bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing trait networks and structural equation models as tools to interpret multi-trait genome-wide association studies
Authors: Momen Mehdi , Campbell Malachy T. , Walia Harkamal , Morota Gota 
Published: September 2019

AbstractBackgroundPlant breeders seek to develop cultivars with maximal agronomic value, which is often assessed using numerous, often genetically correlated traits. As intervention on one trait will affect the value of another, breeding decisions should consider the relationships among traits in the context of putative causal structures (i.e., trait networks). While multi-trait genome-wide association studies (MTM-GWAS) can infer putative genetic signals at the multivariate scale, standard MTM-GWAS does not accommodate the network structure of phenotypes, and therefore does not address how the traits are interrelated. We extended the scope of MTM-GWAS by incorporating trait network structures into GWAS using structural equation models (SEM-GWAS). Here, we illustrate the utility of SEM-GWAS using a digital metric for shoot biomass, root biomass, water use, and water use efficiency in rice.ResultsA salient feature of SEM-GWAS is that it can partition the total single nucleotide polymorphism (SNP) effects acting on a trait into direct and indirect effects. Using this novel approach, we show that for most QTL associated with water use, total SNP effects were driven by genetic effects acting directly on water use rather that genetic effects originating from upstream traits. Conversely, total SNP effects for water use efficiency were largely due to indirect effects originating from the upstream trait, projected shoot area.ConclusionsWe describe a robust framework that can be applied to multivariate phenotypes to understand the interrelationships between complex traits. This framework provides novel insights into how QTL act within a phenotypic network that would otherwise not be possible with conventional multi-trait GWAS approaches. Collectively, these results suggest that the use of SEM may enhance our understanding of complex relationships among agronomic traits.
Improving plant transient expression through the rational design of synthetic 5′ and 3′ untranslated regions
Authors: Peyret Hadrien , Brown James K. M. , Lomonossoff George P. 
Published: September 2019

AbstractBackgroundThe growing field of plant molecular farming relies on expression vectors that allow high yields of recombinant proteins to be produced through transient gene expression. While numerous expression vectors currently exist for this purpose, there are very few examples of systematic efforts to improve upon these. Moreover, the current generation of expression systems makes use of naturally-occurring regulatory elements, typically selected from plant viruses, to maximise yields. This study aims to use rational design to generate synthetic sequences that can rival existing ones.ResultsIn this work, we present the rational design of novel synthetic 5′ and 3′ untranslated regions (UTRs) which can be used in various combinations to modulate accumulation levels of transiently-expressed recombinant proteins. Using the pEAQ-HTexpression vector as a point of comparison, we show that pre-existing expression systems can be improved by the deployment of rationally designed synthetic UTRs. Notably, we show that a suite of short, synthetic 5′UTRs behave as expression enhancers that outperform theHT5′UTR present in the CPMV-HTexpression system. Furthermore, we confirm the critical role played by the 3′UTR of cowpea mosaic virus RNA-2 in the performance of the CPMV-HTsystem. Finally, we use the knowledge obtained from these results to develop novel expression vectors (named pHRE and pHREAC) that equal or outperform pEAQ-HTin terms of recombinant protein yield. These new vectors are also domesticated for the use of certain Type IIS restriction enzymes, which allows for quicker cloning and straightforward assessment of different combinations of UTRs.ConclusionsWe have shown that it is possible to rationally design a suite of expression modulators in the form of synthetic UTRs. We have created novel expression vectors that allow very high levels of recombinant protein expression in a transient expression context. This will have important consequences for future efforts to develop ever-better plant transient overexpression vectors for research or industrial applications.
Factor structure of the depression anxiety stress Scale-21 (DASS-21): Unidimensionality of the Arabic version among Egyptian drug users
Authors: Ali Amira Mohammed , Green Joseph 
Published: September 2019

AbstractBackgroundEmotional distress is common among illicit drug users, and it can negatively affect treatment outcomes and increase the risk of relapse. Nonetheless, instruments that properly measure emotional distress are lacking. Therefore, this study investigated the factor structure of the Arabic Depression Anxiety Stress Scale-21 (DASS-21) in that population.MethodsThe DASS-21 and the Self-stigma of Alcohol Dependence Scale (SSAD) were completed by 149 inpatient Egyptian drug users. The DASS-21 was examined using exploratory factor analysis, partial confirmatory factor analysis, and parallel analysis. For validation testing, correlations between stigma scores and DASS scores were computed.ResultsA one-factor solution provided the best fit to the DASS-21 data. Four items with low loadings were removed. The resulting DASS-17 was also unidimensional, and its reliability was high (0.88). On the validation tests, the DASS scores correlated with the stigma scores as hypothesized.ConclusionSubscales of the Arabic version of the DASS-21 do not differentiate between depression and anxiety. A modified 17-item version (the DASS-17) was suitable for measuring overall distress, and the results of convergent validation testing indicated that it was superior to the DASS-21.
Capturing implementation knowledge: applying focused ethnography to study how implementers generate and manage knowledge in the scale-up of obesity prevention programs
Authors: Conte Kathleen P. , Shahid Abeera , Grøn Sisse , Loblay Victoria , Green Amanda , Innes-Hughes Christine , Milat Andrew , Persson Lina , Williams Mandy , Thackway Sarah , Mitchell Jo , Hawe Penelope 
Published: September 2019

Abstract

Background
Bespoke electronic information management systems are being used for large-scale implementation delivery of population health programs. They record sites reached, coordinate activity, and track target achievement. However, many systems have been abandoned or failed to integrate into practice. We investigated the unusual endurance of an electronic information management system that has supported the successful statewide implementation of two evidence-based childhood obesity prevention programs for over 5 years. Upwards of 80% of implementation targets are being achieved.

Methods
We undertook co-designed partnership research with policymakers, practitioners, and IT designers. Our working hypothesis was that the science of getting evidence-based programs into practice rests on an in-depth understanding of the role programs play in the ongoing system of local relationships and multiple accountabilities. We conducted a 12-month multisite ethnography of 14 implementation teams, including their use of an electronic information management system, the Population Health Information Management System (PHIMS).

Results
All teams used PHIMS, but also drew on additional informal tools and technologies to manage, curate, and store critical information for implementation. We identified six functions these tools performed: (1) relationship management, (2) monitoring progress towards target achievement, (3) guiding and troubleshooting PHIMS use, (4) supporting teamwork, (5) evaluation, and (6) recording extra work at sites not related to program implementation. Informal tools enabled practitioners to create locally derived implementation knowledge and provided a conduit between knowledge generation and entry into PHIMS.

Conclusions
Implementation involves knowing and formalizing what to do, as well as how to do it. Our ethnography revealed the importance of hitherto uncharted knowledge about how practitioners develop implementation knowledge about how to do implementation locally, within the context of scaling up. Harnessing this knowledge for local use required adaptive and flexible systems which were enabled by informal tools and technologies. The use of informal tools also complemented and supported PHIMS use suggesting that both informal and standardized systems are required to support coordinated, large-scale implementation. While the content of the supplementary knowledge required to deliver the program was specific to context, functions like managing relationships with sites and helping others in the team may be applicable elsewhere.
A placebo-controlled study comparing the efficacy of intra-articular injections of hyaluronic acid and a novel hyaluronic acid-platelet-rich plasma conjugate in a canine model of osteoarthritis
Authors: Lee Mun-Ik , Kim Jun-Hyung , Kwak Ho-Hyun , Woo Heung-Myong , Han Jeong-Hee , Yayon Avner , Jung Yun-Chan , Cho Jin-Man , Kang Byung-Jae 
Published: September 2019

AbstractBackgroundThe objective of this study was to assess the efficacy of intra-articular injections of hyaluronic acid (HA) and a novel, on-site conjugate of HA with autologous fibrinogen in platelet-rich plasma (HA-PRP) in a canine model of osteoarthritis (OA)MethodsTwelve beagle dogs underwent a unilateral resection of the cranial cruciate ligament (CrCL) of the stifle joint. Clinical and radiographic signs of OA were confirmed in all dogs 8 weeks following CrCL resection and prior to treatment. The dogs were randomized into three groups: saline (n= 4), HA (n= 4), and HA-PRP (n= 4). Each dog received intra-articular injections of the respective substance into the affected joint at pre-determined time points. The dogs were assessed for adverse effects for 3 days after each injection and for lameness, pain, range of motion, kinetics, and radiographic OA severity prior to treatment and 3 months after injection. OA severity as determined by radiographic examination was not significantly different among the groups at any time point. The dogs were then humanely euthanatized and the stifle joint assessed by gross and histological examinations.ResultsDogs treated with four weekly injections of HA or two biweekly injections of HA-PRP were significantly (p< 0.05) better than dogs treated with four weekly injections of saline at 2-, 4-, and 12-week time points based on a comfortable range of motion (CROM) and clinical lameness score. Gait analysis measuring symmetry and weight distribution on pressure sensor walkway showed significantly (p< 0.05) improved limb function for dogs treated with HA and HA-PRP compared with dogs treated with saline yet with better clinical outcome for the HA-PRP-treated group at 12 and 20 weeks follow-up. Gross and histological analysis of synovium and articular cartilage demonstrated significant (p< 0.05) improvement by both treatments groups compared to controls. There was however significantly (p< 0.05) less damage to the cartilage in the HA-PRP group compared to the HA-treated group.ConclusionsThese data suggest that while injection of HA and HA-PRP may be sufficient for short-term amelioration of the symptoms associated with OA, treatment with HA-PRP conjugates may be superior, providing significantly better long-term cartilage preservation.
Would early removal of indwelling catheter effectively prevent urinary retention after hip fracture surgery in elderly patients?
Authors: Kwak Dae-Kyung , Oh Chul-Young , Lim Jeong-Seop , Lee Hyung-Min , Yoo Je-Hyun 
Published: September 2019

Abstract

Background
This study aimed to investigate the incidence and risk factors of postoperative urinary retention (POUR) among elderly patients who underwent hip fracture surgery and to evaluate the effect of indwelling catheterization on the occurrence of POUR.

Materials and methods
From January 2012 to January 2015, consecutive patients aged over 70 years who underwent hip fracture surgery were enrolled in this study. All patients underwent indwelling catheterization due to voiding difficulty upon admission. Demographic data, perioperative variables, and postoperative duration of patient-controlled analgesia and indwelling catheterization, postoperative complications, and mortality were collected. The incidence of POUR was investigated, and the risk factors related to POUR were analyzed using a logistic regression analysis. The cutoff value for the timing of catheter removal was determined using receiver operating characteristic (ROC) curve analysis.

Results
POUR developed in 68 patients (31.8%) of the 214 patients. Of these, 24 (35.3%) were male. The indwelling catheter was left in place for an average of 3.4 days (range, 0–7 days) postoperatively. A significant difference was noted in gender and duration of indwelling catheterization between patients with POUR and without. The cutoff value for the timing of catheter removal as determined by ROC curve analysis was 3.5 postoperative day with 51.4% sensitivity and 71.5% specificity. Multiple logistic regression revealed that the duration of the indwelling catheter [odds ratios (OR), 0.31; p = 0.016)] and male gender (OR, 2.22; p = 0.014) were independent risk factors related to the occurrence of POUR.

Conclusions
The significant risk factors of POUR among elderly patients undergoing hip fracture surgery were early indwelling catheter removal and male gender. Therefore, early removal of indwelling catheter in elderly patients following hip fracture surgery may increase the risk of POUR, especially in male patients.
Combined intrapleural and intrabronchial injection of fibrin glue for closing alveolar pleural fistula: a case report
Authors: Fiorelli Alfonso , Odierna Italia , Scarano Daniele , Caronia Francesco , Failla Andrea , Iannotti Mario , Santini Mario , Pace Caterina 
Published: September 2019

Abstract

Background
The treatment of persistent air leak is a challenge. Herein, we reported the combined intrabronchial and intrapleural injection of fibrin glue using fiber bronchoscopy to seal off an alveolar pleura fistula developed following necrotizing pneumonia in high-risk patient.

Case presentation
A 74-year-old man was intubated in emergency for acute ischemic stroke. Percutaneous dilatational tracheostomy was then performed, and 15 days later patient returned to spontaneous breathing. However, he developed alveolar pleural fistula following necrotizing pneumonia with persistent air leaks. The intrabronchial and intrapleural injection of fibrin glue using fiber bronchoscopy sealed off the alveolar pleura fistula after that other endoscopic treatments as bronchial valve and intrabronchial fibrin glue application had failed.

Conclusions
Our strategy is safe and easy to reproduce. It represents an additional method in the armamentarium of the physicians for the management of PAL when all standard strategies are unfeasible or fail.
Polyglycolic acid sutures embedded in abdominal acupoints for treatment of simple obesity in adults: a randomized control trial
Authors: Chen Li-Shu , Li Yue-Ying , Chen Hao , Liu Bo-Wen , Wang Da-Wei , Zhao Yong-Hua 
Published: September 2019

Abstract
Background
Acupoint catgut embedding therapy characterized by acupoint, needle and catgut are superior to traditional acupuncture, due to exerting more comprehensive therapeutic efficacy. However, it is still deficient in clinical evidence for polyglycolic acid sutures, a novel biodegradable material instead of catgut, embedded for the treatment of simple obesity. In our study, we investigate the efficacy and related mechanism of polyglycolic acid sutures embedded in abdominal acupoints on simple obese persons by a randomized control trial.

Methods
A total of 51 eligible participators were randomly allocated to a polyglycolic acid sutures embedding therapy (PASET) group (n = 28) or control group (n = 23). Participators in PASET group received polyglycolic acid sutures alternatively embedded in abdominal I group and II group acupoints in odd and even number therapeutic courses, and participators in control group were required to perform lifestyle modification. The duration of the study was 10 weeks.

Results
It suggested that PASET significantly reduced weight, body mass index, hip circumference, waist circumference, waist/hip ratio, waist-to-height ratio and thickness of abdominal subcutaneous fat tissue compared with those before treatment (p < 0.01), but lifestyle modification only illustrated downward trend of weight (p < 0.05). Moreover, PASET group also improved the evaluated scores in aspects of physical function, self-esteem, public distress and sexual life, as well as decreased blood pressure, glycemia, low density lipoprotein, uric acid and the levels of tumor necrosis factor-alpha, interleukin-1β, and increased high density lipoprotein in comparison with those before treatment (p < 0.05), whose efficacies are superior to control group. Additionally, our results also indicate PASET is relative safe and its pain and discomfort can be tolerable.

Conclusions
PASET distinctly ameliorates anthropometric data and quality of life in obese population, which associates with improvements of metabolic profile and inflammatory response. Based on the advantageous actions, we think PASET is an effective therapeutic approach to simple obesity treatment.
Trial registration ChiCTR, ChiCTR1800015591. Registered 10 April 2018, http://www.chictr.org.cn/showproj.aspx?proj=23258
Ocular manifestations in Gorlin-Goltz syndrome
Authors: Moramarco Antonietta , Himmelblau Ehud , Miraglia Emanuele , Mallone Fabiana , Roberti Vincenzo , Franzone Federica , Iacovino Chiara , Giustini Sandra , Lambiase Alessandro 
Published: September 2019

Abstract

Background
Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare genetic disorder that is transmitted in an autosomal dominant manner with complete penetrance and variable expressivity. It is caused in 85% of the cases with a known etiology by pathogenic variants in the PTCH1 gene, and is characterized by a wide range of developmental abnormalities and a predisposition to multiple neoplasms. The manifestations are multiple and systemic and consist of basal cell carcinomas in various regions, odontogenic keratocistic tumors and skeletal anomalies, to name the most frequent. Despite the scarce medical literature on the topic, ocular involvement in this syndrome is frequent and at the level of various ocular structures. Our study focuses on the visual apparatus and its annexes in subjects with this syndrome, in order to better understand how this syndrome affects the ocular system, and to evaluate with greater accuracy and precision the nature of these manifestations in this group of patients.

Results
Our study confirms the presence of the commonly cited ocular findings in the general literature regarding the syndrome [hypertelorism (45.5%), congenital cataract (18%), nystagmus (9%), colobomas (9%)] and highlights strabismus (63% of the patients), epiretinal membranes (36%) and myelinated optic nerve fiber layers (36%) as the most frequent ophthalmological findings in this group of patients.

Conclusions
The presence of characteristic and frequent ocular signs in the Gorlin- Goltz syndrome could help with the diagnostic process in subjects suspected of having the syndrome who do not yet have a diagnosis. The ophthalmologist has a role as part of a multidisciplinary team in managing these patients. The ophthalmological follow-up that these patients require, can allow, if necessary, a timely therapy that could improve the visual prognosis of such patients.
Individualized treatment with denosumab in children with osteogenesis imperfecta – follow up of a trial cohort
Authors: Hoyer-Kuhn Heike , Rehberg Mirko , Netzer Christian , Schoenau Eckhard , Semler Oliver 
Published: September 2019

Abstract

Background
Osteogenesis imperfecta (OI) is a rare disease leading to hereditary bone fragility. Nearly 90% of cases are caused by mutations in the collagen genes COL1A1/A2 (classical OI) leading to multiple fractures, scoliosis, short stature and nonskeletal findings as blue sclera, hypermobility of joints, bone pain and delayed motor function development. Bisphosphonates are used in most moderate and severely affected patients assuming that an increase of bone mineral density might reduce fractures and bone pain in patients with OI. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. First data from small clinical trials promised a high efficacy of Denosumab in children with OI. Aim of this analysis was a retrospective evaluation of an individualized biomarker-associated treatment regime with Denosumab in 10 children with classical OI which were followed for 1 year after their participation in a pilot trial with Denosumab. Therefore urinary deoxypyridinoline levels were evaluated frequently as an osteoclastic activity marker and depending on that levels Denosumab injections were scheduled individually.

Methods
Ten patients (age range: 6.16–12.13 years; all participated in the former OI-AK phase 2 trial (NCT01799798)) were included in the follow-up period. Denosumab was administered subcutaneously depending on the individual urinary excretion course of deoxypyridinoline (DPD/Crea) as osteoclastic activity marker with 1 mg/kg body weight. DPD/Crea levels were evaluated before denosumab administration and afterwards. If patients present after an initial decrease after injection with a re-increase up to the DPD/crea level before Denosumab injection next dosage was planned. Changes of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 12 month was evaluated. Safety was assessed by bone metabolism markers and side effect reporting.

Results
During follow-up mean relative change of lumbar aBMD was − 6.4%. Lumbar spine aBMD z-Scores decreased from − 1.01 ± 2.61 (mean ± SD) to − 1.91 ± 2.12 (p = 0.015). Mobility changed not significantly (GMFM-88 -6.49 ± 8.85% (p = 0.08). No severe side effects occurred. Dose intervals could be extended in the mean from 12 weeks previously to 20.3 weeks.

Conclusions
On average, it was possible to prolong the intervals between drug administrations and to reduce the total dose about by 25% without a decrease of mobility or change of vertebral shape despite a reduction of lumbar aBMD during 1 year of biomarker-directed Denosumab treatment. Further trials are necessary to balance side effects and highest efficacy in children.