bluuebunny/crossref_metadata_2025 huggingface dataset:
Diurnal profiles of physical activity and postures derived from wrist-worn accelerometry in UK adults
Authors: Perez-Pozuelo Ignacio , White Thomas , Westgate Kate , Wijndaele Katrien , Wareham Nicholas J. , Brage Soren
Published: April 2019

Background

Wrist-worn accelerometry is the commonest objective method for measuring physical activity in large-scale epidemiological studies. Research-grade devices capture raw triaxial acceleration which, in addition to quantifying movement, facilitates assessment of orientation relative to gravity. No population-based study has yet described the interrelationship and variation of these features by time and personal characteristics.

Methods

2043 UK adults (35-65years) wore an accelerometer on the non-dominant wrist and a chest-mounted combined heart-rate-and-movement sensor for 7days free-living. From raw (60Hz) wrist acceleration, we derived movement (non-gravity acceleration) and pitch and roll (arm) angles relative to gravity. We inferred physical activity energy expenditure (PAEE) from combined sensing and sedentary time from approximate horizontal arm-angle coupled with low movement.

Results

Movement differences by time-of-day and day-of-week were associated with arm-angles; more movement in downward arm-positions. Mean(SD) movement was similar between sexes ∼31(42)mg, despite higher PAEE in men, 53(22) vs 48(19)J·min-1·kg-1. Women spent longer with the arm pitched >0° (53% vs 36%) and less time at <0° (37% vs 53%). Diurnal pitch was 2.5-5° above and 0-7.5° below horizontal during night and daytime, respectively; corresponding roll angles were ∼0° and ∼20° (thumb-up). Differences were more pronounced in younger participants. All diurnal profiles indicated later wake-times on weekends. Daytime pitch was closer to horizontal on weekdays; roll was similar. Sedentary time was higher (17 vs 15hours/day) in obese vs normal-weight individuals.

Conclusions

More movement occurred in arm positions below horizontal, commensurate with activities including walking. Findings suggest time-specific population differences in behaviours by age, sex, and BMI.
Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development
Authors: Liu Dong , Kousa Anastasia I. , O’Neill Kathy E. , Guillemot Francois , Popis Martyna , Farley Alison M. , Tomlinson Simon R. , Ulyanchenko Svetlana , Seymour Philip A. , Serup Palle , Koch Ute , Radtke Freddy , Blackburn C. Clare
Published: April 2019

Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH-independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPC at the expense of cTEC differentiation. Finally, we uncover a direct interaction between NOTCH and FOXN1, the master regulator of TEC differentiation. These data establish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development and are thus of high relevance to strategies aimed at generating/regenerating functional thymic tissue in vitro and in vivo.
A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle
Authors: Comai Glenda , Heude Églantine , Mella Sebastien , Paisant Sylvain , Pala Francesca , Gallardo Mirialys , Kardon Gabrielle , Gopalakrishnan Swetha , Tajbakhsh Shahragim
Published: April 2019

In most vertebrates, the upper digestive tract is composed of muscularised jaws linked to the esophagus that permit food uptake and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factorsTbx1andIsl1are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to Met/HGF signalling for antero-posterior migration of esophagus muscle progenitors, where HGF ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish aTbx1-Isl1-Metgenetic hierarchy that uniquely regulate esophagus myogenesis and identify distinct genetic signatures that can be used as a framework to interpret pathologies arising within CPM derivatives.
Precise Memory is Predicted by Learning-Induced Sensory System Neurophysiological Plasticity
Authors: Rotondo Elena K. , Bieszczad Kasia. M.
Published: April 2019

Despite identical learning experiences, individuals differ in the memory formed of those experiences. Memory formed with sensory specificity determines its utility for selectively cueing subsequent behavior, even in novel situations. If an individual forms generalized memory, then there is potential for novel sensory cues to interfere with accurate behavioral performance. Here, a rodent model of auditory learning capitalized on individual differences in learning-induced auditory neuroplasticity to identify and characterize neural substrates for sound-specific (vs. general) memory of the training signal’s acoustic frequency. Animals with naturally or pharmacologically induced signal-“specific” memory revealed behaviorally, exhibited long-lasting signal-specific neurophysiological plasticity in auditory cortical and subcortical evoked responses, while learning-induced changes were not detected in animals with “general” memories. Individual differences validated this brain-behavior relationship, such that the degree of change in neurophysiological responses could be used to determine the precision of memory formation.
Icosahedral viruses defined by their positively charged domains: a signature for viral identity and capsid assembly strategy
Authors: Requião Rodrigo D. , Carneiro Rodolfo L. , Moreira Mariana Hoyer , Ribeiro-Alves Marcelo , Rossetto Silvana , Palhano Fernando L. , Domitrovic Tatiana
Published: April 2019

Capsid proteins often present a positively charged arginine-rich region at the N and/or C-termini that for some icosahedral viruses has a fundamental role in genome packaging and particle stability. These sequences show little to no conservation at the amino-acid level and are structurally dynamic so that they cannot be easily detected by common sequence or structure comparison. As a result, the occurrence and distribution of positively charged protein domain across the viral and the overall protein universe are unknown. We developed a methodology based on the net charge calculation of discrete segments of the protein sequence that allows us to identify proteins containing amino-acid stretches with an extremely high net charge. We observed that among all organisms, icosahedral viruses are especially enriched in extremely positively charged segments (Q ≥ +17), with a distinctive bias towards arginine instead of lysine. We used viral particle structural data to calculate the total electrostatic charge derived from the most positively charged protein segment of capsid proteins and correlated these values with genome charge arising from the phosphates of each nucleotide. We obtained a positive correlation (r = 0.91, p-value < 0001) for a group of 17 viral families, corresponding to 40% of all families with icosahedral structures described so far. These data indicated that unrelated viruses with diverse genome types adopt a common underlying mechanism for capsid assembly and genome stabilization based on R-arms. Outliers from a linear fit pointed to families with alternative strategies of capsid assembly and genome packaging.

Significance Statement

Viruses can be characterized by the existence of a capsid, an intricate proteinaceous container that encases the viral genome. Therefore, capsid assembly and function are essential to viral replication. Here we specify virus families with diverse capsid structure and sequence, for each capsid packing capacity depends on a distinctive structural feature: a highly positively charged segment of amino acids residues, preferentially made of arginine. We also show that proteins with the same characteristics are rarely found in cellular proteins. Therefore, we identified a conserved viral functional element that can be used to infer capsid assembly mechanisms and inspire the design of protein nanoparticles and broad-spectrum antiviral treatments.
Inhibition of Stearoyl-CoA desaturase suppresses follicular help T and germinal center B cell responses
Authors: Min Son Young , Cheon In Su , Goplen Nick P. , Dent Alexander L. , Sun Jie
Published: April 2019

Stearoyl-CoA desaturases (SCD) are endoplasmic reticulum (ER) associated enzymes that catalyze the synthesis of the monounsaturated fatty acids (MUFAs). As such, SCD play important roles in maintaining the intracellular balance between saturated fatty acid (SFAs) and MUFAs. The roles of SCD in CD4+ T helper cell responses are currently unexplored. Here, we have found that murine and human follicular helper T (TFH) cells express higher levels of SCD1 compared to non-TFH cells. Further, the expression of SCD1 in TFH cells is dependent on the TFH lineage-specification transcription factor BCL6. We found that the inhibition of SCD1 impaired TFH cell maintenance and shifted the balance between TFH and follicular regulatory T (TFR) cells in the spleen. Consequently, SCD1 inhibition dampened germinal center B cell responses following influenza immunization. Mechanistically, we found that SCD inhibition led to increased ER stress and enhanced TFH cell apoptosis in vitro and in vivo. These results reveal a possible link between fatty acid metabolism and cellular and humoral responses induced by immunization or potentially, autoimmunity.
In silicoanalysis of coding SNPs and 3′-UTR associated miRNAs inDCAF17gene that may affect the regulation and pathogenesis of Woodhouse-Sakati Syndrome
Authors: Abdelmoneim Abdelrahman H. , Elrashied Asia M. , Mohammed Alaa I. , Mirghani Sara A. , Osman Rania E. , Gadim Esraa O. , Hassan Mohamed A.
Published: April 2019

Background

Woodhouse-Sakati Syndrome refers to a group of inherited disorders characterized by alopecia, hypogonadism, diabetes mellitus, hypothyroidism and progressive extrapyramidal signs. The aim of this study is to identify the pathogenic SNPs in theDCAF17gene with their related mciroRNAs and their effect on the structure and function of the protein.

Material and Methods

We used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein. After that we defined the miRNAs founded in the 3′-UTR region on theDCAF17gene and studied the annotations relative to it.

Results

Ten deleterious SNPs out of 339 were found to have a damaging effect on the protein structure and function, with one significant micoRNA in the 3′-UTR region.

Conclusion

This was the first in silico analysis ofDCAF17gene, in which 10 novel mutations were found using different bioinformatics tools that could be used as a diagnostic markers for Woodhouse-Sakati syndrome, with one relevant microRNA that can regulate the function of the protein.
Seed treatment with chitosan synergizes plant growth promoting ability ofPseudomonas aeruginosa-P17 in sorghum (Sorhum bicolorL.)
Authors: Praveen Kumar G. , Desai Suseelendra , Moerschbacher Bruno M. , Gueddari Nour Eddine-El
Published: April 2019

Inoculation of crop plants with PGPR has in a large number of investigations resulted in increased plant growth and yield both in the greenhouse and in the field. This plant growth promoting effect of bacteria could be due to net result of synergistic effect of various pgpr traits that they exert in the rhizosphere region of the plant. Four (04) bacterial strain of fluorescent Pseudomonas spp. viz. P1, P17, P22 and P28 were identified previously for their plant growth promoting nature and abiotic stress tolerance and selected further to assess their chitinolytic activity and growth promotion on sorghum in combination with chitosans of low and high degree of acetylation. It was found that P1 has no chitin degrading nature and rest of the three strains have this property. When studied for their ability to grow in presence of chitosans of DA 1.6, 11, 35 and 56% all the strains showed growth in presence of chitosans. Seed bacterization of sorghum seeds with 04 bacterial strains in the presence and absence of chitosans (both low and high DA) and assessment of plant growth promotion after 15 days of sowing showed that P17+DA 56% chitosan combination showed higher growth of seedlings in plant growth chamber with highest root length of 25.9 cm, highest shoot length of 32.1 cm and dry mass of 132.7 mg/ plant. In P17+DA 56% chitosan treated seedlings various defence enzymes and PR-proteins were found to be present in highest quantities as compared to P1 and un-inoculated controls. Since this strain showed highest growth promotion of sorghum seedlings chitin-chitosan modifying enzyme (CCME) of this strain was partially characterized using different proteomic tools and techniques. CCME of P17 had one active polypeptide with a Pi in the range of 3.0-4.0. The digestion pattern of acetylated and deacetylated chitosans showed that P17 enzyme has endochitinase activity. Substrate specificity assay showed that the enzyme had more specificity towards highly acetylated chitosans. Two dimensional PAGE and MS analysis of the protein revealed similarities of this enzyme with protein of Pseudomonas aeruginosa chitinase PA01 strain of GenBank. In conclusion, the study established the option of opening new possibilities for developing bacterial-chitosan (P17+DA 56% chitosan) product for plant growth promotion and induced systemic resistance in sorghum.
Bacillus subtilis ALBA01 can mitigate onion pink root symptoms caused by Setophoma terrestris
Authors: Sayago P , Juncosa F , Albarracín Orio A , Luna D.F. , Molina G , Lafi J , Ducasse D.A
Published: April 2019

Soil-borne pathogen Setophoma terrestris is the causal agent of pink root of onion, one of the most challenging diseases in onion production. Conventional approaches for managing the disease like solarization, soil fumigation and crop rotation have not been proven effective enough. In this work, we evaluated the biocontrol capacity of Bacillus subtilis ALBA01 (BsA01) against S. terrestris, in a highly susceptible onion cultivar, both under greenhouse and field conditions. Disease incidence and severity were evaluated together with growth, photosynthesis among other physiological variables and yield parameters. When compared with plants infected with the pathogen, those plants co-inoculated with BsA01 showed significantly less damage and levels of biocontrol above 50%. With regard to physiological parameters, plants challenged with S terrestris and inoculated with BsA01 performed as well as the control non-infected plants revealing a growth promotion effect of BsA01 on onion plants.
Role of sortase-assembled Ebp pili inEnterococcus faecalisadhesion to iron oxides and its impact on extracellular electron transfer
Authors: Ho Foo Kiong , Lam Ling Ning , Matysik Artur , Watts Thomas Dean , Wong Jun Jie , Chong Kelvin Kian Long , Choo Pei Yi , Tolar Joe , Low Pui Man , Chua Zhi Sheng , Paxman Jason J. , Heras Begoña , Marsili Enrico , Ajo-Franklin Caroline M. , Kline Kimberly A.
Published: April 2019

Enterococcus faecalissortase-assembled endocarditis and biofilm-associated pili (Ebp) are a virulence factor implicated in enterococcal biofilm-associated infections and gastrointestinal colonization. We previously showed thatE. faecalisbiofilm metabolism is influenced by extracellular electron transfer (EET) under iron-rich conditions, raising the question of whether Ebp pili also play a role in EET. Here, we report a novel role of Ebp pili inE. faecalisadhesion to the iron oxides magnetite, goethite and hematite, where the EbpA tip adhesin contributes to this interaction. Adhesion by Ebp pili is conditionally important for EET to iron oxides, as pilus mutants are attenuated in EET under non-static growth conditions. In alignment with the established role of EET in redox homeostasis, we find that EET to ferricyanide supportsE. faecalisanaerobic growth on glycerol. Further, in an antibiotic-treated mouse gastrointestinal colonization model, we show thatE. faecalismutants deficient in EET poorly colonize the intestinal niche. Taken together, our findings suggest that Ebp pili can influenceE. faecalismetabolic fitness by promoting EET to iron oxides, raising new questions of how Ebp pili shapeE. faecalisinteractions with environmental ecosystems. Furthermore, the important role of EET inE. faecaliscolonization of the dysbiotic gastrointestinal environment highlights the need for further inquiry into how EET contributes toE. faecalismicrobial pathogenesis.

Importance

In this study, we explored the interplay between extracellular electron transfer (EET) and anEnterococcus faecalisbiofilm factor, the endocarditis and biofilm-associated pili (Ebp). We demonstrate that Ebp pili have a novel role in adhesion to iron oxides, which consequently promotes EET to iron oxides under non-static conditions. Along with our findings thatE. faecalisEET can be coupled to anaerobic cell growth, our results point to a potential ecological role of Ebp pili in natural environments, outside of its established function in adhesion to host ligands. We provide the first evidence of the contribution of EET toE. faecaliscolonization of the antibiotic-treated murine intestinal niche, which adds to the limited experimental evidence linking EET and microbial pathogenesis, as well as highlights the need for further studies of EET in bacterial pathogens.
Imaging chromatin interactions at sub-kilobase resolution Via Tn5-FISH
Authors: Zhang Xu , Niu Jing , Li Guipeng , Dai Qionghai , Jin Dayong , Gao Juntao , Zhang Michael Q.
Published: April 2019

There is increasing interest in understanding how the three-dimensional organization of the genome is regulated. Different strategies have been employed to identify chromatin interactions genome wide. However, due to the current limitations in resolving genomic contacts, visualization and validation of these genomic loci with sub-kilobase resolution remain the bottleneck for many years. Here, we describe Tn5 transposase-based Fluorescence in situ Hybridization (Tn5-FISH), a Polymerase Chain Reaction (PCR)-based, cost-effective imaging method, which achieved the co-localization of genomic loci with sub-kilobase resolution, to fine dissect genome architecture at sub-kilobase resolution and to verify chromatin interactions detected by Chromatin Configuration Capture (3C)-derivative methods. Especially, Tn5-FISH is very useful to verify short-range chromatin interactions inside of contact domain and Topologically Associated Domain (TAD). It also offers one powerful molecular diagnosis tool for clinical detection of cytogenetic changes in cancers.
Drought soil legacy overrides maternal effects on plant growth
Authors: De Long Jonathan R. , Semchenko Marina , Pritchard William J. , Cordero Irene , Fry Ellen L. , Jackson Benjamin G. , Kurnosova Ksenia , Ostle Nicholas J. , Johnson David , Baggs Elizabeth M. , Bardgett Richard D.
Published: April 2019

Maternal effects (i.e. trans‐generational plasticity) and soil legacies generated by drought and plant diversity can affect plant performance and alter nutrient cycling and plant community dynamics. However, the relative importance and combined effects of these factors on plant growth dynamics remain poorly understood.

We used soil and seeds from an existing plant diversity and drought manipulation field experiment in temperate grassland to test maternal, soil drought and diversity legacy effects, and their interactions, on offspring plant performance of two grassland species (Alopecurus pratensis and Holcus lanatus) under contrasting glasshouse conditions.

Our results showed that drought soil legacy effects eclipsed maternal effects on plant biomass. Drought soil legacy effects were attributed to changes in both abiotic (i.e. nutrient availability) and biotic soil properties (i.e. microbial carbon and enzyme activity), as well as plant root and shoot atom 15N excess. Further, plant tissue nutrient concentrations and soil microbial C:N responses to drought legacies varied between the two plant species and soils from high and low plant diversity treatments. However, these diversity effects did not affect plant root or shoot biomass.

These findings demonstrate that while maternal effects resulting from drought occur in grasslands, their impacts on plant performance are likely minor relative to drought legacy effects on soil abiotic and biotic properties. This suggests that soil drought legacy effects could become increasingly important drivers of plant community dynamics and ecosystem functioning as extreme weather events become more frequent and intense with climate change.

A plain language summary is available for this article.
Survival analysis via nomogram of surgical patients with malignant pleural mesothelioma in the Surveillance, Epidemiology, and End Results database
Authors: Zhuo Minglei , Zheng Qiwen , Chi Yujia , Jia Bo , Zhao Jun , WU Meina , AN Tongtong , Wang Yuyan , LI Jianjie , Zhao Xinghui , Yang Xue , Zhong Jia , Chen Hanxiao , Dong Zhi , Wang Jingjing , Zhai Xiaoyu , Wang Ziping
Published: April 2019

Background

Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates from the pleura and has a poor prognosis. Eligible patients can benefit from surgery, but their survival is affected by many factors. Therefore, we created a graphic model that could predict the prognosis of surgically treated patients.

Methods

We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results database from 2004 to 2014 to identify the key factors affecting the prognosis of surgically treated MPM patients. On this basis we built a nomogram to predict survival. We then evaluated the performance of the nomogram in a validation cohort.

Results

In a training cohort of 828 cases, independent prognostic factors, including age, gender, histological type, differentiation, N stage, chemotherapy, type of surgery, and lymph node dissection, were identified. We then developed a nomogram to evaluate individual patient survival. In Kaplan–Meier analysis, a higher score in the nomogram was associated with a worse prognosis. We also used a validation cohort consisting of 312 patients to evaluate the performance of the nomogram, which was well calibrated and had good discrimination ability, with concordance indices of 0.715 and 0.656 for the training and validation cohorts, respectively.

Conclusion

This study has improved our understanding of resected MPM and shown that key factors, including age and histological type, are associated with overall survival. The nomogram is a reliable tool that can help clinicians turn individualized prediction into reality and maximize patient benefit by identifying the most beneficial treatment approach.
Current and emerging statistical techniques for aquatic telemetry data: A guide to analysing spatially discrete animal detections
Authors: Whoriskey Kim , Martins Eduardo G. , Auger‐Méthé Marie , Gutowsky Lee F. G. , Lennox Robert J. , Cooke Steven J. , Power Michael , Mills Flemming Joanna
Published: April 2019

Telemetry, or the remote monitoring of animals with electronic transmitters and receivers, has vastly enhanced our ability to study aquatic animals. Radio telemetry, acoustic telemetry and passive integrated transponders are three common technologies that generate detection data — time‐stamped, tag‐specific records that are logged by receivers.

We review current statistical methods and comment on potential future directions for analysing detection data derived from fixed telemetry receiver arrays.

To illustrate how different methods may be used to achieve diverse study objectives, we provide a case study dataset collected by an array of 42 acoustic telemetry receivers on 187 bull trout in the Kinbasket Reservoir of British Columbia. To close, we present a decision tree for guiding the selection of a method based on study objectives and sampling design.

This paper provides both experienced and novice telemetry researchers with the knowledge and tools to facilitate more comprehensive analysis of detection data and, in so doing, ask a wide variety of ecological questions that will enhance our understanding of aquatic organisms.
Immunological methods for diagnosis and monitoring of IgE‐mediated allergy caused by industrial sensitizing agents (IMExAllergy)
Authors: Baur Xaver , Akdis Cezmi A. , Budnik Lygia Therese , Cruz Maria Jesus , Fischer Axel , Förster‐Ruhrmann Ulrike , Göen Thomas , Goksel Ozlem , Heutelbeck Astrid R. , Jones Meinir , Lux Harald , Maestrelli Piero , Munoz Xavier , Nemery Benoit , Schlünssen Vivi , Sigsgaard Torben , Traidl‐Hoffmann Claudia , Siegel Paul
Published: April 2019

Industrial sensitizing agents (allergens) in living and working environments play an important role in eliciting type 1 allergic disorders including asthma and allergic rhinitis. Successful management of allergic diseases necessitates identifying their specific causes (ie, identify the causative agent(s) and the route of contact to allergen: airborne, or skin contact) to avoid further exposure. Identification of sensitization by a sensitive and validated measurement of specific IgE is an important step in the diagnosis. However, only a limited number of environmental and occupational allergens are available on the market for use in sIgE testing. Accordingly, specific in‐house testing by individual diagnostic and laboratory centers is often required. Currently, different immunological tests are in use at various diagnostic centers that often produce considerably divergent results, mostly due to lack of standardized allergen preparation and standardized procedures as well as inadequate quality control. Our review and meta‐analysis exhibited satisfactory performance of sIgE detection test for most high molecular weight (HMW) allergens with a pooled sensitivity of 0.74 and specificity of 0.71. However, for low molecular weight (LMW) allergens, pooled sensitivity is generally lower (0.28) and specificity higher (0.89) than for HMW tests. Major recommendations based on the presented data include diagnostic use of sIgE to HMW allergens. A negative sIgE result for LMW agents does not exclude sensitization. In addition, the requirements for full transparency of the content of allergen preparations with details on standardization and quality control are underlined. Development of standard operating procedures for in‐house sIgE assays, and clinical validation, centralized quality control and audits are emphasized. There is also a need for specialized laboratories to provide a custom service for the development of tests for the measurement of putative novel occupational allergens that are not commercially available.
Adherence to oxygen saturation targets increased in preterm infants when a higher target range and tighter alarm limits were introduced
Authors: Klevebro S , Hammar U , Holmström G , Bottai M , Hellström A , Hallberg B
Published: April 2019

Aim

European consensus guidelines published in May 2013 recommended a target peripheral capillary oxygen saturation (SpO2) range of 90–95% for preterm infants. These were incorporated into guidelines at the Karolinska University Hospital, Sweden, in November 2013. This study compared clinical practice before and after those local guidelines.

Methods

We included infants who were born between 23 + 0 and 30 + 6 weeks from January 1, 2013 to December, 31 2015 and received intensive care in two Karolinska units. The lower saturation target of 88–92% and alarm limits of 85–95% used before November 2013 were compared to the new higher saturation target of 90–95% and alarm limits of 89–96%.

Results

Data from 399 infants were analysed. The mean SpO2 was 92.4% with the higher target (n = 301) and 91.1% with the lower target (n = 98). Using the higher instead of lower target meant that the SpO2 was within the prescribed target range more frequently (51% versus 30%) and the proportion of time with SpO2 >95% was increased by 9% (95% confidence interval 7–11%, p < 0.001).

Conclusion

The higher saturation target and tighter alarm limits led to higher mean oxygen saturation, increased adherence to the target and increased time with hyperoxaemia.
The development of children's epistemic beliefs across the early years of elementary school
Authors: Walker Sue , Lunn‐Brownlee Jo , Scholes Laura , Johansson Eva
Published: April 2019

Background

A growing body of research shows that the beliefs we hold about the nature of knowing and knowledge (epistemic beliefs) may mediate moral reasoning. However, a limitation of much of the research in the area of epistemic beliefs is the lack of a longitudinal approach.

Aims

The study investigated longitudinal changes in Australian elementary school children's beliefs about knowing and knowledge (epistemic beliefs) across three judgement domains (personal taste, ambiguous facts, and moral values).

Sample

The participants in this longitudinal study were tracked from Year 1 through to Year 3 of primary school. In Year 1, there were 169 participants (83 boys, 86 girls) aged 6–7 years (M = 6.7,SD = 0.32). In Year 2, there were 156 participants (79 boys, 77 girls), and in Year 3, there were 129 participants (65 boys, 64 girls).

Methods

Using vignettes that reflected each of the three judgement domains, children were interviewed about the beliefs held by two puppet characters. The interviews took place each year across the early years of elementary education in Year 1, Year 2, and Year 3.

Results

Findings revealed that children's epistemic beliefs in each of the judgement domains became more subjectivist over time but that the age at which this occurred differed according to the judgement domain in question.

Conclusions

We argue that it is important for teachers to pay attention to children's beliefs about the nature of knowledge and knowing in the process of scaffolding their reasoning about moral values for active citizenship.
MicroRNA‐331‐3p inhibits epithelial‐mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β‐catenin axis in non‐small‐cell lung cancer
Authors: Li Xizhe , Zhu Jiali , Liu Yuanqi , Duan Chaojun , Chang Ruimin , Zhang Chunfang
Published: April 2019

MicroRNAs have been reported to play critical roles in the regulation of non‐small‐cell cancer (NSCLC) development, but the role of microRNA (miR)‐331‐3p in NSCLC is still unclear. In this study, the expression levels of miR‐331‐3p in NSCLC tumor tissues and adjacent normal tissues were examined by quantitative RT‐PCR, and the relationship between miR‐331‐3p expression and patient clinicopathological characteristics was analyzed. The effects of miR‐331‐3p on epithelial‐mesenchymal transition (EMT), migration, and metastasis of NSCLC cells were determined in vitro and vivo. Direct functional targets of miR‐331‐3p were identified by luciferase reporter assay, western blot assay, immunohistochemical staining, and rescue assay. The downstream pathway regulated by miR‐331‐3p was identified by immunofluorescence, immunoprecipitation, and Rac1 activity examination. Our results showed that miR‐331‐3p was significantly downregulated in NSCLC tumor tissues and was correlated with clinicopathological characteristics, and miR‐331‐3p could be an independent prognostic marker for NSCLC patients. Furthermore, miR‐331‐3p significantly suppressed EMT, migration and metastasis of NSCLC cells in vitro and in vivo. Both ErbB2 and VAV2 were direct functional targets of miR‐331‐3p. The activities of Rac1, PAK1, and β‐catenin were regulated by miR‐331‐3p through ErbB2 and VAV2 targeting. These results indicated that miR‐331‐3p suppresses EMT, migratory capacity, and metastatic ability by targeting ErbB2 and VAV2 through the Rac1/PAK1/β‐catenin axis in NSCLC.
Autogenous tooth roots for lateral extraction socket augmentation and staged implant placement. A prospective observational study
Authors: Schwarz Frank , Sahin Didem , Becker Kathrin , Sader Robert , Becker Jürgen
Published: April 2019

Objectives

To assess the feasibility of using autogenous tooth roots (TR) for a lateral augmentation of deficient extraction sockets and two‐stage implant placement.

Material and Methods

A total of 15 patients were recruited to perform a simultaneous, lateral augmentation of deficient (i.e., thickness of the buccal bone < 0.5 mm or buccal dehiscence‐type defects) fresh extraction sockets using the respective non‐retainable but non‐infected teeth (n = 15). After 26 weeks of submerged healing, the primary endpoint was defined as the crestal ridge width (mm) (CW26) being sufficient to place an adequately dimensioned titanium implant at the respective sites.

Results

The surgical procedure could be accomplished in n = 14 patients. Soft tissue healing was uneventful in all patients. CW26 at visit 6 allowed for a successful implant placement in all patients (e.g., 14/14). Mean CW26 values amounted to 10.85 ± 2.71 mm (median: 8.5). The change (4.89 ± 2.29 mm) in CW compared to baseline was statistically significant (p < 0.001).

Conclusions

The usage of TR may represent a feasible approach for lateral augmentation of deficient extraction sockets and two‐stage implant placement.
Thrombin disrupts vascular endothelial‐cadherin and leads to hydrocephalus via protease‐activated receptors‐1 pathway
Authors: Hao Xiao‐Di , Le Chen‐Sheng , Zhang Hong‐Mei , Shang De‐Sheng , Tong Lu‐Sha , Gao Feng
Published: April 2019

Aims

Previous studies indicated that intraventricular injection of thrombin would induce hydrocephalus. But how thrombin works in this process remains unclear. Since cadherin plays a critical role in hydrocephalus, we aimed to explore the mechanisms of how thrombin acted on choroid plexus vascular endothelium and how thrombin interacted with vascular endothelial‐cadherin (VE‐cadherin) during hydrocephalus.

Methods

There were two parts in this study. Firstly, rats received an injection of saline or thrombin into the right lateral ventricle. Magnetic resonance imaging was applied to measure the lateral ventricle volumes. Albumin leakage and Evans blue content were assessed to test the blood‐brain barrier function. Immunofluorescence and Western blot were applied to detect the location and the expression of VE‐cadherin. Secondly, we observed the roles of protease‐activated receptors‐1 (PAR1) inhibitor (SCH79797), Src inhibitor (PP2), p21‐activated kinase‐1 (PAK1) inhibitor (IPA3) in the thrombin‐induced hydrocephalus, and their effects on the regulation of VE‐cadherin.

Results

Our study demonstrated that intraventricular injection of thrombin caused significant downregulation of VE‐cadherin in choroid plexus and dilation of ventricles. In addition, the inhibition of PAR1/p‐Src/p‐PAK1 pathway reversed the decrease of VE‐cadherin and attenuated thrombin‐induced hydrocephalus.

Conclusions

Our results suggested that the thrombin‐induced hydrocephalus was associated with the inhibition of VE‐cadherin via the PAR1/p‐Src/p‐PAK1 pathway.
Decomposing growth in the gender wage gap in urban China: 1989–2011
Authors: Hare Denise
Published: April 2019

This paper examines trends in the gender wage gap observed in urban China during the post‐reform era. Using China Health and Nutrition Survey data, changes to the gap between 1989 and 2011 are analyzed using the Wellington decomposition method. While women's gains in observed characteristics have narrowed the wage gap, they are more than offset by changes in the returns to these characteristics. Men's returns to potential labour market experience have grown particularly rapidly, relative to women's, and this represents the single largest contributing factor towards the widening of the gender wage gap. Further investigation explores gender wage patterns through the dimensions of occupation, ownership sector and birth cohort. Taken together, my results raise concerns that China's urban labour market may increasingly disincentivize women's long‐term labour force attachments.
Maladaptive striatal plasticity and abnormal reward‐learning in cervical dystonia
Authors: Gilbertson Tom , Humphries Mark , Steele J. Douglas
Published: April 2019

In monogenetic generalized forms of dystonia, in vitro neurophysiological recordings have demonstrated direct evidence for abnormal plasticity at the level of the cortico‐striatal synapse. It is unclear whether similar abnormalities contribute to the pathophysiology of cervical dystonia, the most common type of focal dystonia. We investigated whether abnormal cortico‐striatal synaptic plasticity contributes to abnormal reward‐learning behavior in patients with focal dystonia. Forty patients and 40 controls performed a reward gain and loss avoidance reversal learning task. Participant's behavior was fitted to a computational model of the basal ganglia incorporating detailed cortico‐striatal synaptic learning rules. Model comparisons were performed to assess the ability of four hypothesized receptor specific abnormalities of cortico‐striatal long‐term potentiation (LTP) and long‐term depression (LTD): increased or decreased D1:LTP/LTD and increased or decreased D2: LTP/LTD to explain abnormal behavior in patients. Patients were selectively impaired in the post‐reversal phase of the reward task. Individual learning rates in the reward reversal task correlated with the severity of the patient's motor symptoms. A model of the striatum with decreased D2:LTP/ LTD best explained the patient's behavior, suggesting excessive D2 cortico‐striatal synaptic depotentiation could underpin biased reward‐learning in patients with cervical dystonia. Reversal learning impairment in cervical dystonia may be a behavioral correlate of D2‐specific abnormalities in cortico‐striatal synaptic plasticity. Reinforcement learning tasks with computational modeling could allow the identification of molecular targets for novel treatments based on their ability to restore normal reward‐learning behavior in these patients.
A critical review of the impacts of cover crops on nitrogen leaching, net greenhouse gas balance and crop productivity
Authors: Abdalla Mohamed , Hastings Astley , Cheng Kun , Yue Qian , Chadwick Dave , Espenberg Mikk , Truu Jaak , Rees Robert M. , Smith Pete
Published: April 2019

Cover crops play an increasingly important role in improving soil quality, reducing agricultural inputs and improving environmental sustainability. The main objectives of this critical global review and systematic analysis were to assess cover crop practices in the context of their impacts on nitrogen leaching, net greenhouse gas balances (NGHGB) and crop productivity. Only studies that investigated the impacts of cover crops and measured one or a combination of nitrogen leaching, soil organic carbon (SOC), nitrous oxide (N2O), grain yield and nitrogen in grain of primary crop, and had a control treatment were included in the analysis. Long‐term studies were uncommon, with most data coming from studies lasting 2–3 years. The literature search resulted in 106 studies carried out at 372 sites and covering different countries, climatic zones and management. Our analysis demonstrates that cover crops significantly (p < 0.001) decreased N leaching and significantly (p < 0.001) increased SOC sequestration without having significant (p > 0.05) effects on direct N2O emissions. Cover crops could mitigate the NGHGB by 2.06 ± 2.10 Mg CO2‐eq ha−1 year−1. One of the potential disadvantages of cover crops identified was the reduction in grain yield of the primary crop by ≈4%, compared to the control treatment. This drawback could be avoided by selecting mixed cover crops with a range of legumes and non‐legumes, which increased the yield by ≈13%. These advantages of cover crops justify their widespread adoption. However, management practices in relation to cover crops will need to be adapted to specific soil, management and regional climatic conditions.
Association of P wave peak time with left ventricular end‐diastolic pressure in patients with hypertension
Authors: Burak Cengiz , Çağdaş Metin , Rencüzoğulları Ibrahim , Karabağ Yavuz , Artaç Inanç , Yesin Mahmut , Çınar Tufan , Yıldız Ibrahim , Suleymanoglu Muhammed , Tanboğa Halil Ibrahim
Published: April 2019

Left ventricular diastolic dysfunction (LVDD) is commonly seen in hypertensive patients, and it is associated with increased morbidity and mortality. Hence, the detection of LVDD with a simple, inexpensive, and easy‐to‐obtain method can contribute to improving patient prognosis. Therefore, we aimed to evaluate whether there was any association between the electrocardiographic P wave peak time (PWPT) and invasively measured left ventricular end‐diastolic pressure (LVEDP) in hypertensive patients who had undergone coronary angiography following preliminary diagnosis of coronary artery disease. A total of 78 patients were included in this cross‐sectional study. The PWPT was defined as the time from the beginning of the P wave to its peak, and it was calculated from the leads DII and VI. In all patients, LVEDP was measured in steady state. The PWPT in lead DII was significantly longer in patients with high LVEDP; however, there was no significant difference between groups in terms of PWPT in the lead VI. In multivariable analysis, PWPT in lead DII was found to be independent predictor of increased LVEDP (OR: 1.257, 95% CI: 1.094‐1.445; P = 0.001). In receiver operating characteristic curve analysis, the optimal cut‐off value of PWPT in the lead DII for prediction of elevated LVEDP was 64.8 ms, with a sensitivity of 68.7% and a specificity of 91.3% (area under curve: 0.882, 95% CI: 0.789‐0.944, P < 0.001). In conclusion, this study result suggested that prolonged PWPT in the lead DII may be an independent predictor of increased LVEDP among hypertensive patients.
Silencing long non‐coding RNA MEG3 accelerates tibia fraction healing by regulating the Wnt/β‐catenin signalling pathway
Authors: Liu Yu‐Bao , Lin Lu‐Pan , Zou Rui , Zhao Qing‐Hua , Lin Fu‐Qing
Published: April 2019

As fracture healing is related to gene expression, fracture healing is prospected to be implicated in long non‐coding RNAs (lncRNAs). This study focuses on the effects of epigenetic silencing of long non‐coding RNA maternally expressed gene 3 (lncRNA MEG3) on fracture healing by regulating the Wnt/β‐catenin signalling pathway. Genes expressed in fracture were screened using bioinformatics and the subcellular location of MEG3 was determined using FISH. Next, we successfully established tibia fracture (TF) models of C57BL/6J and Col2a1‐ICAT mice and the effect of silencing lncRNA MEG3 on fracture healing was detected after TF mice were treated with phosphate buffer saline (PBS), MEG3 siRNA and scramble siRNA. X‐ray imaging, Safranin‐O/fast green and haematoxylin‐eosin (HE) staining and histomorphometrical and biomechanical analysis were adopted to observe and to detect the fracture healing conditions. Additionally, the positive expression of collagen II and osteocalcin was examined using immunohistochemistry. At last, in the in vitro experiment, the relationship of MEG3 and the Wnt/β‐catenin signalling pathway in fraction healing was investigated. MEG3 was located in the cell nucleus. In addition, it was found that MEG3 and the Wnt/β‐catenin signalling pathway were associated with fraction healing. Moreover, silencing MEG3 was proved to elevate callus area and maximum bending load and to furthermore enhance the recanalization of bone marrow cavity. Finally, MEG3 knockdown elevated levels of Col10a1, Runx2, Osterix, Osteocalcin, Wnt10b and β‐catenin/β‐catenin whereas it reduced p‐GSK‐3β/GSK‐3β levels. Taken together, our data supported that epigenetic silencing of lncRNA MEG3 could promote the tibia fracture healing by activating the Wnt/β‐catenin signalling pathway.
RBM10 inhibits cell proliferation of lung adenocarcinoma via RAP1/AKT/CREB signalling pathway
Authors: Jin Xin , Di Xin , Wang Ruimin , Ma He , Tian Chang , Zhao Min , Cong Shan , Liu Jiaying , Li Ranwei , Wang Ke
Published: April 2019

Initial functional studies have demonstrated that RNA‐binding motif protein 10 (RBM10) can promote apoptosis and suppress cell proliferation; however, the results of several studies suggest a tumour‐promoting role for RBM10. Herein, we assessed the involvement of RBM10 in lung adenocarcinoma cell proliferation and explored the potential molecular mechanism. We found that, both in vitro and in vivo, RBM10 overexpression suppresses lung adenocarcinoma cell proliferation, while its knockdown enhances cell proliferation. Using complementary DNA microarray analysis, we previously found that RBM10 overexpression induces significant down‐regulation of RAP1A expression. In this study, we have confirmed that RBM10 decreases the activation of RAP1 and found that EPAC stimulation and inhibition can abolish the effects of RBM10 knockdown and overexpression, respectively, and regulate cell growth. This effect of RBM10 on proliferation was independent of the MAPK/ERK and P38/MAPK signalling pathways. We found that RBM10 reduces the phosphorylation of CREB via the AKT signalling pathway, suggesting that RBM10 exhibits its effect on lung adenocarcinoma cell proliferation via the RAP1/AKT/CREB signalling pathway.
PTPN2 improved renal injury and fibrosis by suppressing STAT‐induced inflammation in early diabetic nephropathy
Authors: Li Ya , Zhou Huimin , Li Yulin , Han Lu , Song Ming , Chen Fangfang , Shang Guokai , Wang Di , Wang Zhihao , Zhang Wei , Zhong Ming
Published: April 2019

Diabetic nephropathy (DN) is a chronic inflammatory disease triggered by disordered metabolism. Recent studies suggested that protein tyrosine phosphatase non‐receptor type 2 (PTPN2) could ameliorate metabolic disorders and suppress inflammatory responses. This study investigated PTPN2's role in modulating DN and the possible cellular mechanisms involved. In a mouse model combining hyperglycaemia and hypercholesterolaemia (streptozotocin diabetic, ApoE‐/‐ mice), mice showed severe insulin resistance, renal dysfunction, micro‐inflammation, subsequent extracellular matrix expansion and decreased expression of PTPN2. We found that mice treated with PTPN2 displayed reduced serum creatinine, serum BUN and proteinuria. PTPN2 gene therapy markedly attenuated metabolic disorders and hyperglycaemia. In addition, PTPN2 gene transfer significantly suppressed renal activation of signal transducers and activators of transcription (STAT), STAT‐dependent pro‐inflammatory and pro‐fibrotic genes expression, and influx of lymphocytes in DN, indicating anti‐inflammatory effects of PTPN2 by inhibiting the activation of STAT signalling pathway in vivo. Furthermore, PTPN2 overexpression inhibited the high‐glucose induced phosphorylation of STAT, target genes expression and proliferation in mouse mesangial and tubuloepithelial cells, suggesting that the roles of PTPN2 on STAT activation was independent of glycaemic changes. Our results demonstrated that PTPN2 gene therapy could exert protective effects on DN via ameliorating metabolic disorders and inhibiting renal STAT‐dependent micro‐inflammation, suggesting its potential role for treatment of human DN.
Playing the Long Game: Addressing the Shortage of Geriatrics Educators
Authors: van Zuilen Maria H. , Granville Lisa J.
Published: April 2019

This editorial comments on the Education and Training article by Sehgal et al. in this issue.