bluuebunny/crossref_metadata_2025 huggingface dataset:
ComMet: A method for comparing metabolic states in genome-scale metabolic models
Authors: Sarathy Chaitra , Breuer Marian , Kutmon Martina , Adriaens Michiel E. , Evelo Chris T. , Arts Ilja C.W.
Published: September 2020

Being comprehensive knowledge bases of cellular metabolism, Genome-scale metabolic models (GEMs) serve as mathematical tools for studying cellular flux states in various organisms. However, analysis of large-scale (human) GEMs, still presents considerable challenges with respect to objective selection and reaction flux constraints. In this study, we introduce a model-based method, ComMet (Comparison of Metabolic states), for comprehensive analysis of large metabolic flux spaces and comparison of various metabolic states. ComMet allows (a) an in-depth characterisation of achievable flux states, (b) comparison of flux spaces from several conditions of interest and (c) identification and visualization of metabolically distinct network modules. As a proof-of-principle, we employed ComMet to extract the biochemical differences in the human adipocyte network (iAdipocytes1809) arising due to unlimited/blocked uptake of branched-chain amino acids. Our study opens avenues for exploring several metabolic conditions of interest in both microbe and human models. ComMet is open-source and is available athttps://github.com/macsbio/commet.
Deep learning for supervised classification of temporal data in ecology
Authors: Capinha César , Ceia-Hasse Ana , Kramer Andrew M. , Meijer Christiaan
Published: September 2020

Temporal data is ubiquitous in ecology and ecologists often face the challenge of accurately differentiating these data into predefined classes, such as biological entities or ecological states. The usual approach consists of transforming the time series into user-defined features and then using these features as predictors in conventional statistical or machine learning models. Here we suggest the use of deep learning models as an alternative to this approach. Recent deep learning techniques can perform the classification directly from the time series, eliminating subjective and resource-consuming data transformation steps, and potentially improving classification results. We describe some of the deep learning architectures relevant for time series classification and show how these architectures and their hyper-parameters can be tested and used for the classification problems at hand. We illustrate the approach using three case studies from distinct ecological subdisciplines:i) insect species identification from wingbeat spectrograms;ii) species distribution modelling from climate time series andiii) the classification of phenological phases from continuous meteorological data. The deep learning approach delivered ecologically sensible and accurate classifications demonstrating its potential for wide applicability across subfields of ecology.
Minimal detection and low biological fluctuation of mitochondrial CpG methylation at the single-molecule level
Authors: Goldsmith Chloe , Rodríguez-Aguilera Jesús Rafael , El-Rifai Ines , Jarretier Adrien , Hervieu Valérie , de Sánchez Victoria Chagoya , Dante Robert , Ichim Gabriel , Hernandez-Vargas Hector
Published: September 2020

Cytosine DNA methylation in the CpG context (5mCpG) is associated with the transcriptional status of nuclear DNA. Due to technical limitations, it has been less clear if mitochondrial DNA (mtDNA) is methylated and whether 5mCpG has a regulatory role in this context. The main aim of this work was to develop and validate a novel tool for determining methylation of mtDNA and to corroborate its existence across different biological contexts. Using long-read nanopore sequencing we found low levels of CpG methylation (with few exceptions) and little variation across biological processes: differentiation, oxidative stress, and cancer. 5mCpG was overall higher in tissues compared to cell lines, with small additional variation between cell lines of different origin. Although we do show several significant changes in all these conditions, 5mCpG is unlikely to play a major role in defining the transcriptional status of mitochondrial genes.
Microfluidic Antibody Affinity Profiling for In-Solution Characterisation of Alloantibody - HLA Interactions in Human Serum
Authors: Schneider Matthias M. , Scheidt Tom , Priddey Ashley J. , Xu Catherine K. , Hu Mengsha , Devenish Sean R. A. , Meisl Georg , Dobson Christopher M. , Kosmoliaptsis Vasilis , Knowles Tuomas P. J.
Published: September 2020

The detection and characterisation of antibodies in human blood is a key for clinical diagnostics and risk assessment for autoimmunity, infectious diseases and transplanta-tion. Antibody titre derived from immunoassays is a commonly used measure for anti-body response, but this metric does not resolve readily the two fundamental properties of antibodies in solution, namely their affinity and concentration. This difficulty originates from the fact that the fundamental parameters describing the binding interaction, affinity and ligand concentration, are convoluted into the titre measurement; moreover, the difficulty of controlling the surface concentration and activity of the immobilised ligand can make it challenging to distinguish between avidity and affinity. To address these challenges, we developed microfluidic antibody affinity profiling, an assay which allows the simultaneous determination of both affinity and antibody concentration, directly in solution, without surface immobilisation or antibody purification. We demonstrate these measurements in the context of alloantibody characterisation in organ transplantation, using complex patient sera, and quantify the concentration and affinity of alloantibodies against donor Human Leukocyte Antigens (HLA), an extensively used clinical biomarker to access the risk of allograft rejection. These results outline a path towards detection and in depth profiling of antibody response in patient sera.
Transcriptional alterations in opioid use disorder reveal an interplay between neuroinflammation and synaptic remodeling
Authors: Seney Marianne L. , Kim Sam-Moon , Glausier Jill R. , Hildebrand Mariah A. , Xue Xiangning , Zong Wei , Wang Jiebiao , Shelton Micah A. , Phan BaDoi N. , Srinivasan Chaitanya , Pfenning Andreas R. , Tseng George C. , Lewis David A. , Freyberg Zachary , Logan Ryan W.
Published: September 2020

Background

Prevalence rates of opioid use disorder (OUD) have increased dramatically, accompanied by a surge of overdose deaths. While opioid dependence has been extensively studied in preclinical models, an understanding of the biological alterations that occur in the brains of people who chronically use opioids and who are diagnosed with OUD remains limited. To address this limitation, RNA-sequencing (RNA-seq) was conducted on the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), regions heavily implicated in OUD, from postmortem brains in subjects with OUD.

Methods

We performed RNA-seq on the DLPFC and NAc from unaffected comparison subjects (n=20) and subjects diagnosed with OUD (n=20). Our transcriptomic analyses identified differentially expressed (DE) transcripts and investigated the transcriptional coherence between brain regions using rank-rank hypergeometric ordering (RRHO). Weighted gene co-expression analyses (WGCNA) also identified OUD-specific modules and gene networks. Integrative analyses between DE transcripts and GWAS datasets using linkage disequilibrium score (LDSC) assessed the genetic liability psychiatric-related phenotypes.

Results

RRHO analyses revealed extensive overlap in transcripts between DLPFC and NAc in OUD, primarily relating to synaptic remodeling and neuroinflammation. Identified transcripts were enriched for factors that control pro-inflammatory cytokine-mediated, chondroitin sulfate, and extracellular matrix signaling. Cell-type deconvolution implicated a role for microglia as a critical driver for opioid-induced neuroplasticity. Using LDSC, we discovered genetic liabilities for risky behavior, attention deficit hyperactivity disorder, and depression.

Conclusions

Overall, our findings reveal new connections between the brain’s immune system and opioid dependence in the human brain.
Single-cell RNA Expression of SARS-CoV-2 Cell Entry Factors in Human Endometrium during Preconception
Authors: Vilella Felipe , Wang Wanxin , Moreno Inmaculada , Quake Stephen R. , Simon Carlos
Published: September 2020

We investigated potential SARS-CoV-2 tropism in human endometrium by single-cell RNA-sequencing of viral entry-associated genes in healthy women. Percentages of endometrial cells expressingACE2, TMPRSS2, CTSB, orCTSLwere <2%, 12%, 80%, and 80%, respectively, with 0.7% of cells expressing all four genes. Our findings imply low efficiency of SARS-CoV-2 infection in the endometrium before embryo implantation, providing information to assess preconception risk in asymptomatic carriers.
Fast and robust identity-by-descent inference with the templated positional Burrows-Wheeler transform
Authors: Freyman William A. , McManus Kimberly F. , Shringarpure Suyash S. , Jewett Ethan M. , Bryc Katarzyna ,   The 23 and Me Research Team, Auton Adam
Published: September 2020

Estimating the genomic location and length of identical-by-descent (IBD) segments among individuals is a crucial step in many genetic analyses. However, the exponential growth in the size of biobank and direct-to-consumer (DTC) genetic data sets makes accurate IBD inference a significant computational challenge. Here we present the templated positional Burrows-Wheeler transform (TPBWT) to make fast IBD estimates robust to genotype and phasing errors. Using haplotype data simulated over pedigrees with realistic genotyping and phasing errors we show that the TPBWT outperforms other state-of-the-art IBD inference algorithms in terms of speed and accuracy. For each phase-aware method, we explore the false positive and false negative rates of inferring IBD by segment length and characterize the types of error commonly found. Our results highlight the fragility of most phased IBD inference methods; the accuracy of IBD estimates can be highly sensitive to the quality of haplotype phasing. Additionally we compare the performance of the TPBWT against a widely used phase-free IBD inference approach that is robust to phasing errors. We introduce both in-sample and out-of-sample TPBWT-based IBD inference algorithms and demonstrate their computational efficiency on massive-scale datasets with millions of samples. Furthermore we describe the binary file format for TPBWT-compressed haplotypes that results in fast and efficient out-of-sample IBD computes against very large cohort panels. Finally, we demonstrate the utility of the TPBWT in a brief empirical analysis exploring geographic patterns of haplotype sharing within Mexico. Hierarchical clustering of IBD shared across regions within Mexico reveals geographically structured haplotype sharing and a strong signal of isolation by distance. Our software implementation of the TPBWT is freely available for non-commercial use in the code repositoryhttps://github.com/23andMe/phasedibd.
Ex vivotherapeutic base and prime editing using chemically derived hepatic progenitors in a mouse model of tyrosinemia type 1
Authors: Kim Yohan , Yu Jihyeon , Hong Sung-Ah , Eom Jeongyun , Jang Kiseok , Lee Seu-Na , Woo Jae-Sung , Jeong Jaemin , Bae Sangsu , Choi Dongho
Published: September 2020

DNA base editors and prime editing technology capable of therapeutic base conversion enableex vivogene editing therapy for various genetic diseases. For such therapy, it is critical that the target cells survive well both outside the body and after transplantation. In this regard, chemically derived stem/progenitor cells are attracting attention as the most useful cell sources for clinical trials. Here, we generate chemically derived hepatic progenitors from the hereditary tyrosinemia type1 model mouse (HT1-mCdHs) and successfully correct the disease causing mutation using both adenosine base editors (ABEs) and prime editing tools. After transplantation into HT1 mice, ABE-corrected HT1-mCdHs repopulated the liver with fumarylacetoacetate hydrolase-positive cells and dramatically increased the survival rate of HT1 model mice, suggesting a safe and effectiveex vivogene editing therapy.
δ-protocadherins control neural progenitor cell proliferation by antagonizing Ryk and Wnt/β-catenin signaling
Authors: Biswas Sayantanee , Emond Michelle R. , Chenoweth Kurtis , Jontes James D.
Published: September 2020

The proliferation of neural progenitor cells provides the cellular substrate from which the nervous system is sculpted during development. The δ-protocadherin family of homophilic cell adhesion molecules is essential for the normal development of the nervous system and has been linked to an array of neurodevelopmental disorders. However, the biological functions of δ-protocadherins are not well-defined. Here, we show that the δ-protocadherins regulate proliferation in neural progenitor cells, as lesions in each of six, individual δ-protocadherin genes increase cell division in the developing hindbrain. Moreover, Wnt/β-catenin signaling is upregulated in δ-protocadherin mutants and inhibition of the canonical Wnt pathway occludes the observed proliferation increases. We show that the δ-protocadherins physically associate with the Wnt receptor Ryk, and that Ryk is required for the increased proliferation in protocadherin mutants. Thus, the δ-protocadherins act as novel regulators of Wnt/β-catenin signaling during neural development and could provide lineage-restricted local regulation of canonical Wnt signaling and cell proliferation.
A role for the medial temporal lobes in category learning
Authors: Wang Yi-Wen , Ashby F. Gregory
Published: September 2020

Despite much research, the role of the medial temporal lobes (MTL) in category learning is unclear. Two unstructured categorization experiments explored conditions that might recruit MTL category learning and memory systems—namely, whether the stimulus display includes one or two stimuli, and whether category membership depends on configural properties of the stimulus features. The results supported three conclusions. First, in agreement with prior research, learning with single stimulus displays depended on striatal-mediated procedural learning. Second, and most important, learning with pair displays was mediated by MTL declarative memory systems. Third, the use of stimuli in which category membership depends on configural properties of the stimulus features made MTL learning slightly more likely. Overall, the results suggested that the MTL are most likely to mediate learning when the participant must decide which of two configural stimuli belongs to a selected category.
A new soaking procedure for X-ray crystallographic structural determination of protein–peptide complexes
Authors: Ballone Alice , Lau Roxanne A. , Zweipfenning Fabian P. A. , Ottmann Christian
Published: September 2020

Interactions between a protein and a peptide motif of its protein partner are prevalent in nature. Often, a protein also has multiple interaction partners. X-ray protein crystallography is commonly used to examine these interactions in terms of bond distances and angles as well as to describe hotspots within protein complexes. However, the crystallization process presents a significant bottleneck in structure determination since it often requires notably time-consuming screening procedures, which involve testing a broad range of crystallization conditions via a trial-and-error approach. This difficulty is also increased as each protein–peptide complex does not necessarily crystallize under the same conditions. Here, a new co-crystallization/peptide-soaking method is presented which circumvents the need to return to the initial lengthy crystal screening and optimization processes for each consequent new complex. The 14-3-3σ protein, which has multiple interacting partners with specific peptidic motifs, was used as a case study. It was found that co-crystals of 14-3-3σ and a low-affinity peptide from one of its partners, c-Jun, could easily be soaked with another interacting peptide to quickly and easily generate new structures at high resolution. Not only does this significantly reduce the production time, but new 14-3-3–peptide structures that were previously not accessible with the 14-3-3σ isoform, despite screening hundreds of other different conditions, were now also able to be resolved. The findings achieved in this study may be considered as a supporting and practical guide to potentially enable the acceleration of the crystallization process of any protein–peptide system.
2,6-Diamino-4-chloropyrimidine–succinic acid (2/1)
Authors: Chakkarapani Nandhini , Murugan Suganya , Ibrahim Abdul Razak , Kavitha Savaridasan Jose , Hemamalini Madhukar , Rajakannan Venkatachalam
Published: September 2020

In the title 2:1 co-crystal, 2C4H5ClN4·C4H6O4 the complete succinic acid molecule is generated by a crystallographic centre of symmetry. In the crystal, pairwise O—H...N and N—H...O hydrogen bonds link the pyrimidine and succinic acid molecules, generating R
2
2(8) loops. The pyrimidine molecules are linked by pairwise N—H...N hydrogen bonds, again generating R
2
2(8) loops. Collectively, the hydrogen bonds link the components into corrugated (100) sheets. The Hirshfeld surface is presented.
Powered by healthism? Marketing discourses of food and health
Authors: Silchenko Ksenia , Askegaard Søren
Published: September 2020

Purpose

Driven by the visible proliferation of marketing scholarship dedicated to the topics of food marketing and consumer well-being, this study aims to examine the prevailing meanings and assumptions around food and health in marketing research.

Design/methodology/approach

Following the guiding principles of Foucault’s archaeology of knowledge and the methodological orientation of critical discourse analysis, the authors analyze a systematically produced corpus of 190 academic articles from 56 publication outlets.

Findings

The study identifies three discourses of health and food dominant in marketing and consumer research. Each of the three discourses blends the ideology of healthism with market(ing) ideologies and provides a unique perspective on the meanings of health and health risks, the principles of appropriate consumer conduct and the role of marketing in regard to consumer and societal well-being.

Research limitations/implications

The study contributes to research into ideologies in and of marketing by introducing useful concepts that help explain the role of healthism in marketing discourse.

Practical implications

The finding of three dominant discourses could help reduce at least some of the existing complexity in regard to conflicting knowledge existing in the domain of health and food, and thus could inspire a more reflective body of work by researchers, policymakers and marketers towards improved food-related well-being.

Originality/value

This analysis of assumptions and consequences of the meanings mobilized by the dominant marketing discourses contributes to a better understanding of the current state of knowledge about health in the market reality.
How could future professionals excel in wine tourism delivery? Evidence from wine regions in emerging economies
Authors: Duarte Alonso Abel , Kok Seng Kiat
Published: September 2020

Purpose

The purpose of this paper is to investigate the different traits, characteristics and skills future professionals need to contemplate to address the demands of the competitive wine industry, more specifically, concerning the provision of wine tourism experiences. The insights within self-determination theory are considered to develop more robust understanding of this central theme.

Design/methodology/approach

The views of 32 winery representatives in ownership and management roles, operating in two emerging economies were gathered through un-structured, face-to-face interviews conducted on-site.

Findings

Participants’ comments revealed five key dimensions illustrated, notably, through attitudinal aspects (passion, empathy), knowledge-based (constant learning), strategy-based (problem-solver), previous work experience and adaptation-based. This last aspect highlighted coping with the dynamic nature of the industry, while assimilating tasks or learning by doing. These findings have important implications, in particular, for the future delivery of wine tourism experiences.

Originality/value

By empirically examining an important knowledge gap associated with the traits and characteristics of future wine tourism professionals, the study provides original and valuable practical insights. From a theoretical point of view, the study proposes a model originating from the findings and its associations with the revisited theoretical underpinnings.
Do performance measurement models have any impact on primary health care? A systematic review
Authors: Zaadoud Brahim , Chbab Youness , Chaouch Aziz
Published: September 2020

Purpose

The purpose of this article is to analyze and compare between the frameworks of performance measurement in primary health care in the world. The subject of search is to compare if the frameworks of performance measurement in primary health care have an influence on performances of health centers.

Design/methodology/approach

We conducted a systematic review of the literature to (1) identify the conceptual framework for measuring quality management systems, (2) assess the effects of conceptual framework on quality improvement and quality of care outcomes. We opted for the frameworks that are more cited in the literature and we analyzed and compared between these frameworks.

Findings

Eight dimensions were identified for assessing performance in Primary Health Care Facilities “PHCF” in more than 50% frameworks: Effectiveness, Safety, Accessibility, Equity, Efficiency, Acceptability, Patient Centeredness and Timeliness.

Research limitations/implications

The limits of this study can be represented by the following elements: (1) lack of exhaustiveness with regard to the current Frameworks. (2) The evaluation of reliability and validity of the qualitative studies remains difficult to appreciate. (3) Most of the evaluation tools of the primary health care are not validated yet. (4) The difference in performance levels between countries, especially for the developed countries and the multitude of the frames of measure of performance, limits the comparability of the results.

Practical implications

This study provides a conceptual and descriptive literature on the different conceptual frameworks for performance measurement in primary health care, and a practical and useful tool for comparison between the different conceptual frameworks. Several organisations of accreditation or certification introduced, developed, incorporated and checked the indicators of clinical quality in the organizations of health care. Some studies revealed links with the governance, the access, the continuity, the coordination, the efficiency and the strength primary care (Dionne Kringos, 2018). Improvements in the quality of care have been observed in the results of accreditation and certification bodies regarding hospital infection control infrastructure, organization and performance.

Originality/value

Even if the links are not established within the framework of a scientific research, quality approaches are generally recognized as an essential tool to help establishments to improve the quality and the safety of the patients. Until now, it is not still common to make evaluation of the quality of care in the “PHCF” to obtain the relevant information. The necessity of having performance measurement tools, which puts in coherence the piloting of the operational level with the strategy, to integrate the organizational objectives into the measures of operational performances and make estimate its structures towards a real management by the quality.
A decision-support approach under uncertainty for evaluating reverse logistics capabilities of healthcare providers in Iran
Authors: Karbassi Yazdi Amir , Wanke Peter Fernandes , Hanne Thomas , Bottani Eleonora
Published: September 2020

Purpose

This paper aims to assess and prioritize manufacturing companies in the healthcare industry based on critical success factors (CSFs) of their reverse logistics (RL). The research involves seven medical device companies located in the Tehran Province, Iran.

Design/methodology/approach

To identify and prioritize companies based on CSFs of RL, the study proposes a three-phase decision-making framework that integrates the Delphi method, the best-worst method (BWM) and the Additive Ratio Assessment (ARAS) method with Z-numbers. The weights required for this method are obtained by a variant of the BWM based on Z-numbers, denoted as Z-numbers Best-Worst Method, or ZBWM. Since decision-makers face an uncertain environment, Z-numbers, which are a kind of fuzzy numbers, are applied.

Findings

First, after customizing CSFs by the Delphi method and obtaining 15 CSFs of RL, these are ranked by the hybrid BWM-ARAS method with Z-numbers. Results reveal which company appears to perform best with respect to their RL implementations. Based on this result, healthcare device companies should choose the highest priority company based on the selected RL CSFs and results from using the BWM-ARAS method with Z-numbers.

Originality/value

The contribution of this paper is using a hybrid ARAS-BWM method based on Z-numbers. Each of these methods has some merits compared to other similar methods. The combination of these methods contributes a new approach for prioritizing companies based on RL CSFs with high accuracy and reliability.
The intentions to use social commerce from social, technology, and personal trait perspectives: analysis of direct, indirect, and moderating effects
Authors: Handarkho Yonathan Dri
Published: September 2020

Purpose

This study aims to propose a theoretical model to determine factors affecting an individual’s intentions to use social commerce (SC) in generating and sharing information on a vendor’s products and services. This, however, involves the application of three fundamental aspects including social interaction, social technology and personal trait used in constructing SC to propose these factors.

Design/methodology/approach

A cross-sectional time approach of the quantitative field study was used with the data collected from 874 users of SC in Indonesia using questionnaires.

Findings

The results showed social technology to be the dominant aspect influencing users’ intention to use SC followed by social experience and personality traits while, in detail, perceived enjoyment was discovered to have the most influence and this is in line with the findings of previous studies. Moreover, new results were also identified based on direct, indirect and moderating effects of gender, age and experience.

Originality/value

This research is different from previous ones because of its proposal of an extensive model that combines three main perspectives used in constructing SC and its emphasis on the theoretical and practical importance of studying not only the direct but also the indirect and moderating effects.
The mediating role of transformational leadership between learning culture and knowledge application
Authors: Gil Alfonso J. , Rodrigo-Moya Beatriz , Cegarra-Navarro Juan Gabriel
Published: September 2020

Purpose

This study aims to analyse the influence of learning culture (LC) and transformational leadership (TL) on knowledge application (KA) in the school context. Mediation analysis is used to quantify the effects that the LC has on the application of leadership, mediated by TL.

Design/methodology/approach

The method involves two samples of subjects – school managers and teaching staff – from 17 educational organisations. This study used the partial least squares method in the SmartPLS.

Findings

The results prove an effect of total mediation of TL.

Originality/value

This study highlights the importance of KA in educational organisations and propounds the responsibility of leadership in educational management.
Mathematical models for the periodic vehicle routing problem with time windows and time spread constraints
Authors: Öztop Hande , Kizilay Damla , Çil Zeynel Abidin
Published: September 2020

The periodic vehicle routing problem (PVRP) is an extension of the well-known vehicle routing problem. In this paper, the PVRP with time windows and time spread constraints (PVRP-TWTS) is addressed, which arises in the high-value shipment transportation area. In the PVRP-TWTS, period-specific demands of the customers must be delivered by a fleet of heterogeneous capacitated vehicles over the several planning periods. Additionally, the arrival times to a customer should be irregular within its time window over the planning periods, and the waiting time is not allowed for the vehicles due to the security concerns. This study, proposes novel mixed-integer linear programming (MILP) and constraint programming (CP) models for the PVRP-TWTS. Furthermore, we develop several valid inequalities to strengthen the proposed MILP and CP models as well as a lower bound. Even though CP has successful applications for various optimization problems, it is still not as well-known as MILP in the operations research field. This study aims to utilize the effectiveness of CP in solving the PVRP-TWTS. This study presents a CP model for PVRP-TWTS for the first time in the literature to the best of our knowledge. Having a comparison of the CP and MILP models can help in providing a baseline for the problem. We evaluate the performance of the proposed MILP and CP models by modifying the well-known benchmark set from the literature. The extensive computational results show that the CP model performs much better than the MILP model in terms of the solution quality.
Tradeoff Assessments for Part Load Controlled Cooling Air in Stationary Gas Turbines
Authors: Woelki Dominik , Peitsch Dieter
Published: September 2020

The demand for flexible part load operation of stationary gas turbines requires the simultaneous design for sufficient efficiency and lifetime. Both can be addressed by the secondary air system. This paper presents investigations on the concepts of cooling air reduction in off-design, aiming for tradeoffs between fuel burn and turbine blade life. The considered lifetime mechanisms are creep and oxidation. In addition, the effects on emissions from the combustion are outlined. The reference gas turbine is a generic gas turbine in the 300 MW power output segment. The focus is on the first two stages of the four-stage turbine. All simulations are performed by application of a coupled model that essentially connects gas turbine performance with a secondary air system network model. This coupled model is now extended with blade life evaluation and emission models. The results contain tradeoffs for operating points at base and part load. For example, the combined cooling air control of stage 1 rotor blade and stage 2 vane offers savings up to 0.5% fuel flow at 60% of base load in a combined cycle application. This saving is at the expense of creep life. However, some operating points could even operate at higher blade temperatures in order to improve life regarding hot corrosion. Furthermore, generic sensitivities of controlled secondary air supply to cooling layers and hot gas ingestion are discussed. Overall, the presented trades mark promising potentials of modulated secondary air system concepts from a technical point of view.
COVID-19: All the wrong moves in all the wrong places
Authors: Barrett Christopher D. , Yaffe Michael B.
Published: September 2020

Missteps and opportunities in the tackling of the COVID-19 pandemic are discussed.
Multi-omics Approaches To Decipher the Impact of Diet and Host Physiology on the Mammalian Gut Microbiome
Authors: Milani Christian , Alessandri Giulia , Mancabelli Leonardo , Mangifesta Marta , Lugli Gabriele Andrea , Viappiani Alice , Longhi Giulia , Anzalone Rosaria , Duranti Sabrina , Turroni Francesca , Ossiprandi Maria Cristina , van Sinderen Douwe , Ventura Marco
Published: September 2020

Diet and host physiology have been recognized as main factors affecting both taxonomic composition and functional features of the mammalian gut microbiota. However, very few studies have investigated the bacterial biodiversity of mammals by using large sample numbers that correspond to multiple mammalian species, thus resulting in an incomplete understanding of the functional aspects of their microbiome. Therefore, we investigated the bacterial taxonomic composition of 250 fecal samples belonging to 77 host species distributed along the tree of life in order to assess how diet and host physiology impact the intestinal microbial community by selecting specific microbial players. Conversely, the application of shotgun metagenomics and metatranscriptomics approaches to a group of selected fecal samples allowed us to shed light on both metabolic features and transcriptional responses of the intestinal bacterial community based on different diets.
Kasabach-Merritt phenomenon with cellulitis in infant
Authors: Yosi Ariyati , Siregar Abdullah Afif , Siregar Yasmine , Oentari Widyaningsih
Published: September 2020

Kasabach-Merritt phenomenon (KMP) is consumptive coagulopathy in large vascular lesion. This condition is specific in kaposiform haemangioendothelioma (KHE) and tufted angioma, associated with high mortality rate. This condition often involves the limbs, trunk and retroperitoneum. The clinical features that are usually found are purpura, oedema, induration and ecchymosis. A boy baby aged 9 months presented with a history of violaceous tumour that appeared on his left leg at birth that became enlarged since 6 months ago that caused discrepancy between both of his legs. The patient has his left leg massaged through alternative treatment, causing it became bruised and wounded. Blood examination showed normocytic normochromic anaemia with severe thrombocytopenia and high D-dimer. The patient was diagnosed with KMP with cellulitis and treated with oral corticosteroid, propranolol and antibiotics. Diagnosis of KMP can be made through clinical and laboratory findings. Combination therapy with corticosteroid and propranolol can be considered for KMP treatment.
Long-term outcome of transcanalicular microdrill dacryoplasty: a minimally invasive alternative for dacryocystorhinostomy
Authors: Mihailovic Natasa , Blumberg Alina Friederike , Rosenberger Friederike , Brücher Viktoria Constanze , Lahme Larissa , Eter Nicole , Merté Ralph-Laurent , Alnawaiseh Maged
Published: September 2020

Background/Aim

Dacryocystorhinostomy (DCR) remains the gold standard therapy for nasolacrimal duct obstruction (NLDO), but is invasive and does not maintain the physiology of the lacrimal pathway. With transcanlicular microdrill dacryoplasty (MDP), there is a minimally invasive alternative surgical approach. This study aimed to present this modern lacrimal duct surgery technique and to evaluate its long-term success rate in a large study population.

Methods

The medical records of 1010 patients with acquired NLDO were retrospectively reviewed. Adult patients who had undergone transcanalicular MDP were included. The evaluation included the following parameters: age, gender, success rate, complication rate, obstruction grade and patient satisfaction. Long-term results regarding patient satisfaction and success rate were evaluated by a telephone survey. Only a complete resolution of symptoms was defined as success.

Results

793 eyes of 576 patients after transcanalicular MDP could be included in the study. The mean follow-up time was 8.7±0.9 years. Initial surgical success rate was 84.0%. At the time of the follow-up, 57.5% (n=229) still had full resolution of symptoms. The mean patient satisfaction with the procedure was 6.9±3.2 out of 10 points. Heavy bleeding occurred in two cases only (0.25%).

Conclusion

This is the first study to show the success rate of microendoscopic lacrimal duct surgery after such a long follow-up period and in such a large study population. Transcanalicular MDP is a minimally invasive technique with a very low complication rate and can be used as an alternative procedure before performing more invasive lacrimal duct surgery such as DCR.
Quantification of vascular and neuronal changes in the peripapillary retinal area secondary to diabetic retinopathy
Authors: Frizziero Luisa , Parrozzani Raffaele , Londei Davide , Pilotto Elisabetta , Midena Edoardo
Published: September 2020

Purpose

To investigate and quantify peripapillary vascular and neuronal changes secondary to diabetic retinopathy, using spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA).

Design

This was a cross-sectional study.

Methods

51 eyes of 51 patients affected by non-proliferative diabetic retinopathy (NPDR) and 19 age-matched healthy control eyes underwent full ophthalmic examination, including OCT and OCTA in the peripapillary area. Vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI) were quantified in a ring-shaped region of interest of each OCTA image. Capillaries and larger vessels were separately analysed. The thickness of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell complex (GCC) was also analysed.

Results

VAD and VLF of peripapillary capillaries were significantly reduced in NPDR eyes, along with the progression of NPDR (p<0.05). VDI was significantly reduced in mild (p=0.0093) and moderate (p=0.0190) NPDR eyes, but not in severe NPDR (p=0.0841). Larger peripapillary vessels showed a significant increase of both VAD and VDI in NPDR eyes. pRNFL and GCC thickness decreased in NPDR eyes, reaching statistical significance only for GCC. No statistically significant correlation was found between perfusion parameters and pRNFL and GCC thickness.

Conclusions

Retinal capillary remodelling in NPDR involves the peripapillary vascularisation too, as confirmed by OCTA quantitative parameters. The peripapillary macrovasculature and microvasculature need to be separately evaluated. The lack of direct correlation between peripapillary capillaries changes and the loss of retinal nerve fibres suggests that neuronal damage cannot be simply considered secondary to the microvascular one.
Acceptability and feasibility of two interventions in the MooDFOOD Trial: a food-related depression prevention randomised controlled trial in overweight adults with subsyndromal symptoms of depression
Authors: Owens Matthew , Watkins Edward , Bot Mariska , Brouwer Ingeborg Annemarie , Roca Miquel , Kohls Elisabeth , Penninx Brenda , van Grootheest Gerard , Cabout Mieke , Hegerl Ulrich , Gili Margalida , Visser Marjolein
Published: September 2020

Objectives

We report on the acceptability, feasibility, dose-response relationship and adherence of two nutritional strategies to improve mood (multinutrient supplements; food-related behavioural activation (F-BA)) studied in a randomised controlled depression prevention trial (the Multi‐country cOllaborative project on the rOle of Diet, Food‐related behaviour, and Obesity in the prevention of Depression (MooDFOOD) Trial). We also assessed baseline determinants of adherence and assessed whether better adherence resulted in lower depressive symptoms.

Design

Randomised controlled trial with a 2×2 factorial design conducted between 2015 and 2017.

Setting

Germany, the Netherlands, UK and Spain.

Participants

Community sample of 1025 overweight adults with elevated depressive symptoms without a current episode of major depressive disorder. Main eligibility criteria included age (18–75 years), being overweight or obese, and having at least mild depressive symptoms, shown by a Patient Health Questionnaire Score of ≥5. A total of 76% of the sample was retained at the 12-month follow-up.

Interventions

Daily nutritional supplements versus pill placebo or an F-BA therapy, delivered in individual and group sessions versus no behavioural intervention over a 1-year period.

Primary and secondary outcome measures

Primary outcome: self-reported acceptability of the interventions. Secondary outcomes: adherence and self-reported depressive symptoms.

Results

Most participants reported that the F-BA was acceptable (83.61%), feasible to do (65.91%) and would recommend it to a friend (84.57%). Individual F-BA sessions (88.10%) were significantly more often rated as positive than group F-BA sessions (70.17%) and supplements (28.59%). There were statistically significant reductions in depressive symptoms for those who both adhered to the F-BA intervention and had a history of depression (B=−0.08, SE=0.03, p=0.012) versus those who had no history of depression. Supplement intake had no effect on depressive symptoms irrespective of adherence.

Conclusions

F-BA may have scope for development as a depression prevention intervention and public health strategy but further refinement and testing are needed.

Trial registration number

NCT02529423.
Cost–utility and budget impact analysis of tocilizumab for the treatment of refractory systemic juvenile idiopathic arthritis in Thailand
Authors: Kittiratchakool Nitichen , Kulpokin Disorn , Chanjam Chonticha , Vilaiyuk Soamarat , Charuvanij Sirirat , Phongsamart Gun , Khaosut Parichat , Tanya Manasita , Nanagara Ratanavadee , Nantapaisarn Sira , Leelahavarong Pattara
Published: September 2020

Objectives

This study aimed to analyse the cost–utility and budget impact of adding tocilizumab to the standard treatment for patients with refractory systemic juvenile idiopathic arthritis (sJIA) in Thailand.

Design

Economic evaluation using a decision-analytical model.

Setting

Thailand.

Participants

Patients with refractory sJIA who were ≥2 years old.

Methods

The use of tocilizumab as an add-on therapy to standard treatment was compared with standard treatment alone. A simulated health state transition model was used to estimate the lifetime costs and health outcomes from a societal perspective. Direct medical costs were collected from tertiary hospital databases while direct non-medical costs were derived from interviews. Health-related quality of life (QoL) was measured using the proxy version of three-level EuroQol five-dimensional questionnaire (EQ-5D-3L). Future costs and outcomes were discounted at an annual rate of 3%. The base case population was patients aged 9.41 years old at refractory disease onset. The results were reported as incremental cost-effectiveness ratios (ICER) in US dollar (USD). One-way and probabilistic sensitivity analysis were conducted to investigate parameter uncertainty. The 5-year budget impact was estimated from a governmental perspective.

Results

The ICER of standard treatment plus tocilizumab was US$35 799 per quality-adjusted life-year (QALY) gained compared with standard treatment alone, which was not cost-effective at the threshold of US$5128 per QALY gained. The estimated 5 years budget impact was approximately US$4.8 million.

Conclusions

The use of standard treatment plus tocilizumab was not cost-effective in the Thai context, which has limited data. However, there is currently no second-line treatment for refractory sJIA in the Thai National List of Essential Medicines; thus, patients must receive higher doses of standard treatment which can cause many side effects. In contrast, tocilizumab showed obvious efficacy in clinical trials in improving treatment response and QoL. Therefore, the price of tocilizumab should be negotiated to reduce the financial impact on the healthcare system.
Does a complex intervention targeting communities, health facilities and district health managers increase the utilisation of community-based child health services? A before and after study in intervention and comparison areas of Ethiopia
Authors: Berhanu Della , Okwaraji Yemisrach Behailu , Defar Atkure , Bekele Abebe , Lemango Ephrem Tekle , Medhanyie Araya Abrha , Wordofa Muluemebet Abera , Yitayal Mezgebu , W/Gebriel Fitsum , Desta Alem , Gebregizabher Fisseha Ashebir , Daka Dawit Wolde , Hunduma Alemayehu , Beyene Habtamu , Getahun Tigist , Getachew Theodros , Woldemariam Amare Tariku , Wolassa Desta , Persson Lars Åke , Schellenberg Joanna
Published: September 2020

Introduction

Ethiopia successfully reduced mortality in children below 5 years of age during the past few decades, but the utilisation of child health services was still low. Optimising the Health Extension Programme was a 2-year intervention in 26 districts, focusing on community engagement, capacity strengthening of primary care workers and reinforcement of district accountability of child health services. We report the intervention’s effectiveness on care utilisation for common childhood illnesses.

Methods

We included a representative sample of 5773 households with 2874 under-five children at baseline (December 2016 to February 2017) and 10 788 households and 5639 under-five children at endline surveys (December 2018 to February 2019) in intervention and comparison areas. Health facilities were also included. We assessed the effect of the intervention using difference-in-differences analyses.

Results

There were 31 intervention activities; many were one-off and implemented late. In eight districts, activities were interrupted for 4 months. Care-seeking for any illness in the 2 weeks before the survey for children aged 2–59 months at baseline was 58% (95% CI 47 to 68) in intervention and 49% (95% CI 39 to 60) in comparison areas. At end-line it was 39% (95% CI 32 to 45) in intervention and 34% (95% CI 27 to 41) in comparison areas (difference-in-differences −4 percentage points, adjusted OR 0.49, 95% CI 0.12 to 1.95). The intervention neither had an effect on care-seeking among sick neonates, nor on household participation in community engagement forums, supportive supervision of primary care workers, nor on indicators of district accountability for child health services.

Conclusion

We found no evidence to suggest that the intervention increased the utilisation of care for sick children. The lack of effect could partly be attributed to the short implementation period of a complex intervention and implementation interruption. Future funding schemes should take into consideration that complex interventions that include behaviour change may need an extended implementation period.

Trial registration number

ISRCTN12040912.
Management of children visiting the emergency department during out-of-office hours: an observational study
Authors: Schinkelshoek Gina , Borensztajn Dorine M , Zachariasse Joany M , Maconochie Ian K , Alves Claudio F , Freitas Paulo , Smit Frank J , van der Lei Johan , Steyerberg Ewout W , Greber-Platzer Susanne , Moll Henriëtte A
Published: September 2020

Background

The aim was to study the characteristics and management of children visiting the emergency department (ED) during out-of-office hours.

Methods

We analysed electronic health record data from 119 204 children visiting one of five EDs in four European countries. Patient characteristics and management (diagnostic tests, treatment, hospital admission and paediatric intensive care unit admission) were compared between children visiting during office hours and evening shifts, night shifts and weekend day shifts. Analyses were corrected for age, gender, Manchester Triage System urgency, abnormal vital signs, presenting problems and hospital.

Results

Patients presenting at night were younger (median (IQR) age: 3.7 (1.4–8.2) years vs 4.8 (1.8–9.9)), more often classified as high urgent (16.3% vs 9.9%) and more often had ≥2 abnormal vital signs (22.8% vs 18.1%) compared with office hours. After correcting for disease severity, laboratory and radiological tests were less likely to be requested (adjusted OR (aOR): 0.82, 95% CI 0.78–0.86 and aOR: 0.64, 95% CI 0.60–0.67, respectively); treatment was more likely to be undertaken (aOR: 1.56, 95% CI 1.49–1.63) and patients were more likely to be admitted to the hospital (aOR: 1.32, 95% CI 1.24–1.41) at night. Patterns in management during out-of-office hours were comparable between the different hospitals, with variability remaining.

Conclusions

Children visiting during the night are relatively more seriously ill, highlighting the need to keep improving emergency care on a 24-hour-a-day basis. Further research is needed to explain the differences in management during the night and how these differences affect patient outcomes.