bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Tri‐Layered Vascular Construct and In Vitro Evaluation of Endothelization
Authors: Kole Gozde E. , Hasirci Vasif , Yucel Deniz 
Published: December 2023

AbstractAdvances in the development of vascular substitutes for small‐sized arteries are ongoing because the present grafts do not entirely meet the requirements of native equivalents and are suboptimal in clinical performance. This study aims to develop a tri‐layered vascular construct mimicking natural tissue using polyester blends and to investigate its endothelization through in vitro studies as a potential small‐caliber vascular graft. The innermost layer is obtained by dip coating as a tubular porous film with a lumen diameter of 3 mm and a pore size of ≤8 µm. Circumferentially aligned electrospun fiber (diameter 100–800 nm) with a deviation angle of 15° are deposited over the porous film forming the intermediate layer. The random electrospun fibers (diameter 100–1100 nm) deviating at different angles are wrapped as the outermost layer. The mechanical properties of the tri‐layered vascular construct are determined to be 44.80 ± 14.80 MPa for Young's modulus and 4.25 ± 0.75 MPa for ultimate tensile strength. MTS and cell behavior studies show that the isolated human umbilical cord vein endothelial cells proliferate and line the lumen of the vascular substitute. The vascular construct developed, with its biomimetic architecture, mechanical features, size, and endothelization, can be tested with in vivo studies.
Trade policy uncertainty, export destination, and firm's pollution emissions: Analysis from theoretical perspective
Authors: Huang Geng , Lin Xi , Xu Shuying , Wang Junyu , He Ling‐Yun 
Published: December 2023

AbstractIn recent years, global economic and trade frictions have been frequent. Trade policies of many countries have become increasingly uncertain. This may also have an impact on global ecological environment. Trade policy uncertainty (TPU) may lead firms to change export destination, thereby affecting firms' pollution emissions. However, little is known about short‐run environmental effect and long‐run effect of TPU. Using theoretical analysis, this paper incorporates firms' export destination choice into theoretical model. We find that de‐crease in TPU will directly reduce firms' emission intensity. Besides, in the long run, TPU's increase from developed country leads the firm to change export destination to developing country; thus, firm's emission intensity will increase. Altogether, we present the first theoretical explanation on relationship between export destination and environment, providing comprehensive perspective to study TPU's environmental effect.
Hypertension in NF1: A closer look at the primacy of essential hypertension versus secondary causes
Authors: Loponen Niina , Ylä‐Outinen Heli , Kallionpää Roope A. , Valtanen Mikko , Auranen Kari , Järveläinen Hannu , Peltonen Sirkku , Peltonen Juha 
Published: December 2023

AbstractBackgroundWe aimed to analyze hypertension in neurofibromatosis type 1 (NF1) in a Finnish population‐based cohort in 1996–2014.MethodsA cohort of 1365 individuals with confirmed NF1 was compared with a control cohort of 13,923 individuals matched for age, sex, and area of residence. Diagnoses of hypertension were retrieved from the Finnish Care Register for Health Care. These registered data were separately analyzed for secondary and essential hypertension. Purchases of antihypertensive drugs were queried from the Finnish Register of Reimbursed Drug Purchases.ResultsWe identified 115 NF1 patients with hospital diagnosis of hypertension. Our findings revealed a hazard ratio (HR) of 1.64 (95% CI 1.34–2.00, p < 0.001) in NF1 versus controls. NF1 patients presented with a significantly increased hazard for both secondary hypertension (n = 9, HR 3.76, 95% CI 1.77–7.95, p < 0.001) and essential hypertension (n = 98, HR 1.73, 95% CI 1.39–2.14, p < 0.001). No difference in the HR of hypertension was observed between men and women, while NF1 patients with essential hypertension were, on average, younger than the controls. The proportions of individuals with antihypertensive medication did not differ between NF1 patients and controls (OR 0.85).ConclusionNF1 is a risk factor for hypertension. Despite the recognized risk for secondary hypertension, essential hypertension is the predominant type in NF1.
Ramipril therapy in integrin α1‐null, autosomal recessive Alport mice triples lifespan: mechanistic clues from RNA‐seq analysis
Authors: Madison Jacob , Wilhelm Kevin , Meehan Daniel T , Gratton Michael Anne , Vosik Denise , Samuelson Gina , Ott Megan , Fascianella John , Nelson Noa , Cosgrove Dominic 
Published: December 2023

AbstractThe standard of care for patients with Alport syndrome (AS) is angiotensin‐converting enzyme (ACE) inhibitors. In autosomal recessive Alport (ARAS) mice, ACE inhibitors double lifespan. We previously showed that deletion of Itga1 in Alport mice [double‐knockout (DKO) mice] increased lifespan by 50%. This effect seemed dependent on the prevention of laminin 211‐mediated podocyte injury. Here, we treated DKO mice with vehicle or ramipril starting at 4 weeks of age. Proteinuria and glomerular filtration rates were measured at 5‐week intervals. Glomeruli were analyzed for laminin 211 deposition in the glomerular basement membrane (GBM) and GBM ultrastructure was analyzed using transmission electron microscopy (TEM). RNA sequencing (RNA‐seq) was performed on isolated glomeruli at all time points and the results were compared with cultured podocytes overlaid (or not) with recombinant laminin 211. Glomerular filtration rate declined in ramipril‐treated DKO mice between 30 and 35 weeks. Proteinuria followed these same patterns with normalization of foot process architecture in ramipril‐treated DKO mice. RNA‐seq revealed a decline in the expression of Foxc2, nephrin (Nphs1), and podocin (Nphs2) mRNAs, which was delayed in the ramipril‐treated DKO mice. GBM accumulation of laminin 211 was delayed in ramipril‐treated DKO mice, likely due to a role for α1β1 integrin in CDC42 activation in Alport mesangial cells, which is required for mesangial filopodial invasion of the subendothelial spaces of the glomerular capillary loops. Ramipril synergized with Itga1 knockout, tripling lifespan compared with untreated ARAS mice. © 2023 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Design of surpassing damping and modulus nanocomposites with tunable frequency range via hierarchical bio‐architecture
Authors: Xu Chenhao , Feng Haibo , Li Yan , Li Li 
Published: December 2023

AbstractThe challenges of both high stiff and high dissipative properties are critical obstacles in structural engineering, particularly for the wide frequency range. This study proposes an innovative design method for creating nanocomposites with exceptional damping and modulus, offering tunability in temperature or frequency. The design principle is based on the hierarchical microstructure of the nanocomposite encompasses dangling chains at the atomic level, devisable microstructures in intermolecular macromolecules at the molecular level, and compatible domains between multi‐walled carbon nanotubes (MWCNTs) and macromolecules at the coarse level. To enhance damping performance, a self‐healing epoxy resin based on transesterification, known for its atomic‐level dangling chains, serves as the matrix. Control of the glass transition temperature is achieved by adjusting the ratios of glutaric anhydride (stiff) and sebacic acid (flexible) in the curing agent. Dangling chains and the soft curing agent can improve damping, but they are negative to modulus. To counterbalance this, this study introduces high‐modulus MWCNTs, resolving the inherent conflict between stiffness and damping. A damping model is constructed to recognize the continuous distribution of relaxation times of our designed composites. The designed nanocomposites have surpassing damping and modulus with tunable temperature or frequency range, surpassing the limited loss modulus of conventional engineering materials.Highlights
The design principle of both high stiff and lossy properties of bones is revealed.
Microstructural features are employed for fabricating our nanocomposite.
High damping and moduli composites with tunable temperature are attained.
A damping model is established for the distribution of relaxation times.
Hierarchical bio‐architecture defeats the conflict of stiffness versus damping.
Use of physiologically‐based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended‐release nifedipine
Authors: Tan Ming‐Liang , Gao Zongming , Babiskin Andrew , Kim Myong‐Jin , Fang Lanyan , Zhang Lei , Zhao Liang 
Published: December 2023

AbstractProton pump inhibitors (PPIs) can affect the release of drugs from their dosage forms in vivo by elevating the gastric pH. Our recent clinical study has demonstrated that drug–drug interactions (DDIs) exist between a PPI, omeprazole, and nifedipine extended‐release formulations, where systemic exposure of nifedipine was increased in subjects after multiple‐dose pretreatment of omeprazole. However, the mechanism of the observed DDIs between omeprazole and nifedipine has not been well‐understood, as the DDI may also be mediated through CYP3A4 enzyme inhibition in addition to the elevated gastric pH caused by omeprazole. This study used physiologically‐based pharmacokinetic (PBPK) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in in vitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to characterize the potential impact of pH. The PBPK models incorporated two‐stage in vitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple‐dose administration of omeprazole has a minimal effect on nifedipine pharmacokinetics (PKs), whereas CYP3A4‐mediated DDI is likely the main driver to the observed change of nifedipine PKs in the presence of omeprazole. Compared to the osmotic formulation, the slightly increased exposure of nifedipine can be accounted for by the enhanced drug release in the pH‐dependent formulation. The reported model‐based approach may be useful in DDI risk assessments, product formulation designs, and bioequivalence evaluations.
Assessing the calibration of multivariate probabilistic forecasts
Authors: Allen Sam , Ziegel Johanna , Ginsbourger David 
Published: December 2023

AbstractRank and probability integral transform histograms are established tools to assess the calibration of probabilistic forecasts. They not only check whether a forecast is calibrated, but they also reveal what systematic biases (if any) are present in the forecasts. Several extensions of rank histograms have been proposed to evaluate the calibration of probabilistic forecasts for multivariate outcomes. These extensions introduce a so‐called pre‐rank function that condenses the multivariate forecasts and observations into univariate objects, from which a standard rank histogram can be produced. Existing pre‐rank functions typically aim to preserve as much information as possible when condensing the multivariate forecasts and observations into univariate objects. Although this is sensible when conducting statistical tests for multivariate calibration, it can hinder the interpretation of the resulting histograms. In this article, we demonstrate that there are few restrictions on the choice of pre‐rank function, meaning forecasters can choose a pre‐rank function depending on what information they want to extract concerning forecast performance. We introduce the concept of simple pre‐rank functions and provide examples that can be used to assess the mean, spread, and dependence structure of multivariate probabilistic forecasts, as well as pre‐rank functions that could be useful when evaluating probabilistic spatial field forecasts. The simple pre‐rank functions that we introduce are easy to interpret, easy to implement, and they deliberately provide complementary information, meaning several pre‐rank functions can be employed to achieve a more complete understanding of multivariate forecast performance. We then discuss how e‐values can be employed to formally test for multivariate calibration over time. This is demonstrated in an application to wind‐speed forecasting using the EUPPBench post‐processing benchmark dataset.
Gene regulatory network inference based on causal discovery integrating with graph neural network
Authors: Feng Ke , Jiang Hongyang , Yin Chaoyi , Sun Huiyan 
Published: December 2023

AbstractGene regulatory network (GRN) inference from gene expression data is a significant approach to understanding aspects of the biological system. Compared with generalized correlation‐based methods, causality‐inspired ones seem more rational to infer regulatory relationships. We propose GRINCD, a novel GRN inference framework empowered by graph representation learning and causal asymmetric learning, considering both linear and non‐linear regulatory relationships. First, high‐quality representation of each gene is generated using graph neural network. Then, we apply the additive noise model to predict the causal regulation of each regulator‐target pair. Additionally, we design two channels and finally assemble them for robust prediction. Through comprehensive comparisons of our framework with state‐of‐the‐art methods based on different principles on numerous datasets of diverse types and scales, the experimental results show that our framework achieves superior or comparable performance under various evaluation metrics. Our work provides a new clue for constructing GRNs, and our proposed framework GRINCD also shows potential in identifying key factors affecting cancer development.
User‐friendly relative quantification procedure for gas chromatography/mass spectrometry–based plasma metabolome analysis
Authors: Nishiumi Shin , Yokoyama Tomonori , Ojima Noriyuki 
Published: December 2023

RationaleRecently, metabolome analysis has been applied to a variety of research fields, but differences between batches or facilities can cause discrepancies in the results of such analyses. To resolve these issues using comprehensive metabolome analysis, in which it is difficult to perform quantitative analyses of all detected metabolites, internal standard compounds are used to obtain relative metabolite levels. This study investigated gas chromatography/mass spectrometry–based plasma metabolome analysis methods that are superior to relative quantification using internal standard compounds.MethodsIn experiment I, four analyses were performed under different analytical conditions at one facility, and then the data from the four analyses were compared. In experiment II, the same samples were analyzed at three facilities, and then the data from the three facilities were compared.ResultsRegarding the relative values obtained through comparisons with the internal standard compound, differences in the analytical results were observed among the four analytical conditions in experiment I and among the three facilities in experiment II, and the differences observed among the three facilities (experiment II) were larger. When correction was performed using plasma as a quality control, which is the procedure suggested in this study, these differences were markedly ameliorated.ConclusionThe suggested procedure involves the analysis of a plasma standard as a quality control for each batch and the calculation of relative target plasma to quality‐control plasma values for each metabolite. This is an easy and low‐cost method and could be readily employed by researchers during comprehensive plasma metabolome analysis.
Green connection to the world: Building regional responsible sustainable development strategies
Authors: Yang Zhenshan , Wang Haoran 
Published: December 2023

AbstractGreen development and solutions to environmental problems rely on local conditions and green connections between regions during their development. However, it is less understood whether a region's emission of carbon and pollutants is moderate compared to its development. The study proposes the ‘green connection of regional development’ concept from the consumption perspective to enhance the understanding and measurement of regional capacity towards green development and responsible production and consumption. Data envelopment analysis was performed to evaluate the local and embodied emissions of eight pollutants for 30 provinces in China from 2012 to 2017. Twenty provinces had optimal capacity of green growth within the region and 15 had an optimal green connection of regional development. Suboptimal levels of overall green growth and green connection of regional development efficiencies were due to insufficient pure technical and scale efficiency levels, with a stronger impact of the former.
Feminist Pedagogy in the EFL Classroom in Japan: Evaluating a One‐Shot Intervention Approach
Authors: Nagashima Yuzuko , Lawrence Luke 
Published: December 2023

AbstractAt the turn of the century, bell hooks described the overarching lay view of feminism as a negative, man‐hating ideology. Despite the enormous societal overhauls that have occurred in the decades since, it appears that in Japan little has changed. The marginalized position that women occupy in Japanese society is starkly illustrated by Japan's continually low ranking on the Global Gender Gap Index. In this study, we use a single university lesson in advanced elective English classes to stage a one‐shot intervention in feminist pedagogy. The purpose of the study was to assess the students' understanding of and attitude toward feminism and issues related to male privilege before and after the class. We were also interested in evaluating the suitability of the English language class as a vehicle for feminist pedagogy. The results indicated that many students showed a shift in consciousness away from a largely negative view of feminism and an abstract understanding of gender inequality, to a more positive attitude toward feminism and a clearer understanding of the systemic nature of gender inequality. It also found that English language teaching classes were very conducive to feminist pedagogy with language input, group discussion, and reflective writing providing space for consciousness‐raising.
Single‐cell transcriptome analysis reveals intratumoral heterogeneity in lung adenocarcinoma
Authors: Xu Hong , Jiang Lin , Qin Lingshan , Shi Ping , Xu Ping , Liu Changyu 
Published: December 2023

AbstractIntroductionLung adenocarcinoma (LUAD) is a major health concern worldwide. Single‐cell RNA‐sequencing (scRNA‐seq) provides a valuable platform for exploring the intratumoral heterogeneity in LUAD and holds great potential for facilitating the development and application of personalized therapeutic approaches.MethodsThe TCGA‐LUAD (n = 503), GSE68465 (n = 442), GSE72094 (n = 398), and GSE26939 (n = 115) datasets were retrieved for prognostic assessment. Subgroup analysis was performed for the epithelial cells, endothelial cells, immune cells, and fibroblasts, and the transcription factors and tumor‐related pathways enriched in each subgroup were analyzed using PROGENy and DoRothEA package. The InferCNV software was used to calculate the copy number variations (CNVs) in tumor cell subgroups with normal epithelial cells as the reference. The association between the annotated cell types and survival was analyzed using the Scissor software.ResultsWe identified eight major cell types in LUAD, namely epithelial cells, NK cells, T and B cells, endothelial cells, mast cells, myeloid cells, and fibroblasts, of which the epithelial cells and B cells showed a marked increase in the tumor samples. In addition, we also detected an intense signal transduction network from the cancer‐associated fibroblasts (CAFs) to malignant cells, mainly involving the DCN/MET, COLA1/DDR1, COL1A1/SDC1, and COL1A2/SDC1 pathways. The tumor differentiation trajectory consisted of state 1 and state 2, which were enriched in HIF1A, and state 4. Furthermore, only a few B cells originated from the normal tissue, suggesting significant recruitment and infiltration of B cells in LUAD. Based on differentially upregulated genes in the cells positively and negatively associated with survival, we established a prognostic model that showed satisfactory predictive performance in three different cohorts. States 3 and 2 of epithelial cells included the majority of cells with KRAS mutation, whereas state 2 showed high frequency of EGFR mutations.ConclusionWe analyzed intra‐tumor heterogeneity of LUAD at the single‐cell level and developed a prognostic index that was highly effective across multiple cohorts.
Visitor engagement with zoo staff and interpretive demonstrations increases visitor stay time in two free‐flight aviaries
Authors: Lyon Cassandra E. M. , Alba Andrew C. , Burgess Amy , Weibel Chelsea J. , Miller Dave , Alligood Christina , Ferrie Gina M. 
Published: December 2023

AbstractUnderstanding how visitors spend time in zoo exhibits is important as zoological facilities work to enhance visitor experience and conservation education outcomes. We explored a variety of factors we hypothesized would influence visitor stay times in two aviaries at Disney's Animal Kingdom®. Within these aviaries, visitors could utilize educational materials, listen to staff‐led demonstrations, or talks, view animal training sessions, or speak directly with animal care or education staff. We observed visitors and recorded the opportunities they utilized in the exhibit. Visitors to either aviary who conversed with exhibit‐specific staff stayed between 67% and 89% longer than visitors who did not. In addition, visitors who used a bird guide while in either aviary stayed between 59% and 82% longer than those who did not. Those who listened to an animal care talk or engaged with a staff‐led demonstration stayed between 50% and 68% longer than those who did not have the option to participate in such activities. This study provides insight into how exhibit offerings can influence visitor behavior. Implementing strategies used in this study to increase visitors' time in an exhibit may enhance visitor experience and improve learning outcomes.
Afterword
Authors: Dessai Suraje , Lonsdale Kate , Lowe Jason , Harcourt Rachel 
Published: December 2023

Abstract

Investing in ‘gluing’ roles, as was performed by the UKCR Champions, is essential for building community and delivering impact, as is a strong online and social media presence and a programme of community building events.

Resilience research should be ‘user’ or ‘challenge’ led and needs to invest in ways of working that facilitate innovative and transdisciplinary approaches. Key research gaps remain including in understanding compound, transboundary, cascading and systemic risks; place-based vulnerability assessments that combine risk information with other socioeconomic and behavioural factors; and scaling-up climate services.

Future adaptation research programmes should prioritise further developing the research-practice community to adequately address the complex challenge of building resilience.
Towards a Step Change in Co-Production for Climate Resilience
Authors: Golding Nicola , Ashton Jenna , Brown Kate , Chan Steven , Coles Tim , Fowler Hayley , Fuller Elizabeth , Harrison Paula , Harvey-Fishenden Alice , Macdonald Neil , Sefton Christine 
Published: December 2023

Abstract

Co-production brought clear benefits to a range of projects across the UK Climate Resilience Programme (UKCR).

Experiences were deeply context specific; dependent on those involved, their motivations and expectations.

A range of barriers currently exist to achieving the benefits of co-production more fully.

Skills associated with using co-productive approaches need to be developed, taught and mentored in the research community.