bluuebunny/crossref_metadata_2025 huggingface dataset:
Added value of post-mortem computed tomography (PMCT) to clinical findings for cause of death determination in adult “natural deaths”
Authors: Vester M. E. M. , van Rijn R. R. , Duijst W. L. J. M. , Beenen L. F. M. , Clerkx M. , Oostra R. J.
Published: December 2019

Purpose

The aim of this study was to investigate whether post-mortem computed tomography (PMCT) provides additional information regarding the cause of death and underlying diseases in a general practitioners’ (GP), out-of-hospital population.

Methods and materials

Bodies donated to our anatomy department between January 2014 and January 2018, who consecutively underwent a total body PMCT and had given permission for retrieval of their medical records during life, were included. PMCT scans were assessed by a radiologist and compared with the cause of death as stated in the medical records. Discrepancies were analyzed with an adjusted Goldman classification.

Results

Ninety-three out of the 274 scanned donors during the inclusion period had given consent for the retrieval of their medical records, of which 79 GP’s responded to the request thereof (31 men, 48 women, average age 72.8 years, range 36–99). PMCT identified 49 (62%) cases of cancer, 10 (12.7%) cardiovascular diseases, 8 (10.1%) severe organ failures, 5 (6.3%) cases with signs of pneumonia, 2 (2.5%) other causes, and 7 (8.9%) cases without an (underlying) definitive cause of death. Eleven major discrepancies on the Goldman classification scale, with possible relevance to survival between PMCT and GP records, were identified.

Conclusion

PMCT can have added value for the detection of additional findings regarding the cause of death in an out-of-hospital, GP’s population, especially to identify or exclude major (previously non-diagnosed) underlying diseases.
Cognitive behavioural therapy interventions for insomnia among shift workers: RCT in an occupational health setting
Authors: Järnefelt Heli , Härmä Mikko , Sallinen Mikael , Virkkala Jussi , Paajanen Teemu , Martimo Kari-Pekka , Hublin Christer
Published: December 2019

Introduction

The aim of the study was to compare the effectiveness of cognitive behavioural therapy interventions for insomnia (CBT-I) to that of a sleep hygiene intervention in a randomized controlled design among shift workers. We also studied whether the features of shift work disorder (SWD) affected the results.

Methods

A total of 83 shift workers with insomnia disorder were partially randomized into a group-based CBT-I, self-help CBT-I, or sleep hygiene control intervention. The outcomes were assessed before and after the interventions and at 6-month follow-up using questionnaires, a sleep diary, and actigraphy.

Results

Perceived severity of insomnia, sleep-related dysfunctional beliefs, burnout symptoms, restedness, recovery after a shift, and actigraphy-based total sleep time improved after the interventions, but we found no significant differences between the interventions. Mood symptoms improved only among the group-based CBT-I intervention participants. Non-SWD participants had more mental diseases and symptoms, used more sleep-promoting medication, and had pronounced insomnia severity and more dysfunctional beliefs than those with SWD. After the interventions, non-SWD participants showed more prominent improvements than those with SWD.

Conclusions

Our results showed no significant differences between the sleep improvements of the shift workers in the CBT-I interventions and of those in the sleep hygiene control intervention. Alleviation of mood symptoms seemed to be the main added value of the group-based CBT-I intervention compared to the control intervention. The clinical condition of the non-SWD participants was more severe and these participants benefitted more from the interventions than the SWD participants did.

Trial registration

ClinicalTrials.gov, NCT02523079.
Double-Distance Frameworks and Mixed Sparsity Graphs
Authors: Nixon Anthony , Power Stephen Charles
Published: December 2019

A rigidity theory is developed for frameworks in a metric space with two types of distance constraints. Mixed sparsity graph characterisations are obtained for the infinitesimal and continuous rigidity of completely regular bar-joint frameworks in a variety of such contexts. The main results are combinatorial characterisations for (i) frameworks restricted to surfaces with both Euclidean and geodesic distance constraints, (ii) frameworks in the plane with Euclidean and non-Euclidean distance constraints, and (iii) direction-length frameworks in the non-Euclidean plane.
Predict cognitive decline with clinical markers in Parkinson’s disease (PRECODE-1)
Authors: Wilson Heather , Pagano Gennaro , Yousaf Tayyabah , Polychronis Sotirios , De Micco Rosa , Giordano Beniamino , Niccolini Flavia , Politis Marios
Published: December 2019

Over the course of the disease, about 80% of Parkinson’s disease patients will develop cognitive impairment. However, predictive factors associated with cognitive decline are still under investigation. Here, we investigated which clinically available markers are predictive of cognitive impairment in a cohort of early drug-naïve Parkinson’s disease patients. 294 drug-naïve Parkinson’s disease patients, who were cognitively normal at baseline, were recruited from the Parkinson’s Progression Markers Initiative. At 36-month follow-up, patients were diagnosed with cognitive impairment according to two levels: Level 1 diagnosis was defined as MoCA < 26 and Level 2 diagnosis was defined as MoCA < 26, alongside an impaired score on at least two neuropsychological tests. Predictive variables with a validated cut-off were divided into normal or abnormal measures, whilst others were divided into normal or abnormal measures based on the decile with the highest power of prediction. At 3 years’ follow-up, 122/294 Parkinson’s disease (41.5%) patients had cognitive decline. We found that age at Parkinson’s disease onset, MDS-UPDRS Part-III, Hopkin’s Learning Verbal Test-Revised Recall, Semantic Fluency Test and Symbol Digit Modalities Test were all predictors of cognitive decline. Specifically, age at Parkinson’s disease onset, Semantic Fluency Test and symbol Digit Modalities Test were predictors of cognitive decline defined by Level 2. The combination of three abnormal tests, identified as the most significant predictors of cognitive decline, gave a 63.6–86.7% risk of developing cognitive impairment defined by Level 2 and Level 1 criteria, respectively, at 36-month follow-up. Our findings show that these clinically available measures encompass the ability to identify drug-naïve Parkinson’s disease patients with the highest risk of developing cognitive impairment at the earliest stages. Therefore, by implementing this in a clinical setting, we can better monitor and manage patients who are at risk of cognitive decline.
Assimilation of multiple linearly dependent data vectors
Authors: Mannseth Trond
Published: December 2019

Assimilation of a sequence of linearly dependent data vectors, $\{d_{l}\}^{L}_{l=1}${dl}l=1L such that ${d_{l} = B_{l}d_{L}}^{L-1}_{ l=1}$dl=BldLl=1L−1, is considered for a parameter estimation problem. Such a data sequence can occur, for example, in the context of multilevel data assimilation. Since some information is used several times when linearly dependent data vectors are assimilated, the associated data-error covariances must be modified. I develop a condition that the modified covariances must satisfy in order to sample correctly from the posterior probability density function of the uncertain parameter in the linear-Gaussian case. It is shown that this condition is a generalization of the well-known condition that must be satisfied when assimilating the same data vector multiple times. I also briefly discuss some qualitative and computational issues related to practical use of the developed condition.
Plasma-based processes for planar and 3D surface patterning of functional nanoparticles
Authors: Askari S. , Machhadani H. , Benedikt J. , Helmersson U.
Published: December 2019

We present a gas-phase process for surface patterning and 3D self-assembly of nanoparticles (NPs) of functional materials such as metals, oxides, and nitrides. The method relies on electrostatic assembly of free-flying NPs with unipolar charge produced in plasma sources. We demonstrate the capability of the process in self-assembly of NPs, with the size in the range 10–60 nm, into arrays of free-standing 3D microstructures with complex morphologies. Considering that the plasma nanoparticle sources are compatible with synthesis of a large library of material NPs, the process introduces a novel approach for 3D printing of various functional NPs, high-precision device integration of NPs on sub-micrometer scales, and large-area parallel surface patterning of NPs.
Are We All Predictably Irrational? An Experimental Analysis
Authors: Doces John A. , Wolaver Amy
Published: December 2019

We examine the question of rationality, replicating two core experiments used to establish that people deviate from the rational actor model. Our analysis extends existing research to a developing country context. Based on our theoretical expectations, we test if respondents make decisions consistent with the rational actor framework. Experimental surveys were administered in Côte d’Ivoire and Ghana, two developing countries in West Africa, focusing on issues of risk aversion and framing. Findings indicate that respondents make decisions more consistent with the rational actor model than has been found in the developed world. Extending our analysis to test if the differences in responses are due to other demographic differences between the African samples and the United States, we replicated these experiments on a nationally representative analysis in the U.S., finding results primarily consistent with the seminal findings of irrationality. In the U.S. and Côte d’Ivoire, highly educated people make decisions that are less consistent with the rational model while low-income respondents make decisions more consistent with the rational model. The degree to which people are irrational thus is contextual, possibly western, and not nearly as universal as has been concluded.
Correction to: Mechanically Induced Periprosthetic Osteolysis: A Systematic Review
Authors: McArthur Benjamin A. , Scully Ryan , Ross F. Patrick , Bostrom Mathias P. G. , Fahlgren Anna
Published: December 2019

Figure 2 and its caption were inadvertently omitted from the original article. The figure and caption are given below.
Correction to: The Scientific Basis for Modern Physical Therapy
Authors: Cornell Charles N.
Published: December 2019

The names of the guest editors of the issue on Rehabilitation and Musculoskeletal Health (October 2019) were omitted. Editor-in-Chief Charles N. Cornell, MD, wishes to acknowledge the contributions of Sherry Backus.
A review of the development of maternity leave policy in China over the past 70 years
Authors: Liu Hongyan , Yu Dian , Wang Hui
Published: December 2019

This study analyzes the changes in maternity leave policy in China during the past 70 years by reviewing the documents issued since 1949. During these years, the length of maternity leave increased from 56 days initially to 98 days, and finally to as much as 128 to 365 days. The sums paid to women taking maternity leave gradually increased and an insurance mechanism was introduced. There were changes in the intent and focus of policies: (1) A change in the intention of maternity leave policy from protecting the rights and interests of women only to protecting those of both women and children. (2) A change in focus from one of implementing national family planning policy to one of protecting the rights of individuals. (3) A change in the focus point of policies from the home only to the workplace and the home. (4) An increased focus on gender equity evidenced by gradual introduction of paternity leave policy. Although maternity leave policy has improved over the years, challenges still exist including significant differences in the policy environment at the provincial level, and difficulties in implementing policy in some regions and enterprises.
Utilitarianism
Authors: Mulgan Tim
Published: December 2019

Moral theories can be distinguished, not only by the answers they give, but also by the questions they ask. Utilitarianism's central commitment is to the promotion of well-being, impartially considered. This commitment shapes utilitarianism in a number of ways. If scarce resources should be directed where they will best promote well-being, and if theoretical attention is a scarce resource, then moral theorists should focus on topics that are most important to the future promotion of well-being. A theme of this Element is that, as times change, the priorities (both practical and theoretical) of utilitarianism also change. Questions that were once theoretical curiosities move centre stage. And themes from earlier utilitarians that have become unfashionable may come to the fore again. Utilitarianism is a living tradition, not an abstract set of timeless principles or a purely historical artefact.
Using Multistaged Magnetic Survey and Excavation to Assess Community Settlement Organization: A Case Study from the Central Peninsular Gulf Coast of Florida
Authors: Sampson Christina Perry , Horsley Timothy J.
Published: December 2019

Integrating geophysical survey with the study of community settlement patterns can be challenging because of cultural and environmental factors including (1) site formation and house preservation, (2) the coordination of domestic tasks at extra-household scales, and (3) the survey environment of the study area. In this article, we present the results of a program of geophysical survey comprising magnetic susceptibility and magnetometry at Weeden Island (8Pi1)—a shell-bearing, wooded site with nearly pure sand soils on the Gulf Coast of Florida. Combining remote sensing techniques mitigated some of the challenges of surveying forested terrain while providing insight into community organization at a site with minimal preserved structural remains. Compared with previous traditional surveys of the area, the geophysical survey extended the recognized boundaries of occupational activity, provided additional definition to the spatial structure of deposits, and allowed us to identify specific domestic features. Excavations at each area of intensive occupation provided evidence about the organization of the domestic economy at the site and showed the potential of this approach to reveal significant patterns of community settlement.
The application of critical realism as a basis for agency in environmental education: The case of Roy Bhaskar
Authors: Mirzaei Rafe Mehri , Bagheri Noaparast Khosrow , Sadat Hosseini Afzal , Sajadieh Narges
Published: December 2019

This article will investigate the philosophy of science of Roy Bhaskar (1944–2014) as a coherent basis for environmental education. The work of Bhaskar serves as an in-depth approach to understanding how to apply critical realism (the critical and the realist) to matters such as environmental education, because he concretely theorises the connections between science, social change and metaphysics. By mobilising key Bhaskarian motifs — that is, the primacy of ontology over epistemology, the laminated system as a means to understand reality, the ways in which inquiry may be organised through the real, actual and the empirical, and the positive application of dialectics — this article constructs a new approach to environmental education and positions it in the field of environmental education by comparing it to posthumanism and the new materialisms. This article contains inquiry-based study outlines for enhanced thinking around: (1) climate change and social justice; (2) movements towards a carbon-free economy; (3) water, food and population; and (4) the future of human habitation.
Sexual activity by marital status and age: a comparative perspective
Authors: Ueffing Philipp , Dasgupta Aisha N. Z. , Kantorová Vladimíra
Published: December 2019

This paper presents an analysis of trends in sexual activity by marital status and age, and their associations with contraceptive use. Understanding levels of, and trends in, sexual activity is important for assessing the needs for family planning services and for analysing commonly used family planning indicators. Data were taken from 220 Demographic and Health Surveys (DHSs) and 62 Multiple Indicator Cluster Surveys (MICSs) to provide insights into sexual activity by marital status and age in a total of 94 countries in different regions of the world. The results show the sensitivity of the indicator with respect to the definition of currently sexually active, based on the timing of last sexual intercourse (during the last 4 weeks, 3 months, or 1 year). Substantial diversity in sexual activity by marital status and age was demonstrated across countries. The proportion of married women reporting recent sexual activity (sexual intercourse during the last 4 weeks) ranged from 50% to 90%. The proportion of unmarried women reporting recent sexual activity did not exceed 50% in any of the 94 countries with available data, but showed substantial regional differences: it appeared to be rare in Asia and extremely varied within Africa, Europe and Latin America and the Caribbean. Among married women, sexual activity did not vary much by age group, while for unmarried women, there was an inverted U-pattern by age, with the youngest age group (15–19 years old) having the lowest proportion sexually active. The proportion of women who reported currently using contraception and reported not being sexually active varied by the contraceptive method used and was overall much greater among unmarried women. The evidence presented in this paper can be used to improve family planning policies and programmes to serve the diverse needs, for example regarding method choice and service provision, of unmarried women.
Solving Her Problems? Beyond the Seductive Appeal of Specialist Problem-Solving Courts for Women Offenders in England and Wales
Authors: BIRKETT GEMMA
Published: December 2019

At the nexus of the social and penal policy fields, problem-solving justice promises to punish offenders while working to address the complex issues that drive their law-breaking behaviour. Appealing to the left and right due to its dual focus on pragmatism and welfarism, the concept has floated in and out of political fashion for the past two decades. Recent years have heralded a renewed political interest in the approach, closely aligned to the Conservative government’s commitment to ‘transforming justice’. With a focus on empowerment and collaboration, the problem-solving model has much to offer women offenders in particular. Drawing on data from a large-scale study into the sentencing and punishment of women under the new probation arrangements, this article reveals a divergence of views on gender-specific courts among sentencers, probation officers and third sector workers. Moral concerns about up-tariffing sit alongside the practical barriers of government bureaucracy and hindering legislation. With data pertaining to effectiveness (rather than potential) still required, this article argues that specialist problem-solving courts for women present a risky strategy, however seductive their promise.
Risk factors for adverse events within one year after atrial septal closure in children: a retrospective follow-up study
Authors: Tanghöj Gustaf , Liuba Petru , Sjöberg Gunnar , Naumburg Estelle
Published: December 2019

Introduction:

Secundum atrial septal defect is one of the most common congenital heart defects. Previous paediatric studies have mainly addressed echocardiographic and few clinical factors among children associated with adverse events. The aim of this study was to identify neonatal and other clinical risk factors associated with adverse events up to one year after closure of atrial septal defect.

Methods:

This retrospective case–control study includes children born in Sweden between 2000 and 2014 that were treated surgically or percutaneously for an atrial septal defect. Conditional logistic regression was used to evaluate the association between major and minor adverse events and potential risk factors, adjusting for confounding factors including prematurity, neonatal sepsis, neonatal general ventilatory support, symptomatic atrial septal defects, and pulmonary hypertension.

Results:

Overall, 396 children with 400 atrial septal defect closures were included. The median body weight at closure was 14.5 (3.5–110) kg, and the median age was 3.0 (0.1–17.8) years. Overall, 110 minor adverse events and 68 major events were recorded in 87 and 49 children, respectively. Only symptomatic atrial septal defects were associated with both minor (odds ratio (OR) = 2.18, confidence interval (CI) 95% 1.05–8.06) and major (OR = 2.80 CI 95% 1.23–6.37) adverse events.

Conclusion:

There was no association between the investigated neonatal comorbidities and major or minor events after atrial septal defect closure. Patients with symptomatic atrial septal defects had a two to four times increased risk of having a major event, suggesting careful management and follow-up of these children prior to and after closure.
Social determinants, lifestyle and diet quality: a population-based study from the 2015 Health Survey of São Paulo, Brazil
Authors: Mello Aline Veroneze de , Pereira Jaqueline Lopes , Leme Ana Carolina Barco , Goldbaum Moises , Cesar Chester Luiz Galvao , Fisberg Regina Mara
Published: December 2019

Objective:

To investigate the association among social determinants, lifestyle variables and diet quality in São Paulo, Brazil.

Design:

Cross-sectional study, 2015 Health Survey of São Paulo (Inquérito de Saúde de São Paulo (2015 ISA-Capital)) with Focus on Nutrition Study (2015 ISA-Nutrition).

Setting:

Population-based study, with a representative sample of adults living in São Paulo, Brazil.

Participants:

Adults (aged 20–59 years, n 643) and older adults (aged ≥60 years, n 545).

Results:

We observed differences in the Brazilian Healthy Eating Index-Revised (BHEI-R) by education, income, occupation, sex and race. Whole grains (0·63 points, 12·6 % of the maximum score), sodium (2·50 points, 25·0 %) and solid fat, alcohol and added sugars (9·28 points, 46·4 %) components had the lowest BHEI-R scores. Factors positively associated with diet quality included the presence of one disease or more (e.g. diabetes mellitus, hypertension, cancer, hypercholesterolaemia: β = 0·636, P < 0·001), income (middle income: β = 0·478, P < 0·001; high income: β = 0·966, P < 0·001) and occupation (other: β = 1·418, P < 0·001). Energy (β = –0·001, P < 0·001), alcohol consumption (β = –0·207, P = 0·027), education level (middle education: β = –0·975, P < 0·001; high education: β = –1·376, P < 0·001), races other than white (β = –0·366, P < 0·001) and being unemployed (β = –0·369, P < 0·046) were negatively associated with diet quality.

Conclusions:

Groups affected by socio-economic inequalities need better diet quality. Governmental actions should be implemented to reduce the consumption of energy-dense and sodium-rich foods, facilitate access and information on healthy eating, and conduct nutritional education.
A scoping review of ‘big data’, ‘informatics’, and ‘bioinformatics’ in the animal health and veterinary medical literature
Authors: Ouyang Zenhwa , Sargeant Jan , Thomas Alison , Wycherley Kate , Ma Rebecca , Esmaeilbeigi Rosa , Versluis Ali , Stacey Deborah , Stone Elizabeth , Poljak Zvonimir , Bernardo Theresa M.
Published: December 2019

Research in big data, informatics, and bioinformatics has grown dramatically (Andreu-Perez J, et al., 2015, IEEE Journal of Biomedical and Health Informatics 19, 1193–1208). Advances in gene sequencing technologies, surveillance systems, and electronic medical records have increased the amount of health data available. Unconventional data sources such as social media, wearable sensors, and internet search engine activity have also contributed to the influx of health data. The purpose of this study was to describe how ‘big data’, ‘informatics’, and ‘bioinformatics’ have been used in the animal health and veterinary medical literature and to map and chart publications using these terms through time. A scoping review methodology was used. A literature search of the terms ‘big data’, ‘informatics’, and ‘bioinformatics’ was conducted in the context of animal health and veterinary medicine. Relevance screening on abstract and full-text was conducted sequentially. In order for articles to be relevant, they must have used the words ‘big data’, ‘informatics’, or ‘bioinformatics’ in the title or abstract and full-text and have dealt with one of the major animal species encountered in veterinary medicine. Data items collected for all relevant articles included species, geographic region, first author affiliation, and journal of publication. The study level, study type, and data sources were collected for primary studies. After relevance screening, 1093 were classified. While there was a steady increase in ‘bioinformatics’ articles between 1995 and the end of the study period, ‘informatics’ articles reached their peak in 2012, then declined. The first ‘big data’ publication in animal health and veterinary medicine was in 2012. While few articles used the term ‘big data’ (n = 14), recent growth in ‘big data’ articles was observed. All geographic regions produced publications in ‘informatics’ and ‘bioinformatics’ while only North America, Europe, Asia, and Australia/Oceania produced publications about ‘big data’. ‘Bioinformatics’ primary studies tended to use genetic data and tended to be conducted at the genetic level. In contrast, ‘informatics’ primary studies tended to use non-genetic data sources and conducted at an organismal level. The rapidly evolving definition of ‘big data’ may lead to avoidance of the term.
The Magnitude of Surface Ocean Acidification and Carbon Release During Eocene Thermal Maximum 2 (ETM‐2) and the Paleocene‐Eocene Thermal Maximum (PETM)
Authors: Harper D. T. , Hönisch B. , Zeebe R. E. , Shaffer G. , Haynes L. L. , Thomas E. , Zachos J. C.
Published: December 2019

Eocene Thermal Maximum 2 (ETM‐2; 54.1 Ma) was the second largest Eocene hyperthermal. Like the Paleocene‐Eocene Thermal Maximum (PETM), ETM‐2 was characterized by massive carbon emissions and several degrees of global warming and thus can serve as a case study for assessing the impacts of rapid CO2 emissions on ocean carbonate chemistry, biota, and climate. Marine carbonate records of ETM‐2 are better preserved than those of the PETM due to more subdued carbonate dissolution. As yet, however, the magnitude of this carbon cycle perturbation has not been well constrained. Here, we present the first records of surface ocean acidification for ETM‐2, based on stable boron isotope records in mixed‐layer planktic foraminifera from two midlatitude ODP sites (1210 in the North Pacific and 1265 in the SE Atlantic), which indicate conservative minimum global sea surface acidification of −0.20 +0.12/−0.13 pH units. Using these estimates of pH and temperature as constraints on carbon cycle model simulations, we conclude that the total mass of C, released over a period of 15 to 25 kyr during ETM‐2, likely ranged from 2,600 to 3,800 Gt C, which is greater than previously estimated on the basis of other observations (i.e., stable carbon isotopes and carbonate compensation depth) alone.
Identifying Critical Input Parameters for Improving Drag‐Based CME Arrival Time Predictions
Authors: Kay C. , Mays M. L. , Verbeke C.
Published: December 2019

Coronal mass ejections (CMEs) typically cause the strongest geomagnetic storms, so a major focus of space weather research has been predicting the arrival time of CMEs. Most arrival time models fall into two categories: (1) drag‐based models that integrate the drag force between a simplified CME structure and the background solar wind and (2) full magnetohydrodynamic models. Drag‐based models typically are much more computationally efficient than magnetohydrodynamic models, allowing for ensemble modeling. While arrival time predictions have improved since the earliest attempts, both types of models currently have difficulty achieving mean absolute errors below 10 hr. Here we use a drag‐based model ANTEATR (Another Type of Ensemble Arrival Time Results) to explore the sensitivity of arrival times to various input parameters. We consider CMEs of different strengths from average to extreme size, speed, and mass (kinetic energies between
and
erg). For each scale CME, we vary the input parameters to reflect the current observational uncertainty in each and determine how accurately each must be known to achieve predictions that are accurate within 5 hr. We find that different scale CMEs are the most sensitive to different parameters. The transit time of average strength CMEs depends most strongly on the CME speed, whereas an extreme strength CME is the most sensitive to the angular width. A precise CME direction is critical for impacts near the flanks but not near the CME nose. We also show that the Drag‐Based Model has similar sensitivities, suggesting that these results are representative for all drag‐based models.
TLR5: A prognostic and monitoring indicator for triple-negative breast cancer
Authors: Shi Dai , Zhao Shanshan , Jiang Wen , Zhang Chao , Liang Ting , Hou Guihua
Published: December 2019

A novel, highly selective biomarker is urgently needed to predict and monitor triple-negative breast cancer (TNBC) because targeting molecules are not currently available. Although associated with various malignant tumors, the role of toll-like receptor 5 (TLR5) in TNBC remains uncertain. We aimed to define the effects of TLR5 in TNBC to determine whether it could serve as a prognostic and monitoring indicator for TNBC. We established TNBC cell line 4T1 with low TLR5 expression (GFP tag; TLR5−4T1) and with normal TLR5 expression (GFP tag; TLR5+4T1) using lentivirus-shRNA-TLR5 knockdown transfection and negative lentivirus transfection, respectively. Detected by western blot and qPCR, we found knockdown of TLR5 resulted in decreased expression of TLR5 and E-cadherin and increased expression of N-cadherin, vimentin, fibronectin, TRAF6, SOX2, and Twist1, which were related to EMT (epithelial–mesenchymal transition). In addition, downregulation of TLR5 increased the invasion and migration of 4T1 cells in vitro, which were investigated by CCK-8 and wound healing, as well as transwell assay and colony formation. Furthermore, the metastatic ability of TLR5−4T1 cells to the lungs was also increased compared to TLR5+4T1 cells in vivo. To verify the effect of TLR5 as a monitor indicator, mice bearing TLR5+and TLR5−4T1 tumors injected with125I-anti-TLR5 mAb or isotype125I-IgG were assessed by whole body phosphor-autoradiography and fluorescence imaging in vivo. Phosphor-autoradiography of model mice revealed early tumors at 6 days after inoculation with TLR5+4T1, but not TLR5−4T1 cells. Intratumoral accumulation of radioactivity positively correlated with TLR5 expression, and fluorescence imaging in vivo revealed both TLR5+and TLR5−4T1 tumors. Our results suggested that downregulation of TLR5 in TNBC increased tumor invasiveness and EMT expression via TRAF6 and SOX2 pathway and TLR5 could serve as a prognostic and monitoring indicator for TLR5-positive tumors.
The apricot (Prunus armeniaca L.) genome elucidates Rosaceae evolution and beta-carotenoid synthesis
Authors: Jiang Fengchao , Zhang Junhuan , Wang Sen , Yang Li , Luo Yingfeng , Gao Shenghan , Zhang Meiling , Wu Shuangyang , Hu Songnian , Sun Haoyuan , Wang Yuzhu
Published: December 2019

Apricots, scientifically known asPrunus armeniacaL, are drupes that resemble and are closely related to peaches or plums. As one of the top consumed fruits, apricots are widely grown worldwide except in Antarctica. A high-quality reference genome for apricot is still unavailable, which has become a handicap that has dramatically limited the elucidation of the associations of phenotypes with the genetic background, evolutionary diversity, and population diversity in apricot. DNA fromP. armeniacawas used to generate a standard, size-selected library with an average DNA fragment size of ~20 kb. The library was run on Sequel SMRT Cells, generating a total of 16.54 Gb of PacBio subreads (N50 = 13.55 kb). The high-qualityP. armeniacareference genome presented here was assembled using long-read single-molecule sequencing at approximately 70× coverage and 171× Illumina reads (40.46 Gb), combined with a genetic map for chromosome scaffolding. The assembled genome size was 221.9 Mb, with a contig NG50 size of 1.02 Mb. Scaffolds covering 92.88% of the assembled genome were anchored on eight chromosomes. Benchmarking Universal Single-Copy Orthologs analysis showed 98.0% complete genes. We predicted 30,436 protein-coding genes, and 38.28% of the genome was predicted to be repetitive. We found 981 contracted gene families, 1324 expanded gene families and 2300 apricot-specific genes. The differentially expressed gene (DEG) analysis indicated that a change in the expression of the 9-cis-epoxycarotenoid dioxygenase (NCED) gene but not lycopene beta-cyclase (LcyB) gene results in a low β-carotenoid content in the white cultivar “Dabaixing”. This complete and highly contiguousP. armeniacareference genome will be of help for future studies of resistance toplum pox virus(PPV) and the identification and characterization of important agronomic genes and breeding strategies in apricot.
Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation
Authors: Hasegawa Shunsuke , Fukushima Hotaka , Hosoda Hiroshi , Serita Tatsurou , Ishikawa Rie , Rokukawa Tomohiro , Kawahara-Miki Ryouka , Zhang Yue , Ohta Miho , Okada Shintaro , Tanimizu Toshiyuki , Josselyn Sheena A. , Frankland Paul W. , Kida Satoshi
Published: December 2019

Cognitive performance in people varies according to time-of-day, with memory retrieval declining in the late afternoon-early evening. However, functional roles of local brain circadian clocks in memory performance remains unclear. Here, we show that hippocampal clock controlled by the circadian-dependent transcription factor BMAL1 regulates time-of-day retrieval profile. Inducible transgenic dominant negative BMAL1 (dnBMAL1) expression in mouse forebrain or hippocampus disrupted retrieval of hippocampal memories at Zeitgeber Time 8–12, independently of retention delay, encoding time and Zeitgeber entrainment cue. This altered retrieval profile was associated with downregulation of hippocampal Dopamine-cAMP signaling in dnBMAL1 mice. These changes included decreases in Dopamine Receptors (D1-R and D5-R) and GluA1-S845 phosphorylation by PKA. Consistently, pharmacological activation of cAMP-signals or D1/5Rs rescued impaired retrieval in dnBMAL1 mice. Importantly, GluA1 S845A knock-in mice showed similar retrieval deficits with dnBMAL1 mice. Our findings suggest mechanisms underlying regulation of retrieval by hippocampal clock through D1/5R-cAMP-PKA-mediated GluA1 phosphorylation.
MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors
Authors: Chen Xinyue , Burkhardt Daniel B. , Hartman Amaleah A. , Hu Xiao , Eastman Anna E. , Sun Chao , Wang Xujun , Zhong Mei , Krishnaswamy Smita , Guo Shangqin
Published: December 2019

Cancer is a hyper-proliferative disease. Whether the proliferative state originates from the cell-of-origin or emerges later remains difficult to resolve. By tracking de novo transformation from normal hematopoietic progenitors expressing an acute myeloid leukemia (AML) oncogene MLL-AF9, we reveal that the cell cycle rate heterogeneity among granulocyte–macrophage progenitors (GMPs) determines their probability of transformation. A fast cell cycle intrinsic to these progenitors provide permissiveness for transformation, with the fastest cycling 3% GMPs acquiring malignancy with near certainty. Molecularly, we propose that MLL-AF9 preserves gene expression of the cellular states in which it is expressed. As such, when expressed in the naturally-existing, rapidly-cycling immature myeloid progenitors, this cell state becomes perpetuated, yielding malignancy. In humans, high CCND1 expression predicts worse prognosis for MLL fusion AMLs. Our work elucidates one of the earliest steps toward malignancy and suggests that modifying the cycling state of the cell-of-origin could be a preventative approach against malignancy.
Blood transcriptome profile induced by an efficacious vaccine formulated with salivary antigens from cattle ticks
Authors: Maruyama Sandra R. , Carvalho Benilton , González-Porta Mar , Rung Johan , Brazma Alvis , Gustavo Gardinassi Luiz , Ferreira Beatriz R. , Banin Tamy M. , Veríssimo Cecília J. , Katiki Luciana M. , de Miranda-Santos Isabel K. F.
Published: December 2019

Ticks cause massive damage to livestock and vaccines are one sustainable alternative for the acaricide poisons currently heavily used to control infestations. An experimental vaccine adjuvanted with alum and composed by four recombinant salivary antigens mined with reverse vaccinology from a transcriptome of salivary glands from Rhipicephalus microplus ticks was previously shown to present an overall efficacy of 73.2% and cause a significant decrease of tick loads in artificially tick-infested, immunized heifers; this decrease was accompanied by increased levels of antigen-specific IgG1 and IgG2 antibodies, which were boosted during a challenge infestation. In order to gain insights into the systemic effects induced by the vaccine and by the tick challenge we now report the gene expression profile of these hosts’ whole-blood leukocytes with RNA-seq followed by functional analyses. These analyses show that vaccination induced unique responses to infestations; genes upregulated in the comparisons were enriched for processes associated with chemotaxis, cell adhesion, T-cell responses and wound repair. Blood transcriptional modules were enriched for activation of dendritic cells, cell cycle, phosphatidylinositol signaling, and platelets. Together, the results indicate that by neutralizing the tick’s salivary mediators of parasitism with vaccine-induced antibodies, the bovine host is able to mount normal homeostatic responses that hinder tick attachment and haematophagy and that the tick otherwise suppresses with its saliva.
The water lily genome and the early evolution of flowering plants
Authors: Zhang Liangsheng , Chen Fei , Zhang Xingtan , Li Zhen , Zhao Yiyong , Lohaus Rolf , Chang Xiaojun , Dong Wei , Ho Simon Y. W. , Liu Xing , Song Aixia , Chen Junhao , Guo Wenlei , Wang Zhengjia , Zhuang Yingyu , Wang Haifeng , Chen Xuequn , Hu Juan , Liu Yanhui , Qin Yuan , Wang Kai , Dong Shanshan , Liu Yang , Zhang Shouzhou , Yu Xianxian , Wu Qian , Wang Liangsheng , Yan Xueqing , Jiao Yuannian , Kong Hongzhi , Zhou Xiaofan , Yu Cuiwei , Chen Yuchu , Li Fan , Wang Jihua , Chen Wei , Chen Xinlu , Jia Qidong , Zhang Chi , Jiang Yifan , Zhang Wanbo , Liu Guanhua , Fu Jianyu , Chen Feng , Ma Hong , Van de Peer Yves , Tang Haibao
Published: December 2019

Water lilies belong to the angiosperm order Nymphaeales. Amborellales, Nymphaeales and Austrobaileyales together form the so-called ANA-grade of angiosperms, which are extant representatives of lineages that diverged the earliest from the lineage leading to the extant mesangiosperms1–3. Here we report the 409-megabase genome sequence of the blue-petal water lily (Nymphaea colorata). Our phylogenomic analyses support Amborellales and Nymphaeales as successive sister lineages to all other extant angiosperms. The N. colorata genome and 19 other water lily transcriptomes reveal a Nymphaealean whole-genome duplication event, which is shared by Nymphaeaceae and possibly Cabombaceae. Among the genes retained from this whole-genome duplication are homologues of genes that regulate flowering transition and flower development. The broad expression of homologues of floral ABCE genes in N. colorata might support a similarly broadly active ancestral ABCE model of floral organ determination in early angiosperms. Water lilies have evolved attractive floral scents and colours, which are features shared with mesangiosperms, and we identified their putative biosynthetic genes in N. colorata. The chemical compounds and biosynthetic genes behind floral scents suggest that they have evolved in parallel to those in mesangiosperms. Because of its unique phylogenetic position, the N. colorata genome sheds light on the early evolution of angiosperms.
Congruent audio-visual stimulation during adaptation modulates the subsequently experienced visual motion aftereffect
Authors: Park Minsun , Blake Randolph , Kim Yeseul , Kim Chai-Youn
Published: December 2019

Sensory information registered in one modality can influence perception associated with sensory information registered in another modality. The current work focuses on one particularly salient form of such multisensory interaction: audio-visual motion perception. Previous studies have shown that watching visual motion and listening to auditory motion influence each other, but results from those studies are mixed with regard to the nature of the interactions promoting that influence and where within the sequence of information processing those interactions transpire. To address these issues, we investigated whether (i) concurrent audio-visual motion stimulation during an adaptation phase impacts the strength of the visual motion aftereffect (MAE) during a subsequent test phase, and (ii) whether the magnitude of that impact was dependent on the congruence between auditory and visual motion experienced during adaptation. Results show that congruent direction of audio-visual motion during adaptation induced a stronger initial impression and a slower decay of the MAE than did the incongruent direction, which is not attributable to differential patterns of eye movements during adaptation. The audio-visual congruency effects measured here imply that visual motion perception emerges from integration of audio-visual motion information at a sensory neural stage of processing.
Fusion of Bipolar Tetraether Lipid Membranes Without Enhanced Leakage of Small Molecules
Authors: Leriche Geoffray , Stengel Dillan , Onofrei David , Koyanagi Takaoki , Holland Gregory P. , Yang Jerry
Published: December 2019

A major challenge in liposomal research is to minimize the leakage of encapsulated cargo from either uncontrolled passive permeability across the liposomal membrane or upon fusion with other membranes. We previously showed that liposomes made from pure Archaea-inspired bipolar tetraether lipids exhibit exceptionally low permeability of encapsulated small molecules due to their capability to form more tightly packed membranes compared to typical monopolar lipids. Here, we demonstrate that liposomes made of synthetic bipolar tetraether lipids can also undergo membrane fusion, which is commonly accompanied by content leakage of liposomes when using typical bilayer-forming lipids. Importantly, we demonstrate calcium-mediated fusion events between liposome made of glycerolmonoalkyl glycerol tetraether lipids with phosphatidic acid headgroups (GMGTPA) occur without liposome content release, which contrasts with liposomes made of bilayer-forming EggPA lipids that displayed ~80% of content release under the same fusogenic conditions. NMR spectroscopy studies of a deuterated analog of GMGTPA lipids reveal the presence of multiple rigid and dynamic conformations, which provide evidence for the possibility of these lipids to form intermediate states typically associated with membrane fusion events. The results support that biomimetic GMGT lipids possess several attractive properties (e.g., low permeability and non-leaky fusion capability) for further development in liposome-based technologies.
Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: A meta-analysis
Authors: Castellana Marco , Cignarelli Angelo , Brescia Francesco , Perrini Sebastio , Natalicchio Annalisa , Laviola Luigi , Giorgino Francesco
Published: December 2019

GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (−0.74%), body weight (−1.61 kg), and systolic blood pressure (−3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control.
Biosecurity risks posed by a large sea-going passenger vessel: challenges of terrestrial arthropod species detection and eradication
Authors: McKirdy Simon J. , O’Connor Simon , Thomas Melissa L. , Horton Kristin L. , Williams Angus , Hardie Darryl , Coupland Grey T. , van der Merwe Johann
Published: December 2019

Large sea-going passenger vessels can pose a high biosecurity risk. The risk posed by marine species is well documented, but rarely the risk posed by terrestrial arthropods. We conducted the longest running, most extensive monitoring program of terrestrial arthropods undertaken on board a passenger vessel. Surveillance was conducted over a 19-month period on a large passenger (cruise) vessel that originated in the Baltic Sea (Estonia). The vessel was used as an accommodation facility to house workers at Barrow Island (Australia) for 15 months, during which 73,061 terrestrial arthropods (222 species - four non-indigenous (NIS) to Australia) were collected and identified on board. Detection of Tribolium destructor Uytt., a high-risk NIS to Australia, triggered an eradication effort on the vessel. This effort totalled more than 13,700 human hours and included strict biosecurity protocols to ensure that this and other non-indigenous species (NIS) were not spread from the vessel to Barrow Island or mainland Australia. Our data demonstrate that despite the difficulties of biosecurity on large vessels, stringent protocols can stop NIS spreading from vessels, even where vessel-wide eradication is not possible. We highlight the difficulties associated with detecting and eradicating NIS on large vessels and provide the first detailed list of species that inhabit a vessel of this kind.