bluuebunny/crossref_metadata_2025_split huggingface dataset:
CARer-ADministration of as-needed subcutaneous medication for breakthrough symptoms in homebased dying patients (CARiAD): study protocol for a UK-based open randomised pilot trial
Authors: Poolman Marlise , Roberts Jessica , Byrne Anthony , Perkins Paul , Hoare Zoe , Nelson Annmarie , Hiscock Julia , Hughes Dyfrig , Foster Betty , O'Connor Julie , Reymond Liz , Healy Sue , Roberts Rossela , Wee Bee , Lewis Penney , Johnstone Rosalynde , Roberts Sian , Holmes Emily , Wright Stella , Hendry Annie , Wilkinson Clare 
Published: December 2018

Abstract
Background: Whilst the majority of seriously ill people wish to die at home, only half achieve this. The likelihood of someone dying at home often depends on the availability of able and willing lay carers to support them. Dying people are usually unable to take oral medication. When top-up symptom relief medication is required, a clinician travels to the home to administer injectable medication, with attendant delays. The administration of subcutaneous injections by lay carers, though not widespread practice in the UK, has proven key in achieving home deaths in other countries. Our aim is to determine if carer-administration of as-needed subcutaneous medication for four frequent breakthrough symptoms (pain, nausea, restlessness and noisy breathing) in home-based dying patients is feasible and acceptable in the UK.
Methods: The paper describes a randomised pilot trial across three UK sites, with an embedded qualitative study. Dyads of adult patients/carers are eligible, where patients are in the last weeks of life, wish to die at home, and lay carers who are willing to be trained to give subcutaneous medication. Dyads who do not meet strict risk assessment criteria (including known history of substance abuse or carer ability to be trained to competency) will not be approached. Carers in the intervention arm will receive a manualised training package delivered by their local nursing team. Dyads in the control arm will receive usual care. The main outcomes of interest are feasibility, acceptability, recruitment rates, attrition and selection of the most appropriate outcome measures. Interviews with carers and healthcare professionals will explore attitudes to, experiences of and preferences for giving subcutaneous medication and experience of trial processes. The study has obtained full ethical approval.
Discussion: This study will rehearse the procedures and logistics which will be undertaken in a future definitive randomised controlled trial, and will inform the design of such a study. Findings will illuminate methodological and ethical issues pertaining to researching last days of life care.
The study is funded by the National Institute for Health Research (Health Technology Assessment [HTA] project 15/10/37).
Trial registration: ISRCTN, ISRCTN 11211024. Assigned 27 September 2016, http://www.isrctn.com/ISRCTN11211024.
Keywords: End-of-life care, Care of the dying, Palliative care, Symptom control, Carer administration, Randomised pilot trial
Winter Cereal Cover Crops for Spring Forage in Temperate Climates
Authors: Landry E. , Janovicek K. , Lee E. A. , Deen W. 
Published: December 2018

Core Ideas
Barley is not a suitable cover or forage crop for southern Ontario due to winter‐kill.
Flag leaf, boot, and heading of cereal rye are about 1 wk earlier than for wheat or triticale.
Forage quality of winter cereals was high from flag leaf to boot stages.
Nitrogen fertilization (50–67 kg N ha−1) optimized forage yield without affecting quality.
In this study four winter cereals commonly used as cover crops were evaluated for forage yield potential and nutritional quality when harvested in early spring. Wheat (Triticum aestivum L.), triticale (X Triticosecale Wittm.), cereal rye (Secale cereale L.), and barley (Hordeum vulgare L.) were evaluated via experimental plots and on‐farm trials in southern Ontario, Canada, between 2013 and 2015. Barley was the only species that failed to overwinter. The average forage yield of all other winter cereal species was 2.9 Mg ha−1 dry matter (DM) at boot stage with total digestible nutrient (TDN) values above 700 g kg−1 at flag leaf and boot stages of development. At the flag leaf and boot stages of development the fiber content of cereal rye was higher and nonfiber carbohydrates lower than wheat or triticale. However, crude protein (CP) and TDN were indistinguishable among species. Across species and experimental plot site‐years, a spring N application of 50 kg N ha−1 increased forage yield by 0.9 Mg ha−1 DM and CP by 26 g kg−1, but all other quality parameters were unaffected. Additional N fertilization, on‐farm, increased DM yield, but economically optimum N rates remained low, at 42, 50, and 65 kg N ha−1 for cereal rye, triticale, and wheat, respectively. While wheat and triticale may be used as spring forage, the approximately 7d earlier flag leaf or boot stage of cereal rye makes it a better fit for rotations with corn (Zea mays L.) and soybean [Glycine max (L.) Merr].
Can a Mixture of Perennial Grasses with Contrasting Growth Strategies Compose Productive and Stable Swards?
Authors: Duchini Paulo Gonçalves , Guzatti Gabriela Cristina , Echeverria Joilson Roda , Américo Luana Fidelis , Sbrissia André Fischer 
Published: December 2018

Core Ideas
Mixing grass forage species can increase forage yield and stability.
Overyielding was more influenced by increasing leaf biomass rather than stem biomass.
Dominant grasses with contrasting growth strategies can compose productive and stable pastures.
Mixtures composed of species with different growth strategies (e.g., exploitative and conservative), which have different abilities for resource capture and use, are thought to improve grassland ecosystem services. However, plant species that compete better for limiting resources can become dominant. This study examined whether potential dominant perennial grasses with different growth strategies can compose productive and stable forage mixtures under low competition for resources (nutrients and light). Arrhenatherum elatius L. (exploitative), Festuca arundinacea Schreb. (conservative), and Dactylis glomerata L. (moderately exploitative) were sowed as monocultures and as a three‐species mixture. Pastures were fertilized to maintain high soil fertility levels and mowed by half when their canopies reached 20 cm in height (95% of light interception in the vegetative stage) allowing for over 2 yr of data collection. The proportion of each species in the mixture remained unaltered throughout the experimental period. Transgressive overyielding was not observed; however, the mixture presented a similar yield to the most productive monocultures (10,200 kg DM ha−1 yr−1), although D. glomerata, which presented the lowest yield in monoculture (6400 kg DM ha−1 yr−1), comprised 68.1% of post‐cutting biomass in the mixture. Arrhenatherum elatius and F. arundinacea populations presented less yield variance in monoculture, but higher yield stability was observed in the mixture. Overyielding in the three studied species was strongly affected by leaf production. Mixtures composed of perennial grasses with different growth strategies when grown in nutrient‐rich soil and under conditions of low light competition can compose productive and stable swards, while maximizing leaf production.
Effects of Seed‐Placed Hog Manure‐Recovered Struvite on Canola Seedling Emergence
Authors: Katanda Yeukai , Zvomuya Francis , Flaten Don , Cicek Nazim , Amarakoon Inoka 
Published: December 2018

Core Ideas
Struvite and coated monoammonium phosphate did not cause significant seedling toxicity regardless of rate.
Monoammonium phosphate reduced canola seedling emergence in the clay loam at high P rate (15 mg kg−1).
Final emergence count decreased in the order: struvite (88%) > CMAP (86%) > MAP (69%).
Struvite can be applied at higher rates than monoammonium phosphate with minimal risk of seedling damage.
Seedling toxicity is a major limitation to P fertilizer rates that can be seed‐placed with sensitive crops such as canola (Brassica napus L.). In this growth room bioassay, we tested whether struvite recovered from liquid hog (Sus domesticus L.) manure could improve seedling emergence in canola relative to monoammonium phosphate (MAP) and polymer‐coated monoammonium phosphate (CMAP). Twenty canola seeds per pot were planted in two low‐P soils (a Gleyed Regosolic sand [Entisol] and an Orthic Black Chernozemic clay loam [Udic Boroll]). The P sources were applied in the seedrow at rates of 7.5 or 15 mg P kg−1 soil (∼25 or 50 kg P2O5 ha−1), either at 5.4 or 10.9% seedbed utilization (SBU). Final emergence (percent of seeds planted), emergence rate, and lag were predicted using the Gompertz function. The higher rate of MAP reduced overall seedling emergence by 47% in the clay loam and 34% in the sand while the slow‐release P sources, struvite and CMAP, showed no significant evidence of seedling toxicity in either soil. Emergence was 0.6 d faster with struvite than with MAP, regardless of soil or P rate. Averaged across soils, SBUs, and P rates, final emergence decreased in the order: struvite (87%) > CMAP (86%) > MAP (69%), indicating the superiority of struvite and CMAP with respect to seedling toxicity. These results indicate that struvite can be seed‐placed at higher rates than those recommended for MAP on canola, with a much lower risk of seedling damage, thereby minimizing yield losses and replanting costs.
SNO KARST: A French Network of Observatories for the Multidisciplinary Study of Critical Zone Processes in Karst Watersheds and Aquifers
Authors: Jourde H. , Massei N. , Mazzilli N. , Binet S. , Batiot-Guilhe C. , Labat D. , Steinmann M. , Bailly-Comte V. , Seidel J.L. , Arfib B. , Charlier J.B. , Guinot V. , Jardani A. , Fournier M. , Aliouache M. , Babic M. , Bertrand C. , Brunet P. , Boyer J.F. , Bricquet J.P. , Camboulive T. , Carrière S.D. , Celle-Jeanton H. , Chalikakis K. , Chen N. , Cholet C. , Clauzon V. , Soglio L. Dal , Danquigny C. , Défargue C. , Denimal S. , Emblanch C. , Hernandez F. , Gillon M. , Gutierrez A. , Sanchez L. Hidalgo , Hery M. , Houillon N. , Johannet A. , Jouves J. , Jozja N. , Ladouche B. , Leonardi V. , Lorette G. , Loup C. , Marchand P. , de Montety V. , Muller R. , Ollivier C. , Sivelle V. , Lastennet R. , Lecoq N. , Maréchal J. C. , Perotin L. , Perrin J. , Petre M.A. , Peyraube N. , Pistre S. , Plagnes V. , Probst A. , Probst J.L. , Simler R. , Stefani V. , Valdes-Lao D. , Viseur S. , Wang X. 
Published: December 2018

Core Ideas
SNO KARST is dedicated to the study of karst functioning.
Hydrodynamics and geochemistry are measured at springs and in karst compartments.
Process sampling was set up at nine sites in various climatic contexts.
Continuous monitoring concerns timescales from 10 to >50 yr.
New tools and findings are due to the complementarity of gathered data.
Karst aquifers and watersheds represent a major source of drinking water around the world. They are also known as complex and often highly vulnerable hydrosystems due to strong surface–groundwater interactions. Improving the understanding of karst functioning is thus a major issue for the efficient management of karst groundwater resources. A comprehensive understanding of the various processes can be achieved only by studying karst systems across a wide range of spatiotemporal scales under different geological, geomorphological, climatic, and soil cover settings. The objective of the French Karst National Observatory Service (SNO KARST) is to supply the international scientific community with appropriate data and tools, with the ambition of (i) facilitating the collection of long‐term observations of hydrogeochemical variables in karst, and (ii) promoting knowledge sharing and developing cross‐disciplinary research on karst. This paper provides an overview of the monitoring sites and collective achievements, such as the KarstMod modular modeling platform and the PaPRIKa toolbox, of SNO KARST. It also presents the research questions addressed within the framework of this network, along with major research results regarding (i) the hydrological response of karst to climate and anthropogenic changes, (ii) the influence of karst on geochemical balance of watersheds in the critical zone, and (iii) the relationships between the structure and hydrological functioning of karst aquifers and watersheds.
Water Stress in Maize Production in the Drylands of the Loess Plateau
Authors: Zhu Wei , Li Huijie , Qu Hongchao , Wang Yilin , Misselbrook Tom , Li Xiao , Jiang Rui 
Published: December 2018

Core Ideas
HYDRUS‐1D was successfully used to simulate the change in soil water in a 0–200‐cm soil profile.
We quantified the process of soil water balance in detail during the maize growing season.
This study indicated the plow pan's effect on soil water storage.
Water stress during two maize (Zea mays L.) growing seasons (2013 and 2014) was investigated in a semiarid region of northwest China. The HYDRUS‐1D model gave good simulation of the soil water content in different layers throughout a 0‐ to 200‐cm depth during the maize growing season, with R2 values of 70.6 and 77.0% for the calibration and validation periods, respectively. Water stress for maize production was observed in June of 2013 and in July of 2014. The soil water storage (SWS) decreased significantly during the early stage of the maize growing season, especially in 2014. The root depth and crop height were 20 cm deeper and 100 cm higher, respectively, in 2014 than in 2013 at the early stage. These results suggest that in the early stage of the maize growing season, pre‐seeding SWS can alleviate crop water stress effectively via deep roots. Model simulation showed that the plow pan layer (at a depth of 20–40 cm), with high soil bulk density and a lower soil water retention curve, significantly reduced infiltration. High evapotranspiration and low precipitation result in a temporary dry layer during the early stage, highlighting the plow pan as the sensitive layer for water stress during the drought period. Effective management practices such as deep plowing, plastic film mulching, or water conservation treatments in the fallow period are needed to avoid the formation of this temporary dry layer during the drought period at the early stage and thus improve maize production in rainfed agriculture on the Loess Plateau of China.
A Century of Denial: Preferential and Nonequilibrium Water Flow in Soils, 1864‐1984
Authors: Beven Keith 
Published: December 2018

Core Ideas
In the 20th century there was a general denial of the evidence for preferential flow.
The development of models of preferential flow is reviewed.
Some critical areas for future research in this field are identified.
This review provides a historical summary of the development of knowledge on preferential and non‐equilibrium flows in soils, particularly in the period 1864 to 1984. It is pointed out that preferential flows were recognized long before the equilibrium concepts of Edgar Buckingham and Lorenzo A. Richards were developed and became the dominant underpinnings of soil physics in the 20th century, effectively in denial of all the evidence that the Buckingham–Richards theory was inadequate to deal with water flows in field soils. Summaries of evidence from soil microscopy, tracing and breakthrough curve experiments, infiltration and throughflow observations, and studies of natural pipes are presented. Approaches to modeling preferential flows at soil profile and hillslope responses are also reviewed, including viscous flow theory and particle tracking methods. Further research is required into the integration of viscosity and capillarity‐dominated flows, into nonlaminar flows in larger pores, and into upscaling from core and profile experiments to larger hillslope scales. Also, more rigorous hypothesis testing is required in soil physics and hillslope hydrology using both flow and tracer data. This might lead to a new paradigm in representing the detail complexity of flow in soils in applications at larger scales.
Toward Better Understanding of Terrestrial Processes through Long‐Term Hydrological Observatories
Authors: Bogena H.R. , White T. , Bour O. , Li X. , Jensen K.H. 
Published: December 2018

Core Ideas
Awareness of hydrological observatories needs to be increased.
These 23 papers document hydrological observatories on four continents.
Hydrological observatories can help to solve relevant and important scientific questions.
Observation of hydrological processes has a long‐standing tradition covering various climatic, hydrologic, geologic, and geomorphologic conditions. Hydrological observations are either organized in dedicated observatories focused on hydrology or within larger environmental observatories that address processes from the atmosphere to the groundwater. In this special section, we document hydrological observations currently conducted in long‐term hydrological observatories and other multidisciplinary observatories across the world. Besides monitoring basic climatic and hydrological variables, dedicated experiments are performed in many of these observatories. Hydrological observatories have proven to be crucial for the advance of the hydrological and greater Earth surface and environmental sciences. The accrued benefits include the development of integrated hydrological models that consider complex feedbacks between hydrological compartments. It is of utmost importance to increase awareness and knowledge of these infrastructures to optimize exploration of new hypotheses in hydrology and neighboring and allied disciplines. This special section consists of 23 papers documenting hydrological observatories on four continents covering diverse environmental conditions and research aspects of catchment science. We expect that the use of worldwide long‐term hydrological observatories across multiple compartments will help to solve important relevant scientific and societal questions.
An Integrated Feature Selection Algorithm for Cancer Classification using Gene Expression Data
Authors: Ahmed Saeed , Kabir Muhammad , Ali Zakir , Arif Muhammad , Ali Farman , Yu Dong-Jun 
Published: December 2018

Aim and Objective:
Cancer is a dangerous disease worldwide, caused by somatic
mutations in the genome. Diagnosis of this deadly disease at an early stage is exceptionally new
clinical application of microarray data. In DNA microarray technology, gene expression data have a
high dimension with small sample size. Therefore, the development of efficient and robust feature
selection methods is indispensable that identify a small set of genes to achieve better classification
performance.

Materials and Methods:
In this study, we developed a hybrid feature selection method that
integrates correlation-based feature selection (CFS) and Multi-Objective Evolutionary Algorithm
(MOEA) approaches which select the highly informative genes. The hybrid model with Redial base
function neural network (RBFNN) classifier has been evaluated on 11 benchmark gene expression
datasets by employing a 10-fold cross-validation test.

Results:
The experimental results are compared with seven conventional-based feature selection and
other methods in the literature, which shows that our approach owned the obvious merits in the
aspect of classification accuracy ratio and some genes selected by extensive comparing with other
methods.

Conclusion:
Our proposed CFS-MOEA algorithm attained up to 100% classification accuracy for
six out of eleven datasets with a minimal sized predictive gene subset.
Synthesis, Plasmodium falciparum Inhibitory Activity, Cytotoxicity and Solubility of N2 ,N4 -Disubstituted Quinazoline-2,4-diamines.
Authors: Pobsuk Nattakarn , Suphakun Praphasri , Hannongbua Supa , Nantasenamat Chanin , Choowongkomon Kiattawee , Gleeson M. Paul 
Published: December 2018

Background:
Despite the development of extensive control strategies and treatment options,
approximately 200 million malaria cases, leading to approximately 450,000 deaths, were reported
in 2015. Due to issue of disease resistance, additional drug development efforts are needed
to produce new, more effective treatments. Quinazoline-2,4-diamines were identified as antiparasitic
compounds over three decades ago and have remained of interest to date in industry and
academia.

Objective:
An anti-malarial SAR evaluation of previously unreported N2
,N4
-disubstituted quinazoline-
2,4-diamines have been undertaken in this study. We have synthesized and evaluated new
derivatives against P. falciparum in our attempt to better characterize their biological activity and
overall physical properties.

Methods:
The synthesis of N2
,N4
-disubstituted quinazoline-2,4-diamines inhibitors is reported
along with activities in a radioactive labeled hypoxanthine incorporation assay against the f Plasmodium
falciparum (Pf.) K1 strain. In addition, cytotoxicity was determined in the A549 and Vero
cell lines using an MTT based. The aqueous solubility of key compounds was assessed at pH 7.4
using a shake flask-based approach.

Results:
We identified compounds 1 and 6p as sub µM inhibitors of P. falciparum, having equivalent
anti-malarial activity to Chloroquine. Compounds 1 and 6m are low µM inhibitors of P. falciparum
with improved cytotoxicity profiles. Compound 6m displayed the best balance between P.
falciparum Inhibitory activity (2 µM) and cytotoxicity, displaying >49 fold selectivity over A549
and Vero cell lines.

Conclusion:
Twenty one N2
,N4
-Disubstituted Quinazoline-2,4-diamines have been prepared in our
group and characterized in terms of their antimalarial activity, cytotoxicity and physical properties.
Compounds with good activity and reasonable selectivity over mammalian cell lines have been
identified. SAR analyses suggest further exploration is are necessary to improve the balance of P.
falciparum Inhibitory activity, cytotoxicity and solubility.
Discovery of N-Phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine Derivatives as Potent Mnk2 Inhibitors: Design, Synthesis, SAR Analysis, and Evaluation of in vitro Anti-leukaemic Activity
Authors: Abdelaziz Ahmed M. , Diab Sarah , Islam Saiful , Basnet Sunita K.C. , Noll Benjamin , Li Peng , Mekonnen Laychiluh B. , Lu Jingfeng , Albrecht Hugo , Milne Robert W. , Gerber Cobus , Yu Mingfeng , Wang Shudong 
Published: December 2018

Background:Aberrant expression of eukaryotic translation initiation factor 4E (eIF4E) is common in many types of cancer including acute myeloid leukaemia (AML). Phosphorylation of eIF4E by MAPK-interacting kinases (Mnks) is essential for the eIF4E-mediated oncogenic activity. As such, the pharmacological inhibition of Mnks can be an effective strategy for the treatment of cancer.Methods:A series of N-phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine derivatives was designed and synthesised. The Mnk inhibitory activity of these derivatives as well as their anti-proliferative activity against MV4-11 AML cells was determined.Results:These compounds were identified as potent Mnk2 inhibitors. Most of them demonstrated potent anti-proliferative activity against MV4-11 AML cells. The cellular mechanistic studies of the representative inhibitors revealed that they reduced the level of phosphorylated eIF4E and induced apoptosis by down-regulating the anti-apoptotic protein myeloid cell leukaemia 1 (Mcl-1) and by cleaving poly(ADP-ribose)polymerase (PARP). The lead compound 7k possessed desirable pharmacokinetic properties and oral bioavailability.Conclusion:This work proposes that exploration of the structural diversity in the context of Nphenyl- 4-(1H-pyrrol-3-yl)pyrimidin-2-amine would offer potent and selective Mnk inhibitors.