bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital innovation evaluation: user perceptions of innovation readiness, digital confidence, innovation adoption, user experience and behaviour change
Authors: Benson Tim 
Published: June 2019

BackgroundInnovation spread is a key policy objective for health systems world-wide, but adoption success varies enormously. We have developed a set of short generic user-reported measures to help understand how and why healthcare innovations spread. This work builds on the literature and on practical experience in developing and using patient-reported outcome measures.MeasuresTheInnovation Readiness Scoremeasures user perceptions of how much they are open to and up-to-date with new ideas, and whether their organisations are receptive to and capable of innovation. It is based on Rogers’ classification of innovativeness (innovator, early adopter, early majority, etc).TheDigital Confidence Scorerates users’ digital literacy and confidence to use digital products, with dimensions of familiarity, social pressure, support and digital self-efficacy.TheInnovation Adoption Scorerates the adoption process in terms of coherence and reflective thought before, during and after implementation. It is based on Normalisation Process Theory.TheUser Satisfactionmeasure assesses a digital product in terms of usefulness, ease of use, support and satisfaction.TheBehaviour Changemeasure covers user perceptions of their capability, opportunity and motivation to change behaviour, based on the COM-B model.These measures have been mapped onto Greenhalgh’s NASSS Framework (non-adoption, abandonment and challenges to scale-up, spread and sustainability of health and care technologies).ConclusionThese tools measure different aspects of digital health innovations and may help predict the success of innovation dissemination, diffusion and spread programmes.
Developing a telerehabilitation programme for postoperative recovery from knee surgery: specifications and requirements
Authors: Naeemabadi MReza , Dinesen Birthe , Andersen Ole Kæseler , Madsen Niels Kragh , Simonsen Ole Højgaard , Hansen John 
Published: June 2019

IntroductionTelerehabilitation programmes have been attracting increasing attention as a potential alternative to conventional rehabilitation. Video conferencing can facilitate communication between healthcare professionals and patients. However, in certain cases, video conferencing may face practical limitations. As an alternative to real-time conferencing, sensor-based technologies can transmit the acquired data to healthcare providers. This study aimed to design and develop a sensor-based telerehabilitation programme and to outline the corresponding requirements for such a system.DevelopmentThe development of the sensor-based telerehabilitation programme was carried out based on user needs. The programme includes a portable platform for the patient as well as a web-based platform for the healthcare professional, thus allowing for an individualised rehabilitation programme. Communication, training, reporting, and information services were provided for the patients. Moreover, the portability and usability of the programme were enhanced by utilising the system in offline mode as well.ApplicationThe programme is currently being tested in the North Denmark Region to assess the feasibility and acceptance of a telerehabilitation programme as an alternative solution to the self-training programme for patients who have been discharged from knee surgery. The preliminary results of our assessment showed a high level of acceptance among the users.DiscussionIn this study, a semi-online sensor-based telerehabilitation programme was tested. It is argued that a similar sensor-based telerehabilitation programme can be utilised as an alternative solution for self-training rehabilitation in the future; however; further studies and development are required to ensure the quality and reliability of sensor-based services.
Morphological classification of pancreatic ductal adenocarcinoma that predicts molecular subtypes and correlates with clinical outcome
Authors: N Kalimuthu Sangeetha , Wilson Gavin W , Grant Robert C , Seto Matthew , O’Kane Grainne , Vajpeyi Rajkumar , Notta Faiyaz , Gallinger Steven , Chetty Runjan 
Published: June 2019

IntroductionTranscriptional analyses have identified several distinct molecular subtypes in pancreatic ductal adenocarcinoma (PDAC) that have prognostic and potential therapeutic significance. However, to date, an indepth, clinicomorphological correlation of these molecular subtypes has not been performed. We sought to identify specific morphological patterns to compare with known molecular subtypes, interrogate their biological significance, and furthermore reappraise the current grading system in PDAC.DesignWe first assessed 86 primary, chemotherapy-naive PDAC resection specimens with matched RNA-Seq data for specific, reproducible morphological patterns. Differential expression was applied to the gene expression data using the morphological features. We next compared the differentially expressed gene signatures with previously published molecular subtypes. Overall survival (OS) was correlated with the morphological and molecular subtypes.ResultsWe identified four morphological patterns that segregated into two components (‘gland forming’ and ‘non-gland forming’) based on the presence/absence of well-formed glands. A morphological cut-off (≥40% ‘non-gland forming’) was established using RNA-Seq data, which identified two groups (A and B) with gene signatures that correlated with known molecular subtypes. There was a significant difference in OS between the groups. The morphological groups remained significantly prognostic within cancers that were moderately differentiated and classified as ‘classical’ using RNA-Seq.ConclusionOur study has demonstrated that PDACs can be morphologically classified into distinct and biologically relevant categories which predict known molecular subtypes. These results provide the basis for an improved taxonomy of PDAC, which may lend itself to future treatment strategies and the development of deep learning models.
Identification of Novel RAS Signaling Therapeutic Vulnerabilities in Diffuse Intrinsic Pontine Gliomas
Authors: Koncar Robert F. , Dey Brittany R. , Stanton Ann-Catherine J. , Agrawal Nishant , Wassell Michelle L. , McCarl Lauren H. , Locke Abigail. L. , Sanders Lauren , Morozova-Vaske Olena , Myers Max I. , Hamilton Ronald L. , Carcaboso Angel M. , Kohanbash Gary , Hu Baoli , Amankulor Nduka M. , Felker James , Kambhampati Madhuri , Nazarian Javad , Becher Oren J. , James C. David , Hashizume Rintaro , Broniscer Alberto , Pollack Ian F. , Agnihotri Sameer 
Published: June 2019

Abstract

Diffuse intrinsic pontine gliomas (DIPG) are incurable brain tumors with an aggressive onset. Apart from irradiation, there are currently no effective therapies available for patients with DIPG, who have a median survival time of less than one year. Most DIPG cells harbor mutations in genes encoding histone H3 (H3K27M) proteins, resulting in a global reduction of H3K27 trimethylation and activation of oncogenic signaling pathways. Here we show that the H3K27M mutations contribute to RAS pathway signaling, which is augmented by additional RAS activators including PDGFRA. H3K27M mutation led to increased expression of receptor tyrosine kinases (RTK). A RAS pathway functional screen identified ERK5, but not ERK1/2, as a RAS pathway effector important for DIPG growth. Suppression of ERK5 decreased DIPG cell proliferation and induced apoptosis in vitro and in vivo. In addition, depletion or inhibition of ERK5 significantly increased survival of mice intracranially engrafted with DIPG cells. Mechanistically, ERK5 directly stabilized the proto-oncogene MYC at the protein level. Collectively, our data demonstrate an underappreciated role of H3K27M in RAS activation and reveal novel therapeutic targets for treating DIPG tumors.

Significance:
These findings identify the H3K27M mutation as an enhancer of RAS activation in DIPG and ERK5 as a novel, immediately actionable molecular target.
Where Sin3a Meets STAT3: Balancing STAT3-Mediated Transcriptional Activation and Repression
Authors: Monteleone Emanuele , Poli Valeria 
Published: June 2019

Abstract
STAT3 can mediate epigenetic silencing of tumor suppressor genes (TSG). However, little is known about the molecular mechanisms involved, except that this action is mediated by DNA methylation and requires STAT3 acetylation. In this issue of Cancer Research, Gambi and colleagues confirm that oncogene-driven constitutive STAT3 acetylation is responsible for TSG silencing. Furthermore, they show that the Sin3a transcriptional repressor complex is an obligatory partner of STAT3 on the promoters of the repressed genes, shedding light on the mechanisms involved in STAT3-mediated transcriptional repression, and more importantly, identifying that the STAT3–Sin3a axis is a potential selective therapeutic target in STAT3-dependent tumors.
See related article by Gambi et al., p. 3076
Biomarker Predictors of Adverse Acute Kidney Injury Outcomes in Critically Ill Patients: The Dublin Acute Biomarker Group Evaluation Study
Authors: McMahon Blaithin A. , Galligan Marie , Redahan Lynn , Martin Terri , Meaney Edel , Cotter Eoin J. , Murphy Niamh , Hannon Claire , Doran Peter , Marsh Brian , Nichol Alistair , Murray Patrick T. 
Published: June 2019

<b><i>Background:</i></b> The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective 2-center observational study investigating the utility of urinary biomarker combinations for the diagnostic and prognostic assessment of acute kidney injury (AKI) in a heterogeneous adult intensive care unit (ICU) population. The objective of this study is to evaluate whether serial urinary biomarker measurements, in combination with a simple clinical model, could improve biomarker performance in the diagnostic prediction of severe AKI and clinical outcomes such as death and need for renal replacement therapy (RRT). <b><i>Methods:</i></b> Urine was collected daily from patients admitted to the ICU, for a total of 7 post-admission days. Urine biomarker concentrations (neutrophil gelatinase-associated lipocalin [NGAL], α-glutathione S-transferase [GST], π-GST, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], Cystatin C, creatinine, and albumin) were measured. Urine biomarkers were combined with a clinical prediction of AKI model, to determine ability to predict AKI (any stage, within 2 days or 7 days of ICU admission), or a ­30-day composite clinical outcome (RRT – or death). <b><i>Results:</i></b> A total of 257 (38%) patients developed AKI within 7 days of ICU admission. Of those who developed AKI, 106 (41%) patients met stage 3 AKI within 7 days of ICU admission and 208 patients of the entire study cohort (31%) met the composite clinical endpoint of in-hospital mortality or RRT within 30 days of ICU admission. The addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI (area under the curve [AUC] of 0.9 from 0.87, <i>p</i> = 0.369) and the prediction of 30-day RRT or death (AUC 0.83 from 0.79, <i>p</i> = 0.139). <b><i>Conclusion:</i></b> A clinical model incorporating severity of illness, patient demographics, and chronic illness with currently available clinical biomarkers of renal function was strongly predictive of development of AKI and associated clinical outcomes in a heterogeneous adult ICU population. The addition of urinary NGAL/albumin to this simple clinical model improved the prediction of severe AKI, need for RRT and death, but not at a statistically or clinically significant level, when compared to the clinical model alone.
Coronary Artery Calcium From Early Adulthood to Middle Age and Left Ventricular Structure and Function
Authors: Yared Guilherme S. , Moreira Henrique T. , Ambale-Venkatesh Bharath , Vasconcellos Henrique D. , Nwabuo Chike C. , Ostovaneh Mohammad R. , Reis Jared P. , Lloyd-Jones Donald M. , Schreiner Pamela J. , Lewis Cora E. , Sidney Stephen , Carr John J. , Gidding Samuel S. , Lima João A.C. 
Published: June 2019

Background:
The relationship of coronary artery calcium (CAC) with adverse cardiac remodeling is not well established. We aimed to study the association of CAC in middle age and change in CAC from early adulthood to middle age with left ventricular (LV) function.

Methods:
CAC score was measured by computed tomography at CARDIA study (Coronary Artery Risk Development in Young Adults) year-15 examination and at year-25 examination (Y25) in 3043 and 3189 participants, respectively. CAC score was assessed as a continuous variable and log-transformed to account for nonlinearity. Change in CAC from year-15 examination to Y25 was evaluated as the absolute difference of log-transformed CAC from year-15 examination to Y25. LV structure and function were evaluated by echocardiography at Y25.

Results:

At Y25, mean age was 50.1±3.6 years, 56.6% women, 52.4% black. In the multivariable analysis at Y25, higher CAC was related to higher LV mass (β=1.218; adjusted
P
=0.007), higher LV end-diastolic volume (β=0.811; adjusted
P
=0.007), higher LV end-systolic volume (β=0.350; adjusted
P
=0.048), higher left atrial volume (β=0.214; adjusted
P
=0.009), and higher E/e′ ratio (β=0.059; adjusted
P
=0.014). CAC was measured at both year-15 examination and Y25 in 2449 individuals. Higher change in CAC score during follow-up was independently related to higher LV mass index in blacks (β=4.789; adjusted
P
<0.001), but not in whites (β=1.051; adjusted
P
=0.283).

Conclusions:
Higher CAC in middle age is associated with higher LV mass and volumes and worse LV diastolic function. Being free of CAC from young adulthood to middle age correlates to better LV function at middle age. Higher change in CAC score during follow-up is independently related to higher LV mass index in blacks.
Improving Lake-Breeze Simulation with WRF Nested LES and Lake Model over a Large Shallow Lake
Authors: Zhang Xiaoyan , Huang Jianping , Li Gang , Wang Yongwei , Liu Cheng , Zhao Kaihui , Tao Xinyu , Hu Xiao-Ming , Lee Xuhui 
Published: June 2019

AbstractThe Weather Research and Forecasting (WRF) Model is used in large-eddy simulation (LES) mode to investigate a lake-breeze case occurring on 12 June 2012 over the Lake Taihu region of China. Observational data from 15 locations, wind profiler radar, and the Moderate Resolution Imaging Spectroradiometer (MODIS) are used to evaluate the WRF nested-LES performance in simulating lake breezes. Results indicate that the simulated temporal and spatial variations of the lake breeze by WRF nested LES are consistent with observations. The simulations with high-resolution grid spacing and the LES scheme have a high correlation coefficient and low mean bias when evaluated against 2-m temperature, 10-m wind, and horizontal and vertical lake-breeze circulations. The atmospheric boundary layer (ABL) remains stable over the lake throughout the lake-breeze event, and the stability becomes even stronger as the lake breeze reaches its mature stage. The improved ABL simulation with LES at a grid spacing of 150 m indicates that the non-LES planetary boundary layer parameterization scheme does not adequately represent subgrid-scale turbulent motions. Running WRF fully coupled to a lake model improves lake-surface temperature and consequently the lake-breeze simulations. Allowing for additional model spinup results in a positive impact on lake-surface temperature prediction but is a heavy computational burden. Refinement of a water-property parameter used in the Community Land Model, version 4.5, within WRF and constraining the lake-surface temperature with observational data would further improve lake-breeze representation.
How Does Latent Cooling Affect Baroclinic Development in an Idealized Framework?
Authors: Haualand Kristine F. , Spengler Thomas 
Published: June 2019

Abstract
Latent cooling by evaporating or melting hydrometeors has recently been shown to contribute to the positive low-level potential vorticity (PV) anomaly below the layer of latent heating in midlatitude cyclones. While the low-level PV anomaly might be intensified by latent cooling, the influence on the overall baroclinic development remains unclear. Including both latent heating and cooling in the Eady model, this study finds that latent cooling reduces baroclinic growth. While the PV anomaly between the layers of latent cooling and heating increases for realistic heating intensities, the PV anomaly at the top of the heating layer decreases, as latent heating is weakened because of reduced vertical motion within the cyclone. Consequently, the relative contribution from diabatic heating to the generation of eddy available potential energy decreases when latent cooling is included. Thus, despite the recently emphasized role of evaporation for the low-level PV anomaly in developing cyclones, the overall effect of latent cooling is detrimental to baroclinic growth.
Interdecadal Change in the Intensity of Interannual Variation of Spring Precipitation over Southern China and Possible Reasons
Authors: Xu Chao , Qiao Yunting , Jian Maoqiu 
Published: June 2019

AbstractThe intensity of interannual variation of spring precipitation over southern China during 1979–2014 and possible reasons for it are investigated in this paper. There is a significant interdecadal change in the intensity of interannual variation of spring precipitation over southern China around 1995/96. The intensity of interannual variation of spring rainfall over South China is stronger during 1979–95 than that during 1996–2014. The possible reason may be the larger amplitude of the sea surface temperature anomaly (SSTA) in the western Pacific Ocean (WP) before 1995/96. The cooler (warmer) SSTA in WP may trigger an abnormal local anticyclone (cyclone) at lower levels. The anomalous southwesterly (northeasterly) flow at the northwestern flank of the WP anticyclone (cyclone) covers South China, transporting more (less) moisture to South China. Meanwhile, the anomalous winds converge (diverge) in South China at lower levels and diverge (converge) at upper levels, which causes the anomalous ascent (descent) to enhance (reduce) the precipitation over there. However, during 1996–2014, the intensity of interannual variation of spring rainfall over the middle and lower reaches of the Yangtze River valley becomes much stronger than that during 1979–95, which is related to the intensified interannual variation of the atmospheric circulation in the middle and high latitudes over Eurasia. The weak (strong) Siberian high and East Asian trough may reduce (enhance) the northerly wind from the middle and high latitudes. As a result, the middle and lower reaches of the Yangtze River valley are subjected to the anomalous southerly wind, favoring more (less) precipitation over there.
Projected Slowdown of Antarctic Bottom Water Formation in Response to Amplified Meltwater Contributions
Authors: Lago Véronique , England Matthew H. 
Published: June 2019

Abstract
The sinking and recirculation of Antarctic Bottom Water (AABW) are a major regulator of the storage of heat, carbon, and nutrients in the ocean. This sinking is sensitive to changes in surface buoyancy, in particular because of freshening since salinity plays a greater role in determining density at cold temperatures. Acceleration in Antarctic ice-shelf and land-ice melt could thus significantly impact the ventilation of the world’s oceans, yet future projections do not usually include this effect in models. Here we use an ocean–sea ice model to investigate the potential long-term impact of Antarctic meltwater on ocean circulation and heat storage. The freshwater forcing is derived from present-day estimates of meltwater input from drifting icebergs and basal melt, combined with RCP2.6, RCP4.5, and RCP8.5 scenarios of projected amplification of Antarctic meltwater. We find that the additional freshwater induces a substantial slowdown in the formation rate of AABW, reducing ventilation of the abyssal ocean. Under both the RCP4.5 and RCP8.5 meltwater scenarios, there is a near-complete shutdown of AABW formation within just 50 years, something that is not captured by climate model projections. The abyssal overturning at ~30°S also weakens, with an ~20-yr delay relative to the onset of AABW slowdown. After 200 years, up to ~50% of the original volume of AABW has disappeared as a result of abyssal warming, induced by vertical mixing in the absence of AABW ventilation. This result suggests that climate change could induce the disappearance of present-day abyssal water masses, with implications for the global distribution of heat, carbon, and nutrients.
Separating the Impact of Individual Land Surface Properties on the Terrestrial Surface Energy Budget in both the Coupled and Uncoupled Land–Atmosphere System
Authors: Laguë Marysa M. , Bonan Gordon B. , Swann Abigail L. S. 
Published: June 2019

AbstractChanges in the land surface can drive large responses in the atmosphere on local, regional, and global scales. Surface properties control the partitioning of energy within the surface energy budget to fluxes of shortwave and longwave radiation, sensible and latent heat, and ground heat storage. Changes in surface energy fluxes can impact the atmosphere across scales through changes in temperature, cloud cover, and large-scale atmospheric circulation. We test the sensitivity of the atmosphere to global changes in three land surface properties: albedo, evaporative resistance, and surface roughness. We show the impact of changing these surface properties differs drastically between simulations run with an offline land model, compared to coupled land–atmosphere simulations that allow for atmospheric feedbacks associated with land–atmosphere coupling. Atmospheric feedbacks play a critical role in defining the temperature response to changes in albedo and evaporative resistance, particularly in the extratropics. More than 50% of the surface temperature response to changing albedo comes from atmospheric feedbacks in over 80% of land areas. In some regions, cloud feedbacks in response to increased evaporative resistance result in nearly 1 K of additional surface warming. In contrast, the magnitude of surface temperature responses to changes in vegetation height are comparable between offline and coupled simulations. We improve our fundamental understanding of how and why changes in vegetation cover drive responses in the atmosphere, and develop understanding of the role of individual land surface properties in controlling climate across spatial scales—critical to understanding the effects of land-use change on Earth’s climate.
Feasibility RCT protocol evaluating a powered-wheelchair training program for older adults
Authors: Smith Emma M. , Miller William C. , Mortenson W. Ben , Mihailidis Alex 
Published: June 2019

Background. Powered-wheelchair use improves participation for people with mobility limitations; however, many individuals do not receive powered-wheelchair skills training that meets their learning needs. Purpose. The aim of this work is to evaluate the feasibility of a powered-wheelchair training program for older adults with cognitive impairment, using errorless learning strategies facilitated by shared control technology. Method. A feasibility 2 × 2 factorial randomized controlled trial will recruit 32 older adults in residential care with mild to moderate cognitive impairment who are new powered-wheelchair use. The intervention consists of six or 12 training sessions, facilitated by shared control technology, using errorless learning techniques. Control participants will receive six or 12 training sessions using trial-and-error methods. Feasibility and clinical outcomes data (primary outcome: powered-wheelchair skills) will be collected. Implications. Errorless learning facilitated by shared control technology may be an alternative to meet the powered-wheelchair learning needs of older adults with cognitive impairments.