and outcomes) elements and map these snippets to normalized MeSH (Medical Subject Headings) vocabulary terms. We additionally identify sample sizes, predict the risk of bias, and extract text conveying key findings. We store all extracted data in a database, which we make freely available for download, and via a search portal, which allows users to enter structured clinical queries. Results are ranked automatically to prioritize larger and higher-quality studies.

Results
As of early June 2020, we have indexed 673 191 publications of RCTs, of which 22 363 were published in the first 5 months of 2020 (142 per day). We additionally include 304 111 trial registrations from the International Clinical Trials Registry Platform. The median trial sample size was 66.

Conclusions
We present an automated system for finding and categorizing RCTs. This yields a novel resource: a database of structured information automatically extracted for all published RCTs in humans. We make daily updates of this database available on our website (https://trialstreamer.robotreviewer.net).
Epidemiology and Outcome Analysis of Burns During Explosion Accident at a Major Center in Southwestern China From 2002 to 2016
Authors: Wang Yangping , Zhang Xiaorong , Liu Tengfei , Liu Menglong , Li Haisheng , Huang Yong , Hu Xiaohong , He Weifeng , Luo Gaoxing , Qian Wei 
Published: July 2020

Abstract
Explosions always lead to serious public health, social, and economic problems. We investigated the epidemiology, outcomes, and costs of burn patients caused by explosion accident in Southwest China to explore more effective prevention and treatment strategies. This retrospective study included 497 inpatients with burns during explosion accident admitted to the Institute of Burn Research of Army Medical University from 2002 to 2016. A total of 497 cases (77.78% males) were found, accounting for 2.37% of the total burn patients. The average age was 34.38 ± 15.02 years. The most common etiology was gas explosions (51.51%). Most of the cases were caused by work-related activities. The average TBSA was 31.30 ± 28.32%. The median length of stay (LOS) was 31 days. The LOS was correlated with TBSA, full-thickness burns, older age, number of operations and outcome. The major factors determining the cost were larger TBSA, full-thickness burns, and higher cure rate. The mortality was 6.44%. Larger TBSA and older age were the most important risk factors for the mortality. This study suggested that special attention should be paid to prevent burns during explosion accident in adult males with occupational exposure. In the future, more effective and practical strategies for preventing and treating burns during explosion accident based on related risk factors should be implemented.
Genetic and physiological regulation of folate in pak choi (Brassica rapa subsp. Chinensis) germplasm
Authors: Shohag M J I , Wei Yanyan , Zhang Jie , Feng Ying , Rychlik Michael , He Zhenli , Yang Xiaoe 
Published: July 2020

AbstractFolates are one of the essential micronutrients for all living organisms. Due to inadequate dietary intake, folate deficiency remains prevalent in humans. Genetically diverse germplasms can potentially be used as parents in breeding programs and also for understanding the folate regulatory network. Therefore, we investigated the natural genetic diversity of folates and their physiological regulation in pak choi (Brassica rapa subsp. Chinensis) germplasm. The total folate concentration ranged from 52.7 μg 100 gFW–1 to 166.9 μg 100 gFW–1, with 3.2-fold variation. The main folate vitamer was represented by 5-CH3-H4folate, with 4.5-fold variation. The activities of GTP cyclohydrolase I and aminodeoxy chorismate synthase, the first step of folate synthesis, were high in high folate accessions and low in low folate accessions. Analysis of the transcription levels of 11 genes associated with folate metabolism demonstrated that the difference in folate concentrations may be primarily controlled at the post-transcriptional level. A general correlation between total folate and their precursors was observed. Folate diversity and chlorophyll content were tightly regulated through the methyl cycle. The diverse genetic variation in pak choi germplasm indicated the great genetic potential to integrate breeding programs for folate biofortification and unravel the physiological basis of folate homeostasis in planta.