bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solar-powered oxygen delivery for the treatment of children with hypoxemia: protocol for a cluster-randomized stepped-wedge controlled trial in Uganda
Authors: Conradi Nicholas , Mian Qaasim , Namasopo Sophie , Conroy Andrea L. , Hermann Laura L. , Olaro Charles , Amone Jackson , Opoka Robert O. , Hawkes Michael T. 
Published: December 2019

Abstract
Background
Child mortality due to pneumonia is a major global health problem and is associated with hypoxemia. Access to safe and continuous oxygen therapy can reduce mortality; however, low-income countries may lack the necessary resources for oxygen delivery. We have previously demonstrated proof-of-concept that solar-powered oxygen (SPO2) delivery can reliably provide medical oxygen remote settings with minimal access to electricity. This study aims to demonstrate the efficacy of SPO2 in children hospitalized with acute hypoxemic respiratory illness across Uganda.

Methods
Objectives: Demonstrate efficacy of SPO2 in children hospitalized with acute hypoxemic respiratory illness. Study design: Multi-center, stepped-wedge cluster-randomized trial. Setting: Twenty health facilities across Uganda, a low-income, high-burden country for pediatric pneumonia. Site selection: Facilities with pediatric inpatient services lacking consistent O2 supply on pediatric wards. Participants: Children aged < 5 years hospitalized with hypoxemia (saturation < 92%) warranting hospital admission based on clinical judgement. Randomization methods: Random installation order generated a priori with allocation concealment. Study procedure: Patients receive standard of care within pediatric wards with or without SPO2 system installed. Outcome measures: Primary: 48-h mortality. Secondary: safety, efficacy, SPO2 system functionality, operating costs, nursing knowledge, skills, and retention for oxygen administration. Statistical analysis of primary outcome: Linear mixed effects logistic regression model with 48-h mortality (dependent variable) as a function of SPO2 treatment (before versus after installation), while adjusting for confounding effects of calendar time (fixed effect) and site (random effect). Sample size: 2400 patients across 20 health facilities, predicted to provide 80% power to detect a 35% reduction in mortality after introduction of SPO2, based on a computer simulation of > 5000 trials.

Discussion
Overall, our study aims to demonstrate mortality benefit of SPO2 relative to standard (unreliable) oxygen delivery. The innovative trial design (stepped-wedge, cluster-randomized) is supported by a computer simulation. Capacity building for nursing care and oxygen therapy is a non-scientific objective of the study. If successful, SPO2 could be scaled across a variety of resource-constrained remote or rural settings in sub-Saharan Africa and beyond.

Trial registration
Clinicaltrials.gov, NCT03851783. Registered on 22 February 2019.
Compression therapy following ClariVein® ablation therapy: a randomised controlled trial of COMpression Therapy Following MechanO-Chemical Ablation (COMMOCA)
Authors: Joyce Doireann P. , Walsh Stewart R. , Yap Charyl J. Q. , Chong Tze T. , Tang Tjun Y. 
Published: December 2019

Abstract
Background
Endovenous treatment of varicose veins has increased in popularity over the last decade. There remains, however, a degree of uncertainty regarding the role of compression bandaging or hosiery following this intervention. The National Institute for Clinical Excellence Guideline Development Group has advocated further research to evaluate the clinical and cost-effectiveness of this post-procedure intervention. In addition to this, the duration of compression bandaging also warrants clarification.

Methods
Ethical approval for the study was obtained from the Singhealth Centralised Institutional Review Board (CIRB Ref: 2017/2710). Consent to enter the study will be sought from each participant only after a full explanation has been given, an information leaflet offered and time allowed for consideration. Signed participant consent will be obtained. Patients will be randomised to either compression (group A) or no compression (group B). The primary aim of the study is to assess the patient’s pain scores for the first 10 days post procedure using a visual analogue scale. Secondary aims include an assessment of patient compliance with compression, quality of life scores, clinical effectiveness, rates of bruising and phlebitis, time taken to return to normal activities, patient satisfaction and occlusion rate at 6 months.

Discussion
The purpose of this study is to examine the effect of compression therapy in patients having mechano-chemical ablation (MOCA) therapy for truncal incompetence of their varicose veins using the ClariVein® device. This study may provide clarification on the role of compression therapy in patients undergoing MOCA.

Trial registration
ClinicalTrials.gov, NCT03685838. Registered on 26 September 2018.
Elimination of the flavodiiron electron sink facilitates long-term H2 photoproduction in green algae
Authors: Jokel Martina , Nagy Valéria , Tóth Szilvia Z. , Kosourov Sergey , Allahverdiyeva Yagut 
Published: December 2019

Abstract
Background
The development of renewable and sustainable biofuels to cover the future energy demand is one of the most challenging issues of our time. Biohydrogen, produced by photosynthetic microorganisms, has the potential to become a green biofuel and energy carrier for the future sustainable world, since it provides energy without CO2 emission. The recent development of two alternative protocols to induce hydrogen photoproduction in green algae enables the function of the O2-sensitive [FeFe]-hydrogenases, located at the acceptor side of photosystem I, to produce H2 for several days. These protocols prevent carbon fixation and redirect electrons toward H2 production. In the present work, we employed these protocols to a knockout Chlamydomonas reinhardtii mutant lacking flavodiiron proteins (FDPs), thus removing another possible electron competitor with H2 production.

Results
The deletion of the FDP electron sink resulted in the enhancement of H2 photoproduction relative to wild-type C. reinhardtii. Additionally, the lack of FDPs leads to a more effective obstruction of carbon fixation even under elongated light pulses.

Conclusions
We demonstrated that the rather simple adjustment of cultivation conditions together with genetic manipulation of alternative electron pathways of photosynthesis results in efficient re-routing of electrons toward H2 photoproduction. Furthermore, the introduction of a short recovery phase by regular switching from H2 photoproduction to biomass accumulation phase allows to maintain cell fitness and use photosynthetic cells as long-term H2-producing biocatalysts.
Potential yields and emission reductions of biojet fuels produced via hydrotreatment of biocrudes produced through direct thermochemical liquefaction
Authors: van Dyk Susan , Su Jianping , Ebadian Mahmood , O’Connor Don , Lakeman Michael , Saddler Jack (John) 
Published: December 2019

AbstractBackgroundThe hydrotreatment of oleochemical/lipid feedstocks is currently the only technology that provides significant volumes (millions of litres per year) of “conventional” biojet/sustainable aviation fuels (SAF). However, if biojet fuels are to be produced in sustainably sourced volumes (billions of litres per year) at a price comparable with fossil jet fuel, biomass-derived “advanced” biojet fuels will be needed. Three direct thermochemical liquefaction technologies, fast pyrolysis, catalytic fast pyrolysis and hydrothermal liquefaction were assessed for their potential to produce “biocrudes” which were subsequently upgraded to drop-in biofuels by either dedicated hydrotreatment or co-processed hydrotreatment.ResultsA significant biojet fraction (between 20.8 and 36.6% of total upgraded fuel volume) was produced by all of the processes. When the fractions were assessed against general ASTM D7566 specifications they showed significant compliance, despite a lack of optimization in any of the process steps. When the life cycle analysis GHGenius model was used to assess the carbon intensity of the various products, significant emission reductions (up to 74%) could be achieved.ConclusionsIt was apparent that the production of biojet fuels based on direct thermochemical liquefaction of biocrudes, followed by hydrotreating, has considerable potential.
Validation of prediction models of severe disease course and non-achievement of remission in juvenile idiopathic arthritis: part 1—results of the Canadian model in the Nordic cohort
Authors:   for the ReACCh-Out and NoSPeR Investigators, Rypdal Veronika , Guzman Jaime , Henrey Andrew , Loughin Thomas , Glerup Mia , Arnstad Ellen Dalen , Aalto Kristiina , Rygg Marite , Nielsen Susan , Herlin Troels , Fasth Anders , Berntson Lillemor , Rypdal Martin , Nordal Ellen 
Published: December 2019

AbstractBackgroundModels to predict disease course and long-term outcome based on clinical characteristics at disease onset may guide early treatment strategies in juvenile idiopathic arthritis (JIA). Before a prediction model can be recommended for use in clinical practice, it needs to be validated in a different cohort than the one used for building the model. The aim of the current study was to validate the predictive performance of the Canadian prediction model developed by Guzman et al. and the Nordic model derived from Rypdal et al. to predict severe disease course and non-achievement of remission in Nordic patients with JIA.MethodsThe Canadian and Nordic multivariable logistic regression models were evaluated in the Nordic JIA cohort for prediction of non-achievement of remission, and the data-driven outcome denoted severe disease course. A total of 440 patients in the Nordic cohort with a baseline visit and an 8-year visit were included. The Canadian prediction model was first externally validated exactly as published. Both the Nordic and Canadian models were subsequently evaluated with repeated fine-tuning of model coefficients in training sets and testing in disjoint validation sets. The predictive performances of the models were assessed with receiver operating characteristic curves and C-indices. A model with a C-index above 0.7 was considered useful for clinical prediction.ResultsThe Canadian prediction model had excellent predictive ability and was comparable in performance to the Nordic model in predicting severe disease course in the Nordic JIA cohort. The Canadian model yielded a C-index of 0.85 (IQR 0.83–0.87) for prediction of severe disease course and a C-index of 0.66 (0.63–0.68) for prediction of non-achievement of remission when applied directly. The median C-indices after fine-tuning were 0.85 (0.80–0.89) and 0.69 (0.65–0.73), respectively. Internal validation of the Nordic model for prediction of severe disease course resulted in a median C-index of 0.90 (0.86–0.92).ConclusionsExternal validation of the Canadian model and internal validation of the Nordic model with severe disease course as outcome confirm their predictive abilities. Our findings suggest that predicting long-term remission is more challenging than predicting severe disease course.
Networked information technologies and patient safety: a protocol for a realist synthesis
Authors: Keen Justin , Greenhalgh Joanne , Randell Rebecca , Gardner Peter , Waring Justin , Longo Roberta , Fistein Jon , Abdulwahid Maysam , King Natalie , Wright Judy 
Published: December 2019

Abstract
Background
There is a widespread belief that information technologies will improve diagnosis, treatment and care. Evidence about their effectiveness in health care is, however, mixed. It is not clear why this is the case, given the remarkable advances in hardware and software over the last 20 years. This review focuses on interoperable information technologies, which governments are currently advocating and funding. These link organisations across a health economy, with a view to enabling health and care professionals to coordinate their work with one another and to access patient data wherever it is stored. Given the mixed evidence about information technologies in general, and current policies and funding, there is a need to establish the value of investments in this class of system. The aim of this review is to establish how, why and in what circumstances interoperable systems affect patient safety.

Methods
A realist synthesis will be undertaken, to understand how and why inter-organisational systems reduce patients’ clinical risks, or fail to do so. The review will follow the steps in most published realist syntheses, including (1) clarifying the scope of the review and identifying candidate programme and mid-range theories to evaluate, (2) searching for evidence, (3) appraising primary studies in terms of their rigour and relevance and extracting evidence, (4) synthesising evidence, (5) identifying recommendations, based on assessment of the extent to which findings can be generalised to other settings.

Discussion
The findings of this realist synthesis will shed light on how and why an important class of systems, that span organisations in a health economy, will contribute to changes in patients’ clinical risks. We anticipate that the findings will be generalizable, in two ways. First, a refined mid-range theory will contribute to our understanding of the underlying mechanisms that, for a range of information technologies, lead to changes in clinical practices and hence patients’ risks (or not). Second, many governments are funding and implementing cross-organisational IT networks. The findings can inform policies on their design and implementation.

Systematic review registration
PROSPERO CRD42017073004
Determination of source term for the fractional Rayleigh–Stokes equation with random data
Authors: Binh Tran Thanh , Baleanu Dumitru , Luc Nguyen Hoang , Can Nguyen-H 
Published: December 2019

AbstractIn this article, we consider the problem of finding a source term of a Rayleigh–Stokes equation. Our problem is not well-posed in the sense of Hadamard. The sought solution does not depend continuously on the given data. Using the truncation method and some new techniques on trigonometric estimators, we give the regularized solution. Moreover, the mean square error and convergence rates are established.
Upper class of type I on coupled coincidence point results for some contractions in partially ordered JS-metric spaces
Authors: Ansari A. H. , Khemphet A. , Phudolsitthiphat N. , Wiriyapongsanon A. 
Published: December 2019

AbstractIn this research work, the necessary and sufficient conditions of a coupled coincidence point of certain type of generalized contractions are explored. These results are considered under JS-metric spaces equipped with a partial order. Moreover, examples satisfying theorems are given. Finally, an application to a system of integral equations is obtained using our results. In addition, an example of the system is provided.
Aldo Rossi: the ‘autobiography’ and its fragments
Authors: Marotta Antonello 
Published: December 2019

AbstractThe year 1966 demarcated a borderline in the urban design discipline. Three books published that indicated a change of direction: City architecture by Aldo Rossi, The territory of architecture by Vittorio Gregotti and Complexity and contradiction in architecture by Robert Venturi. Aldo Rossi, in contact with Ernesto Nathan Rogers and “Casabella-Continuità”, shifted the attention to the historic, consolidated city, the monument and urban rules of archaeological fabric, while Vittorio Gregotti developed a research trend that founded architecture on geography. Finally, Robert Venturi opened up the architectural project, revealing its relations with media culture and with the contradictions of the consumer society. Critical essays investigated the phase following the second half of the Sixties, at the time when Aldo Rossi began, in 1976, to travel across America, invited by the Institute for Architecture and Urban Studies to show his works at a series of exhibitions. His book A Scientific Autobiography, written and developed in America, belonged to this phase, which characterised at an international level by the birth of Paper Architecture (the movement that had placed design at the centre of reflection as the expression of new spatial poetics). The essay aimed to show a change in the paradigm of Rossi’s thought, no longer and solely focusing on past and physical architecture, but unrelentingly entwined with the individual and personal destiny of the Milanese architect. Memory became an active, live field of investigation, as Rafael Moneo maintains on Rossi’s thought, in which an objective vision of architecture no longer counted but one that included the subject and his fragments.
The transcriptional coactivator and histone acetyltransferase CBP regulates neural precursor cell development and migration
Authors: Schoof Melanie , Launspach Michael , Holdhof Dörthe , Nguyen Lynhda , Engel Verena , Filser Severin , Peters Finn , Immenschuh Jana , Hellwig Malte , Niesen Judith , Mall Volker , Ertl-Wagner Birgit , Hagel Christian , Spohn Michael , Lutz Beat , Sedlacik Jan , Indenbirken Daniela , Merk Daniel J. , Schüller Ulrich 
Published: December 2019

AbstractCREB (cyclic AMP response element binding protein) binding protein (CBP, CREBBP) is a ubiquitously expressed transcription coactivator with intrinsic histone acetyltransferase (KAT) activity. Germline mutations within theCBPgene are known to cause Rubinstein-Taybi syndrome (RSTS), a developmental disorder characterized by intellectual disability, specific facial features and physical anomalies. Here, we investigate mechanisms of CBP function during brain development in order to elucidate morphological and functional mechanisms underlying the development of RSTS. Due to the embryonic lethality of conventional CBP knockout mice, we employed a tissue specific knockout mouse model (hGFAP-cre::CBPFl/Fl, mutant mouse) to achieve a homozygous deletion of CBP in neural precursor cells of the central nervous system.Our findings suggest that CBP plays a central role in brain size regulation, correct neural cell differentiation and neural precursor cell migration. We provide evidence that CBP is both important for stem cell viability within the ventricular germinal zone during embryonic development and for unhindered establishment of adult neurogenesis. Prominent histological findings in adult animals include a significantly smaller hippocampus with fewer neural stem cells. In the subventricular zone, we observe large cell aggregations at the beginning of the rostral migratory stream due to a migration deficit caused by impaired attraction from the CBP-deficient olfactory bulb. The cerebral cortex of mutant mice is characterized by a shorter dendrite length, a diminished spine number, and a relatively decreased number of mature spines as well as a reduced number of synapses.In conclusion, we provide evidence that CBP is important for neurogenesis, shaping neuronal morphology, neural connectivity and that it is involved in neuronal cell migration. These findings may help to understand the molecular basis of intellectual disability in RSTS patients and may be employed to establish treatment options to improve patients’ quality of life.
Single-nucleus chromatin accessibility reveals intratumoral epigenetic heterogeneity in IDH1 mutant gliomas
Authors: Al-Ali Ruslan , Bauer Katharina , Park Jong-Whi , Al Abdulla Ruba , Fermi Valentina , von Deimling Andreas , Herold-Mende Christel , Mallm Jan-Philipp , Herrmann Carl , Wick Wolfgang , Turcan Şevin 
Published: December 2019

AbstractThe presence of genome-wide DNA hypermethylation is a hallmark of lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) mutations. Further molecular classification of IDH mutant gliomas is defined by the presence (IDHmut-codel) or absence (IDHmut-noncodel) of hemizygous codeletion of chromosome arms 1p and 19q. Despite the DNA hypermethylation seen in bulk tumors, intra-tumoral heterogeneity at the epigenetic level has not been thoroughly analyzed. To address this question, we performed the first epigenetic profiling of single cells in a cohort of 5 gliomas with IDH1 mutation using single nucleus Assay for Transposase-Accessible Chromatin with high-throughput sequencing (snATAC-seq). Using the Fluidigm HT IFC microfluidics platform, we generated chromatin accessibility maps from 336 individual nuclei, and identified variable promoter accessibility of non-coding RNAs in LGGs. Interestingly, local chromatin structures of several non-coding RNAs are significant factors that contribute to heterogeneity, and show increased promoter accessibility in IDHmut-noncodel samples. As an example for clinical significance of this result, we identifyCYTORas a poor prognosis factor in gliomas with IDH mutation. Open chromatin assay points to differential accessibility of non-coding RNAs as an important source of epigenetic heterogeneity within individual tumors and between molecular subgroups. Rare populations of nuclei that resemble either IDH mutant molecular group co-exist within IDHmut-noncodel and IDHmut-codel groups, and along with non-coding RNAs may be an important issue to consider for future studies, as they may help guide predict treatment response and relapse.A web-based explorer for the data is available atshiny.turcanlab.org.
Kinesin light chain-1 serine-460 phosphorylation is altered in Alzheimer’s disease and regulates axonal transport and processing of the amyloid precursor protein
Authors: Mórotz Gábor M. , Glennon Elizabeth B. , Greig Jenny , Lau Dawn H. W. , Bhembre Nishita , Mattedi Francesca , Muschalik Nadine , Noble Wendy , Vagnoni Alessio , Miller Christopher C. J. 
Published: December 2019

AbstractDamage to axonal transport is an early pathogenic event in Alzheimer’s disease. The amyloid precursor protein (APP) is a key axonal transport cargo since disruption to APP transport promotes amyloidogenic processing of APP. Moreover, altered APP processing itself disrupts axonal transport. The mechanisms that regulate axonal transport of APP are therefore directly relevant to Alzheimer’s disease pathogenesis. APP is transported anterogradely through axons on kinesin-1 motors and one route for this transport involves calsyntenin-1, a type-1 membrane spanning protein that acts as a direct ligand for kinesin-1 light chains (KLCs). Thus, loss of calsyntenin-1 disrupts APP axonal transport and promotes amyloidogenic processing of APP. Phosphorylation of KLC1 on serine-460 has been shown to reduce anterograde axonal transport of calsyntenin-1 by inhibiting the KLC1-calsyntenin-1 interaction. Here we demonstrate that in Alzheimer’s disease frontal cortex, KLC1 levels are reduced and the relative levels of KLC1 serine-460 phosphorylation are increased; these changes occur relatively early in the disease process. We also show that a KLC1 serine-460 phosphomimetic mutant inhibits axonal transport of APP in both mammalian neurons in culture and inDrosophilaneurons in vivo. Finally, we demonstrate that expression of the KLC1 serine-460 phosphomimetic mutant promotes amyloidogenic processing of APP. Together, these results suggest that increased KLC1 serine-460 phosphorylation contributes to Alzheimer’s disease.