bluuebunny/crossref_metadata_2025_split huggingface dataset:
An update of the suicide plasmid‐mediated genome editing system in Corynebacterium glutamicum
Authors: Wang Ting , Li Yanjun , Li Juan , Zhang Dezhi , Cai Ningyun , Zhao Guihong , Ma Hongkun , Shang Can , Ma Qian , Xu Qingyang , Chen Ning 
Published: June 2019

SummaryCorynebacterium glutamicum is an important industrial microorganism, but the availability of tools for its genetic modification has lagged compared to other model microorganisms such as Escherichia coli. Despite great progress in CRISPR‐based technologies, the most feasible genome editing method in C. glutamicum is suicide plasmid‐mediated, the editing efficiency of which is low due to high false‐positive rates of sacB counter selection, and the requirement for tedious two‐round selection and verification of rare double‐cross‐over events. In this study, an rpsL mutant conferring streptomycin resistance was harnessed for counter selection, significantly increasing the positive selection rate. More importantly, with the aid of high selection efficiencies through the use of antibiotics, namely kanamycin and streptomycin, the two‐step verification strategy can be simplified to just one‐step verification of the final edited strain. As proof of concept, a 2.5‐kb DNA fragment comprising aroGfbrpheAfbr expressing cassettes was integrated into the genome of C. glutamicum, with an efficiency of 20% out of the theoretical 50%. The resulting strain produced 110 mg l−1 l‐tyrosine in shake‐flask fermentation. This updated suicide plasmid‐mediated genome editing system will greatly facilitate genetic manipulations including single nucleotide mutation, gene deletion and gene insertion in C. glutamicum and can be easily applied to other microbes.
The Burmese cat as a genetic model of type 2 diabetes in humans
Authors: Samaha G. , Beatty J. , Wade C. M. , Haase B. 
Published: June 2019

SummaryThe recent extension of genetic tools to the domestic cat, together with the serendipitous consequences of selective breeding, have been essential to the study of the genetic diseases that affect them. Cats are increasingly presented for veterinary surveillance and share many of human's heritable diseases, allowing them to serve as natural models of these conditions. Feline diabetes mellitus is a common condition in domestic cats that bears close pathological and clinical resemblance to type 2 diabetes in humans, including pancreatic β‐cell dysfunction and peripheral insulin resistance. In Australia, New Zealand and Europe, diabetes mellitus is almost four times more common in cats of the Burmese breed than in other breeds. This geographically based breed predisposition parallels familial and population clustering of type 2 diabetes in humans. As a genetically isolated population, the Australian Burmese breed provides a spontaneous, naturally occurring genetic model of type 2 diabetes. Genetically isolated populations typically exhibit extended linkage disequilibrium and increased opportunity for deleterious variants to reach high frequencies over many generations due to genetic drift. Studying complex diseases in such populations allows for tighter control of confounding factors including environmental heterogeneity, allelic frequencies and population stratification. The homogeneous genetic background of Australian Burmese cats may provide a unique opportunity to either refine genetic signals previously associated with type 2 diabetes or identify new risk factors for this disease.
Response‐adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children’s Oncology Group
Authors: Kelly Kara M. , Cole Peter D. , Pei Qinglin , Bush Rizvan , Roberts Kenneth B. , Hodgson David C. , McCarten Kathleen M. , Cho Steve Y. , Schwartz Cindy 
Published: June 2019

SummaryThe AHOD0831 study for paediatric patients with high risk Hodgkin lymphoma tested a response‐based approach designed to limit cumulative alkylator exposure and reduce radiation volumes. Patients (Stage IIIB/IVB) received two cycles of ABVE‐PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide). Rapid early responders [RER, no positron emission tomography (PET) activity above mediastinal blood pool] were consolidated with 2 cycles of ABVE‐PC. Slow early responders (SER) received 2 cycles of ifosfamide/vinorelbine and 2 cycles of ABVE‐PC. Radiotherapy was administered to sites of initial bulk and/or SER. By intent‐to‐treat analysis, 4‐year second event‐free survival (EFS; freedom from second relapse or malignancy) was 91·9% [95% confidence interval (CI): 86·1–95·3%], below the projected baseline of 95% (P = 0·038). Five‐year first EFS and overall survival (OS) rates are 79·1% (95% CI: 71·5–84·8%) and 95% (95% CI: 88·8–97·8%). Eight of 11 SER patients with persistent PET positive lesions at the end of chemotherapy had clinical evidence of active disease (3 biopsy‐proven, 5 with progressive disease or later relapses). Although this response‐directed approach did not reach the ambitiously high pre‐specified target for second EFS, EFS and OS rates are comparable with results of recent trials despite the reduction in radiotherapy volumes from historical involved fields. Persistent PET at end of chemotherapy identifies a cohort at an especially high risk for relapse/early progression.
The dual‐functional memantine nitrate MN‐08 alleviates cerebral vasospasm and brain injury in experimental subarachnoid haemorrhage models
Authors: Luo Fangcheng , Wu Liangmiao , Zhang Zhixiang , Zhu Zeyu , Liu Zheng , Guo Baojian , Li Ning , Ju Jun , Zhou Qiang , Li Shupeng , Yang Xifei , Mak Shinghung , Han Yifan , Sun Yewei , Wang Yuqiang , Zhang Gaoxiao , Zhang Zaijun 
Published: June 2019

Background and PurposeCerebral vasospasm and neuronal apoptosis after subarachnoid haemorrhage (SAH) is the major cause of morbidity and mortality in SAH patients. So far, single‐target agents have not prevented its occurrence. Memantine, a non‐competitive NMDA re3ceptor antagonist, is known to alleviate brain injury and vasospasm in experimental models of SAH. Impairment of NO availability also contributes to vasospasm. Recently, we designed and synthesized a memantine nitrate MN‐08, which has potent dual functions: neuroprotection and vasodilation. Here, we have tested the therapeutic effects of MN‐08 in animal models of SAH.Experimental ApproachBinding to NMDA receptors (expressed in HEK293 cells), NO release and vasodilator effects of MN‐08 were assessed in vitro. Therapeutic effects of MN‐08 were investigated in vivo, using rat and rabbit SAH models.Key ResultsMN‐08 bound to the NMDA receptor, slowly releasing NO in vitro and in vivo. Consequently, MN‐08 relaxed the pre‐contracted middle cerebral artery ex vivo and increased blood flow velocity in small vessels of the mouse cerebral cortex. It did not, however, lower systemic blood pressure. In an endovascular perforation rat model of SAH, MN‐08 improved the neurological scores and ameliorated cerebral vasospasm. Moreover, MN‐08 also alleviated cerebral vasospasm in a cisterna magna single‐injection model in rabbits. MN‐08 attenuated neural cell apoptosis in both rat and rabbit models of SAH. Importantly, the therapeutic benefit of MN‐08 was greater than that of memantine.Conclusion and ImplicationsMN‐08 has neuroprotective potential and can ameliorate vasospasm in experimental SAH models.
The influence of abutment macro‐design on clinical and radiographic peri‐implant tissue changes for guided, placed, and restored implants: A 1‐year randomized controlled trial
Authors: Koutouzis Theofilos , Adeinat Bashar , Ali Abdulaziz 
Published: June 2019

AbstractObjectivesThe aim was to evaluate the peri‐implant tissue levels over a 1‐year period for implants connected to either convex or concave final abutments at the time of implant placement.Materials and MethodsIn this randomized, double masked, controlled clinical study, twenty‐eight patients with one missing maxillary premolar were allocated to receive one single implant with abutment of either convex (CX Group) or concave (CV Group) emergence shape. A block randomization sequence was used to allocate treatments. Opaque sealed randomization envelopes were used for allocation concealment. All implants received final abutments and interim crowns at implant placement and permanent crowns following 3 months. Clinical and radiographic data were collected at the time of implant placement (IP), final prosthesis delivery (PR), and 12 months following implant placement (FU‐1).ResultsOne patient from the CX Group (n = 13) dropped out from the study and for one patient from CV Group (n = 13), the implant failed to integrate. The mean change in peri‐implant buccal mucosa position (MP) from IP to FU‐1 was −0.76 ± 0.72 mm for CX Group and −0.69 ± 0.89 mm for CV Group (p = 0.8). The amount of bone remodeling above the implant platform from IP to FU‐1 was −0.66 ± 0.46 mm for the CX Group and −0.24 ± 0.25 mm for the CV Group (p = 0.007). Buccal bone thickness was significantly correlated with the amount of buccal MP change from IP to FU‐1 (r = 0.4, p = 0.038).ConclusionThe study failed to support the hypothesis that abutment macro‐design has an effect on peri‐implant mucosa margin position changes over time.
Left ventricular adaptation following orthotopic heart transplantation in children: A speckle tracking echocardiographic imaging study
Authors: Sahewalla Rini , Sehgal Swati , Blake Jennifer , Aggarwal Sanjeev 
Published: June 2019

AbstractBackgroundEvolution of left ventricle (LV) function in the pediatric OHT population has not been well described. Our hypothesis was that, in children following OHT without any rejection, there would be progressive normalization of LV size and function over 2 years.MethodsLV function was evaluated using STE and conventional echo parameters at five time points in pediatric OHT patients without any rejection in the first 2 years following OHT and normal controls. LV global peak systolic longitudinal strain (LVPLS) and strain rate, LV peak systolic radial and circumferential strain (LVRS and LVCS), and strain rate were analyzed.ResultsWe had twenty two patients with median age at OHT of 1.27 years ( IQR 0.19, 5.6 years). The LVPLS (mean ± SD) was abnormal in the post‐OHT echocardiograms at 1 week (−12.4 ± 3.7) and 1 month (−13.9 ± 3.7) and significantly improved at 6 months (−15.8 ± 3.2), 1 year (−15.7 ± 3.1), and 2 years (−17.8 ± 2.8). However, LVPLS remained below the normal group even at 2 years following OHT (−21.3 ± 1.76).ConclusionIn children following OHT, despite the absence of rejection, strain values are significantly impaired in the initial months, improve progressively over the first 2 years but remain abnormal compared with healthy controls.
Visual Function Classification System for children with cerebral palsy: development and validation
Authors: Baranello Giovanni , Signorini Sabrina , Tinelli Francesca , Guzzetta Andrea , Pagliano Emanuela , Rossi Andrea , Foscan Maria , Tramacere Irene , Romeo Domenico M M , Ricci Daniela ,   On Behalf of the VFCS Study Group
Published: June 2019

AimTo develop and validate the Visual Function Classification System (VFCS), which was created to classify how children with cerebral palsy (CP) use visual abilities in daily life.MethodThe process of development and validation of the VFCS involved four phases: (1) drafting of the five levels from the analysis of literature and clinical experience; (2) validation of constructs and revision of the levels for concept meaningfulness, using nominal group process; (3) refinement by international Delphi survey; and(4) assessment of interrater reliability among professionals and with caregivers, and of test–retest reliability.ResultsFive nominal groups involved 29 participants; 65 people completed the first round and 51 the second round of the Delphi survey. Construct validity was demonstrated within an expert group and external validation through several stakeholders, with the involvement of patients and families to ensure meaningfulness of the concept. Discussions continued until consensus was reached about the construct and content of the five levels. Participants in the reliability study included 29 professionals, 39 parents, and a total sample of 160 children with CP (mean age [SD] 6y 6mo [3y 4mo]; median 5y 7mo, range 1–19y). Absolute interrater agreement among professionals was 86% (weighted κ=0.88; 95% confidence interval [CI] 0.83–0.93). Test–retest reliability was high (weighted κ=0.97; 95% CI 0.95–0.99). Parent–professional interrater reliability on 39 children was moderate (weighted κ=0.51; 95% CI 0.39–0.63).InterpretationThe VFCS has been appropriately constructed and provides a reliable system to classify visual abilities of children with CP both in clinical and in research settings.What this paper adds

The Visual Function Classification System is a valid and reliable system.

It classifies visual abilities of children with cerebral palsy in clinical and research settings.

At a clinical level, it can be used to harmonize communication among professionals and identify patients’ strengths and weaknesses.

In research settings, it can be used to stratify patients, define natural history evolution, and interpret intervention studies.
Diagnosis and management of follicular lymphoma: A comprehensive review
Authors: Dada Reyad 
Published: June 2019

AbstractFollicular Lymphoma (FL) is an indolent lymphoma and may have various clinical courses. Worldwide, FL is the second most common non‐Hodgkin lymphoma (NHL) type after diffuse large B‐cell lymphoma. In this review article, the author is discussing relevant diagnostic tools, prognostic factors, and updated study results on the management of patients with newly diagnosed and relapsed/refractory FL. Controversies in the treatment, maintenance therapy, stem cell transplantation, and novel treatment approaches will be comprehensively discussed.
WONOEP appraisal: Network concept from an imaging perspective
Authors: Wykes Robert C. , Khoo Hui Ming , Caciagli Lorenzo , Blumenfeld Hal , Golshani Peyman , Kapur Jaideep , Stern John M. , Bernasconi Andrea , Dedeurwaerdere Stefanie , Bernasconi Neda 
Published: June 2019

AbstractNeuroimaging techniques applied to a variety of organisms—from zebrafish, to rodents to humans—can offer valuable insights into neuronal network properties and their dysfunction in epilepsy. A wide range of imaging methods used to monitor neuronal circuits and networks during evoked seizures in animal models and advances in functional magnetic resonance imaging (fMRI) applied to patients with epilepsy were discussed during the XIV Workshop on Neurobiology of Epilepsy (XIV WONOEP) organized in 2017 by the Neurobiology Commission of the International League Against Epilepsy (ILAE). We review the growing number of technological approaches developed, as well as the current state of knowledge gained from studies applying these advanced imaging approaches to epilepsy research.
Differing climate and landscape effects on regional dryland vegetation responses during wet periods allude to future patterns
Authors: Petrie Matthew D. , Peters Debra P. C. , Burruss N. Dylan , Ji Wenjie , Savoy Heather M. 
Published: June 2019

AbstractDryland vegetation is influenced by biotic and abiotic land surface template (LST) conditions and precipitation (PPT), such that enhanced vegetation responses to periods of high PPT may be shaped by multiple factors. High PPT stochasticity in the Chihuahuan Desert suggests that enhanced responses across broad geographic areas are improbable. Yet, multiyear wet periods may homogenize PPT patterns, interact with favorable LST conditions, and in this way produce enhanced responses. In contrast, periods containing multiple extreme high PPT pulse events could overwhelm LST influences, suggesting a divergence in how climate change could influence vegetation by altering PPT periods. Using a suite of stacked remote sensing and LST datasets from the 1980s to the present, we evaluated PPT‐LST‐Vegetation relationships across this region and tested the hypothesis that enhanced vegetation responses would be initiated by high PPT, but that LST favorability would underlie response magnitude, producing geographic differences between wet periods. We focused on two multiyear wet periods; one of above average, regionally distributed PPT (1990–1993) and a second with locally distributed PPT that contained two extreme wet pulses (2006–2008). 1990–1993 had regional vegetation responses that were correlated with soil properties. 2006–2008 had higher vegetation responses over a smaller area that were correlated primarily with PPT and secondarily to soil properties. Within the overlapping PPT area of both periods, enhanced vegetation responses occurred in similar locations. Thus, LST favorability underlied the geographic pattern of vegetation responses, whereas PPT initiated the response and controlled response area and maximum response magnitude. Multiyear periods provide foresight on the differing impacts that directional changes in mean climate and changes in extreme PPT pulses could have in drylands. Our study shows that future vegetation responses during wet periods will be tied to LST favorability, yet will be shaped by the pattern and magnitude of multiyear PPT events.
Can transfer of development rights programs save farmland in metropolitan counties?
Authors: Fang Li , Howland Marie , Kim Jinyhup , Peng Qiong , Wu Jiemin 
Published: June 2019

AbstractTransfer development rights (TDR) programs have been gaining popularity as a tool for farmland preservation, as they compensate landowners at minimal public cost. This study shows that despite their wide adoption, TDR programs do not save much farmland on the urban fringe. We use Department of Agriculture data and apply two quasi‐experimental methods, synthetic control, and difference‐in‐difference, to evaluate the effect of TDR programs on farm retention for three fringe metropolitan counties in the state of Maryland. We also compare land use patterns before and after TDR implementation in these counties. The result shows limited effects of TDR programs on farm preservation, even in Montgomery County, one of the national models for TDR programs. TDR programs do contribute to low and medium density residential development. This cautions observation planners about their enthusiasm toward TDR programs and highlights the difficulty of preserving farmland on the fringe of metropolitan regions. We compare the features of the studied TDR programs, and highlight those that account for the programs’ relative success/failure. Based on these analyses, we make recommendations to planners to help improve TDR effectiveness.
The disparity in caries and sealants between migrant and native children in Shanghai: A cross‐sectional study
Authors: Zhang Hao , Zeng Xiaoli , Jiang Yiwei , Xu Wei , Wang Xun , Li Cunrong , Zhang Ying , Liu Yuehua , Wang Yan 
Published: June 2019

AbstractObjectiveTo investigate the disparity in dental caries between native and migrant children in Shanghai, China.MethodsBetween 2013 and 2015, a random cluster sample of native and migrant children aged 5, 9, 12 and 15 years was collected from each district in Shanghai. Oral examination was performed following the World Health Organization (WHO) method, and findings were reported as decayed‐missing‐filled teeth of primary dentition (dmft) and permanent dentition (DMFT).ResultsA total of 10 150 children were examined, and 33.6% of them were migrants. Migrant children had a higher prevalence of deciduous caries than native children (the 5‐year‐old age group, 67.8% vs 63.0%, P = 0.024; the 9‐year‐old age group, 75.9% vs 66.1%, P < 0.001), and higher dmft values were found in migrant children. But with respect to permanent teeth, no statistical differences were found between the two groups in caries prevalence or DMFT. After controlling for potential confounders by logistic regression, migrant children showed a higher risk of deciduous caries (odds ratio 1.42, 95% confidence interval 1.25‐1.61, P < 0.001) but not of permanent caries. Migrant children exhibited relatively lower deciduous Restorative Care Index (RCI). However, 9‐ and 15‐year‐old migrant children had a higher permanent RCI than their native counterparts.ConclusionsDental caries prevalence in migrant children was higher in the deciduous teeth but not in the permanent teeth compared to that in their native counterparts. School‐based dental public health services may contribute to reducing the disparity in dental health status between migrant and native children.
The change in pharmacists’ attitude, confidence and job satisfaction following participation in a novel hypertension support service
Authors: Shoji Masaki , Onda Mitsuko , Okada Hiroshi , Sakane Naoki , Nakayama Takeo 
Published: June 2019

Abstract

Objectives
To demonstrate how the confidence, attitude and job satisfaction of pharmacists who provide interventions and lifestyle support services to patients with hypertension are altered.

Methods
This study was a before-and-after study that used data from 50 pharmacists who participated in the Community Pharmacists Assist for Blood Pressure (COMPASS-BP) study, which was an interventional study that was conducted in Japan to evaluate the effects of lifestyle support services provided to hypertension patients. The pharmacists received 4 h of training before the study was initiated to learn how to quickly provide patients with guidance about diet and exercise and tobacco and alcohol consumption. During the interventional period, each pharmacist provided concise lifestyle guidance to 1–3 hypertension patients. The pharmacists met with the patients a total of 5 times. The parameters that were assessed were the pharmacists’ attitudes towards and confidence in their lifestyle support services, as well as their level of job satisfaction. We verified the scores of each parameter assessed before and after the study, as well as changes in the relationships among the different parameters.

Key findings
Significant increases from baseline to the end of the study were observed for Confidence (P &lt; 0.01), Job satisfaction, including ‘Knowledge’ (P &lt; 0.01), ‘Patient counselling management’ (P = 0.04) and ‘Sense of personal growth’ (P &lt; 0.01). Additionally, path analysis results revealed that after the study, the causal relationship between ‘Knowledge’ and ‘Attitude’ disappeared, and a new causal relationship appeared between ‘Patient counselling and management’ and ‘Attitude’.

Conclusions
Providing lifestyle guidance improved pharmacists’ confidence and attitude. Also, ‘Attitude’ tended to improve as the ‘Patient counselling and management’ score increased.