bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive diagnosis of viability in seeds and lichens by infrared thermography under controlled environmental conditions
Authors: Fernández-Marín Beatriz , Buchner Othmar , Kastberger Gerald , Piombino Federica , García-Plazaola José Ignacio , Kranner Ilse
Published: December 2019

Background

Non-invasive procedures for the diagnosis of viability of plant or fungal tissues would be valuable for scientific, industrial and biomonitoring purposes. Previous studies showed that infrared thermography (IRT) enables non-invasive assessment of the viability of individual "orthodox" (i.e. desiccation tolerant) seeds upon water uptake. However, this method was not tested for rehydrating tissues of other desiccation tolerant life forms. Furthermore, evaporative cooling could obscure the effects of metabolic processes that contribute to heating and cooling, but its effects on the shape of the "thermal fingerprints" have not been explored. Here, we further adapted this method using a purpose-built chamber to control relative humidity (RH) and gaseous atmosphere. This enabled us to test (i) the influence of relative humidity on the thermal fingerprints during the imbibition of Pisum sativum (Garden pea) seeds, (ii) whether thermal fingerprints can be correlated with viability in lichens, and (iii) to assess the potential influence of aerobic metabolism on thermal fingerprints by controlling the oxygen concentration in the gaseous atmosphere around the samples. Finally, we developed a method to artificially "age" lichens and validated the IRT-based method to assess lichen viability in three lichen species.

Results

Using either 30% or 100% RH during imbibition of pea seeds, we showed that "live" and "dead" seeds produced clearly discernible "thermal fingerprints", which significantly differed by > |0.15| °C in defined time windows, and that RH affected the shape of these thermal fingerprints. We demonstrated that IRT can also be used to assess the viability of the lichens Lobaria pulmonaria, Pseudevernia furfuracea and Peltigera leucophlebia. No clear relationship between aerobic metabolism and the shape of thermal fingerprints was found.

Conclusions

Infrared thermography appears to be a promising method for the diagnosis of viability of desiccation-tolerant tissues at early stages of water uptake. For seeds, it is possible to diagnose viability within the first hours of rehydration, after which time they can still be re-dried and stored until further use. We envisage our work as a baseline study for the use of IR imaging techniques to investigate physiological heterogeneity of desiccation tolerant life forms such as lichens, which can be used for biomonitoring, and for sorting live and dead seeds, which is potentially useful for the seed trade.
The last 10 years: any changes in perceptions of the seriousness of alcohol, cannabis, and substance use in Canada?
Authors: Cunningham John A. , Koski-Jännes Anja
Published: December 2019

Background

Over the last decade, there have been a number of changes in the Canadian landscape - the deconstruction of alcohol policy in some provinces, the legalization of cannabis, increased availability of gambling options, and the increase in opioid use and its associated problems. Have there been concomitant changes in societal images of addictions?

Methods

A general population survey on societal images of addictions was conducted in multiple countries in 2008 - Finland, Sweden, Canada (Canadian sample size:N = 864; 40% response rate), and part of Russia (St Petersburg). We repeated the same survey in 2018 in Canada (N = 813; response rate = 23%). The survey assessed perceptions of the seriousness of different issues to society - including items about alcohol, tobacco, marijuana, gambling, misuse of medical drugs, and drugs like amphetamine, cocaine, or heroin - among other items (e.g., pollution, violent crime, prostitution).

Results

There were increases in perceptions of the seriousness of misuse of medical drugs (p = .001), of illicit drugs (p = .005), ratings of the seriousness of cannabis use (p = .02), and a decrease in ratings of gambling as a social problem (p = .04). Ratings of the seriousness of alcohol and tobacco as social problems did not display significant changes over time (p > .05).

Conclusions

There has been some variation in societal perceptions of the seriousness of different addictions. Increases in perceptions of the seriousness of misusing medical drugs and the use of illicit drugs may reflect increases in societal concerns about opioid use and its associated problems. Despite substantial changes in alcohol control policies, the legalization of cannabis, and the increased availability of options for gambling, there appears to be very little associated change in societal perceptions regarding these addictive behaviours.
Does increased implementation support improve community clinics’ guideline-concordant care? Results of a mixed methods, pragmatic comparative effectiveness trial
Authors: Gold Rachel , Bunce Arwen , Cowburn Stuart , Davis James V. , Nelson Joan C. , Nelson Christine A. , Hicks Elisabeth , Cohen Deborah J. , Horberg Michael A. , Melgar Gerardo , Dearing James W. , Seabrook Janet , Mossman Ned , Bulkley Joanna
Published: December 2019

Background

Disseminating care guidelines into clinical practice remains challenging, partly due to inadequate evidence on how best to help clinics incorporate new guidelines into routine care. This is particularly true in safety net community health centers (CHCs).

Methods

This pragmatic comparative effectiveness trial used a parallel mixed methods design. Twenty-nine CHC clinics were randomized to receive increasingly intensive implementation support (implementation toolkit (arm 1); toolkit + in-person training + training webinars (arm 2); toolkit + training + webinars + offered practice facilitation (arm 3)) targeting uptake of electronic health record (EHR) tools focused on guideline-concordant cardioprotective prescribing for patients with diabetes. Outcomes were compared across study arms, to test whether increased support yielded additive improvements, and with 137 non-study CHCs that share the same EHR as the study clinics. Quantitative data from the CHCs’ EHR were used to compare the magnitude of change in guideline-concordant ACE/ARB and statin prescribing, using adjusted Poisson regressions. Qualitative data collected using diverse methods (e.g., interviews, observations) identified factors influencing the quantitative outcomes.

Results

Outcomes at CHCs receiving higher-intensity support did not improve in an additive pattern. ACE/ARB prescribing did not improve in any CHC group. Statin prescribing improved overall and was significantly greater only in the arm 1 and arm 2 CHCs compared with the non-study CHCs. Factors influencing the finding of no additive impact included: aspects of the EHR tools that reduced their utility, barriers to providing the intended implementation support, and study design elements, e.g., inability to adapt the provided support. Factors influencing overall improvements in statin outcomes likely included a secular trend in awareness of statin prescribing guidelines, selection bias where motivated clinics volunteered for the study, and study participation focusing clinic staff on the targeted outcomes.

Conclusions

Efforts to implement care guidelines should: ensure adaptability when providing implementation support and conduct formative evaluations to determine the optimal form of such support for a given clinic; consider how study data collection influences adoption; and consider barriers to clinics’ ability to use/accept implementation support as planned. More research is needed on supporting change implementation in under-resourced settings like CHCs.

Trial registration

ClinicalTrials.gov, NCT02325531. Registered 15 December 2014.
Epidemiology and prognosis of anti-infective therapy in the ICU setting during acute pancreatitis: a cohort study
Authors: Montravers Philippe , Kantor Elie , Constantin Jean-Michel , Lefrant Jean-Yves , Lescot Thomas , Nesseler Nicolas , Paugam Catherine , Jabaudon Matthieu , Dupont Hervé
Published: December 2019

Background

Recent international guidelines for acute pancreatitis (AP) recommend limiting anti-infective therapy (AIT) to cases of suspected necrotizing AP or nosocomial extrapancreatic infection. Limited data are available concerning empirical and documented AIT prescribing practices in patients admitted to the intensive care unit (ICU) for the management of AP.

Methods

Using a multicentre, retrospective (2009–2014), observational database of ICU patients admitted for AP, our primary objective was to assess the incidence of AIT prescribing practices during the first 30 days following admission. Secondary objectives were to assess the independent impact of centre characteristics on the incidence of AIT and to identify factors associated with crude hospital mortality in a logistic regression model.

Results

In this cohort of 860 patients, 359 (42%) received AIT on admission. Before day 30, 340/359 (95%) AIT patients and 226/501 (45%) AIT-free patients on admission received additional AIT, mainly for intra-abdominal and lung infections. A large heterogeneity was observed between centres in terms of the incidence of infections, therapeutic management including AIT and prognosis. Administration of AIT on admission or until day 30 was not associated with an increased mortality rate. Patients receiving AIT on admission had increased rates of complications (septic shock, intra-abdominal and pulmonary infections), therapeutic (surgical, percutaneous, endoscopic) interventions and increased length of ICU stay compared to AIT-free patients. Patients receiving delayed AIT after admission and until day 30 had increased rates of complications (respiratory distress syndrome, intra-abdominal and pulmonary infections), therapeutic interventions and increased length of ICU stay compared to those receiving AIT on admission. Risk factors for hospital mortality assessed on admission were age (adjusted odds ratio [95% confidence interval] 1.03 [1.02–1.05]; p < 0.0001), Balthazar score E (2.26 [1.43–3.56]; p < 0.0001), oliguria/anuria (2.18 [1.82–4.33]; p < 0.0001), vasoactive support (2.83 [1.73–4.62]; p < 0.0001) and mechanical ventilation (1.90 [1.15–3.14]; p = 0.011), but not AIT (0.63 [0.40–1.01]; p = 0.057).

Conclusions

High proportions of ICU patients admitted for AP receive AIT, both on admission and during their ICU stay. A large heterogeneity was observed between centres in terms of incidence of infections, AIT prescribing practices, therapeutic management and outcome. AIT reflects the initial severity and complications of AP, but is not a risk factor for death.
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

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

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

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

Background

The 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.

Results

A 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.

Conclusions

It 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

Background

Models 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.

Methods

The 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.

Results

The 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).

Conclusions

External 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

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

In 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

In 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

The 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

CREB (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

The 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

Damage 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.
The examination of Van Gogh’s chrome yellow pigments in ‘Field with Irises near Arles’ using quantitative SEM–WDX
Authors: Geldof Muriel , van der Werf Inez Dorothé , Haswell Ralph
Published: December 2019

In this paper we present the results of quantitative measurements on the pigment chrome yellow (PbCr1−xSxO4 with 0 ≤ x ≤ 0.8) using scanning electron microscopy-wavelength dispersive X-ray analysis (SEM–WDX). Traditionally, Optical Microscopy (OM) in combination with scanning electron microscopy-energy dispersive X-ray analysis (SEM–EDX) is used for the identification of many pigments in paint cross-sections based on their particle characteristics and elemental composition. However, in the case of chrome yellow, the lead (Pb) and sulphur (S) peaks overlap, which makes quantitative analysis unreliable. SEM–WDX does not suffer from this problem and we have demonstrated that this technique can distinguish different types of chrome yellow based on the quantification of the sulphur-content of the pigment. This identification can be performed on paint cross-sections, allowing for distinction between chrome yellows in different paint layers. In addition, our study showed that the different types of chrome yellow can still be identified even in low concentrations. Van Gogh made wide use of different hues of chrome yellow. Using this method, we have identified the types of chrome yellow he used in Field with Irises near Arles, which we have been able to correlate with the information in his letters. Raman spectroscopy of the same samples confirmed the SEM–WDX results, but evidenced a higher sensitivity of the latter technique in revealing small amounts of sulphur-rich PbCr1−xSxO4 in mixtures with PbCrO4. SEM–WDX is also more accurate, because it allows the lead(II) sulphate fraction to be determined within 1 mol% absolute, whereas with Raman spectroscopy only relatively broad ranges can be defined. The on-going research of Van Gogh’s paintings as part of a cataloguing project—a collaboration between the Van Gogh Museum, the Cultural Heritage Agency of the Netherlands and Shell—opens the way for a comprehensive comparison of the chrome yellows used by Van Gogh using SEM–WDX.
Investigation on geothermal binary-flashing cycle employing zeotropic mixtures as working fluids
Authors: Wang Lingbao , Bu Xianbiao , Li Huashan
Published: December 2019

The binary-flashing cycle (BFC) is supposed to be a promising technology for geothermal recovery due to the full use of geofluid. For further performance improvement, the potential of using mixtures of a hydrocarbon and a retardant in the BFC system is investigated. R245fa is selected as a retardant and blended with R600 to form zeotropic mixtures. With the thermal efficiency (ηth), exergy efficiency (ηex), net power output per ton geofluid (PRW), and exergy destruction rate (Ed) as evaluation indexes, the flowsheet modeling and optimization are conducted to explore the optimal compositions and operating parameters. It is revealed the optimal mass fraction of R600/R245fa is 0.44/0.56, at which the flammability of R600 is suppressed, the global warming potential (GWP) of R245fa is reduced. The maximum ηex and PRW are higher than those of component fluids. The maximum Ed occurs in the heat exchanger, which should be optimized. The recommended generation pressures are 1200–1430, 1240–1480, 1220–1460, and 1170–1420 kPa, respectively, for R600 mass fraction of 0.2, 0.4, 0.6, and 0.8. In addition, the flashing temperature is also optimized. Although the mixtures do not always yield superior performance, it is still beneficial to apply the mixtures to the BFC system through systematic consideration of safety and environmental friendliness.
Translational applications of photopolymerizable hydrogels for cartilage repair
Authors: Meng Weikun , Gao Liang , Venkatesan Jagadeesh K. , Wang Guanglin , Madry Henning , Cucchiarini Magali
Published: December 2019

Background

Articular cartilage lesions generated by trauma or osteoarthritis are the most common causes of pain and disability in patients.

The development of photopolymerizable hydrogels has allowed for significant advances in cartilage repair procedures. Such three-dimensional (3D) networks of polymers that carry large amounts of water can be created to resemble the physical characteristics of the articular cartilage and be delivered into ill-defined cartilage defects as a liquid solution prior to polymerization in vivo for perfect fit with the surrounding native tissue. These hydrogels offer an adapted environment to encapsulate and propagate regenerative cells in 3D cultures for cartilage repair. Among them, mesenchymal stem cells and chondrocytes may represent the most adapted sources for implantation. They also represent platforms to deliver therapeutic, biologically active factors that promote 3D cell differentiation and maintenance for in vivo repair.

Conclusion

This review presents the benefits of photopolymerization of hydrogels and describes the photoinitiators and materials in current use for enhanced cartilage repair.
Methane and Inflammation - A Review (Fight Fire with Fire)
Authors: Poles Marietta Zita , Juhász László , Boros Mihály
Published: December 2019

Mammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.
Man or machine? Prospective comparison of the version 2018 EASL, LI-RADS criteria and a radiomics model to diagnose hepatocellular carcinoma
Authors: Jiang Hanyu , Liu Xijiao , Chen Jie , Wei Yi , Lee Jeong Min , Cao Likun , Wu Yuanan , Duan Ting , Li Xin , Ma Ling , Song Bin
Published: December 2019

Background

The Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study of the Liver (EASL) criteria are widely used for diagnosing hepatocellular carcinoma (HCC). Radiomics allows further quantitative tumor heterogeneity profiling. This study aimed to compare the diagnostic accuracies of the version 2018 (v2018) EASL, LI-RADS criteria and radiomics models for HCC in high-risk patients.

Methods

Ethical approval by the institutional review board and informed consent were obtained for this study. From July 2015 to September 2018, consecutive high-risk patients were enrolled in our tertiary care hospital and underwent gadoxetic acid-enhanced magnetic resonance (MR) imaging and subsequent hepatic surgery. We constructed a multi-sequence-based three-dimensional whole-tumor radiomics signature by least absolute shrinkage and selection operator model and multivariate logistic regression analysis. The diagnostic accuracies of the radiomics signature was validated in an independent cohort and compared with the EASL and LI-RADS criteria reviewed by two independent radiologists.

Results

Two hundred twenty-nine pathologically confirmed nodules (173 HCCs, mean size: 5.74 ± 3.17 cm) in 211 patients were included. Among them, 201 patients (95%) were infected with hepatitis B virus (HBV). The sensitivity and specificity were 73 and 71% for the radiomics signature, 91 and 71% for the EASL criteria, and 86 and 82% for the LI-RADS criteria, respectively. The areas under the receiver operating characteristic curves (AUCs) of the radiomics signature (0.810), LI-RADS (0.841) and EASL criteria (0.811) were comparable.

Conclusions

In HBV-predominant high-risk patients, the multi-sequence-based MR radiomics signature, v2018 EASL and LI-RADS criteria demonstrated comparable overall accuracies for HCC.
Sustaining collaborative preschool partnerships and the challenges of educating the whole child
Authors: Alverson Ryan , Ginn Laken , Gilbert Jaesook
Published: December 2019

Introduction

Our study examined whole-child preschool programming from a policy perspective. We suggest that whole-child wellness must include sustainable approaches that are systematic and holistic approaches for educating children. The Preschool Partnership Grant was a means of funding preschool districts, who successfully applied for the grant across our state to initiate, continue, and sustain quality programming with their respective local preschool partners. Funding also enabled districts to increase access to quality programming while fostering kindergarten readiness in participating children.

Case description

We conducted a case study by analyzing data provided by district Preschool Partnership Grantees. Data included quantitative measures of district and partner preschools and open-ended items describing professional development opportunities, holistic interventions, and effective preschool activities afforded by grant funding.

Results

Grant recipients (n = 79) reported that they engaged in a number of different public and private partnerships. They reported being able to serve more children due to grant funding, and gave a variety of reasons for serving more children, with improved collaboration being the most reported reason. District grantees also indicated increased consultation, intervention services, and professional development opportunities through grant funding. Finally, they reported on key challenges they faced during the grant period.

Discussion and evaluation

Data suggested that school districts recognized the importance of collaboration, trust, and relationship building among districts, partners, and families. Descriptive data indicated the importance of sustaining quality programming during the grant period. Districts also clearly voiced their appreciation of the importance of relationships and collaboration among key stakeholders who touched the lives of children enrolled in the grantee districts.

Conclusions

Our study suggests that early childhood policy should enable systematic and sustainable partnerships that approach preschool programming from a holistic perspective.
Policy levers to promote cultural competence in early childhood programs in the USA: recommendations from system specialists
Authors: Porterfield Mary L. , Scott-Little Catherine
Published: December 2019

The purpose of the study was to investigate ways in which early childhood systems that rate and license child care programs, known as Quality Rating and Improvement Systems (QRISs), might incorporate requirements related to cultural competence into the system, including incentives, supports, and rewards for programs that foster cultural competence of the early care and education (ECE) workforce. The study employed a focus group design to consider the research problem from the vantage point of key informants such as coaches and other system staff who routinely support ECE programs to meet system requirements and to engage in quality improvement work. Three focus groups were convened, with a total ofN = 28 participants. The meetings were audio-recorded, transcribed, and analyzed using the constant comparative method. Emergent themes were noted and grouped into four categories: QRIS requirements; system alignment; ECE progrm administrator training; and ECE teacher training and technical assistance. Focus group members advocated for incorporation of system-level requirements related to cultural competence as well as program supports to ensure that ECE providers could succeed in meeting new requirements. Policy recommendations to support cultural competence development in the ECE workforce and to embed cultural competence in ECE systems are discussed.
Induction of labor and early-onset Sepsis guidelines: impact on NICU admissions in Erie County, NY
Authors: Dumpa Vikramaditya , Avulakunta Indira , Shelton James , Yu Taechin , Lakshminrusimha Satyan
Published: December 2019

Background

Elective delivery prior to term gestation is associated with adverse neonatal outcomes. The impact of American College of Obstetricians and Gynecologists (ACOG) guidelines recommending against induction of labor (IOL) < 39 weeks’ postmenstrual age (PMA) on the frequency of early-term births and NICU admissions in Erie County, NY was evaluated in this study.

Methods

This is a population-based retrospective comparison of all live births and NICU admissions in Erie County, NY between pre-and post-ACOG IOL guideline epochs (2005–2008 vs. 2011–2014). Information on early-term, full/late/post-term births and NICU admissions was obtained. A detailed chart analysis of indications for admission to the Regional Perinatal Center was performed.

Results

During the 2005–2008 epoch, early-term births constituted 27% (11,968/44,617) of live births. The NICU admission rate was higher for early-term births (1134/11968 = 9.5%) compared to full/late/post-term (1493/27541 = 5.4%).

In the 2011–2014 epoch, early-term births decreased to 23% (10,286/44,575) of live births. However, NICU admissions for early-term (1072/10286 = 10.4%) and full/late/post-term births (1892/29508 = 6.4%) did not decrease partly due to asymptomatic infants exposed to maternal chorioamnionitis admitted for empiric antibiotic therapy as per revised early-onset sepsis guidelines.

Conclusions

ACOG recommendations against elective IOL or cesarean delivery < 39 weeks PMA were rapidly translated to clinical practice and decreased early-term births in Erie County, NY. This decrease did not translate to reduced NICU admissions partly due to increased NICU admissions for empiric antibiotic therapy.