bluuebunny/crossref_metadata_2025_split huggingface dataset:
Educational concussion module for professional footballers: from systematic development to feasibility and effect
Authors: Gouttebarge Vincent , Cowie Charlotte , Goedhart Edwin , Kemp Simon P T , Kerkhoffs Gino M M J , Patricios Jon , Stokes Keith A 
Published: March 2019

ObjectivesTo describe: (1) how we developed a concussion module and (2) whether the concussion module is feasible (in terms of relevance, added value and suitability) and enhances knowledge and changes attitude of professional footballers about concussion.Developing the concussion moduleWe developed the concussion module based on two structured and systematic processes. First, our needs assessment (questionnaire and interviews) in professional football (especially players) revealed that a 5–10 min concussion module was needed, ideally disseminated during club visits. Second, the objectives were defined (from published literature and by experts) as to disseminate essential information about what concussion is (definition), how to recognise it and the importance of removing a player with (suspected) concussion from the football field. We included an introductory video featuring a high-profile professional footballer and an animated educational component on defining concussion, recognising it and removing affected players from the field.Feasibility and effectA quasiexperimental study (pretest post-test design) was conducted among 61 professional footballers. These players were asked to complete two questionnaires related to knowledge about and attitude towards concussion and feasibility of the module: one before and one after viewing the concussion module. Potential increase in knowledge and attitude was explored by comparing the pretest and post-test scores of the Rosenbaum Concussion Knowledge and Attitudes Survey with the non-parametric Wilcoxon signed-rank test (p<0.05). The mean knowledge score of the participants was stable between tests (Z=213; p=0.16), while mean attitude score increased significantly (Z=331; p=0.01). Nearly all participants (85%–100%) were positive about the relevance, added value, duration and form of the concussion module.ConclusionThe developed educational concussion module leads to better attitude of professional footballers towards concussion.
Occupational biomechanical risk factors for radial nerve entrapment in a 13-year prospective study among male construction workers
Authors: Jackson Jennie A , Olsson David , Burdorf Alex , Punnett Laura , Järvholm Bengt , Wahlström Jens 
Published: March 2019

ObjectivesThe aim was to assess the association between occupational biomechanical exposure and the occurrence of radial nerve entrapment (RNE) in construction workers over a 13-year follow-up period.MethodsA cohort of 229 707 male construction workers who participated in a national occupational health surveillance programme (1971–1993) was examined prospectively (2001–2013) for RNE. Height, weight, age, smoking status and job title (construction trade) were obtained on health examination. RNE case status was defined by surgical release of RNE, with data from the Swedish national registry for out-patient surgery records. A job exposure matrix was developed, and biomechanical exposure estimates were assigned according to job title. Highly correlated exposures were summed into biomechanical exposure scores. Negative binomial models were used to estimate the relative risks (RR) (incidence rate ratios) of RNE surgical release for the biomechanical factors and exposure sum scores. Predicted incidence was assessed for each exposure score modelled as a continuous variable to assess exposure–response relationships.ResultsThe total incidence rate of surgically treated RNE over the 13-year observation period was 3.53 cases per 100 000 person-years. There were 92 cases with occupational information. Increased risk for RNE was seen in workers with elevated hand-grip forces (RR=1.79, 95% CI 0.97 to 3.28) and exposure to hand-arm vibration (RR=1.47, 95% CI 1.08 to 2.00).ConclusionsOccupational exposure to forceful handgrip work and vibration increased the risk for surgical treatment of RNE.
Memory-Side Protection With a Capability Enforcement Co-Processor
Authors: Azriel Leonid , Humbel Lukas , Achermann Reto , Richardson Alex , Hoffmann Moritz , Mendelson Avi , Roscoe Timothy , Watson Robert N. M. , Faraboschi Paolo , Milojicic Dejan 
Published: March 2019

Byte-addressable nonvolatile memory (NVM) blends the concepts of storage and memory and can radically improve data-centric applications, from in-memory databases to graph processing. By enabling large-capacity devices to be shared across multiple computing elements, fabric-attached NVM changes the nature of rack-scale systems and enables short-latency direct memory access while retaining data persistence properties and simplifying the software stack.
An adequate protection scheme is paramount when addressing shared and persistent memory, but mechanisms that rely on virtual memory paging suffer from the tension between performance (pushing toward large pages) and protection granularity (pushing toward small pages). To address this tension, capabilities are worth revisiting as a more powerful protection mechanism, but the long time needed to introduce new CPU features hampers the adoption of schemes that rely on instruction-set architecture support.
This article proposes the Capability Enforcement Co-Processor (CEP), a programmable memory controller that implements fine-grain protection through the capability model without requiring instruction-set support in the application CPU. CEP decouples capabilities from the application CPU instruction-set architecture, shortens time to adoption, and can rapidly evolve to embrace new persistent memory technologies, from NVDIMMs to native NVM devices, either locally connected or fabric attached in rack-scale configurations. CEP exposes an application interface based on memory handles that get internally converted to extended-pointer capabilities.
This article presents a proof of concept implementation of a distributed object store (Redis) with CEP. It also demonstrates a capability-enhanced file system (FUSE) implementation using CEP. Our proof of concept shows that CEP provides fine-grain protection while enabling direct memory access from application clients to the NVM, and that by doing so opens up important performance optimization opportunities (up to 4× reduction in latency in comparison to software-based security enforcement) without compromising security.
Finally, we also sketch how a future hybrid model could improve the initial implementation by delegating some CEP functionality to a CHERI-enabled processor.
Endoplasmic reticulum stress inhibition blunts the development of essential hypertension in the spontaneously hypertensive rat
Authors: Naiel Safaa , Carlisle Rachel E. , Lu Chao , Tat Victor , Dickhout Jeffrey G. 
Published: March 2019

Essential hypertension is the leading cause of premature death worldwide. However, hypertension’s cause remains uncertain. endoplasmic reticulum (ER) stress has recently been associated with hypertension, but it is unclear whether ER stress causes hypertension. To clarify this question, we examined if ER stress occurs in blood vessels before the development of hypertension and if ER stress inhibition would prevent hypertension development. We used the spontaneously hypertensive rat (SHR) as a model of human essential hypertension and the Wistar-Kyoto (WKY) rat as its normotensive control. Resistance arteries collected from young rats determined that ER stress was present in SHR vessels before the onset of hypertension. To assess the effect of ER stress inhibition on hypertension development, another subset of rats were treated with 4-phenylbutyric acid (4-PBA; 1 g·kg−1·day−1) for 8 wk from 5 wk of age. Blood pressure was measured via radiotelemetry and compared with untreated SHR and WKY rats. Mesenteric resistance arteries were collected and assessed for structural and functional changes associated with hypertension. Systolic and diastolic blood pressures were significantly lower in the 4-PBA-treated SHR groups than in untreated SHRs. Additionally, 4-PBA significantly decreased the media-to-lumen ratio and ER stress marker expression, improved vasodilatory response, and reduced contractile responses in resistance arteries from SHRs. Overall, ER stress inhibition blunted the development of hypertension in the SHR. These data add evidence to the hypothesis that a component of hypertension in the SHR is caused by ER stress. NEW & NOTEWORTHY In this study, 4-phenylbutyric acid’s (4-PBA’s) molecular chaperone capability was used to inhibit endoplasmic reticulum (ER) stress in the small arteries of young spontaneously hypertensive rats (SHRs) and reduce their hypertension. These effects are likely mediated through 4-PBA's effects to reduce resistant artery contractility and increase nitric oxide-mediated endothelial vasodilation through a process preventing endothelial dysfunction. Overall, ER stress inhibition blunted the development of hypertension in this young SHR model. This suggests that a component of the increase in blood pressure found in SHRs is due to ER stress. However, it is important to note that inhibition of ER stress was not able to fully restore the blood pressure to normal, suggesting that a component of hypertension may not be due to ER stress. This study points to the inhibition of ER stress as an important new physiological pathway to lower blood pressure, where other known approaches may not achieve blood pressure-lowering targets.
Extracellular histones induce calcium signals in the endothelium of resistance-sized mesenteric arteries and cause loss of endothelium-dependent dilation
Authors: Collier Daniel M. , Villalba Nuria , Sackheim Adrian , Bonev Adrian D. , Miller Zachary D. , Moore Jesse S. , Shui Bo , Lee Jane C. , Lee Frank K. , Reining Shaun , Kotlikoff Michael I. , Nelson Mark T. , Freeman Kalev 
Published: March 2019

Histone proteins are elevated in the circulation after traumatic injury owing to cellular lysis and release from neutrophils. Elevated circulating histones in trauma contribute to coagulopathy and mortality through a mechanism suspected to involve endothelial cell (EC) dysfunction. However, the functional consequences of histone exposure on intact blood vessels are unknown. Here, we sought to understand the effects of clinically relevant concentrations of histones on the endothelium in intact, resistance-sized, mesenteric arteries (MAs). EC Ca2+ was measured with high spatial and temporal resolution in MAs from mice selectively expressing the EC-specific, genetically encoded ratiometric Ca2+ indicator, Cx40-GCaMP-GR, and vessel diameter was measured by edge detection. Application of purified histone protein directly to the endothelium of en face mouse and human MA preparations produced large Ca2+ signals that spread within and between ECs. Surprisingly, luminal application of histones had no effect on the diameter of pressurized arteries. Instead, after prolonged exposure (30 min), it reduced dilations to endothelium-dependent vasodilators and ultimately caused death of ~25% of ECs, as evidenced by markedly elevated cytosolic Ca2+ levels (793 ± 75 nM) and uptake of propidium iodide. Removal of extracellular Ca2+ but not depletion of intracellular Ca2+ stores prevented histone-induced Ca2+ signals. Histone-induced signals were not suppressed by transient receptor potential vanilloid 4 (TRPV4) channel inhibition (100 nM GSK2193874) or genetic ablation of TRPV4 channels or Toll-like receptor receptors. These data demonstrate that histones are robust activators of noncanonical EC Ca2+ signaling, which cause vascular dysfunction through loss of endothelium-dependent dilation in resistance-sized MAs. NEW & NOTEWORTHY We describe the first use of the endothelial cell (EC)-specific, ratiometric, genetically encoded Ca2+ indicator, Cx40-GCaMP-GR, to study the effect of histone proteins on EC Ca2+ signaling. We found that histones induce an influx of Ca2+ in ECs that does not cause vasodilation but instead causes Ca2+ overload, EC death, and vascular dysfunction in the form of lost endothelium-dependent dilation.
A Novel ACKR2-Dependent Role of Fibroblast-Derived CXCL14 in Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer
Authors: Sjöberg Elin , Meyrath Max , Milde Laura , Herrera Mercedes , Lövrot John , Hägerstrand Daniel , Frings Oliver , Bartish Margarita , Rolny Charlotte , Sonnhammer Erik , Chevigné Andy , Augsten Martin , Östman Arne 
Published: March 2019

Abstract

Purpose:
Fibroblasts expressing the orphan chemokine CXCL14 have been previously shown to associate with poor breast cancer prognosis and promote cancer growth. This study explores the mechanism underlying the poor survival associations of stromal CXCL14.

Experimental Design:
Tumor cell epithelial-to-mesenchymal transition (EMT), invasion, and metastasis were studied in in vitro and in vivo models together with fibroblasts overexpressing CXCL14. An approach for CXCL14 receptor identification included loss-of-function studies followed by molecular and functional endpoints. The clinical relevance was further explored in publicly available gene expression datasets.

Results:
CXCL14 fibroblasts stimulated breast cancer EMT, migration, and invasion in breast cancer cells and in a xenograft model. Furthermore, tumor cells primed by CXCL14 fibroblasts displayed enhanced lung colonization after tail-vein injection. By loss-of function experiments, the atypical G-protein–coupled receptor ACKR2 was identified to mediate CXCL14-stimulated responses. Downregulation of ACKR2, or CXCL14-induced NOS1, attenuated the pro-EMT and migratory capacity. CXCL14/ACKR2 expression correlated with EMT and survival in gene expression datasets.

Conclusions:
Collectively, the findings imply an autocrine fibroblast CXCL14/ACKR2 pathway as a clinically relevant stimulator of EMT, tumor cell invasion, and metastasis. The study also identifies ACKR2 as a novel mediator for CXCL14 function and thereby defines a pathway with drug target potential.
See related commentary by Zhang et al., p. 3476
Cohort Study Examining the Association Between Blood Pressure and Cardiovascular Events in Patients With Peripheral Artery Disease
Authors: Thomas Manapurathe Diana , Moxon Joseph Vaughan , Krishna Smriti Murali , Rowbotham Sophie , Quigley Frank , Jenkins Jason , Bourke Michael , Bourke Bernard , Jones Rhondda E. , Golledge Jonathan 
Published: March 2019

Background

Hypertension is an important risk factor for cardiovascular events in patients with peripheral artery disease; however, optimal blood pressure targets for these patients are poorly defined. This study investigated the association between systolic blood pressure (
SBP
) and cardiovascular events in a prospectively recruited patient cohort with peripheral artery disease.

Methods and Results

A total of 2773 patients were included and were grouped according to
SBP
at recruitment (≤120 mm Hg, n=604; 121–140 mm Hg, n=1065; and >140 mm Hg, n=1104). Adjusted Cox proportional hazards analyses suggested that patients with
SBP
≤120 mm Hg were at greater risk of having a major cardiovascular event (myocardial infarction, stroke, or cardiovascular death) than patients with
SBP
of 121–140 mm Hg (adjusted hazard ratio, 1.36; 95%
CI,
1.08–1.72;
P
=0.009). Patients with
SBP
>140 mm Hg had an adjusted hazard ratio of 1.23 (95%
CI,
1.00–1.51;
P
=0.051) of major cardiovascular events compared with patients with
SBP
of 121–140 mm Hg. These findings were similar in sensitivity analyses only including patients receiving antihypertensive medications or focused on patients with a minimum of 3 months of follow‐up.

Conclusions

This cohort study suggests that patients with peripheral artery disease and
SBP
≤120 mm Hg are at increased risk of major cardiovascular events. The findings suggest caution in intensive
SBP
lowering in this patient group.
Changes in Extreme Precipitation in the Northeast United States: 1979–2014
Authors: Howarth Macy E. , Thorncroft Christopher D. , Bosart Lance F. 
Published: March 2019

Abstract
Extreme precipitation can have significant adverse impacts on infrastructure and property, human health, and local economies. This paper examines recent changes in extreme precipitation in the northeast United States. Daily station data from 58 stations missing less than 5% of days for the years 1979–2014 from the U.S. Historical Climatology Network were used to analyze extreme precipitation, defined as the top 1% of days with precipitation. A statistically significant (95% confidence level) increasing trend of the threshold for the top 1% of extreme precipitation events was found (0.3 mm yr−1). This increasing trend was due to both an increase in the frequency of extreme events and the magnitude of extreme events. Rainfall events ≥ 150 mm (24-h accumulation) increased in frequency from 6 events between 1979 and 1996 to 25 events between 1997 and 2014, a 317% increase. The annual daily maximum precipitation, or the highest recorded precipitation amount in a given year, increased by an average of 1.6 mm yr−1, a total increase of 58.0 mm. Decreasing trends in extreme precipitation were observed east of Lake Erie during the warm season. Increasing trends in extreme precipitation were most robust during the fall months of September, October, and November, and particularly at locations further inland. The analysis showed that increases in events that were tropical in nature, or associated with tropical moisture, led to the observed increase in extreme precipitation during the fall months.
Origin and Attenuation of Mesoscale Structure in Circumpolar Deep Water Intrusions to an Antarctic Shelf
Authors: McKee Darren C. , Martinson Douglas G. , Schofield Oscar 
Published: March 2019

AbstractCross-isobath transport of Upper Circumpolar Deep Water (UCDW) provides a major source of heat to the Antarctic continental shelves. Adaptive sampling with a Slocum glider revealed that the UCDW regularly intrudes onto the western Antarctic Peninsula shelf within mesoscale eddies, and a linear stability analysis of the shelf-break current upstream confirmed eddy length scales and vertical structure are consistent with the baroclinic instability of the current. The properties of the most unstable mode are insensitive to current orientation but sensitive to bottom slope in accordance with modified Eady theory. Once on the shelf, the eddies’ core properties mix with ambient shelf water to form modified CDW (mCDW). Concurrent shipboard CTD and ADCP data are used to diagnose the responsible mixing processes and highlight the importance of thermohaline intrusions. The genesis mechanism of the interleaving layers cannot be confirmed, however a simple analytic model suggests the upper limit contribution of advection by internal waves cannot account for the observed temperature variance unless the cross-eddy temperature gradient is large. Data-adaptive sampling of an eddy with the glider revealed it lost heat across two isopycnals and a fixed radius at a rate of 7 × 109 J s−1 over 3.9 days. This rate is corroborated by a diffusion model initialized with the eddy’s initial hydrographic properties and informed by the heat fluxes parameterized from the shipboard data. The results suggest eddies predominately lose heat laterally and downward, which preserves subsurface heat for melting of marine-terminating glaciers.
Mechanisms of Barrier Layer Formation and Erosion from In Situ Observations in the Bay of Bengal
Authors: George Jenson V. , Vinayachandran P. N. , Vijith V. , Thushara V. , Nayak Anoop A. , Pargaonkar Shrikant M. , Amol P. , Vijaykumar K. , Matthews Adrian J. 
Published: March 2019

AbstractDuring the Bay of Bengal (BoB) Boundary Layer Experiment (BoBBLE) in the southern BoB, time series of microstructure measurements were obtained at 8°N, 89°E from 4 to 14 July 2016. These observations captured events of barrier layer (BL) erosion and reformation. Initially, a three-layer structure was observed: a fresh surface mixed layer (ML) of thickness 10–20 m; a BL below of 30–40-m thickness with similar temperature but higher salinity; and a high salinity core layer, associated with the Summer Monsoon Current. Each of these three layers was in relative motion to the others, leading to regions of high shear at the interfaces. However, the destabilizing influence of the shear regions was not enough to overcome the haline stratification, and the three-layer structure was preserved. A salinity budget using in situ observations suggested that during the BL erosion, differential advection brought high salinity surface waters (34.5 psu) with weak stratification to the time series location and replaced the three-layer structure with a deep ML (~60 m). The resulting weakened stratification at the time series location then allowed atmospheric wind forcing to penetrate deeper. The turbulent kinetic energy dissipation rate and eddy diffusivity showed elevated values above 10−7 W kg−1 and 10−4 m2 s−1, respectively, in the upper 60 m. Later, the surface salinity decreased again (33.8 psu) through differential horizontal advection, stratification became stronger and elevated mixing rates were confined to the upper 20 m, and the BL reformed. A 1D model experiment suggested that in the study region, differential advection of temperature–salinity characteristics is essential for the maintenance of BL and to the extent to which mixing penetrates the water column.
Dementia with Lewy bodies: Challenges in the diagnosis and management
Authors: Chin Kai Sin , Teodorczuk Andrew , Watson Rosie 
Published: March 2019

Objective: Dementia with Lewy bodies is the second most common form of neurodegenerative dementia in older age yet is often under-recognised and misdiagnosed. This review aims to provide an overview of the clinical features of dementia with Lewy bodies, discussing the frequent challenges clinicians experience in diagnosing dementia with Lewy bodies, and outlines a practical approach to the clinical management, particularly in the Australian setting. Methods: This paper is a narrative review and a semi-structured database (PubMed and MEDLINE) search strategy was implemented. Articles were screened and clinically relevant studies were selected for inclusion. Results: Dementia with Lewy bodies is clinically characterised by complex visual hallucinations, spontaneous motor parkinsonism, prominent cognitive fluctuations and rapid eye movement sleep behaviour disorder. Neuropsychiatric features and autonomic dysfunction are also common. The new diagnostic criteria and specific diagnostic biomarkers help to improve detection rates and diagnostic accuracy, as well as guide appropriate management. Clinical management of dementia with Lewy bodies is challenging and requires an individualised multidisciplinary approach with specialist input. Conclusion: Dementia with Lewy bodies is a common form of dementia. It often presents as a diagnostic challenge to clinicians, particularly at early stages of disease, and in patients with mixed neuropathological changes, which occur in over 50% of people with dementia with Lewy bodies. Prompt diagnosis and comprehensive treatment strategies are important in improving patients’ care.