bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of lysyl oxidase in venous malformations: Association with vascular destabilization and sclerotherapy
Authors: Zhu Junyi , Shao Ming , Guo Fengyuan , Ren Jiangang , Tang Zirong , Geng Jinhuan , Xu Zhi , Jia Jun , Chen Lili , Jia Yulin 
Published: March 2020

AbstractVenous malformations (VM) are localized defects in vascular morphogenesis manifested by dilated venous channels with reduced perivascular cell coverage. As a vital enzyme for extracellular matrix (ECM) deposition, lysyl oxidase (LOX) plays important roles in vascular development and diseases. However, the expression and significance of LOX are unknown in VM. Herein, 22 VM specimens and eight samples of normal skin tissues were evaluated immunohistochemically for the expression of LOX, α‐smooth muscle cell actin (α‐SMA) and transforming growth factor‐β (TGF‐β). In vitro studies on human umbilical vein endothelial cells (HUVEC) were employed for determining potential mechanisms. Our results showed that LOX expression was significantly reduced in VM compared with normal skin tissues, in parallel with attenuated perivascular α‐SMA+ cell coverage and TGF‐β downregulation in VM. Further correlation analysis indicated that LOX expression was positively correlated with perivascular α‐SMA+ cell coverage and TGF‐β expression in VM. Moreover, marked elevation of LOX, TGF‐β and α‐SMA was observed in bleomycin‐treated VM samples. Furthermore, our in vitro data demonstrated that both recombinant TGF‐β and bleomycin induced obvious increase of LOX expression and activity and a concomitant increase in ECM components in HUVEC, which could be reversed by LOX inhibition. To our best knowledge, this study revealed for the first time the downregulation of LOX in VM and its correlation with vascular destabilization and TGF‐β‐induced endothelial ECM deposition. Moreover, our results highlighted that LOX may be implicated in the sclerotherapy of VM and holds promise as a therapeutic target.
SSRI use during pregnancy and risk for postpartum haemorrhage: a national register‐based cohort study in Sweden
Authors: Skalkidou A , Sundström‐Poromaa I , Wikman A , Hesselman S , Wikström AK , Elenis E 
Published: March 2020

ObjectiveEvaluate whether selective serotonin reuptake inhibitor (SSRI) use during pregnancy, as well as prior or current untreated psychiatric illness is associated with postpartum haemorrhage (PPH).DesignNational register‐based cohort study based on data from the Swedish Pregnancy Register.SettingSweden, nationwide coverage.PopulationA total of 31 159 pregnant women with singleton deliveries after gestational week 22+0 between January 2013 and July 2017.MethodsPregnant women with self‐reported SSRI use at any time point during pregnancy were compared with non‐SSRI‐treated women with prior or current psychiatric illness, as well as wiith healthy women with no psychiatric illness or reporting SSRI use.Main outcome measuresPostpartum haemorrhage defined as blood loss >1000 ml during the first 2 hours postpartum reported by the delivering midwife or obstetrician.ResultsPostpartum haemorrhage prevalence was 7.0% among healthy women, 7.6% among women with prior or current psychiatric illness and 9.1% among women treated with SSRI. The unadjusted odds for PPH among women with prior or current psychiatric illness and women on SSRI treatment were increased by 9 and 34%, respectively, compared with healthy unmedicated women without a history of psychiatric illness (odds ratio [OR] 1.09, 95% CI 1.04–1.14 and OR 1.34, 95% CI 1.24–1.44, respectively). The estimates remained unchanged after adjustment for several confounders (such as maternal age, body mass index [BMI], parity, prior caesarean section, smoking, occupation and country of birth) and potential covariates (such as delivery mode, polyhydramnion, preterm delivery, labour dystocia and infant birthweight >4000 g).ConclusionsHigher risk for PPH was observed both among women treated with SSRI during pregnancy and among women with prior or current psychiatric illness.Tweetable abstractSSRI use at any point during pregnancy and prior or current history of psychiatric illness was associated with an increased likelihood for PPH.
Can reintroductions to degraded habitat succeed? A test using the common brushtail possum
Authors: Moseby Katherine E. , Brandle Robert , Hodgens Patrick , Bannister Hannah L. 
Published: March 2020

AbstractHabitat degradation contributes to species decline, and habitat quality is an important factor influencing reintroduction success globally. Habitat quality can include a range of physical resources such as nest sites and food resources but also anything that can restrict the use of these resources such as predation risk or competition. In arid Australia, introduced predators are thought to be the primary cause of mammal extinction and reintroduction failure although habitat clearance and alteration are also major causes of population decline. Common brushtail possums are one arid Australian marsupial close to regional extinction. To understand whether habitat quality was limiting their recovery, we reintroduced 148 possums into an area where introduced red foxes were controlled but historic overgrazing had degraded the habitat. We measured both direct (hollow availability, midstorey cover and high‐quality plant foods) and indirect (survival, condition, reproduction, movement) measures of habitat quality. Sixty‐seven released possums and 26 post‐release recruits were radiocollared for up to 2 years after release. Post‐release survival of radiocollared possums was high after 12 months (0.70), and there were no deaths from starvation. Predation by feral cats was the most common cause of mortality, and the open, degraded habitat may have exacerbated predation risk. Continuous breeding, good body condition and comparative home ranges with other sites suggested that food resources were not limiting. Possums used natural tree hollows in Eucalyptus spp. with no use of artificial nest boxes. Results suggest that historically degraded habitat was not a barrier to short‐term reintroduction success when foxes were controlled and natural tree hollows were plentiful. However, demographic data on hollow‐bearing tree species suggest a possible future decline in availability of hollows. These factors, combined with the unknown effects of drought, and synergistic effects of predation and poor quality habitat, suggest long‐term reintroduction success may require improved habitat and cat control.
Exposure–response characterisation of tildrakizumab in chronic plaque psoriasis: Pooled analysis of 3 randomised controlled trials
Authors: Kerbusch Thomas , Li Hanbin , Wada Russell , Jauslin Petra M. , Wenning Larissa 
Published: March 2020

AimsIn this exposure–response analysis, the dosing regimen for tildrakizumab, an antibody for treating moderate‐to‐severe chronic plaque psoriasis, was determined using data from 3 randomised controlled trials (P05495/NCT01225731: phase 2b, n = 355; reSURFACE 1/NCT01722331: phase 3, n = 772; reSURFACE 2/NCT01729754: phase 3, n = 1090).MethodsA maximum drug effect (Emax) logistic‐regression exposure–efficacy model was used to describe the week 12 Psoriasis Area and Severity Index (PASI) responses with average concentration of tildrakizumab during weeks 1–12 (Cavg12) as exposure metric. The impact of covariates (e.g., body weight, region) was tested. Exposure–safety, longitudinal pharmacokinetic–pharmacodynamic and risk–benefit analyses were also conducted.ResultsAt week 12, Emax was estimated at 62.2, 37.9 and 14.6% of responders for PASI75/90/100, respectively. Exposure–response curves plateaued at exposures >5 μg mL−1. Heavier subjects had a lower response rate to placebo as measured by PASI75/90/100 than lighter subjects. PASI100 placebo response was less in subjects with higher baseline PASI score and older age. Simulated week 12 PASI75 increased by ≤4% on increasing the dose from 100 to 200 mg every 12 weeks (Q12W). The pharmacokinetic–pharmacodynamic model adequately described the time course of PASI change after treatment in the entire population and in each subject. Risk–benefit profiles were favourable for the 100‐ and 200‐mg doses in different weight subgroups.ConclusionsPatients with moderate‐to‐severe psoriasis should receive 100‐mg subcutaneous tildrakizumab Q12W. Patients with high body weight (>90 kg) may benefit from a higher dose (200‐mg Q12W).
Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain
Authors: Graves Sara I. , Baker Darren J. 
Published: March 2020

AbstractCerebrovascular endothelial cells (CECs) are integral components of both the blood‐brain barrier (BBB) and the neurovascular unit (NVU). As the primary cell type of the BBB, CECs are responsible for the tight regulation of molecular transport between the brain parenchyma and the periphery. Additionally, CECs are essential in neurovascular coupling where they help regulate cerebral blood flow in response to regional increases in cellular demand in the NVU. CEC dysfunction occurs during both normative ageing and in cerebrovascular disease, which leads to increased BBB permeability and neurovascular uncoupling. This MiniReview compiles what is known about the molecular changes underlying CEC dysfunction, many of which are reminiscent of cells that have become senescent. In general, cellular senescence is defined as an irreversible growth arrest characterized by the acquisition of a pro‐inflammatory secretory phenotype in response to DNA damage or other cellular stresses. We discuss evidence for endothelial cell senescence in ageing and cardiovascular disease, and how CEC senescence may contribute to age‐related cerebrovascular dysfunction.
Bayesian latent multi‐state modeling for nonequidistant longitudinal electronic health records
Authors: Luo Yu , Stephens David A. , Verma Aman , Buckeridge David L. 
Published: March 2020

AbstractLarge amounts of longitudinal health records are now available for dynamic monitoring of the underlying processes governing the observations. However, the health status progression across time is not typically observed directly: records are observed only when a subject interacts with the system, yielding irregular and often sparse observations. This suggests that the observed trajectories should be modeled via a latent continuous‐time process potentially as a function of time‐varying covariates. We develop a continuous‐time hidden Markov model to analyze longitudinal data accounting for irregular visits and different types of observations. By employing a specific missing data likelihood formulation, we can construct an efficient computational algorithm. We focus on Bayesian inference for the model: this is facilitated by an expectation‐maximization algorithm and Markov chain Monte Carlo methods. Simulation studies demonstrate that these approaches can be implemented efficiently for large data sets in a fully Bayesian setting. We apply this model to a real cohort where patients suffer from chronic obstructive pulmonary disease with the outcome being the number of drugs taken, using health care utilization indicators and patient characteristics as covariates.
CD14+CD16+ monocytes are involved in daratumumab‐mediated myeloma cells killing and in anti‐CD47 therapeutic strategy
Authors: Storti Paola , Vescovini Rosanna , Costa Federica , Marchica Valentina , Toscani Denise , Dalla Palma Benedetta , Craviotto Luisa , Malavasi Fabio , Giuliani Nicola 
Published: March 2020

SummaryA deep elucidation of the mechanisms of action of anti‐CD38 monoclonal antibodies (mAbs), such as daratumumab (DARA), is required to identify patients with multiple myeloma (MM) who are more responsive to this treatment. In the present study, an autologous ex vivo approach was established, focussing on the role of the monocytes in the anti CD38‐mediated killing of MM cells. In bone marrow (BM) samples from 29 patients with MM, we found that the ratio between monocytes (CD14+) and MM cells (CD138+) influences the response to DARA. Further, the exposure of the BM samples to DARA is followed by the formation of a CD138+CD14+ double‐positive (DP) population, that quantitatively correlates with the anti‐MM cells killing. These effects were dependent on the presence of a CD14+CD16+ monocyte subset and on high CD16 expression levels. Lastly, the addition of a mAb neutralising the CD47/signal‐regulatory protein α (SIRPα) axis was able to increase the killing mediated by DARA. The effects were observed only in coincidence with high CD14+:CD138+ ratio, with a significant presence of the DP population and were correlated with CD16 expression. In conclusion, the present study underlines the critical role of the CD16+ monocytes in DARA anti‐MM killing effects and gives a rationale to test the combination of an anti‐CD47 mAb with anti‐CD38 mAbs.
Prediction of the haemostatic effects of bypassing therapy using comprehensive coagulation assays in emicizumab prophylaxis‐treated haemophilia A patients with inhibitors
Authors: Furukawa Shoko , Nogami Keiji , Shimonishi Naruto , Nakajima Yuto , Matsumoto Taisei , Shima Midori 
Published: March 2020

SummaryIn emicizumab prophylaxis, the concomitant therapy using bypassing agents (BPAs) is required for breakthrough bleeding and invasive procedures with attention to thrombotic complications. To predict coagulant effects of BPAs in emicizumab‐treated patients with haemophilia A (PwHA) with inhibitor (PwHAwI), blood samples from emicizumab‐treated PwHAwI (n = 8) and PwHA without inhibitor (n = 2) in phase 1/2 and HAVEN 1 study, spiked with activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa (rFVIIa) ex vivo, and blood samples from emicizumab‐treated PwHAwI‐receiving BPAs were analysed by Ca2+‐triggered rotational thromboelastometry (ROTEM) and ellagic acid/tissue factor‐triggered clot waveform analysis (CWA). Spiked aPCC, corresponded to 10–100 U/kg, markedly shortened ROTEM parameters beyond the normal range, while spiked rFVIIa, corresponded to 90–270 μg/kg, shortened them within near‐normal range. Each of the spiked BPA‐improved adjusted maximum coagulation velocity of CWA to within or near the normal range. In blood samples at post‐infusion of aPCC (44–73 U/kg) or rFVIIa (79–93 μg/kg), the parameters of both assays improved to approximately the normal range. Taken together, ex vivo results of spiking tests in ROTEM and CWA, except aPCC spiking test in ROTEM, were relatively consistent with in vivo ones, and could usefully predict the coagulant effects of concomitant bypassing therapy for emicizumab‐treated PwHAwI.
Metagenomic characterization of lysine acetyltransferases in human cancer and their association with clinicopathologic features
Authors: Jiang Yuanyuan , Guo Xuhui , Liu Lanxin , Rode Shomita , Wang Rui , Liu Hui , Yang Zeng‐Quan 
Published: March 2020

AbstractLysine acetyltransferases (KATs) are a highly diverse group of epigenetic enzymes that play important roles in various cellular processes including transcription, signal transduction, and cellular metabolism. However, our knowledge of the genomic and transcriptomic alterations of KAT genes and their clinical significance in human cancer remains incomplete. We undertook a metagenomic analysis of 37 KATs in more than 10 000 cancer samples across 33 tumor types, focusing on breast cancer. We identified associations among recurrent genetic alteration, gene expression, clinicopathologic features, and patient survival. Loss‐of‐function analysis was carried out to examine which KAT has important roles in growth and viability of breast cancer cells. We identified that a subset of KAT genes, including NAA10, KAT6A, and CREBBP, have high frequencies of genomic amplification or mutation in a spectrum of human cancers. Importantly, we found that 3 KATs, NAA10, ACAT2, and BRD4, were highly expressed in the aggressive basal‐like subtype, and their expression was significantly associated with disease‐free survival. Furthermore, we showed that depletion of NAA10 inhibits basal‐like breast cancer growth in vitro. Our findings provide a strong foundation for further mechanistic research and for developing therapies that target NAA10 or other KATs in human cancer.
The potential effects of autonomous vehicles on alcohol consumption and drink‐driving behaviours
Authors: Booth Leon , Norman Richard , Pettigrew Simone 
Published: March 2020

AbstractIntroductionBy removing the need for a driver, autonomous vehicles (AV) are expected to substantially reduce rates of drink‐driving. However, this benefit may be accompanied by an unintended negative consequence in the form of greater overall alcohol consumption due to increased availability of affordable and convenient transport.AimsTo assess: (i) the extent to which drinkers may choose to use AVs after consuming alcohol; (ii) the extent to which drinkers may consume more alcohol if they are using an AV afterwards; and (iii) whether demographic, alcohol‐related and AV‐related factors are associated with the likelihood of engaging in these behaviours.Design and MethodsA total of 1334 Australians of legal driving age who consume alcohol completed an online survey. Two regression models were used to calculate whether the analysed respondent characteristics were associated with intentions to use AVs after drinking and to consume more alcohol if using an AV afterwards.ResultsAround half of the respondents (49%) reported being likely to use an AV after consuming alcohol, and over one‐third (37%) reported being likely to consume more alcohol if using an AV afterwards. Younger age, more frequent alcohol consumption, a positive attitude to AVs and a preference for using 'ride‐share' AVs were associated with a greater likelihood of engaging in these behaviours.Discussion and ConclusionsThe results suggest that the introduction of AVs is likely to reduce drink‐driving rates while facilitating greater participation in heavy episodic drinking. This will constitute a challenge to policymakers in their efforts to minimise alcohol‐related harms.
Soil health cluster analysis based on national monitoring of soil indicators
Authors: Seaton Fiona M. , Barrett Gaynor , Burden Annette , Creer Simon , Fitos Eleonora , Garbutt Angus , Griffiths Rob I. , Henrys Pete , Jones Davey L. , Keenan Patrick , Keith Aidan , Lebron Inma , Maskell Lindsay , Pereira M. Gloria , Reinsch Sabine , Smart Simon M. , Williams Bronwen , Emmett Bridget A. , Robinson David A. 
Published: March 2020

AbstractA major challenge in soil science is to monitor and understand the state and change of soils at a national scale to inform decision making and policy. To address this, there is a need to identify key parameters for soil health and function and determine how they relate to other parameters, including traditional soil surveys. Here we present a national‐scale dataset of topsoil sampled as part of a wider agri‐environment monitoring scheme in Wales, UK. Over 1,350 topsoils (0–15 cm) were sampled across a very wide range of habitats and a range of physical, chemical and biological soil quality indicators were measured. We show consistent differences in soil physicochemical properties across habitat types, with carbon decreasing and pH increasing across the habitat productivity gradient from bogs through woodlands and grasslands to arable systems. The soils within our dataset are largely within the limits identified as important for supporting habitat function, with the exception of excessive phosphate levels in mesotrophic grassland. Cluster detection methods identified four soil functional classes based on measured topsoil properties, which were more related to habitat type than the genesis‐based soil classification from soil maps. These soil functional classes can be interpreted as phenoforms within the soil genoforms found by traditional soil classification. This shows the importance of land‐use management in determining the soil health and functional capacity of soils. Our work provides an account of the current state of soil health in Wales, its relationship to soil function and a baseline for future monitoring to track changes against agri‐environment and other policy targets.HighlightsWe measured soil physicochemical properties in ~1,350 sites in a variety of temperate habitatsThere was a strong gradient in soil carbon and pH, with other variables being correlated with theseMesotrophic grassland sites had phosphate levels above the identified limit for good functioningSoil classes from topsoil properties were more related to land use than soil map classifications
On the Superior Statistical Properties of Frequency Scales in Job Analyses
Authors: Babcock Ben , Risk Nicole M. , Wyse Adam E. 
Published: March 2020

AbstractThis study compared the statistical properties of four job analysis task survey response scale types: criticality, difficulty in learning, importance, and frequency. We used nine job analysis studies spanning two fields, medical imaging and allied health professionals, to compare the job analysis scales in terms of variability and interrater agreement. Results showed that frequency scales using absolute anchors had greater between‐task variability and higher interrater agreement for all nine studies. This may have occurred due to what has been described by past research as self‐presentation bias. In this case, an aggregate base percentage of respondents always responded that tasks in their domain are highly critical, highly important, and easy to learn. These results showed that frequency scales with absolute anchors yielded data with better statistical performance than other more subjective scales. These properties do not answer the question of whether a scale matches an exam's purpose, which is the most important consideration for job analyses. They do, however, suggest that, if statistics are a primary deciding factor, strong consideration should be given to using frequency scales with absolute anchors.
Labour Force Participation among MENA Women in the United States: Exploring the Role of Ethnically Homogamous Relationships
Authors: Bulut Elif , Carlson Elwood 
Published: March 2020

AbstractThis study uncovers variations in female labour force participation (FLFP) among women in the US originating from the Middle East and North Africa (MENA), with a focus on differences by nativity status, and investigates the role of ethnically homogamous relationships in explaining these variations. Lower levels of US labour force participation among women from the Middle East and North Africa (MENA) is puzzling, given that these women have higher educational attainments than most women in the US. Recent work has suggested that looking more closely at the influence of homogamy on immigrant women’s economic activity may help to explain this puzzle. Drawing from prior research on FLFP and immigrant integration, we hypothesized that foreign‐born women from MENA will report lower labour force participation rates relative to their US‐born counterparts, and ethnically homogamous marriage will explain differences in FLFP across nativity status. Data come from the Public Use Microdata Samples (PUMS) from 2012–2016 American Community Surveys (ACS). The analytic sample consists of 33,133 women in the United states of MENA origin who are in the prime working ages of 25 to 59. As hypothesized, we found that foreign‐born MENA women reported significantly lower labour force participation rates than their US‐born counterparts. We also found that after controlling for all relevant characteristics, MENA women (both US‐born and foreign‐born) with MENA husbands remained dramatically less likely to be in the labour force than women with non‐MENA husbands. Our findings suggest the disadvantage in FLFP experienced by foreign‐born MENA women is due mostly to high rates of ethnically homogamous relationships among this population relative to their US‐born counterparts. Thus, our study highlights ethnic homogamy as a structural‐cultural barrier for MENA women’s labour force activity in the US and suggests that empirical research on FLFP and immigrant integration should consider partner characteristics as a key determinant of women’s labour force participation.