bluuebunny/crossref_metadata_2025 huggingface dataset:
Galectin-10, the protein that forms Charcot-Leyden crystals, is not stored in granules but resides in the peripheral cytoplasm of human eosinophils
Authors: Melo Rossana C N , Wang Haibin , Silva Thiago P , Imoto Yoshimasa , Fujieda Shigeharu , Fukuchi Mineyo , Miyabe Yui , Hirokawa Makoto , Ueki Shigeharu , Weller Peter F
Published: February 2020

A predominant protein of human eosinophils is galectin-10 (Gal-10), also known as Charcot-Leyden crystal protein (CLC-P) because of its remarkable ability to form Charcot-Leyden crystals (CLCs), which are frequently found in tissues from patients with eosinophilic disorders. CLC-P/Gal-10 is highly expressed in human eosinophils and considered a biomarker of eosinophil involvement in inflammation. However, the intracellular sites where large pools of CLC-P/Gal-10 constitutively reside are still unclear, and whether this protein is derived or not from eosinophil granules remains to be established. Here, we applied pre-embedding immunonanogold transmission electron microscopy combined with strategies for optimal antigen and cell preservation and quantitative imaging analysis to investigate, for the first time, the intracellular localization of CLC-P/Gal-10 at high resolution in resting and activated human eosinophils. We demonstrated that CLC-P/Gal-10 is mostly stored in the peripheral cytoplasm of human eosinophils, being accumulated within an area of ∼250 nm wide underneath the plasma membrane and not within specific (secretory) granules, a pattern also observed by immunofluorescence. High-resolution analysis of single cells revealed that CLC-P/Gal-10 interacts with the plasma membrane with immunoreactive microdomains of high CLC-P/Gal-10 density being found in ∼60% of the membrane area. Eosinophil stimulation with CCL11 or TNF-α, which are known inducers of eosinophil secretion, did not change the peripheral localization of CLC-P/Gal-10 as observed by both immunofluorescence and immuno-EM (electron microscopy). Thus, in contrast to other preformed eosinophil proteins, CLC-P/Gal-10 neither is stored within secretory granules nor exported through classical degranulation mechanisms (piecemeal degranulation and compound exocytosis).
Chicken-or-egg question: Which came first, extracellular vesicles or autoimmune diseases?
Authors: Maione Federica , Cappellano Giuseppe , Bellan Mattia , Raineri Davide , Chiocchetti Annalisa
Published: February 2020

Extracellular vesicles (EVs) have attracted great interest as contributors to autoimmune disease (AD) pathogenesis, owing to their immunomodulatory potential; they may also play a role in triggering tolerance disruption, by delivering auto-antigens. EVs are released by almost all cell types, and afford paracrine or distal cell communication, functioning as biological carriers of active molecules including lipids, proteins, and nucleic acids. Depending on stimuli from the external microenvironment or on their cargo, EVs can promote or suppress immune responses. ADs are triggered by inappropriate immune-system activation against the self, but their precise etiology is still poorly understood. Accumulating evidence indicates that lifestyle and diet have a strong impact on their clinical onset and development. However, to date the mechanisms underlying AD pathogenesis are not fully clarified, and reliable markers, which would provide early prediction and disease progression monitoring, are lacking. In this connection, EVs have recently been indicated as a promising source of AD biomarkers. Although EV isolation is currently based on differential centrifugation or density-gradient ultracentrifugation, the resulting co-isolation of contaminants (i.e., protein aggregates), and the pooling of all EVs in one sample, limit this approach to abundantly-expressed EVs. Flow cytometry is one of the most promising methods for detecting EVs as biomarkers, and may have diagnostic applications. Furthermore, very recent findings describe a new method for identifying and sorting EVs by flow cytometry from freshly collected body fluids, based on specific EV surface markers.
Impact of RAS mutations on the immune infiltrate of colorectal liver metastases: A preliminary study
Authors: Polidoro Michela Anna , Milana Flavio , Soldani Cristiana , Franceschini Barbara , Anselmo Achille , Colombo Federico Simone , Di Tommaso Luca , Cimino Matteo , Carnevale Silvia , Lleo Ana , Jaillon Sebastien , Torzilli Guido , Donadon Matteo
Published: February 2020

Kirsten rat sarcoma viral oncogene homolog KRAS proto-oncogene is the most common altered gene in colorectal cancer (CRC). Determining its mutational status, which is associated with worse prognosis and resistance to anti-epidermal growth factor receptor (EGFR) inhibitors, is essential for managing patients with CRC and colon liver metastases (CLM). Emerging studies highlighted the relationship of KRAS-mutated cancers and tumor microenvironment components, mainly with T cells. The aim of this study was to analyze the relationship of CLM immune cell infiltrate with KRAS mutational status. We performed a retrospective study on paraffin-embedded CLM tissue sections from patients surgically resected at the Department of Hepatobiliary and General Surgery of Humanitas Clinical and Cancer Center. We studied the distribution of lymphocytes (CD3+ cells), macrophages (CD163+), and neutrophils (CD66b+) in CLM tumoral and peritumoral area. Percentage of positive cells was correlated with tumor macroscopic characteristic, clinical aspects, and KRAS mutation. We observed a significant increase in CD66b+ cells in the peritumoral area in patients KRAS-mutated compared to KRAS wild-type patients. Percentages of lymphocytes and macrophages did not show significant differences. Further, neutrophils were found to be significantly increased also in the bloodstream of KRAS-mutated patients, indicating increased mobilization of neutrophils and recruitment in the CLM site. In conclusion, this study reveals a new intriguing aspect of the peritumoral microenvironment, which could pave the way for new prognostic and predictive markers for patient stratification.
Clinical trial analysis of 2019‐nCoV therapy registered in China
Authors: Zhang Qi , Wang Yakun , Qi Changsong , Shen Lin , Li Jian
Published: February 2020

So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.
Human papillomavirus E6: Host cell receptor, GRP78, binding site prediction
Authors: Elfiky Abdo A.
Published: February 2020

Human papillomavirus (HPV) is the main cervical cancer‐promoting element that is transmitted through sexual routes. Anal, head, and throat cancers are also reported to be accompanied by HPV infection. E6 is one of the HPV nonstructural proteins, which is responsible for cell differentiation by targeting tumor suppressor genes, p105Rb and p53. E6 was reported to be stabilized by two chaperone proteins; glucose‐regulated protein 78 (GRP78) and heat shock protein 90. GRP78 is responsible for the unfolded protein response of the cells, and it was reported to be upregulated in many cancers, including cervical cancer. It was reported that knocking out GRP78 destabilizes E6 leading to faster degradation of E6 in vivo. The current work predicts the possible binding mode between E6 and GRP78 based on sequence and structural similarities.
Testing Shortened Versions of Smell Tests to Screen for Hyposmia in Parkinson's Disease
Authors: Auger Stephen D. , Kanavou Sofia , Lawton Michael , Ben‐Shlomo Yoav , Hu Michele T. , Schrag Anette E. , Morris Huw R. , Grosset Donald G. , Noyce Alastair J.
Published: February 2020

Background

Hyposmia is an early feature in neurodegenerative diseases, most notably Parkinson's disease (PD). Using abbreviated smell tests could provide a cost‐effective means for large‐scale hyposmia screening. It is unclear whether short smell tests can effectively detect hyposmia in patient populations.

Objectives

To test the ability of short smell combinations to “prescreen” for probable hyposmia in people with PD and target administration of more extensive tests, such as the University of Pennsylvania Smell Identification Test.

Methods

We assessed the screening performance of a short 4‐smell combination previously derived from use of the 40‐item University of Pennsylvania Smell Identification Test in healthy older people and its ability to detect hyposmia in a large cohort of PD patients.

Results

The novel 4‐smell combination included menthol, clove, onion, and orange and had a sensitivity of 87.1% (95% confidence interval, 84.9%–89.2%) and specificity of 69.7% (63.3%–75.5%) for detecting hyposmia in patients with PD. A different (also novel) 4‐item combination developed using a data‐driven approach in PD patients only achieved 81.3% (78.2%–84.4%) sensitivity for equivalent specificity.

Conclusions

A short 4‐smell combination derived from a healthy population demonstrated high sensitivity to detect those with hyposmia and PD.
Neonatal exposure to bisphenol A advances pubertal development in female rats
Authors: Qiu Jing , Sun Yanyan , Sun Wen , Wang Yonghong , Fan Teng , Yu Jian
Published: February 2020

Neonatal exposure to bisphenol A (BPA) is hypothesized to advance pubertal development. However, the effects of neonatal BPA exposure on pubertal development has not been described. In this study, female Sprague‐Dawley rats were exposed to 0.05, 0.5, 5, or 10 mg·kg−1·day−1 BPA, or corn oil vehicle alone from postnatal day 1 (PND1) to PND10 via subcutaneous injection. We evaluated day of vaginal opening (DVO), ovarian morphology, serum hormone concentrations, and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35. DVO was significantly advanced in rats exposed to 5 and 10 mg·kg−1·day−1 BPA. Serum hormone concentrations increased as BPA dose increased. Additionally, hypothalamic Gnrh1 and Kiss1 expression were increased with BPA exposure; rats exposed to 10 mg·kg−1·day−1 BPA had significantly upregulated hypothalamic Gnrh1 and Kiss1 expressions in terms of both messenger RNA and protein levels. Our results suggest that exposure to a 10 mg·kg−1·day−1 dose of BPA might advance pubertal development significantly. In addition, within the range of 0 to 10 mg·kg−1·day−1, neonatal exposure to BPA may affect pubertal development in a dose‐dependent manner.
Absence of MyD88 from Skeletal Muscle Protects Female Mice from Inactivity‐Induced Adiposity and Insulin Resistance
Authors: Mahmassani Ziad S. , Reidy Paul T. , McKenzie Alec I. , Petrocelli Jonathan J. , Matthews O’Connor , de Hart Naomi M. , Ferrara Patrick J. , O’Connell Ryan M. , Funai Katsuhiko , Drummond Micah J.
Published: February 2020

Objective

Inactivity and inflammation are linked to obesity and insulin resistance. It was hypothesized that MyD88 (mediates inflammation) knockout from muscle (MusMyD88−/−) would prevent, whereas miR146a−/− (MyD88 inhibitor) would exacerbate, inactivity‐induced metabolic disturbances.

Methods

Cre‐control, MusMyD88−/−, and miR146a−/− mice were given running wheels for 5 weeks to model an active phenotype. Afterward, half were placed into a small mouse cage (SMC) to restrict movement for 8 days. Body composition, muscle (3H)2‐deoxyglucose uptake, visceral fat histology, and tissue weight (hind limb muscles, visceral fat, and liver) were assessed. In skeletal muscle and visceral fat, RNA sequencing and mitochondrial function were performed on female MusMyD88−/− and Cre‐control SMC mice.

Results

The SMC induced adiposity, hyperinsulinemia, and muscle insulin‐stimulated glucose uptake, which was worsened in miR146a−/− mice. In females, MusMyD88−/− mice were protected. Female MusMyD88−/− mice during the SMC period (vs. Cre‐control) exhibited higher Igf1 and decreased Ip6k3 and Trim63 muscle expression. Visceral fat transcript changes corresponded to improved lipid metabolism, decreased adipose expansion (Gulp1↑, Anxa2↓, Ehd1↓) and meta‐inflammation (Hmox1↓), and increased beiging (Fgf10↑). Ralgapa2, negative regulator of GLUT4 translocation, and inflammation‐related gene 993011J21Rik2 were decreased in both muscle and fat.

Conclusions

Whole‐body miR146a−/− exacerbated inactivity‐induced fat gain and muscle insulin resistance, whereas MusMyD88−/− prevented insulin resistance in female mice.
Interfacial crystallization behavior of poly(ether‐ether‐ketone) on polyimide‐modified CCF300 carbon fibers
Authors: Li Xuekuan , Zhao Yan , Wang Kai
Published: February 2020

Thermostable polyimide (PI) was synthesized and used as a sizing agent to modify carbon fiber (CF) surfaces. In order to investigate the influence of the PI sizing agent on interfacial properties of continuous CF reinforced poly(ether‐ether‐ketone) (CF/PEEK) composites, a comparative investigation on the interfacial crystallization behavior of PEEK on CF surface with and without PI modification was performed by in situ polarized optical microscope (POM) and differential scanning calorimetry (DSC) analysis. The POM images showed that the unsized CFs acted as heterogeneous nucleating agents to accelerate the formation of transcrystals, whereas CFs with PI sizing agents reduced nucleation site density, inducing nonuniform crystal layers. Quantitative investigation on the kinetics of interfacial crystallization growth also revealed that the PI sizing agent was an obvious obstacle to nucleation and subsequent crystallization growth. Based on the Jeziorny‐modified Avrami model, nonisothermal crystallization kinetics was studied over a large range of cooling rates, whose results were found consistent with the results in POM observation. Moreover, a theoretical model was proposed to reveal the mechanisms for the considerable influence of the PI sizing agent on the interfacial crystallization behavior of PEEK in CF/PEEK composites, and the predication for other systems was also performed.
Efficacy and Safety of AbobotulinumtoxinA for the Treatment of Hemiparesis in Adults with Lower Limb Spasticity Previously Treated With Other Botulinum Toxins: A Secondary Analysis of a Randomized Controlled Trial
Authors: Esquenazi Alberto , Stoquart Gaëtan , Hedera Peter , Jacinto Luis Jorge , Dimanico Ugo , Constant‐Boyer Francois , Brashear Allison , Grandoulier Anne‐Sophie , Vilain Claire , Picaut Philippe , Gracies Jean‐Michel
Published: February 2020

Objective

To examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT‐A) products other than abobotulinumtoxinA.

Design

Secondary analysis from a phase 3, double‐blind, single‐cycle, randomized, placebo‐controlled study.

Setting

Fifty‐two centers (11 countries).

Patients

Adults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb.

Main Outcome Measurements

Muscle tone (6‐point Modified Ashworth Scale [MAS], 0‐5) for the gastrocnemius‐soleus complex (GSC); proportion of MAS responders (≥1‐point improvement); angle of catch (XV3) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post‐injection. Only descriptive statistics are presented.

Results

Of 388 patients, 84 received previous BoNT‐A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were − 0.8 (1.1), −0.9 (1.0), and − 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, −0.4 (0.7), −0.6 (0.8) and − 0.0 (0.9); soleus, −0.5 (0.7), −0.5 (0.7) and − 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA.

Conclusions

Patients previously treated with other BoNT‐As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other BoNT‐A products.
Management of extensive subcutaneous emphysema using negative pressure wound therapy dressings
Authors: Huan Nai‐Chien , Mohamed Arifin Noorasyikin , Khoo Teng‐Shin , Lai Yean‐Chen
Published: February 2020

Subcutaneous emphysema (SE) is a common but usually self‐limiting complication of cardiothoracic procedures. Rarely, it can be life threatening and is characterized by extensive cutaneous tension and airway compromise requiring immediate intervention. There is a paucity of data on the most efficacious treatment methods for extensive SE. We report an 80‐year‐old gentleman who developed massive SE necessitating intubation for airway protection following a right chest tube insertion for spontaneous secondary pneumothorax. His SE persisted despite adequate thoracic drainage via a new chest tube. It was then decided to insert two negative pressure wound therapy dressings (NPWTD) or vacuum dressings in the patient's subcutaneous tissue layer via incisions made at anterior chest wall. The dressings were removed after four days in view of significant improvements. NPWTD appears to be an effective, well‐tolerated, safe, and inexpensive approach that hastens the resolution of SE without the need for invasive thoracic surgeries.
Variance estimation when using propensity‐score matching with replacement with survival or time‐to‐event outcomes
Authors: Austin Peter C. , Cafri Guy
Published: February 2020

Propensity‐score matching is a popular analytic method to estimate the effects of treatments when using observational data. Matching on the propensity score typically requires a pool of potential controls that is larger than the number of treated or exposed subjects. The most common approach to matching on the propensity score is matching without replacement, in which each control subject is matched to at most one treated subject. Failure to find a matched control for each treated subject can lead to “bias due to incomplete matching.” To avoid this bias, it is important to identify a matched control subject for each treated subject. An alternative to matching without replacement is matching with replacement, in which control subjects are allowed to be matched to multiple treated subjects. A limitation to the use of matching with replacement is that variance estimation must account for both the matched nature of the sample and for some control subjects being included in multiple matched sets. While a variance estimator has been proposed for when outcomes are continuous, no such estimator has been proposed for use with time‐to‐event outcomes, which are common in medical and epidemiological research. We propose a variance estimator for the hazard ratio when matching with replacement. We conducted a series of Monte Carlo simulations to examine the performance of this estimator. We illustrate the utility of matching with replacement to estimate the effect of smoking cessation counseling on survival in smokers discharged from hospital with a heart attack.
Phosphorylated Starches: Preparation, Properties, Functionality, and Techno‐Applications
Authors: Ramadan Mohamed Fawzy , Sitohy Mahmoud Z.
Published: February 2020

Starches are valuable biopolymers with several functional and technical applications. Physical and chemical modifications are needed to enhance starch functionality. Modified starches exhibit high technological properties in food and non‐food applications. Modified starches are designed to overcome some physicochemical shortcomings of native starches, such as loss of thickening power and viscosity during thermal treatments, storage, retrogradation, and syneresis. Phosphorylation is an effective technique to enhance the functional traits of starches and to modify its physicochemical characteristics (i.e., pasting, gelatinization, and retrogradation). This review summarizes preparation methods, physicochemical properties as well as food and non‐food applications of phosphorylated starch (PS). PSs are being used as a thickener, emulsifier, and stabilizer in food applications. Furthermore, PS can be used as a sedimentation agent for the reclamation of wastes of spent water from the processing of fruits, meat, fishes, vegetables, and brewage. Because PS can substitute and reduce the amount of polyvinyl alcohol, it is used for fixing and sizing in the textile industry. In addition, PS can be used for paper sizing or paper cardboard adhesive coating. It is anticipated that new ventures for PS and their diverse applications will continue to be of a major interest in applied sciences.
Recovery of Au Nanoparticles via High‐Solubility Carboxylic Starch and its Significantly Improved Catalysis of Propylene Epoxidation
Authors: Zhang Shuidong , Shi Tao , Lin Zesheng , Chen Chuanrui , Chen Yukun , Odoom‐Wubah Tareque
Published: February 2020

Recovery of Au nanoparticles (Au NPs) catalysts via bioreduction method has attracted much attention due to its cost‐effective and eco‐friendly. However, it is a great challenge to recover Au NPs by starch due to its poor solubility. Herein, a novel biomolecule, carboxyl corn starch (CCS), exhibited high solubility and low viscosity is successfully fabricated and utilized to reduce HAuCl4 in the homogeneous phase environment. Effects of CCS concentration on the structure and performances of Au NPs and its loading in the TS‐1 support (Au/TS‐1) are investigated. The results reveal that both the particle size and Au NPs recovery rate increased with the increase of CCS concentration, while the BET data of Au/TS‐1 decreased. The Au/TS‐1 catalyst achieved 353.01 m2g−1 surface area and 0.293 cm3g−1 pore volume with 2.0 ± 0.3 nm average diameter of loaded Au NPs. When this catalyst is employed to catalyze the vapor phase propylene epoxidation with H2/O2 mixture, the propylene conversion rate (19.2%) achieved 67% and 5.8 fold increases when in data reported (11.5%) and soluble starch are used as the control, respectively. The study develops a green and facile method for Au recovery via carboxyl starch bioreduction and Au/TS‐1 exhibited significantly improves catalysis of propylene epoxidation.
Combining visible near‐infrared spectroscopy and water vapor sorption for soil specific surface area estimation
Authors: Knadel Maria , de Jonge Lis Wollesen , Tuller Markus , Rehman Hafeez Ur , Jensen Peter Weber , Moldrup Per , Greve Mogens H. , Arthur Emmanuel
Published: February 2020

The soil specific surface area (SSA) is a fundamental property governing a range of soil processes relevant to engineering, environmental, and agricultural applications. A method for SSA determination based on a combination of visible near‐infrared spectroscopy (vis‐NIRS) and vapor sorption isotherm measurements was proposed. Two models for water vapor sorption isotherms (WSIs) were used: the Tuller–Or (TO) and the Guggenheim–Anderson–de Boer (GAB) model. They were parameterized with sorption isotherm measurements and applied for SSA estimation for a wide range of soils (N = 270) from 27 countries. The generated vis‐NIRS models were compared with models where the SSA was determined with the ethylene glycol monoethyl ether (EGME) method. Different regression techniques were tested and included partial least squares (PLS), support vector machines (SVM), and artificial neural networks (ANN). The effect of dataset subdivision based on EGME values on model performance was also tested. Successful calibration models for SSATOand SSAGABwere generated and were nearly identical to that of SSAEGME. The performance of models was dependent on the range and variation in SSA values. However, the comparison using selected validation samples indicated no significant differences in the estimated SSATO, SSAGAB, and SSAEGME, with an average standardized RMSE (SRMSE = RMSE/range) of 0.07, 0.06 and 0.07, respectively. Small differences among the regression techniques were found, yet SVM performed best. The results of this study indicate that the combination of vis‐NIRS with the WSI as a reference technique for vis‐NIRS models provides SSA estimations akin to the EGME method.
Multilevel Linear Regression Using MLwiN: Mortality in England and Wales, 1979–1992
Authors: Leyland Alastair H. , Groenewegen Peter P.
Published: February 2020

In this chapter, the reader becomes a user. This chapter contains the first of three tutorials that readers can work through, using the specialist multilevel modelling software MLwiN. We introduce MLwiN as a package; this software will also be used in the other two tutorials. This tutorial introduces practical linear multilevel analysis. It uses data on mortality in England and Wales over time. The dependent or outcome variable is the standard mortality ratio in a given year between 1972 and 1996, for districts which are nested within counties.

Because this is the first tutorial, we go into some detail regarding the use of MLwiN, and how to use it to manipulate and explore the data. The tutorial starts with the estimation of a single-level model, then moves on to a two-level and three-level model. We begin with a random intercept model and progress to a random slope model. Throughout the tutorial graphs are used to enable visualisation of the results of the analyses. At the end of this tutorial, we detail an alternative analysis of the data using a multilevel Poisson model.
Children’s Explorative Activities in Kindergarten Playgrounds: A Case Study in China and Norway
Authors: Sørensen Hanne Værum , Birkeland Åsta
Published: February 2020

Nordic countries have historically emphasized play in early childhood education to a higher degree than China. However, recent educational reforms have reformulated its importance in early childhood education. In this chapter, we discuss young children’s activities in the playground as a basis for conceptualising diverse conditions for children’s exploration and cultural formation. Prevailing assumptions in the Nordic countries seem to indicate that children’s free play facilitates exploration, whereas teacher-structured activities limit children’s exploration and agentic position. The aim of the article is to challenge these dichotomies through examples from Chinese and Norwegian kindergartens, and to contribute to a conceptualisation of children’s activities in the playground as exploration. The research takes a cultural-historical approach to human development as a dialectical process in which humans constantly and actively interact with their surroundings. We investigate children’s participation in the activity setting of the playground organized by kindergarten teachers in one kindergarten in China and one in Norway to examine varieties in conditions for children’s explorative activities in kindergartens. Our findings illustrate the influence of weather conditions on the activity settings. Despite major differences in climate and the institutional and societal level, kindergarten teachers’ dialogical engagement with children is crucial for children’s exploration. These findings led to an elaboration of Hedegaard’s model (2012) of child development in a personal, institutional and societal perspective by adding the perspective of climate and air quality that is central for children’s explorative activity.
Denmark
Authors: Jensen Per H.
Published: February 2020

This chapter discusses the preconditions for high and rising female labour force participationratesamongolder workers in Denmark, marked by a highly developed welfare state and flexible labour markets. Main findings are that changing labour market practices of older women are conditioned by economic and symbolic stimuli encouraging older workers voluntarily to prolong their working life as well as measures combatting exclusionary mechanisms in the Danish labour market.
Serbia
Authors: Jakovljevic Mihajlo , Jovanovic Mirjana , Milovanovic Olivera , Radevic Svetlana
Published: February 2020

Serbia is a post-socialist country with approximately 7.1 million people undergoing a strong and continuous process of demographic ageing. The average age of the population has increased to 43.2 years and the proportion older than 65 years has increased to 17.4%. The period of rapid ageing of the population coincided with political and economic crisis in Serbia during the last decade of the 20th century. This period was marked by extensive emigration of the younger population, the delay of birth and a strong decline in fertility. The major economic challenges ahead include: high unemployment rates, the need for job creation in the public sector, structural reforms of state-owned companies, strategic public sector reforms and the need for new foreign direct investment. Serbia has been gradually implementing structural economic reforms needed to ensure the country’s long-term prosperity. Policies designed to extend working life have been one of the dominant responses to population ageing.
Turkey
Authors: Mercan Murat A.
Published: February 2020

Turkish residents 65 and older comprise 8.8% of the total population yet the academic literature on the relationships among the effects of ageing, gender and the labour market is very limited. This chapter describes the characteristics ofolderworkers and discusses changes in the legal structure of the labour market and their implications in Turkey. It also focuses on the SocialSecurity system (especially the pension scheme) and the historically very low female labour force participationrates which reduce self-sufficiency for women at older ages. Finally, the chapter considers precarious employment and work-related healthpolicies in Turkey.
Roles of Stem Cell Antigen-1 in the Pulmonary Endothelium
Authors: Maeda Jun , Uchida Keiko , Kodo Kazuki , Yamagishi Hiroyuki
Published: February 2020

There is growing evidence that resident progenitor cell populations exist in murine lung tissues and differentiate into a mesenchymal cell lineage [1, 2]. Stem cell antigen-1 (Sca-1) is a cell surface glycoprotein, initially found in murine bone marrow–derived stem cell subtypes, such as hematopoietic stem cells. Some studies showed Sca-1 expression in the pulmonary vascular endothelium of adult murine lungs [3], while a subset of Sca-1-expressing cells formed vascular-like structures under specific conditions [1].
Morphological Characterization of Pulmonary Microvascular Disease in Bronchopulmonary Dysplasia Caused by Hyperoxia in Newborn Mice
Authors: Nakanishi Hidehiko , Morikawa Shunichi , Kitahara Shuji , Yoshii Asuka , Uchiyama Atsushi , Kusuda Satoshi , Ezaki Taichi
Published: February 2020

Bronchopulmonary dysplasia (BPD) is one of the most significant medical complications in preterm infants, and pulmonary microvascular injury is associated with the pathogenesis of BPD [1]. Furthermore, impairments of developing pulmonary vasculature may cause secondary pulmonary hypertension (PH), which contributes significantly to morbidity and mortality among preterm infants [2]. To characterize the mechanisms of pulmonary vascular disease resulting from BPD, we studied the ultrastructural changes affecting pulmonary microvasculature.
Involvement of CXCR4 and Stem Cells in a Rat Model of Pulmonary Arterial Hypertension
Authors: Zhang Tingting , Kawaguchi Nanako , Hayama Emiko , Furutani Yoshiyuki , Nakanishi Toshio
Published: February 2020

Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome. C-X-C chemokine receptor type 4 (CXCR4) is known to be expressed in cancer and stem/progenitor cells. In the present study, PAH was induced in a rat model by 5 weeks of 10% hypoxia and treatment with a single subcutaneous injection of monocrotaline (60 mg/kg) [1] to investigate the involvement of CXCR4 in PAH development [2].
Genotypes and Phenotypes of Chinese Pediatric Patients with Idiopathic and Heritable Pulmonary Arterial Hypertension: Experiences from a Single Center
Authors: Zhang Hong-Sheng , Liu Qian , Piao Chun-Mei , Zhu Yan , Li Qiang-Qiang , Du Jie , Gu Hong
Published: February 2020

The aim of this study was to determine the clinical outcomes of gene mutations in Chinese pediatric patients with idiopathic and heritable pulmonary arterial hypertension. We screened gene mutations in 62 pediatric patients who visited Beijing Anzhen Hospital from 2008 September to 2017 August with targeted exome kits containing 22 pulmonary arterial hypertension-related genes. The clinical and hemodynamic characteristics and outcomes of these patients were retrospectively analyzed. In a cohort of 62 patients, a total of 27 gene mutations were identified with 20 mutations in BMPR2, two mutations in ACVRL1, two mutations in KCNK3 and three mutations in NOTCH3. The average age at diagnosis was 77.5 ± 53.8 months. 28 patients (14 mutation carriers) underwent cardiac catherization examinations, with the acute vasodilator testing. Mutation carriers had higher right atrial pressure and tended to have higher pulmonary arterial pressure and pulmonary vascular resistance index than mutation non-carriers. Eight patients responded to acute vasodilator testing and all were mutation non-carriers (p = 0.002). The median survival for mutation carriers was 24.0 months. Although similar treatments were employed, mutation carriers had higher mortality rates than mutation non-carriers (p = 0.036). The 1-, 2-, 3- year survival rate of mutation non-carriers were 93.6%, 90.0%, and 66.9%, respectively, while for mutation carriers, the proportion were 79.8%, 49.9%, and 33.3%. In conclusion, early gene screening for pediatric patients with idiopathic pulmonary arterial hypertension and heritable pulmonary arterial hypertension is recommended, and more aggressive treatment for mutation carriers is advisable.
Microscopic Lung Airway Abnormality and Pulmonary Vascular Disease Associated with Congenital Systemic-to-Pulmonary Shunt
Authors: Sawada Hirofumi , Mitani Yoshihide , Ohashi Hiroyuki , Otsuki Shoichiro , Yodoya Noriko , Hayakawa Hidetoshi , Oshita Hironori , Kabwe Jane C. , Konuma Takeshi , Imanaka-Yoshida Kyoko , Shimpo Hideto , Maruyama Kazuo , Hirayama Masahiro
Published: February 2020

Links between impaired lung development/growth and pulmonary hypertension (PH) have been demonstrated in infants with bronchopulmonary dysplasia or congenital diaphragmatic hernia. Experimental studies also suggest that a complex interplay of epithelial-endothelial cells is required for normal pre/postnatal lung morphogenesis [1]. In this chapter, we focus on the role of lung development/growth abnormality in the development of pulmonary vascular disease (PVD) associated with congenital heart defect (CHD).
New Insights on How to Treat Patent Ductus Arteriosus
Authors: Yokoyama Utako , Aoki Rika , Fujita Shujiro , Iwasaki Shiho , Seki Kazuo , Toshihide Asou , Masuda Munetaka , Minamisawa Susumu , Ishikawa Yoshihiro
Published: February 2020

The ductus arteriosus (DA) must be closed after birth for the establishment of adult circulation. Extremely preterm infants, however, frequently have patent ductus arteriosus (PDA), which associates with significant morbidity and mortality. At birth, the separation of the fetus from its maternal environment constitutes a dramatic change for the infant. Initiation of respiration changes serum composition and oxygen tension resulting in the closure of the DA. We found that serum osmolality was significantly decreased early after birth in rats, and that the hypo-osmolality sensor transient receptor potential melastatin (TRPM) 3 had increased expression in the rat DA compared to the aorta. Our data suggest that a decrease in serum osmolality promotes DA closure via TRPM3 and that an increase in osmolality dilates the DA. For extremely preterm infants, recent recommendations include immediate amino acid supplementation. We examined plasma amino acid composition and found an association between low glutamate concentration and PDA. Our data suggest that glutamate induces DA contraction through the AMPA receptor GluR-mediated noradrenaline production. Based on these data, maintaining proper levels of serum osmolality and amino acid composition may improve the therapeutic outcome of PDA in extremely preterm infants.
Prostaglandin E-EP4-Mediated Fibulin-1 Up-regulation Plays a Role in Intimal Thickening of the Ductus Arteriosus
Authors: Ito Satoko , Yokoyama Utako , Saito Junichi , Masuda Munetaka , Asou Toshihide , Ishikawa Yoshihiro
Published: February 2020

The normal closure of the ductus arteriosus (DA) consists of two steps: vasoconstriction and intimal thickening (IT). We have revealed that prostaglandin E2 (PGE2)-EP4 signaling plays a critical role in IT formation via smooth muscle cell (SMC) migration through hyaluronic acid [1]. In this study, we found that fibulin-1 was the most significantly up-regulated gene by EP4 stimulation in DA smooth muscle cells (SMCs).
Significance of SGK1 as a Protein Kinase Transcriptionally Regulated by ALK1 Signaling in Vascular Endothelial Cells
Authors: Nakagawa Osamu , Watanabe Yusuke , Harada Yukihiro , Tanaka Toru , Kawamura Teruhisa
Published: February 2020

Bone morphogenetic protein 9 (BMP9)/BMP10-ALK1 receptor signaling is essential for endothelial differentiation and vascular morphogenesis and is implicated in hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension [1]. The ALK1 signal induces SMAD1/5/9-dependent transcription of its own signaling components, transcription factors and membrane ligands/receptors. In addition, we recently identified Serum/glucocorticoid-regulated kinase 1 (SGK1) to be transcriptionally regulated by ALK1 signaling in vascular endothelial cells [2] (Fig. 45.1a). The ALK1 signal is known to evoke post-translational activation of protein kinases such as TAK1 and ERK as a non-canonical pathway, but SGK1 is the first example of protein kinases whose expression is controlled by the SMAD-dependent pathway (Fig. 45.1b).
Searches for decays of new particles in the DUNE Multi-Purpose near Detector
Authors: Berryman Jeffrey M. , de Gouvêa André , Fox Patrick J. , Kayser Boris J. , Kelly Kevin J. , Raaf Jennifer L.
Published: February 2020

Abstract

One proposed component of the upcoming Deep Underground Neutrino Experiment (DUNE) near detector complex is a multi-purpose, magnetized, gaseous argon time projection chamber: the Multi-Purpose Detector (MPD). We explore the new-physics potential of the MPD, focusing on scenarios in which the MPD is significantly more sensitive to new physics than a liquid argon detector, specifically searches for semi-long-lived particles that are produced in/near the beam target and decay in the MPD. The specific physics possibilities studied are searches for dark vector bosons mixing kinetically with the Standard Model hypercharge group, leptophilic vector bosons, dark scalars mixing with the Standard Model Higgs boson, and heavy neutral leptons that mix with the Standard Model neutrinos. We demonstrate that the MPD can extend existing bounds in most of these scenarios. We illustrate how the ability of the MPD to measure the momentum and charge of the final state particles leads to these bounds.
The factorization problem in Jackiw-Teitelboim gravity
Authors: Harlow Daniel , Jafferis Daniel
Published: February 2020

Abstract

In this note we study the 1 + 1 dimensional Jackiw-Teitelboim gravity in Lorentzian signature, explicitly constructing the gauge-invariant classical phase space and the quantum Hilbert space and Hamiltonian. We also semiclassically compute the Hartle-Hawking wave function in two different bases of this Hilbert space. We then use these results to illustrate the gravitational version of the factorization problem of AdS/CFT: the Hilbert space of the two-boundary system tensor-factorizes on the CFT side, which appears to be in tension with the existence of gauge constraints in the bulk. In this model the tension is acute: we argue that JT gravity is a sensible quantum theory, based on a well-defined Lorentzian bulk path integral, which has no CFT dual. In bulk language, it has wormholes but it does not have black hole microstates. It does however give some hint as to what could be added to rectify these issues, and we give an example of how this works using the SYK model. Finally we suggest that similar comments should apply to pure Einstein gravity in 2 + 1 dimensions, which we’d then conclude also cannot have a CFT dual, consistent with the results of Maloney and Witten.
To be, or not to be finite? The Higgs potential in Gauge-Higgs Unification
Authors: Hisano Junji , Shoji Yutaro , Yamada Atsuyuki
Published: February 2020

Abstract

In this paper, we investigate the finiteness of the Higgs effective potential in an SU($$ \mathcal{N} $$
N
) Gauge-Higgs Unification (GHU) model defined on M4× S1. We obtain the Higgs effective potential at the two-loop level and find that it is finite. We also discuss that the Higgs effective potential is generically divergent for three- or higher-loop levels. As an example, we consider an SU($$ \mathcal{N} $$
N
) gauge theory on M5× S1, where the one-loop corrections to the four-Fermi operators are divergent. We find that the Higgs effective potential depends on their counter terms at the three-loop level.
Classification of dark pion multiplets as dark matter candidates and collider phenomenology
Authors: Beauchesne Hugues , di Cortona Giovanni Grilli
Published: February 2020

Abstract

New confining sectors can contain a set of pseudo-Goldstone mesons that exhibit a complicated structure in terms of stability and relative masses. Stable ones can act as dark matter candidates, while their interactions with the unstable ones determine their relic abundances. The overall structure, by specifying which channels are kinematically forbidden or not, affects the cosmology, constraints and collider phenomenology. In this paper, we present a classification of these pseudo-Goldstone meson structures. We find that the structures can be classified into three categories, corresponding to strong, suppressed and essentially non-existent constraints from indirect detection. Limits on decay lengths of the unstable mesons and dark jet properties are presented for several benchmark models.
Chain flexibility and dynamics of alginate solutions in different solvents
Authors: Maciel Bruna , Oelschlaeger Claude , Willenbacher Norbert
Published: February 2020

Mechanical rheometry, specifically rotational rheometry, squeeze flow, and capillary rheometry, and two microrheology methods, namely multiple-particle tracking (MPT) and diffusing wave spectroscopy (DWS) have been used to get new insight into structural and dynamical properties of alginate dissolved in solvents widely used for bioprinting, namely deionized water, phosphate-buffered saline (PBS), and Dulbecco Modified Eagle Medium (DMEM) cell media. Results demonstrate that alginate rheological properties depend on the solvent quality at concentrations higher than 1 wt.%. In this high concentration regime, in aqueous salt-free and PBS solutions, experimental scaling exponents for the concentration dependence of the specific viscosity ηsp and the plateau modulus G0 agree well with theoretical predictions for neutral polymers in good solvent whereas for the terminal relaxation time TR, the exponent is slightly higher than theoretically predicted, presumably due to the formation of aggregates. For alginate dissolved in DMEM, all exponents for ηsp, G0, and TR agree with predictions for polymers in theta solvents, which might be related to the formation of polyelectrolyte complex as a result of interactions between alginate and amino acids. Chain persistence length lp values, as determined directly from high frequency rheometry for the first time, are independent of alginate concentration and temperature. Lower absolute lp values were found for DMEM solutions compared with the other solvents. Moreover, scaling exponents for ηsp, G0, and TR do not change with temperature, within 20 and 60 °C. These findings suggest no change in the conformation of alginate chains with temperature.
A detaching, V-shaped tibial tubercle osteotomy is a safe procedure with a low complication rate
Authors: Rood Akkie , van Sambeeck Jordy , Koëter Sander , van Kampen Albert , van de Groes Sebastiaan A. W.
Published: February 2020

Introduction

In patients with recurrent patellar dislocations, a tibial tubercle osteotomy (TTO) can be indicated to correct patella alta or an increased trochlear groove–tibial tubercle distance. Several surgical techniques are described. Previous studies emphasize that detaching osteotomies results in devascularisation, which can lead to non-union and tibial shaft fractures. The aim of this study was to report the complication rates directly related to the surgical technique of a V-shaped TTO, where the tubercle is completely released from its periosteum using a step-cut osteotomy.

Methods

The retrospective case series comprised a large cohort of 263 knees with patella alta in 203 patients who underwent a V-shaped TTO, with or without additional realignment procedures, between March 2004 and October 2017. Data were obtained from available patient files. Complications were defined as minor or major.

Results

Thirteen major complications were registered (4.9%) including two tibial fractures (0.75%) and one non-union (0.37%). Five complications (1.9%) were defined as minor. Removal of the screws because of irritation or pain was seen in 22 cases (8.2%).

Conclusion

A V-shaped TTO is a safe procedure. The presumed higher risk for tibial fractures or pseudo-arthrosis could not be confirmed.