bluuebunny/crossref_metadata_2025_split huggingface dataset:
Luminal A versus luminal B breast cancer: MammaTyper mRNA versus immunohistochemical subtyping with an emphasis on standardised Ki67 labelling‐based or mitotic activity index‐based proliferation assessment
Authors: Finsterbusch Kai , Decker Thomas , van Diest Paul J , Focke Cornelia M 
Published: December 2019

AimsProliferation assessment by the use of Ki67 is a crucial component in intrinsic subtyping of luminal breast cancers (BCs), but suffers from variability between laboratories, observers, and methods. MammaTyper is a quantitative molecular tool that measures mRNA levels of ERBB2, ESR1, PGR and MKI67 in BC, and interprets the results according to the St Gallen 2013 consensus recommendations. We compared MammaTyper with immunohistochemistry (IHC)‐based subtypes, with a focus on standardised proliferation assessment.Methods and resultsWe analysed the agreement in assigning subtypes between MammaTyper and receptor IHC in 101 unifocal luminal HER2‐negative early BCs of no special type. Two Ki67 counting protocols, Ki67‐Global (Ki67‐G) and Ki67‐HotSpot (Ki67‐H), recommended by the International Ki67 in BC Working Group, and the mitotic activity index (MAI) were used for proliferation assessment. The proportions of BCs identified as luminal A and as luminal B were 55% and 45% for MammaTyper, 55% and 45% for IHC + Ki67‐G, 36% and 64% for IHC + Ki67‐H, and 56% and 44% for IHC + MAI. The levels of agreement between MammaTyper‐based and IHC‐based subtyping were 84% (κ = 0.679) for IHC + Ki67‐G, 72% (κ = 0.462) for IHC + Ki67‐H, and 89% (κ = 0.779) for IHC + MAI.ConclusionsHigh rates of agreement between mRNA‐based and IHC‐based intrinsic subtyping of luminal HER2‐negative BC can be achieved. However, the agreement between IHC‐based and MammaTyper‐based luminal subtypes depends on the proliferation assessment method, and was highest when the MAI was used. Further comparative clinical studies are needed to determine which method is to be preferred, including analysis of cost‐effectiveness.
miR‐18a promotes Mycobacterial survival in macrophages via inhibiting autophagy by down‐regulation of ATM
Authors: Yuan Qiulu , Chen Haotian , Yang Yuxin , Fu Yurong , Yi Zhengjun 
Published: December 2019

AbstractTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of leading causes of global deaths. This study aimed to explore the role of miR‐18a in RAW264.7 cells response to Mtb infection. Exosomes derived from Mtb‐infected cells were isolated and further validated by size, transmission electron microscopy and Western blot. RT‐PCR was utilized to measure miR‐18a expression. Cell viability and ultrastructure were examined by CFU counting, CCK‐8 and electron microscope, respectively. Potential target genes of miR‐18a were predicted with bioinformatics and further confirmed using RT‐PCR, Western blot and laser confocal microscope analysis, respectively. LC3, AMPK and mTOR were measured using Western blot. We found that miR‐18a was induced both in Mtb‐infected RAW264.7 cells and its derived exosomes compared with the controls. In addition, up‐regulation of miR‐18a promoted intracellular Mtb survival, attenuated cell viability and reduced LC3‐II level, while its down‐regulation had the opposite effect. miR‐18a overexpression suppressed level of ATM, one possible target of miR‐18a, while its underexpression enhanced ATM. We also found that inhibition of ATM induced LC3‐II decrease in Mtb‐infected cells and could reverse the increase of LC3‐II caused by inhibition of miR‐18a. Moreover, down‐regulation of miR‐18a increased p‐AMPK level while reduction of ATM could reverse the change. Taken together, our results suggest that miR‐18a is up‐regulated in macrophages response to Mtb infection, and it promotes intracellular Mtb survival through repressing autophagic process by down‐regulation of ATM pathway. This provides new thought for TB pathogenesis, diagnosis and treatment.
Susceptibility of betanodavirus in a newly established vertebra‐derived cell line from Mosquitofish (Gambusia affinis)
Authors: Jyotsna  , Vijayakumar Parameswaran , Mani Ravi , Raja Sudhakaran , Dhas Tharmathass Stalin 
Published: December 2019

AbstractIn the present study, a new cell line from the vertebra of mosquitofish Gambusia affinis was successfully established and characterized. The cell line is named as bone Gambusia affinis (BGA) and subcultured for more than 55 passages in Leibovitz's/L15 medium supplemented with 15% FBS at 28°C. The cell line has a modal chromosome number of 48. Molecular characterization of the partial sequence of the coi gene confirmed the origin of the BGA cell line from mosquitofish. These cells exhibited epithelial morphology confirmed by the cytokeratin marker. The BGA cells showed mineralization of their extracellular matrix when stained with alizarin red and von Kossa stain. BGA cells were found to be susceptible to RGNNV and SJNNV strains of betanodavirus (NNV) showing cytopathic effect with multiple vacuolations in the cells. The RT‐PCR confirmed the betanodavirus infections in BGA cells. The SEM micrograph showed the morphological changes observed in the cell during virus infection. The in vivo challenge experiment also showed the viral replicating efficiency in the Gambusia affinis with increasing viral titre. Thus, our present results show that the BGA cell line is a useful tool for isolating betanodavirus and could be used to investigate bone cell differentiation and extracellular matrix mineralization.
Supply versus use designs of environmental extensions in input–output analysis: Conceptual and empirical implications for the case of energy
Authors: Wieland Hanspeter , Giljum Stefan , Eisenmenger Nina , Wiedenhofer Dominik , Bruckner Martin , Schaffartzik Anke , Owen Anne 
Published: December 2019

AbstractInput–output analysis is one of the central methodological pillars of industrial ecology. However, the literature that discusses different structures of environmental extensions (EEs), that is, the scope of physical flows and their attribution to sectors in the monetary input–output table (MIOT), remains fragmented. This article investigates the conceptual and empirical implications of applying two different but frequently used designs of EEs, using the case of energy accounting, where one represents energy supply while the other energy use in the economy. We derive both extensions from an official energy supply–use dataset and apply them to the same single‐region input–output (SRIO) model of Austria, thereby isolating the effect that stems from the decision for the extension design. We also crosscheck the SRIO results with energy footprints from the global multi‐regional input–output (GMRIO) dataset EXIOBASE. Our results show that the ranking of footprints of final demand categories (e.g., household and export) is sensitive to the extension design and that product‐level results can vary by several orders of magnitude. The GMRIO‐based comparison further reveals that for a few countries the supply‐extension result can be twice the size of the use‐extension footprint (e.g., Australia and Norway). We propose a graph approach to provide a generalized framework to disclosing the design of EEs. We discuss the conceptual differences between the two extension designs by applying analogies to hybrid life‐cycle assessment and conclude that our findings are relevant for monitoring of energy efficiency and emission reduction targets and corporate footprint accounting.
Integrated reporting and cost of capital: The moderating role of cultural dimensions
Authors: Vena Luigi , Sciascia Salvatore , Cortesi Alessandro 
Published: December 2019

AbstractSince its introduction, integrated reporting (IR) has triggered a rich debate covering several aspects, from the structure and the features of a document to the effects of its publication. Very recently, scholars have examined the negative relationship between IR and the cost of capital for firms, completely missing the opportunity to understand whether this fact is contingent on the cultural context that adopting companies operate in. We fill this gap by resorting to a panel sample of 211 adopters from 31 countries over the period spanning 2009–2017, counting 1,455 observations. Our evidence confirms that adopters, on average, benefit from a 1.4% decrease in the cost of capital. Yet, more importantly, IR effectiveness is exalted in countries with low power distance, strong collectivism values, and high level of masculinity, while uncertainty avoidance, long‐term orientation, and indulgence do not seem to play any moderating role.
Oxytocin receptor gene loss influences expression of the oxytocin gene in C57BL/6J mice in a sex‐ and age‐dependent manner
Authors: Vaidyanathan Radhika , Hammock Elizabeth A. D. 
Published: December 2019

AbstractParental care and sensory stimulation are critical environmental factors that influence oxytocin (OXT) and its receptor (OXTR). Because developmental Oxt mRNA expression is enhanced by sensory‐rich early life experience and reduced by sensory deprivation, we predicted that compared to wild‐type (WT) littermates, mice with congenital loss of OXTR (OXTR KO), as a genetically induced deprivation, would show impaired Oxt mRNA expression in the offspring hypothalamus during development. Oxt mRNA levels of male and female OXTR KO mice were not different from WT littermates from postnatal day (P)0 to P6, although, by P8, OXTR KO showed significantly decreased Oxt mRNA expression in the hypothalamus compared to WT littermates. At P14, male and female OXTR KO mice had significantly decreased Oxt mRNA expression specifically in the paraventricular nucleus (PVN), but not the supraoptic nucleus (SON), compared to WT littermates. We investigated whether this effect persisted in adulthood (P90) and found a significant genotype by sex interaction where male OXTR KO mice displayed a reduction in Oxt expression specific to the PVN compared to male WT littermates. By contrast, male and female OXTR KO adults had increased Oxt mRNA levels in the SON. These findings suggest that OXTR plays a role in developmental Oxt mRNA expression with sex by genotype interactions apparent at adulthood. We then measured OXT and neural activation in the PVN and SON at P14. We observed more OXT‐immunoreactive cells in the PVN of OXTR KO mice but significantly fewer c‐Fos immunoreactive cells. There were no genotype differences in immunoreactivity for OXT and no c‐Fos activity in the SON at P14. Combined, these data suggest that OXTR WT P14 mice have more PVN activity and are more likely to release OXT than OXTR KO mice. Future experiments are warranted to understand which OXTR‐expressing neural circuits modulate the development of the PVN oxytocin system.
NEW EVIDENCE ON THE HECKMAN CURVE
Authors: Rea David , Burton Tony 
Published: December 2019

AbstractThe Heckman Curve characterizes the rate of return to public investments in human capital as rapidly diminishing with age. For the disadvantaged, it describes investments early in the life course as having significantly higher rates of return compared to later in life. This paper assesses the Heckman Curve using estimates of program benefit cost ratios from the Washington State Institute for Public Policy. We find no support for the claim that social policy programs targeted early in the life course have the largest benefit cost ratios, or that on average the benefits of adult programs are less than the cost of the intervention.
An educational intervention to update health workers about HIV and infant feeding
Authors: Horwood Christiane , Haskins Lyn , Goga Ameena , Doherty Tanya , John Vaughn , Engebretsen Ingunn M.S. , Feucht Ute , Rollins Nigel , Kroon Max , Sanders David , Tylleskar Thorkild 
Published: December 2019

AbstractClinical guidelines are used to translate research findings into evidence‐based clinical practice but are frequently not comprehensively adopted by health workers (HWs). HIV and infant feeding guidelines were revised by the World Health Organization to align feeding advice for HIV‐exposed and unexposed infants, and these were adopted in South Africa in 2017. We describe an innovative, team‐based, mentoring programme developed to update HWs on these guidelines. The intervention was underpinned by strong theoretical frameworks and aimed to improve HWs' attitudes, knowledge, confidence, and skills about breastfeeding in the context of HIV. On‐site workshops and clinical mentoring used interactive participatory methods and a simple low‐tech approach, guided by participants' self‐reported knowledge gaps. Workshops were conducted at 24 participating clinics over three sessions, each lasting 1–2 hr. Evaluation data were collected using a self‐administered questionnaire. Of 303 participating HWs, 249/303 (82.2%) attended all workshops. Achieving high workshop attendance was challenging and “catch‐up” sessions were required to achieve good coverage. Common knowledge gaps identified included antiretroviral therapy adherence monitoring during breastfeeding and management of viral load results (173 participants), management of breast conditions (79), and advice about expressing and storing breastmilk (64). Most participants reported all their knowledge gaps were addressed and anticipated that their practice would change.We describe a feasible, sustainable approach to updating HWs on HIV and infant feeding guidelines and improving skills in breastfeeding counselling in resource‐constrained settings. This approach could be adapted to other topics and, with further evaluation, implemented at scale using existing resources.
Host dispersal shapes the population structure of a tick‐borne bacterial pathogen
Authors: Norte Ana Cláudia , Margos Gabriele , Becker Noémie S. , Albino Ramos Jaime , Núncio Maria Sofia , Fingerle Volker , Araújo Pedro Miguel , Adamík Peter , Alivizatos Haralambos , Barba Emilio , Barrientos Rafael , Cauchard Laure , Csörgő Tibor , Diakou Anastasia , Dingemanse Niels J. , Doligez Blandine , Dubiec Anna , Eeva Tapio , Flaisz Barbara , Grim Tomas , Hau Michaela , Heylen Dieter , Hornok Sándor , Kazantzidis Savas , Kováts David , Krause František , Literak Ivan , Mänd Raivo , Mentesana Lucia , Morinay Jennifer , Mutanen Marko , Neto Júlio Manuel , Nováková Markéta , Sanz Juan José , Pascoal da Silva Luís , Sprong Hein , Tirri Ina‐Sabrina , Török János , Trilar Tomi , Tyller Zdeněk , Visser Marcel E. , Lopes de Carvalho Isabel 
Published: December 2019

AbstractBirds are hosts for several zoonotic pathogens. Because of their high mobility, especially of longdistance migrants, birds can disperse these pathogens, affecting their distribution and phylogeography. We focused onBorrelia burgdorferisensu lato, which includes the causative agents of Lyme borreliosis, as an example for tick‐borne pathogens, to address the role of birds as propagation hosts of zoonotic agents at a large geographical scale. We collected ticks from passerine birds in 11 European countries.B. burgdorferis.l. prevalence inIxodesspp. was 37% and increased with latitude. The fieldfareTurdus pilarisand the blackbirdT. merulacarried ticks with the highestBorreliaprevalence (92 and 58%, respectively), whereas robinErithacus rubeculaticks were the least infected (3.8%).Borrelia gariniiwas the most prevalent genospecies (61%), followed byB. valaisiana(24%),B. afzelii(9%),B. turdi(5%) andB. lusitaniae(0.5%). A novelBorreliagenospecies “CandidatusBorrelia aligera” was also detected. Multilocus sequence typing (MLST) analysis ofB. gariniiisolates together with the global collection ofB. gariniigenotypes obtained from theBorreliaMLSTpublic database revealed that: (a) there was little overlap among genotypes from different continents, (b) there was no geographical structuring within Europe, and (c) there was no evident association pattern detectable amongB. gariniigenotypes from ticks feeding on birds, questing ticks or human isolates. These findings strengthen the hypothesis that the population structure and evolutionary biology of tick‐borne pathogens are shaped by their host associations and the movement patterns of these hosts.
The asymmetric innervation of the circular and longitudinal muscle of the mouse colon differently modulates myogenic slow phasic contractions
Authors: Traserra Sara , Villarte Sonia , Traini Chiara , Palacin Sara , Vergara Patri , Vannucchi Maria Giuliana , Jimenez Marcel 
Published: December 2019

AbstractBackgroundNeuromuscular transmission has been extensively studied in the circular layer of the mouse colon where a co‐transmission of purines acting on P2Y1 receptors and NO has been previously described. However, the corresponding mechanisms in the longitudinal layer are less known.MethodsElectrophysiological and myography techniques were used to evaluate spontaneous phasic contractions (SPC) and neural‐mediated responses in the proximal, mid, and distal colon devoid of CD1 mice. Immunohistochemistry against c‐kit and PDGFRα was performed in each colonic segment.Key ResultsSPC were recorded in both muscle layers at a similar frequency being about four contractions per minute (c.p.m.) in the proximal and distal colon compared to the mid colon (2 c.p.m.). In non‐adrenergic, non‐cholinergic conditions, L‐NNA (1 mmol/L) increased contractility in the circular but not in the longitudinal layer. In the longitudinal muscle, both electrophysiological and mechanical neural‐mediated inhibitory responses were L‐NNA and ODQ (10 µmol/L) sensitive. NaNP (1 µmol/L) caused cessation of SPC and the response was blocked by ODQ. Neither ADPßS (10 µmol/L) nor CYPPA (10 µmol/L), which both targeted the purinergic pathway, altered longitudinal contractions. PDGFRα + cells were located in both muscle layers and were more numerous compared with cKit + cells, which both formed a heterologous cellular network. A decreasing gradient of the PDGFRα labeling was observed along the colon.ConclusionAn inhibitory neural tone was absent in the longitudinal layer and neuronal inhibitory responses were mainly nitrergic. Despite the presence of PDGFRα + cells, purinergic responses were absent. Post‐junctional pathways located in different cell types might be responsible for neurotransmitter transduction.
Clinical characteristics of boys with comorbid autism spectrum disorder and attention deficit/hyperactivity disorder
Authors: Yamawaki Kaori , Ishitsuka Kazue , Suyama Satoshi , Suzumura Shunsuke , Yamashita Hiroshi , Kanba Shigenobu 
Published: December 2019

AbstractBackgroundAutism spectrum disorder (ASD) and attention deficit / hyperactivity disorder (ADHD) are frequently comorbid and, as both are defined as neurodevelopmental disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, simultaneous diagnosis is possible. However, despite the frequency of this comorbid state, its endophenotypic features remain unclear. This study thus aimed to describe the behavioral and emotional problems in boys with comorbid ASD and ADHD using the Strengths and Difficulties Questionnaire (SDQ).MethodsIn total, 102 boys (age, 6–12 years) diagnosed with one or both disorders were divided into three groups according to their clinical diagnosis: ASD + ADHD (N = 39), ASD (N = 37), and ADHD (N = 25). Symptoms and related behaviors were compared among the groups using parents’ ratings of the autism spectrum quotient, ADHD rating scale‐IV, and SDQ.ResultsIn the ASD + ADHD group, the proportion of “clinical‐range” cases was as high as 76.9% for the SDQ total difficulties score (TDS). The ASD + ADHD and ADHD groups had significantly higher TDS as well as behavioral problems and hyperactivity subscale scores than did the ASD group; however, the ASD + ADHD group did not have significantly different scores on any subscale compared with the other two groups. The ASD + ADHD and ASD groups also had significantly lower prosocial behavior scores than the ADHD group.ConclusionsWhen using the SDQ as a screening tool for neurodevelopmental disorders, a high TDS, conduct problems, hyperactivity, and low prosocial behavior can be considered characteristic of ASD and ADHD comorbidity in 6‐ to 12‐year‐old boys.
Transcutaneous blood gas monitoring among neonatal intensive care units in Japan
Authors: Ochiai Masayuki , Kurata Hiroaki , Inoue Hirosuke , Ichiyama Masako , Fujiyoshi Junko , Watabe Shinichi , Hiroma Takehiko , Nakamura Tomohiko , Ohga Shouichi 
Published: December 2019

AbstractBackgroundThis study aimed to investigate the utility of transcutaneous (tc) measurements of partial pressure of oxygen (tcPO2) and carbon dioxide (tcPCO2) monitoring in neonatal intensive care units (NICUs) in Japan.MethodsAt the end of 2016,we sent a survey questionnaire on tc monitoring to all 106 NICUs registered with the Japanese Neonatologist Association. The questions included usage, subjects, methods, management, and the practical usefulness of tc monitoring.ResultsThe questionnaire was returned by 69 NICUs (65.1% of response rate). Seventeen institutions (24.6%) measured both tcPCO2 and tcPO2, and 42 (60.9%) measured tcPCO2 alone. Transcutaneous PCO2 or tcPO2 monitoring was applied for “pre‐viable” infants born at 22–23 weeks’ gestational age (18.6% vs 23.5%), and infants of <500 g birthweight (30.5% vs 17.6%). The tcPCO2 and tcPO2 monitoring was started at birth in 49.2% and 70.6% of the newborn infants, respectively. The temperature of the sensor was set at <38°C for tcPCO2 in 54.3% and >42°C for tcPO2 in 58.9% of NICUs. The accuracy for tcPO2 was rated as good in 35.3% or moderate in 64.7%, of institutions but or for tcPCO2 as 1.7% or 93.2%of institutions , respectively.ConclusionTranscutaneous monitoring was widely, but limitedly, used for preterm infants. The lower temperature of the tcPCO2 sensor compared to that reported in other developed countries might compromise the accuracy but increase the feasibility of tc monitoring in Japan.
Implementation assessment in confidential enquiry programmes: A scoping review
Authors: Jayakody Hemali , Knight Marian 
Published: December 2019

AbstractBackgroundResponse should be a key part of maternal death surveillance and response (MDSR) programmes, which include confidential enquiries into maternal deaths. The programmes investigate avoidable factors in maternal deaths and make recommendations for improving maternity care. There is a gap in information on how these recommendations are transformed into practice.ObjectiveTo explore the methods used to assess the implementation status of recommendations made in confidential enquiries into maternal deaths and other health outcomes.Data sourcesWe searched PubMed, Web of Science, CINAHL, and Google Scholar databases and general web for grey literature using the “Arksey and O’Malley framework” in all major scientific databases and search engines.Study selection and data extractionAn initial screening was followed by extraction of information using a data chart. Variables in the chart were based on the response component of maternal death and surveillance systems.SynthesisInformation collected was summarised using content analysis method.ResultsWe reviewed 13 confidential enquiry systems into maternal deaths. Many confidential enquiries into maternal deaths published reports with their recommendations and dissemination often involved national‐level scientific presentations. Only five reports provided strategies for implementing the recommendations. Follow‐up of previous recommendations was routinely published in only two reports. However, impact assessment of recommendations on other health outcomes was found only in the UK.ConclusionThere is a gap in monitoring the response generated by confidential enquiries into maternal deaths. Actions to develop this are therefore needed.