bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole‐of‐community interventions to reduce population‐level harms arising from alcohol and other drug use: a systematic review and meta‐analysis
Authors: Stockings Emily , Bartlem Kate , Hall Alix , Hodder Rebecca , Gilligan Conor , Wiggers John , Sherker Shauna , Wolfenden Luke
Published: May 2018

Background and aims

Whole‐of‐community interventions aim to reduce alcohol and other drug (AOD) use and harms by mobilizing community leaders, organizations and policy‐makers to respond effectively to AOD use. The aim of this review is to estimate the effectiveness of whole‐of‐community interventions in reducing population‐level harms arising from AOD use.

Design

A systematic review of electronic databases CENTRAL, Embase, Medline, Medline in Process and PsycINFO was conducted from database inception to August 2017. Eligible trials had a parallel comparison group, implemented interventions in two or more community settings, and reported data on AOD use or harms.

Setting

Intervention settings included schools, sporting clubs, police and law enforcement agencies, community centres, local media and retail premises.

Participants

Twenty‐four trials from 63 publications were included (n = 249 125 participants).

Measurements

Outcomes from AOD consumption (quantity and frequency), AOD‐related crime and AOD‐related accidents, injuries and hospital admissions. Data were pooled using random‐effects inverse variance meta‐analysis in Review Manager version 5.3.

Findings

Risk of bias was mostly high, due to lack of random allocation, selective reporting and significant attrition. Meta‐analyses indicated significant reductions in risky drinking [Alcohol Use Disorders Identification Scale (AUDIT) > 8; three trials (7 data points), relative risk (RR) = 0.78, 95% confidence interval (CI) = 0.62–0.99)], but found no impact on past‐month alcohol use (five trials, RR = 0.95, 95% CI = 0.89–1.02), binge drinking (five trials, RR = 0.97, 95% CI = 0.89–1.06) or 12‐month marijuana use (two trials, RR = 0.98, 95% CI = 0.86–1.11). Narrative synthesis indicated some reductions in AOD‐related assault rates and arrests, but were equivocal for quantity of alcohol consumed, 12‐month illicit drug use, assault or abuse, motor vehicle accidents and hospital admissions.

Conclusions

Interventions to reduce alcohol and other drug use and harms applied to whole communities have resulted so far in small reductions in risky alcohol consumption, but have had little impact upon past month alcohol use, binge drinking or 12‐month marijuana use and the studies have been subject to high risk of bias.
Effects of chlorogenic acid (CGA) supplementation during in vitro maturation culture on the development and quality of porcine embryos with electroporation treatment after in vitro fertilization
Authors: Nguyen Thanh‐Van , Wittayarat Manita , Do Lanh Thi Kim , Nguyen Thanh Van , Nii Masahiro , Namula Zhao , Kunihara Toshiki , Tanihara Fuminori , Hirata Maki , Otoi Takeshige
Published: May 2018

Electroporation is the technique of choice to introduce an exogenous gene into embryos for transgenic animal production. Although this technique is practical and effective, embryonic damage caused by electroporation treatment remains a major problem. This study was conducted to evaluate the optimal culture system for electroporation‐treated porcine embryos by supplementation of chlorogenic acid (CGA), a potent antioxidant, during in vitro oocyte maturation. The oocytes were treated with various concentrations of CGA (0, 10, 50, and 100 μmol/L) through the duration of maturation for 44 hr. The treated oocytes were then fertilized, electroporated at 30 V/mm with five 1 msec unipolar pulses, and subsequently cultured in vitro until development into the blastocyst stage. Without electroporation, the treatment with 50 μmol/L CGA had useful effects on the maturation rate of oocytes, the total cell number, and the apoptotic nucleus indices of blastocysts. When the oocytes were electroporated after in vitro fertilization, the treatment with 50 μmol/L CGA supplementation significantly improved the rate of oocytes that developed into blastocysts and reduced the apoptotic nucleus indices (4.7% and 7.6, respectively) compared with those of the untreated group (1.4% and 13.0, respectively). These results suggested that supplementation with 50 μmol/L CGA during maturation improves porcine embryonic development and quality of electroporation‐treated embryos.
ASP8273 tolerability and antitumor activity in tyrosine kinase inhibitor‐naïve Japanese patients with EGFR mutation‐positive non‐small‐cell lung cancer
Authors: Azuma Koichi , Nishio Makoto , Hayashi Hidetoshi , Kiura Katsuyuki , Satouchi Miyako , Sugawara Shunichi , Hida Toyoaki , Iwamoto Yasuo , Inoue Akira , Takeda Koji , Ikeda Satoshi , Nakagawa Tomoki , Takeda Kentaro , Asahina Seitaro , Komatsu Kanji , Morita Satoshi , Fukuoka Masahiro , Nakagawa Kazuhiko
Published: May 2018

Epidermal growth factor receptor (EGFR) activating mutations occur in approximately 50% of East Asian patients with non‐small‐cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitors (TKIs). ASP8273 is an irreversible EGFR‐TKI, given orally, that inhibits EGFR activating mutations and has shown clinical activity in patients with EGFR mutation‐positive NSCLC. Epidermal growth factor receptor‐TKI‐naïve Japanese adult patients (≥20 years) with NSCLC harboring EGFR mutations were enrolled in this open‐label, single‐arm, phase II study (ClinicalTrials.gov identifier NCT02500927). Patients received ASP8273 300 mg once daily until discontinuation criteria were met. The primary end‐point was to determine the safety of ASP8273 300 mg; the secondary end‐point was antitumor activity defined by RECIST version 1.1. Thirty‐one patients (12 men and 19 women; median age, 64 years [range, 31‐82 years]) with EGFR mutation‐positive NSCLC were enrolled; as of 23 February 2016, 25 patients (81%) were still on study. Of the 31 patients, 27 (87%) had an exon 19 deletion (n = 13, 42%) or an L858R (n = 14, 45%) EGFR activating mutation, and two (7%) had an L861Q mutation. Five patients (16%) had other EGFR activating mutations, two had an activating mutation and the T790M resistance mutation. The most commonly reported treatment‐emergent adverse event was diarrhea (n = 24, 77%). All patients had at least one post‐baseline scan; one patient (3%) achieved a confirmed complete response, 13 (42%) had a confirmed partial response, and 15 (48%) had confirmed stable disease (disease control rate, 94% [n = 29/31]) per investigator assessment. Once‐daily ASP8273 at 300 mg was generally well tolerated and showed antitumor activity in TKI‐naïve Japanese patients with EGFR mutation‐positive NSCLC.
Immediate placement and provisionalization of implants in the aesthetic zone with or without a connective tissue graft: A 1‐year randomized controlled trial and volumetric study
Authors: van Nimwegen Wouter G. , Raghoebar Gerry M. , Zuiderveld Elise G. , Jung Ronald E. , Meijer Henny J. A. , Mühlemann Sven
Published: May 2018

Objective

To volumetrically compare peri‐implant mid‐facial soft tissue changes in immediately placed and provisionalized implants in the aesthetic zone, with or without a connective tissue graft.

Material and methods

Sixty patients were included. All implants were placed immediately after extraction. After randomization, in one group, a connective tissue graft (test group, n = 30) was inserted at the buccal aspect of the implant. The other group (control group, n = 30) received no connective tissue graft. Clinical parameters, digital photographs and conventional impressions were obtained before extraction (Tpre) and at 12 months following definitive crown placement (T12). The casts were digitized by a laboratory scanner, and a volumetric analysis was performed between Tpre and T12.

Results

Twenty‐five patients in each group were available for analysis at T12. Volumetric change, transformed to a mean (±SD) change in thickness, was −0.68 ± 0.59 mm (test) and −0.49 ± 0.54 mm (control) with a non‐significant difference between groups (p = .189). The mid‐facial mucosa level was significantly different between both groups (p = .014), with a mean (±SD) change of +0.20 ± 0.70 mm (test) and −0.48 ± 1.13 mm (control). The Pink Esthetic Score was similar between both groups.

Conclusions

The use of a CTG in immediately placed and provisionalized implants in the aesthetic zone did not result in less mucosal volume loss after 12 months, leading to the assumption that a CTG cannot fully compensate for the underlying facial bone loss, although a significantly more coronally located mid‐facial mucosa level was found when a CTG was performed.
The need for appropriate registration of pregnancy outcomes under newer oral glucose‐lowering therapies
Authors: Benhalima Katrien , Mathiesen Elisabeth R. , Paldanius Päivi M. , Mathieu Chantal
Published: May 2018

Because of the increase in type 2 diabetes (T2DM) in young adults, women of childbearing age are frequently treated with newer glucose‐lowering therapies, and an increase in unintentional exposure to therapies unapproved for use during pregnancy is expected. The clinician is left with the dilemma of deciding between discontinuation of a novel agent that is providing excellent glycaemic control, while switching to other agents may cause deterioration of glycaemia, and continued use of novel agents that may have uncertain effects on the unborn child. For T2DM, pregnancy data are collected only via spontaneous reporting systems. Therefore, we evaluated the available data on pregnancy outcomes under newer glucose‐lowering agents in pharmaceutical safety databases. We found that data on pregnancy outcomes with new glucose‐lowering agents in T2DM are scarce, with a high risk of bias towards negative outcomes, limiting their usefulness in robustly assessing safety. Because of the lack of information at present, these agents are not recommended for use during pregnancy or when planning pregnancy. To better guide clinical practice, structured systems of assessing pregnancy outcomes in women receiving these novel agents are urgently needed.
The predictive value of left ventricular myocardium mechanics evaluation in asymptomatic patients with aortic regurgitation and preserved left ventricular ejection fraction. A long‐term speckle‐tracking echocardiographic study
Authors: Verseckaite Raimonda , Mizariene Vaida , Montvilaite Aiste , Auguste Indre , Bieseviciene Monika , Laukaitiene Jolanta , Jonkaitiene Regina , Jurkevicius Renaldas
Published: May 2018

Background

The management of asymptomatic patients with aortic regurgitation (AR) and preserved left ventricular (LV) ejection fraction (LVEF) remains challenging. The purpose of the study was to assess the early changes of LV mechanics by 2D speckle‐tracking echocardiography (2D‐STE) in order to predict a decrease in LVEF.

Methods

Sixty‐seven patients (age, 47 ± 15 years) with asymptomatic moderate (n = 27) and severe AR (n = 40) with preserved LVEF were prospectively followed for about 5 years. Sixty healthy age‐matched controls were included in the study. Standard echocardiography and 2D‐STE were performed at the baseline and follow‐up. The primary endpoint was a deterioration of the LVEF (≤50%).

Results

At baseline, global LV longitudinal peak systolic strain (GLS) and strain rate (GLSRs) were decreased in patients with severe AR compared to controls (−18.9 ± 2.4 vs 20.0 ± 2.1%; −1.05 ± 0.19 vs −1.18 ± 0.15 1/s, P < .05, respectively). In the moderate AR group, GLS was not different from that of the control group, but GLSRs was significantly lower than in controls. The primary endpoint was reached in 12 patients with severe AR, while this was not observed in patients with moderate AR. In multivariate analysis, GLS was an independent predictor of LVEF. According to ROC curve analysis, probability of primary endpoint occurrence was significantly greater in patients with GLS values ≥−18.5% (AUC: 0.89, P < .01).

Conclusions

The reduction of LV longitudinal deformation is a sign of early subclinical LV dysfunction. GLS is a prognostic predictor of LV dysfunction and may be potentially useful for optimal timing of surgery for patients with significant AR.
Homoarginine and all‐cause mortality: A systematic review and meta‐analysis
Authors: Zinellu Angelo , Paliogiannis Panagiotis , Carru Ciriaco , Mangoni Arduino A.
Published: May 2018

Background

Homoarginine, a basic amino acid and analogue of L‐arginine, has been shown to exert salutary effects on vascular homoeostasis, possibly through interaction with the enzymes nitric oxide synthase and arginase. This might translate into improved survival outcomes, particularly in subjects with moderate‐high cardiovascular risk. We conducted a systematic review and meta‐analysis to investigate the association between circulating homoarginine concentrations and all‐cause mortality in observational studies of human cohorts.

Materials and methods

Studies reporting baseline circulating homoarginine concentrations and all‐cause mortality as outcome were searched using the MEDLINE, Scopus and Cochrane databases until January 2018. Hazard ratios (HRs) with 95% confidence intervals (CIs) derived from multivariate Cox's proportional‐hazards analysis were extracted from individual studies.

Results

A total of 13 studies in 11 964 participants were included in the final analysis. Homoarginine concentrations were inversely associated with all‐cause mortality (HR 0.64, 95% CI 0.57‐0.73). This association remained significant in participant sub‐groups with predominant cardiovascular disease (HR 0.64, 95% CI 0.55‐0.76) and renal disease (HR 0.60, 95% CI 0.46‐0.68).

Conclusions

This meta‐analysis of observational studies showed an inverse association between circulating homoarginine concentrations and all‐cause mortality. Further research is warranted to investigate the direct effects of homoarginine on cardiovascular homoeostasis, the associations between homoarginine and all‐cause mortality in other population groups, and the effects of interventions on homoarginine concentrations on clinical outcomes.
Effect of propolis on preserving human periodontal ligament cells and regulating pro‐inflammatory cytokines
Authors: Yuan Xiaojing , Wang Yuanyuan , Shi Bingqing , Zhao Yuming
Published: May 2018

Background/Aim

Propolis has been suggested as a storage medium for avulsed teeth. The aim of this study was to compare the effectiveness of Brazilian propolis with Hank's balanced salt solution and milk in maintaining the viability of human periodontal ligament cells, their osteogenic differentiation potential, and pro‐inflammatory cytokine expression.

Material and Methods

Cell Counting Kit 8 assays were performed to test human periodontal ligament cell viability in different storage media. The preservative effect on osteogenic differentiation was evaluated using alkaline phosphatase staining and activity assays, Alizarin Red S staining, and western blotting. Quantification of pro‐inflammatory cytokines was performed using real‐time PCR and enzyme‐linked immunosorbent assays.

Results

Brazilian propolis at 10 μg/mL was not cytotoxic toward human periodontal ligament cells. The milk group showed the highest cell viability. Brazilian propolis and Hank's balanced salt solution groups showed similar cell viabilities. Alkaline phosphatase staining and activity were similar in all groups. Calcium deposition and mineralization nodule formation were similar in the Brazilian propolis and Hank's balanced salt solution groups but were higher in the milk group. Osteogenic marker gene and protein levels were similar in all groups. The genes and protein expression levels of IL1β, IL6, and IL8 decreased significantly after treatment with Brazilian propolis. TNFα mRNA expression showed no significant difference among the experimental groups. Pro‐inflammatory cytokine levels in the milk group were higher than in the Brazilian propolis and Hank's balanced salt solution groups.

Conclusions

Brazilian propolis, Hank's balanced salt solution, and milk maintained the viability of human periodontal ligament cells and preserved their osteogenic differentiation ability similarly. However, Brazilian propolis showed a better anti‐inflammatory effect.
Human activities and landscape features interact to closely define the distribution and dispersal of an urban commensal
Authors: Tang Qian , Low Gabriel Weijie , Lim Jia Ying , Gwee Chyi Yin , Rheindt Frank E.
Published: May 2018

The rock pigeon,Columba livia, is a cosmopolitan human commensal, domesticated thousands of years ago. However, the human‐mediated factors governing its distribution and dispersal are not well understood. In this study, we performed (a) hierarchical distance sampling on ~400 island‐wide point transects, (b) a population genomic inquiry based on ~7,000SNPs from almost 150 individuals, and (c) landscape genomic analyses on the basis of extensive ecological and socio‐economic databases to characterize the distribution and dispersal patterns of rock pigeons across Singapore. Our distance sampling results indicated that the volume of intentional “mercy feeding” and availability of high‐rise buildings are the most reliable predictors of high pigeon densities in Singapore. Genomic analyses demonstrated that rock pigeons in Singapore form a single population possibly derived from rapid expansion from a genetically homogenous group of founder individuals. In specific, rock pigeons in Singapore lack sex‐biased dispersal and are clustered with a genetic patch size of ~3 km. Landscape genomic analyses of great precision pointed to the presence of dense trees as agents of resistance to dispersal, whereas a high road density reduces this resistance. By pinpointing a range of ecological and socio‐economic variables determining the distribution and dispersal of pigeons, our study provides urban planners with the tools for optimal management of this human commensal, such as a curtailment of the practice of mercy feeding and modifications to the urban landscape to reduce pigeon density and to lower the likelihood of repopulation by dispersal.
Epidemiology of race‐day distal limb fracture in flat racing Thoroughbreds in Great Britain (2000–2013)
Authors: Rosanowski S. M. , Chang Y. M. , Stirk A. J. , Verheyen K. L. P.
Published: May 2018

Background

A key focus of the racing industry is to minimise the number of race‐day distal limb fractures although no studies have identified risk factors for both fatal and non‐fatal distal limb fractures.

Objective

To determine risk factors for race‐day distal limb fractures experienced by Thoroughbred racehorses participating in flat racing in Great Britain (GB).

Study design

Retrospective cohort.

Methods

Information was collected from all flat racing starts occurring onGBracecourses between 2000 and 2013, including horse, race, course, trainer and jockey data for each horse start and race‐day injury data as reported by on‐course veterinarians. Associations between exposure variables and cases of distal limb fracture were assessed using mixed‐effects logistic regression analyses using data from all starts, and turf starts only.

Results

A total of 806,764 starts and 624 cases of distal limb fracture were included, of which 548,571 starts and 379 cases of distal limb fracture occurred on turf surfaces. In both models, increasing firmness of the going, increasing racing distance and horses in their first year of racing were at a higher risk of distal limb fracture while increasing number of previous race starts were protective. Trainer performance was associated with distal limb fracture. Generally, the risk of distal limb fracture increased with increasing horse age. Starts in selling or claiming races or Group 1, Group 3 or claiming races were at higher odds of distal limb fracture in the all starts and turf models, respectively.

Main limitations

Clinical diagnosis of distal limb fracture and all types of distal limb fracture considered as one outcome.

Conclusions

This study confirmed previously identified risk factors for distal limb fracture including going, race distance and number of horse starts. Novel risk factors were related to trainer and horse performance, and race type. Identification of at risk groups will help inform interventions to reduce distal limb fracture occurrence in flat racing horses.
FLIP as a therapeutic target in cancer
Authors: Humphreys Luke , Espona‐Fiedler Margarita , Longley Daniel B.
Published: May 2018

One of the classic hallmarks of cancer is disruption of cell death signalling. Inhibition of cell death promotes tumour growth and metastasis, causes resistance to chemo‐ and radiotherapies as well as targeted agents, and is frequently due to overexpression of antiapoptotic proteins rather than loss of pro‐apoptotic effectors. FLIP is a major apoptosis‐regulatory protein frequently overexpressed in solid and haematological cancers, in which its high expression is often correlated with poor prognosis. FLIP, which is expressed as long (FLIP(L)) and short (FLIP(S)) splice forms, achieves its cell death regulatory functions by binding to FADD, a critical adaptor protein which links FLIP to the apical caspase in the extrinsic apoptotic pathway, caspase‐8, in a number of cell death regulating complexes, such as the death‐inducing signalling complexes (DISCs) formed by death receptors. FLIP also plays a key role (together with caspase‐8) in regulating another form of cell death termed programmed necrosis or ‘necroptosis’, as well as in other key cellular processes that impact cell survival, including autophagy. In addition, FLIP impacts activation of the intrinsic mitochondrial‐mediated apoptotic pathway by regulating caspase‐8‐mediated activation of the pro‐apoptotic Bcl‐2 family member Bid. It has been demonstrated that FLIP can not only inhibit death receptor‐mediated apoptosis, but also cell death induced by a range of clinically relevant chemotherapeutic and targeted agents as well as ionizing radiation. More recently, key roles for FLIP in promoting the survival of immunosuppressive tumour‐promoting immune cells have been discovered. Thus, FLIP is of significant interest as an anticancer therapeutic target. In this article, we review FLIP's biology and potential ways of targeting this important tumour and immune cell death regulator.
The interruptive effect of electric shock on odor response requires mushroom bodies in Drosophila melanogaster
Authors: Song W. , Zhao L. , Tao Y. , Guo X. , Jia J. , He L. , Huang Y. , Zhu Y. , Chen P. , Qin H.
Published: May 2018

Nociceptive stimulus involuntarily interrupts concurrent activities. This interruptive effect is related to the protective function of nociception that is believed to be under stringent evolutionary pressure. To determine whether such interruptive effect is conserved in invertebrate and potentially uncover underlying neural circuits, we examined Drosophila melanogaster. Electric shock (ES) is a commonly used nociceptive stimulus for nociception related research in Drosophila. Here, we showed that background noxious ES dramatically interrupted odor response behaviors in a T‐maze, which is termed blocking odor response by electric shock (BOBE). The interruptive effect is not odor specific. ES could interrupt both odor avoidance and odor approach. To identify involved brain areas, we focused on the odor avoidance to 3‐OCT. By spatially abolishing neurotransmission with temperature sensitive ShibireTS1, we found that mushroom bodies (MBs) are necessary for BOBE. Among the 3 major MB Kenyon cell (KCs) subtypes, α/β neurons and γ neurons but not α’/β’ neurons are required for normal BOBE. Specifically, abolishing the neurotransmission of either α/β surface (α/βs), α/β core (α/βc) or γ dorsal (γd) neurons alone is sufficient to abrogate BOBE. This pattern of MB subset requirement is distinct from that of aversive olfactory learning, indicating a specialized BOBE pathway. Consistent with this idea, BOBE was not diminished in several associative memory mutants and noxious ES interrupted both innate and learned odor avoidance. Overall, our results suggest that MB α/β and γ neurons are parts of a previously unappreciated central neural circuit that processes the interruptive effect of nociception.
Vulnerability of the global terrestrial ecosystems to climate change
Authors: Li Delong , Wu Shuyao , Liu Laibao , Zhang Yatong , Li Shuangcheng
Published: May 2018

Climate change has far‐reaching impacts on ecosystems. Recent attempts to quantify such impacts focus on measuring exposure to climate change but largely ignore ecosystem resistance and resilience, which may also affect the vulnerability outcomes. In this study, the relative vulnerability of global terrestrial ecosystems to short‐term climate variability was assessed by simultaneously integrating exposure, sensitivity, and resilience at a high spatial resolution (0.05°). The results show that vulnerable areas are currently distributed primarily in plains. Responses to climate change vary among ecosystems and deserts and xeric shrublands are the most vulnerable biomes. Global vulnerability patterns are determined largely by exposure, while ecosystem sensitivity and resilience may exacerbate or alleviate external climate pressures at local scales; there is a highly significant negative correlation between exposure and sensitivity. Globally, 61.31% of the terrestrial vegetated area is capable of mitigating climate change impacts and those areas are concentrated in polar regions, boreal forests, tropical rainforests, and intact forests. Under current sensitivity and resilience conditions, vulnerable areas are projected to develop in high Northern Hemisphere latitudes in the future. The results suggest that integrating all three aspects of vulnerability (exposure, sensitivity, and resilience) may offer more comprehensive and spatially explicit adaptation strategies to reduce the impacts of climate change on terrestrial ecosystems.
Temporal response of soil organic carbon after grassland‐related land‐use change
Authors: Li Wei , Ciais Philippe , Guenet Bertrand , Peng Shushi , Chang Jinfeng , Chaplot Vincent , Khudyaev Sergey , Peregon Anna , Piao Shilong , Wang Yilong , Yue Chao
Published: May 2018

The net flux of CO2 exchanged with the atmosphere following grassland‐related land‐use change (LUC) depends on the subsequent temporal dynamics of soil organic carbon (SOC). Yet, the magnitude and timing of these dynamics are still unclear. We compiled a global data set of 836 paired‐sites to quantify temporal SOC changes after grassland‐related LUC. In order to discriminate between SOC losses from the initial ecosystem and gains from the secondary one, the post‐LUC time series of SOC data was combined with satellite‐based net primary production observations as a proxy of carbon input to the soil. Globally, land conversion from either cropland or forest into grassland leads to SOC accumulation; the reverse shows net SOC loss. The SOC response curves vary between different regions. Conversion of cropland to managed grassland results in more SOC accumulation than natural grassland recovery from abandoned cropland. We did not consider the biophysical variables (e.g., climate conditions and soil properties) when fitting the SOC turnover rate into the observation data but analyzed the relationships between the fitted turnover rate and these variables. The SOC turnover rate is significantly correlated with temperature and precipitation (p < 0.05), but not with the clay fraction of soils (p > 0.05). Comparing our results with predictions from bookkeeping models, we found that bookkeeping models overestimate by 56% of the long‐term (100 years horizon) cumulative SOC emissions for grassland‐related LUC types in tropical and temperate regions since 2000. We also tested the spatial representativeness of our data set and calculated SOC response curves using the representative subset of sites in each region. Our study provides new insight into the impact grassland‐related LUC on the global carbon budget and sheds light on the potential of grassland conservation for climate mitigation.
Detailed large‐scale mapping of geographical variation of Yellowhammer Emberiza citrinella song dialects in a citizen science project
Authors: Diblíková Lucie , Pipek Pavel , Petrusek Adam , Svoboda Jiří , Bílková Jana , Vermouzek Zdeněk , Procházka Petr , Petrusková Tereza
Published: May 2018

Song dialects, as a special case of geographical variation in vocalization, are useful tools in the study of a number of topics ranging from cultural evolution to the emergence of reproductive barriers, and thus continue to be the focus of many bird‐song studies. The Yellowhammer Emberiza citrinella is a common Palaearctic bird with a long breeding season and song period, whose distinctive song exhibits clearly distinguishable dialects differing in the composition of the final phrase. The species is therefore particularly suitable for large‐scale studies of dialect distribution involving not only experts but also members of the public. Here we demonstrate that citizen science can indeed allow mapping of songbird dialect distribution on a national scale in unprecedented detail. During the project Dialects of Czech Yellowhammers, which collected almost 4000 recordings over 6 years (2011–2016), we obtained information on dialect distribution for almost 90% of the territory of Czechia. We detected most of the common dialect types known elsewhere in Europe, and these were distributed in a fragmented fashion, with several unusual and rare dialects also detected in small areas. However, the highly scattered distribution of birds using some final phrases traditionally assigned to distinct dialects suggests that classification of Yellowhammer dialects warrants a thorough re‐assessment based on quantitative data. Successful involvement of the public in this and other ongoing citizen science projects has contributed to the establishment of the Yellowhammer as a model species for dialect research. The dataset will serve as a foundation for future studies investigating processes responsible for the origin and maintenance of avian dialects, and may be particularly useful for evaluating their spatial and temporal stability.
Does a tailored guideline implementation strategy have an impact on clinical physiotherapy practice? A nonrandomized controlled study
Authors: Bernhardsson Susanne , Larsson Maria E. H.
Published: May 2018

Rationale, aims, and objectives

Clinical practice guidelines are a common strategy for implementing research findings into practice and facilitating evidence‐based practice in health care settings. There is a paucity of knowledge about the impact of different guideline implementation strategies on clinical practice in a physiotherapy context. The study aimed to assess the impact of a guideline implementation intervention on clinical physiotherapy practice.

Methods

A tailored, multicomponent guideline implementation was compared with usual practice. Clinical practice was evaluated in physiotherapy treatment methods used for 3 common musculoskeletal disorders. Data were collected with a validated web‐based questionnaire.

Results

Postimplementation data were collected from 168 physiotherapists in the intervention group and 88 in the control group. The most frequently reported treatment methods for low back pain were advice on posture (reported by 95% in the intervention group vs 90% in the control group), advice to stay active (93% vs 90%), and stabilization exercise (88% vs 80%). Differences between groups were not significant. Reported use of body awareness training (23% vs 6%, P = .023) and spinal manipulation (9% vs 23%, P = .044) differed between the groups. The most frequently used treatment methods for neck pain were advice on posture (95% vs 92%), advice to stay active (89% vs 87%), and ROM exercise (85% vs 71%) (no significant differences between groups). Reported use of body awareness training (24% vs 7%, P = .023) differed between the groups. The most frequently used treatment methods for subacromial pain were range of motion exercises (reported by 93% in both groups), advice on posture (90% vs 87%), home exercise (77% vs 74%), and stabilization exercise (69% vs 66%) (no significant difference between groups).

Conclusions

Treatment methods used were largely in line with evidence already before the guideline implementation, which may explain why the guideline implementation had only little impact on clinical practice.
Rapid visual detection of cyprinid herpesvirus 2 by recombinase polymerase amplification combined with a lateral flow dipstick
Authors: Wang H , Sun M , Xu D , Podok P , Xie J , Jiang Ys , Lu Lq
Published: May 2018

Herpesviral haematopoietic necrosis (HVHN), caused by cyprinid herpesvirus 2 (CyHV‐2), causes significant losses in crucian carp (Carassius carassius) aquaculture. Rapid and convenient DNA assay detection of CyHV‐2 is useful for field diagnosis. Recombinase polymerase amplification (RPA) is a novel isothermal DNA amplification and detection technology that can amplify DNA within 30 min at ~37°C by simulating in vivo DNA recombination. Herein, a rapid and convenient detection assay based on RPA with a lateral flow dipstick (LFD) was developed for detecting CyHV‐2. The highly conserved ORF72 of CyHV‐2 was targeted by specific and sensitive primers and probes. The optimized assay takes only 15 min at 38°C using a water bath, with analysis of products by 2% agarose gel electrophoresis within 30 min. A simple lateral flow strip based on the unique probe in reaction buffer was developed for visualization. The entire RPA‐LFD assay takes 50 min less than the routine PCR method, is 100 times more sensitive and displays no cross‐reaction with other aquatic viruses. The combined isothermal RPA and lateral flow assay (RPA‐LFD) provides a simple, rapid, reliable method that could improve field diagnosis of CyHV‐2 when resources are limited.
A natural infection by the red sea bream iridovirus‐type Megalocytivirus in the golden mandarin fish Siniperca scherzeri
Authors: Kim K I , Hwang S D , Cho M Y , Jung S H , Kim Y C , Jeong H D
Published: May 2018

An outbreak of a Megalocytivirus infection was found in the golden mandarin fish Siniperca scherzeri during September and October 2016, in Korea. Phylogeny and genetic diversity based on the major capsid protein (MCP) and adenosine triphosphatase (ATPase) genes showed a new strain. Designated as GMIV, this strain derived from the golden mandarin fish was suggested to belong to the red sea bream iridovirus (RSIV)‐subgroup I. Additionally, this train clustered with the ehime‐1 strain from red sea bream Pagrus major in Japan and was distinguished from circulating isolates (RSIV‐type subgroup II and turbot reddish body iridovirus [TRBIV] type) in Korea. The infection level, evaluated by qPCR, ranged from 8.18 × 102 to 7.95 × 106 copies/mg of tissue individually, suggesting that the infected fish were in the disease‐transmitting stage. The diseased fish showed degenerative changes associated with cytomegaly in the spleen as general sign of Megalocytivirus infection. The results confirm that the RSIV‐type Megalocytivirus might have crossed the environmental and species barriers to cause widespread infection in freshwater fish.
In vivo growth and genomic characterization of rickettsia‐like organisms isolated from farmed Chinook salmon (Oncorhynchus tshawytscha) in New Zealand
Authors: Gias E , Brosnahan C L , Orr D , Binney B , Ha H J , Preece M A , Jones B
Published: May 2018

A rickettsia‐like organism, designated NZ‐RLO2, was isolated from Chinook salmon (Oncorhynchus tshawytscha) farmed in the South Island, New Zealand. In vivo growth showed NZ‐RLO2 was able to grow in CHSE‐214, EPC, BHK‐21, C6/36 and Sf21 cell lines, while Piscirickettsia salmonis LF‐89T grew in all but BHK‐21 and Sf21. NZ‐RLO2 grew optimally in EPC at 15°C, CHSE‐214 and EPC at 18°C. The growth of LF‐89 T was optimal at 15°C, 18°C and 22°C in CHSE‐24, but appeared less efficient in EPC cells at all temperatures. Pan‐genome comparison of predicted proteomes shows that available Chilean strains of P. salmonis grouped into two clusters (p‐value = 94%). NZ‐RLO2 was genetically different from previously described NZ‐RLO1, and both strains grouped separately from the Chilean strains in one of the two clusters (p‐value = 88%), but were closely related to each other. TaqMan and Sybr Green real‐time PCR targeting RNA polymerase (rpoB) and DNA primase (dnaG), respectively, were developed to detect NZ‐RLO2. This study indicates that the New Zealand strains showed a closer genetic relationship to one of the Chilean P. salmonis clusters; however, more Piscirickettsia genomes from wider geographical regions and diverse hosts are needed to better understand the classification within this genus.
The recognition of former melt flux through high‐strain zones
Authors: Stuart Catherine A. , Piazolo Sandra , Daczko Nathan R.
Published: May 2018

High‐strain zones are potential pathways of melt migration through the crust. However, the identification of melt‐present high‐strain deformation is commonly limited to cases where the interpreted volume of melt “frozen” within the high‐strain zone is high (>10%). In this contribution, we examine high‐strain zones in the Pembroke Granulite, an otherwise low‐strain outcrop of volcanic arc lower crust exposed in Fiordland, New Zealand. These high‐strain zones display compositional layering, flaser‐shaped mineral grains, and closely spaced foliation planes indicative of high‐strain deformation. Asymmetric leucosome surrounding peritectic garnet grains suggest deformation was synchronous with minor amounts of in situ partial melting. High‐strain zones lack typical mylonite microstructures and instead display typical equilibrium microstructures, such as straight grain boundaries, 120° triple junctions, and subhedral grain shapes. We identify five key microstructures indicative of the former presence of melt within the high‐strain zones: (a) small dihedral angles of interstitial phases; (b) elongate interstitial grains; (c) small aggregates of quartz grains with xenomorphic plagioclase grains connected in three dimensions; (d) fine‐grained, K‐feldspar bearing, multiphase aggregates with or without augite rims; and (e) mm‐ to cm‐scale felsic dykelets. Preservation of key microstructures indicates that deformation ceased as conditions crossed the solidus, breaking the positive feedback loop between deformation and the presence of melt. We propose that microstructures indicative of the former presence of melt, such as the five identified above, may be used as a tool for recognising rocks formed during melt‐present high‐strain deformation where low (<5%) volumes of leucosome are “frozen” within the high‐strain zone.
Synaptic activity induces input‐specific rearrangements in a targeted synaptic protein interaction network
Authors: Lautz Jonathan D. , Brown Emily A. , Williams VanSchoiack Alison A. , Smith Stephen E. P.
Published: May 2018

Cells utilize dynamic, network‐level rearrangements in highly interconnected protein interaction networks to transmit and integrate information from distinct signaling inputs. Despite the importance of protein interaction network dynamics, the organizational logic underlying information flow through these networks is not well understood. Previously, we developed the quantitative multiplex co‐immunoprecipitation platform, which allows for the simultaneous and quantitative measurement of the amount of co‐association between large numbers of proteins in shared complexes. Here, we adapt quantitative multiplex co‐immunoprecipitation to define the activity‐dependent dynamics of an 18‐member protein interaction network in order to better understand the underlying principles governing glutamatergic signal transduction. We first establish that immunoprecipitation detected by flow cytometry can detect activity‐dependent changes in two known protein–protein interactions (Homer1‐mGluR5 and PSD‐95‐SynGAP). We next demonstrate that neuronal stimulation elicits a coordinated change in our targeted protein interaction network, characterized by the initial dissociation of Homer1 and SynGAP‐containing complexes followed by increased associations among glutamate receptors and PSD‐95. Finally, we show that stimulation of distinct glutamate receptor types results in different modular sets of protein interaction network rearrangements, and that cells activate both modules in order to integrate complex inputs. This analysis demonstrates that cells respond to distinct types of glutamatergic input by modulating different combinations of protein co‐associations among a targeted network of proteins. Our data support a model of synaptic plasticity in which synaptic stimulation elicits dissociation of pre‐existing multiprotein complexes, opening binding slots in scaffold proteins and allowing for the recruitment of additional glutamatergic receptors.

Open Practices

This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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Reduced Aβ secretion by human neurons under conditions of strongly increased BACE activity
Authors: Scholz Diana , Chernyshova Yana , Ückert Anna‐Katharina , Leist Marcel
Published: May 2018

The initial step in the amyloidogenic cascade of amyloid precursor protein (APP) processing is catalyzed by beta‐site APP‐cleaving enzyme (BACE), and this protease has increased activities in affected areas of Alzheimer's disease brains. We hypothesized that altered APP processing, because of augmented BACE activity, would affect the actions of direct and indirect BACE inhibitors. We therefore compared post‐mitotic human neurons (LUHMES) with their BACE‐overexpressing counterparts (BLUHMES). Although β‐cleavage of APP was strongly increased in BLUHMES, they produced less full‐length and truncated amyloid beta (Aβ) than LUHMES. Moreover, low concentrations of BACE inhibitors decreased cellular BACE activity as expected, but increased Aβ1‐40 levels. Several other approaches to modulate BACE activity led to a similar, apparently paradoxical, behavior. For instance, reduction in intracellular acidification by bepridil increased Aβ production in parallel with decreased BACE activity. In contrast to BLUHMES, the respective control cells (LUHMES or BLUHMES with catalytically inactive BACE) showed conventional pharmacological responses. Other non‐canonical neurochemical responses (so‐called ‘rebound effects’) are well‐documented for the Aβ pathway, especially for γ‐secretase: a partial block of its activity leads to an increased Aβ secretion by some cell types. We therefore compared LUHMES and BLUHMES regarding rebound effects of γ‐secretase inhibitors and found an Aβ rise in LUHMES but not in BLUHMES. Thus, different cellular factors are responsible for the γ‐secretase‐ versus BACE‐related Aβ rebound. We conclude that increased BACE activity, possibly accompanied by an altered cellular localization pattern, can dramatically influence Aβ generation in human neurons and affect pharmacological responses to secretase inhibitors.

Open Practices

Open Science: This manuscript was awarded with the Open Materials Badge.

For more information see: https://cos.io/our-services/open-science-badges/

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Mitochondria, lysosomes, and dysfunction: their meaning in neurodegeneration
Authors: Audano Matteo , Schneider Anja , Mitro Nico
Published: May 2018

In the last decades, lysosomes and mitochondria were considered distinct and physically separated organelles involved in different cellular functions. While lysosomes were thought to exclusively be the rubbish dump of the cell involved in the degradation of proteins and other cell compartments, mitochondria were considered solely involved in the oxidation of energy substrate to get ATP, together with other minor duties. Nowadays, our view of these organelles is profoundly changed since studies demonstrated that mitochondria and lysosome are mutually functional, maintaining proper cell homeostasis. Furthermore, the onset of neurodegenerative diseases (i.e., Parkinson's disease, Alzheimer's disease, lysosomal storage disorders, and amyotrophic lateral sclerosis) is tightly linked to mutations in mitochondrial and lysosomal regulators. In this context, mitochondrial dysfunction leads to lysosomal impairment and buildup of autophagy by‐products, whereas lysosomal imperfections trigger functional and morphological mitochondrial defects. Here, we provide an updated overview covering recent findings about mitochondria and lysosomal interaction in physiology and pathophysiology, focusing the attention on the molecular mechanism that control their interdependence.

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Clinical implications of high‐sensitivity cardiac troponins
Authors: Holzmann M. J.
Published: May 2018

Cardiac troponin assays have become more sensitive over the years leading to the clinical introduction of high‐sensitivity cardiac troponin assays in 2010. Their use has revolutionized the assessment of patients with chest pain in the emergency department by allowing earlier rule‐in and rule‐out of myocardial infarction leading to shorter stays in the emergency department and reduced admissions for chest pain. The incidence of myocardial infarction has increased slightly, and patients with myocardial infarction diagnosed with high‐sensitivity cardiac troponins have been found to have a reduced risk of reinfarction, though without an impact on survival. High‐sensitivity cardiac troponins are powerful predictors of long‐term mortality and cardiovascular disease in the general population as well as in patients with chest pain with or without cardiovascular disease. The increase in risk for death and cardiovascular disease associated with high‐sensitivity cardiac troponins is graded and starts already at detectable levels, well below the upper normal level. The aim of this review was to describe the clinical use and consequences of the introduction of high‐sensitivity cardiac troponins. In addition, the importance of persistently elevated troponin levels for prognosis and what investigations may be appropriate to perform in patients with stable troponin elevations are discussed.
Association between seizure frequency and fatigue levels in children with epilepsy
Authors: Kanemura Hideaki , Sano Fumikazu , Ohyama Tetsuo , Sugita Kanji , Aihara Masao
Published: May 2018

Aim

The purpose of this study was to examine the association between seizure‐related features and fatigue levels in children with epilepsy.

Methods

All children were classified into three subgroups based on the state of their seizure control: well‐controlled epilepsy (WCE; seizure‐free), intermediate‐controlled epilepsy (ICE; seizure frequency < 1×/month) and uncontrolled epilepsy (UCE; seizure frequency > 1×/month). Participants were asked to rate on a 7‐point scale, from 1 (strongly disagree) to 7 (strongly agree), how often they felt the ways described by nine items on the Fatigue Severity Scale (FSS). A higher score is suggestive of greater fatigue.

Results

The study participants comprised 58 children with epilepsy and 15 children without seizures, who served as the healthy (non‐epilepsy) group. The mean FSS scores of the children with epilepsy were significantly higher than those of the healthy (non‐epilepsy) group (4.40 vs. 1.55, respectively; P < 0.0001). Multiple linear regression analysis showed that seizure frequency was the only characteristic significantly associated with fatigue (P < 0.0001). In the three epilepsy subgroups, the mean FSS scores for the WCE, intermediate‐controlled epilepsy and UCE groups were 2.30, 3.97 and 6.28, respectively. A higher seizure frequency was associated with more severe fatigue. In particular, children in the UCE group had significantly more severe fatigue than those in the WCE group (P < 0.0001).

Conclusions

The results suggest that seizure frequency is also associated with fatigue in children with epilepsy. Improved control of seizures may help reduce fatigue levels and improve the quality of life of children with epilepsy.