bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a three‐dimensional in vitro co‐culture model to increase drug selectivity for humans
Authors: Park Sung Bum , Koh Byumseok , Jung Won Hoon , Choi Kyoung Jin , Na Yoon Ju , Yoo Hee Min , Lee Sunray , Kang Dukjin , Lee Dong‐Mok , Kim Ki Young 
Published: March 2020

AbstractAimInsulin resistance is a metabolic state where insulin sensitivity is lower than normal condition and strongly related to type 2 diabetes. However, an in vitro model mimicking insulin resistance is rare and thus screening drugs for insulin resistance severely depends on an in vivo model. Here, to increase anti‐diabetic drug selectivity for humans, 3D ADMSCs and macrophages were co‐cultured with in‐house fabricated co‐culture plates.Material and methods3D co‐culture plates were designed to load ADMSCs and RAW264.7 cells containing hydrogels in separate wells while allowing cell‐cell interaction with co‐culturing media. Hydrogels were constructed using a 3D cell‐printing system containing 20 mg/ml alginate, 0.5 mg/ml gelatin and 0.5 mg/ml type I collagen. Cells containing hydrogels in 3D co‐culture plates were incubated for 10 min to allow stabilization before the experiment. 3D co‐culture plates were incubated with the CaCl2 solution for 5 min to complete the cross linking of alginate hydrogel. Cells in 3D co‐culture plates were cultured for up to 12 days depending on the experiment and wells containing adipocytes and macrophages were separated and used for assays.ResultsKR‐1, KR‐2 and KR‐3 compounds were applied during differentiation (12 days) in 3D co‐cultured mouse 3T3‐L1 adipocytes and 3D co‐cultured human ADMSCs. Glucose uptake assay using 2‐DG6P and 2‐NBDG and western blot analysis were performed to investigate changes of insulin resistance in the 3D co‐cultured model for interspecies selectivity of drug screening. KR‐1 (mouse potent enantiomer) and KR‐3 (racemic mixture) showed improvement of 2‐DG and 2‐NBDG uptake compared with KR‐2 (human potent enantiomer) in 3D co‐cultured 3T3‐L1 adipocytes. In connection with insulin resistance in a 3D 3T3‐L1 co‐cultured model, KR‐1 and KR‐3 showed improvement of insulin sensitivity compared to KR‐2 by markedly increasing GLUT4 expression. In contrast to the result of 3D co‐cultured 3T3‐L1 adipocytes, KR‐1 failed to significantly improve 2‐DG and 2‐NBDG uptake in 3D co‐cultured ADMSC adipocytes. Results of 2‐NBDG accumulation and western blot analysis also showed that KR‐2 and KR‐3 improved insulin sensitivity relatively better than KR‐1.ConclusionsOur 3D co‐culture model with/without 3D co‐culture plates can successfully mimic insulin resistance while allowing investigation of the effects of anti‐obesity or anti‐diabetic drugs on human or mouse co‐culturing cell type. This 3D co‐culture system may accelerate screening of drugs for insulin resistance depending on species.
Mites and merchants: the crisis of English wool and textile trade revisited, c. 1275–1330†
Authors: Slavin Philip 
Published: March 2020

AbstractOn the basis of 7,871 manorial accounts from 601 sheep‐rearing demesnes and 187 tithe receipts from 15 parishes, this article addresses the origins, scale, and impact of the wool and textile production crisis in England,c. 1275–1350. The article argues that recurrent outbreaks of scab disease depressed sheep population and wool production levels until the early 1330s. The disease, coupled with warfare and taxation, also had a decisive role in depressing the volumes of wool exports. Despite this fact, wool merchants were still conducting business with major wool producers, who desperately needed access to the capital to replenish their flocks.
Continuous aridification since the mid‐Holocene as the main cause of C3/C4 dynamics in the grasslands of northeastern China
Authors: Li Nannan , Xie Manman , Sack Dorothy , Dubois Nathalie , Yang Xiuyun , Gao Guizai , Li Dehui , Liu Lidan , Liu Hongyan , Leng Chengcheng , Wang Jiangyong , Liu Baojian , Jie Dongmei 
Published: March 2020

AbstractEcological responses to past climate change as determined from palaeorecords offer insights into responses that may accompany future climate change. In arid and semi‐arid lands, the interactions between regional vegetation and climate change are not yet well understood, partly due to a lack of suitable palaeovegetation proxies that can provide accurate and continuous tracers for past vegetation dynamics. To gain a better understanding of long‐term vegetation dynamics, this study employs a multiproxy approach applied to sand‐palaeosol sediments of northeastern China's Songnen grasslands. Phytolith analyses and data on the stable carbon isotope composition (δ13C) of organic matter are used to reconstruct palaeovegetation composition, namely, the changing abundance of C3 and C4 species, whereas a geochemical weathering index (Fed/Fet ratios) tracks past East Asian summer monsoon (EASM) intensity. The phytolith assemblages and indices and δ13C of the soil indicate that C4 species' abundance has been increasing in the Songnen grasslands since the mid‐Holocene, although C3 vegetation is still dominant. Statistically significant negative correlations between the δ13C data and Fet/Fed ratios suggest that continuous weakening of the EASM since the mid‐Holocene may be responsible for the 13C‐enrichment of the sediments in the Songnen grasslands. Field vegetation surveys, modern topsoil phytoliths and δ13C calibration data indicate that the expansion of C4 species since the mid‐Holocene is mainly due to their ability to cope with aridity when growing season temperature is not undergoing a significant decrease. Future precipitation decreases in arid and semi‐arid lands should make C4 species more competitive in the grasslands of northeastern China.Highlights
A continuous grassland landscape history is reconstructed from a sand‐palaeosol sequence via phytolith analysis.
Multiple independent approaches were used to reconstruct past EASM intensity and palaeovegetation patterns.
Phytolith and δ13C analyses indicate an increase in C4 species since the mid‐Holocene.
Aridification drives the increase in C4 species within the grassland ecosystem.
The use of hyoscine N‐butylbromide to treat intraoperative bradycardia during isoflurane anaesthesia in three horses
Authors: Loomes K. 
Published: March 2020

SummaryIntraoperative bradycardia is not an uncommon complication in anaesthetised horses and it has been recommended that severe bradycardia (defined as heart rate (HR) <25 beats/min) during general anaesthesia, when associated with hypotension (mean arterial pressure (MAP) <70 mmHg) and other signs of inadequate tissue perfusion, should be treated with anticholinergics. Muscarinic antagonists, such as atropine and glycopyrrolate, cause positive chronotropism and dromotropism (improved atrioventricular conduction) by competitively blocking the effects of acetylcholine at muscarinic receptors in the heart. However, in horses, prolonged intestinal hypomotility and colic have been associated with the use of atropine and glycopyrrolate which has led to the investigation of the use of hyoscine N‐butylbromide (hyoscine NBB) to treat alpha 2 agonist‐induced bradycardia in horses. This report describes the successful use of hyoscine NBB to treat symptomatic intraoperative bradycardia in three isoflurane‐anaesthetised horses.
Modelling material flow using the Milk run and Kanban systems in the automotive industry
Authors: Simić Dragan , Svirčević Vasa , Corchado Emilio , Calvo‐Rolle José L. , Simić Svetislav D. , Simić Svetlana 
Published: March 2020

AbstractMaterial flow management refers to the analysis and specific optimization of the inventory‐production system. Material flow can be characterized as the organized flow of material in a production process with the required sequence determined by a technological procedure. The Milk run system assures the transportation of materials at the right time and in an optimal manner. It should be combined with the Kanban system to highlight when something is required in the production process. This paper presents biological swarm intelligence, in general, and a particular model, particle swarm optimization (PSO), for modelling material flow using a Milk run system supported by a Kanban system in the automotive industry. The aim of this study is to create a new model for the optimal number of trailers for one train and optimal number of containers in a tugger train system when the route time period has been defined. A new modified PSO approach for integrating inventory‐production in a unique optimization model is used. The major modification to the original PSO is using the capacity of a container instead of a velocity component. Each new Kanban trigger is checked, and the total timing for the Milk run delivery solution is calculated for the necessary raw material capacity for each shop floor.
Helicobacter pylori eradication treatment and the risk of Barrett's esophagus and esophageal adenocarcinoma
Authors: Doorakkers Eva , Lagergren Jesper , Santoni Giola , Engstrand Lars , Brusselaers Nele 
Published: March 2020

AbstractBackgroundHelicobacter pylori (H. pylori) is associated with lower risks of Barrett's esophagus and esophageal adenocarcinoma, but whether H. pylori eradication increases the risk of these conditions is unknown. This study aimed to test the hypothesis that H. pylori eradication leads to gradually increased risks of Barrett's esophagus and esophageal adenocarcinoma over time, while esophageal squamous cell carcinoma was assessed for comparison reasons.Material and MethodsThis Swedish nationwide, population‐based cohort study in 2005‐2012 used data from the Swedish Prescribed Drug Registry to assess eradication treatment for H. pylori. Barrett's esophagus was identified from the Swedish Patient Registry, and esophageal adenocarcinoma and squamous cell carcinoma from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by dividing the observed risk in the H. pylori eradication treatment cohort by the expected risk derived from the Swedish population of the same age, sex, and calendar period.ResultsThe cohort included 81 919 patients having had eradication treatment. For Barrett's esophagus (n = 178), the overall SIR was increased (SIR 3.67, 95% CI 3.15‐4.25), but the SIRs slightly decreased over time after eradication treatment. For esophageal adenocarcinoma (n = 11), the overall SIR was 1.26 (95% CI 0.62‐2.26), and the SIRs did not increase over time. The SIRs of esophageal squamous cell carcinoma (n = 10) were not influenced by eradication treatment.ConclusionsThis study did not provide any evidence of an increasing risk of Barrett's esophagus or esophageal adenocarcinoma (or esophageal squamous cell carcinoma) over time after eradication treatment for H. pylori.
Circannual variation in habitat use of the White‐winged SnowfinchMontifringilla nivalis nivalis
Authors: Bettega Chiara , Fernández‐González Ángel , Ramón Obeso José , Delgado Maria Del Mar 
Published: March 2020

High mountain areas are subject to strong seasonal fluctuations, and species inhabiting these particular environments show a high degree of habitat specialization to cope with extreme abiotic conditions. Estimates of habitat use are influenced by the spatial and seasonal scales at which they are evaluated, so studies at multiple scales are important in order to explore adaptive responses to seasonal environments. In the present study, we assessed habitat use of the White‐winged SnowfinchMontifringilla nivalissubsp.nivalis(henceforth Snowfinch) during breeding and non‐breeding seasons at three different spatial scales (diameters of 100, 250 and 500 m). Although Snowfinches clearly used high‐elevation habitats in both seasons, there was evidence that they are less specific during the non‐breeding period: the variance explained by habitat and topographical factors was lower in winter than in the breeding season. Moreover, our results suggest that the use of habitat is scale‐dependent. This pattern was especially relevant in the breeding season, perhaps because habitat use might be more related to nest‐site selection and specific foraging sites to provide food for nestlings. Snowfinches use high mountain habitats throughout the year, probably as a consequence of physiological and morphological specializations typical of high‐elevation species, but in winter they show a certain flexibility in habitat use. Snowfinches might thus adopt a flexible specialist strategy. This could represent a trade‐off to overcome possible effects on survival, condition and fitness, which can be particularly strong in harsh, unpredictable environments.
Maternal antibiotic use and vaginal infections in the third trimester of pregnancy and the risk of obesity in preschool children
Authors: Isaevska Elena , Popovic Maja , Pizzi Costanza , Fiano Valentina , Rusconi Franca , Merletti Franco , Richiardi Lorenzo , Maule Milena 
Published: March 2020

SummaryBackground/objectivesSeveral exposures during pregnancy are associated with offspring body mass index (BMI). The objective of this study was to evaluate whether third trimester antibiotic use and vaginal infections are associated with BMI in preschool children.Subjects/methodsThe study population included singletons from the NINFEA birth cohort with available anthropometric measurements at the age of 4 (3151 born with vaginal and 1111 born with caesarean delivery). Self‐reported use of antibiotics and the presence of vaginal infection in the third trimester were analysed in association with the child's BMI, classified into three categories: thinness, normal and overweight/obesity, using both the International Obesity Task Force (IOTF) and the World Health Organization (WHO) recommended cut‐offs.ResultsMaternal vaginal infections in the third trimester of pregnancy were associated with higher relative risk ratios (RRR) for overweight/obesity at age of four in children delivered vaginally: 1.92 (95% confidence interval [CI]: 1.37 to 2.70). This association appeared stronger for children born to women with pre‐pregnancy BMI >25 kg/m2 (RRR: 4.78; 95% CI 2.45 to 9.35), and was robust when different obesity cut‐offs were used. The results regarding third trimester antibiotic use in vaginal deliveries were less conclusive (RRRs for overweight/obesity: 1.43 (0.92 to 2.21) and 1.11 (0.57 to 2.20), for the IOTF and WHO cut‐offs, respectively). Third trimester vaginal infections were not associated with BMI in children delivered by caesarean section.ConclusionsMaternal third trimester vaginal infections are associated with an increased overweight/obesity risk in children born by vaginal delivery, and especially in children of mothers with pre‐pregnancy overweight/obesity.
Tracking of brachial and central aortic systolic pressure over the normal human lifespan: insight from the arterial pulse waveforms
Authors: Adji Audrey , O'Rourke Michael F. 
Published: March 2020

AbstractDespite multiple studies, it has not been possible to account for the normal changes of blood pressure that occur from infancy to old age. We sought a comprehensive explanation, by linking brachial pressure with the well documented changes in the arterial pulse waveform, whose peak and nadir determine systolic, diastolic and pulse pressure in brachial arteries. Changes in humans arterial pulse wave contour from birth to old age can be readily explained on (i) growth, with increasing length of the body from birth to adolescence, and adult height maintained thereafter, and (ii) degeneration and dilation of the aorta from elastic fibre fracture throughout life, causing progressive increase in aortic pressure wave amplitude from early return of wave reflection, and summation of incident with reflected waves in systole. These changes throughout life complement arterial pulse waveform analysis and explain brachial cuff pressure values, with optimal pulse wave pattern for cardiac interaction apparent in adolescence.
The liver as an immunological barrier redefined by single‐cell analysis
Authors: Stamataki Zania , Swadling Leo 
Published: March 2020

SummaryThe liver is a front‐line immune tissue that plays a major role in the detection, capture and clearance of pathogens and foreign antigens entering the bloodstream, especially from the gut. Our largest internal organ maintains this immune barrier in the face of constant exposure to external but harmless antigens through a highly specialized network of liver‐adapted immune cells. Mapping the immune resident compartment in the liver has been challenging because it requires multimodal single‐cell deep phenotyping approaches of often rare cell populations in difficult to access samples. We can now measure the RNA transcripts present in a single cell (scRNA‐seq), which is revolutionizing the way we characterize cell types. scRNA‐seq has been applied to the diverse array of immune cells present in murine and human livers in health and disease. Here, we summarize how emerging single‐cell technologies have advanced or redefined our understanding of the immunological barrier provided by the liver.
Preparation of tunable full‐color emission carbon dots and their optical applications in ions detection and bio‐imaging
Authors: Xia Chao , Cao Mengmeng , Xia Jinfeng , Jiang Danyu , Zhou Guohong , Yu Caiyan , Li Huili 
Published: March 2020

AbstractIn this work, we synthesized a series of novel carbon dots (CDs) by using phenylenediamines (three isomers: o‐phenylenediamine, m‐phenylenediamine, and p‐phenylenediamine) as starting materials via facile solvothermal approach. As‐prepared CDs could emit bright blue, green, yellow, orange, and red light with relatively high PLQY, individually. Optical properties could be controlled by simply varying reaction parameters. The luminescent mechanism was investigated and analyzed in detail. Finally, the blue‐emitting CDs and green‐emitting CDs showed many appealing properties, such as high sensitivity (limit of detection = 4.52 and 3.50 nmol/L), quick response (<2 minutes), broad response window (0‐70 nmol/L), and excellent selectivity for detecting Cr6+ and Al3+ cations, respectively. Thus, they have potential to be developed as the corresponding optical probes. While as‐prepared orange‐emitting CDs could be applied as a bio‐imaging reagent due to its long‐wavelength emission, relatively high PLQY, low toxicity, excellent water solubility, and good biocompatibility.
Theoretical study on composition‐ and pressure‐dependent mechanical properties of AlON solid solution
Authors: Ren Lu , Wang Hao , Tu Bingtian , Zong Xiao , Wang Weimin , Fu Zhengyi 
Published: March 2020

AbstractIn view of the application of γ‐AlON as transparent structural materials, it is significant to have a deep understanding of mechanical properties of γ‐AlON as well as their response to external pressure. First‐principles calculation combined with bond valence models was used to reconstruct Fd3m structure, and explore the composition and applied pressure dependence of mechanical properties of Al24−8/3xO24+8xN8−8x. The reconstructed Fd3m structure of Al24−8/3xO24+8xN8−8x was proved to be reasonable. The investigation demonstrated that the hardness and bulk modulus of bonds can be enhanced by increasing the ratio of bond valence to bond length and the bonds in octahedra contribute more to hardness and bulk modulus of Al24−8/3xO24+8xN8−8x. The applicability of the inferences was assessed by MgAl2O4 and c‐Si3N4. It can be inferred that the inferences cannot be applied to other spinel‐type compounds but also provide guidance to designing new spinel‐type compounds with desirable hardness and bulk modulus.
Extracellular vesicles in normal pregnancy and pregnancy‐related diseases
Authors: Zhang Jiayin , Li Haibo , Fan Boyue , Xu Wenrong , Zhang Xu 
Published: March 2020

AbstractExtracellular vesicles (EVs) are nanosized, membranous vesicles released by almost all types of cells. Extracellular vesicles can be classified into distinct subtypes according to their sizes, origins and functions. Extracellular vesicles play important roles in intercellular communication through the transfer of a wide spectrum of bioactive molecules, contributing to the regulation of diverse physiological and pathological processes. Recently, it has been established that EVs mediate foetal‐maternal communication across gestation. Abnormal changes in EVs have been reported to be critically involved in pregnancy‐related diseases. Moreover, EVs have shown great potential to serve as biomarkers for the diagnosis of pregnancy‐related diseases. In this review, we discussed about the roles of EVs in normal pregnancy and how changes in EVs led to complicated pregnancy with an emphasis on their values in predicting and monitoring of pregnancy‐related diseases.
Humanin analogue, HNG, inhibits platelet activation and thrombus formation by stabilizing platelet microtubules
Authors: Ren Lijie , Li Qing , You Tao , Zhao Xuefei , Xu Xingshun , Tang Chaojun , Zhu Li 
Published: March 2020

AbstractHNG, a highly potent mutant of the anti‐Alzheimer peptide‐humanin, has been shown to protect against ischaemia‐reperfusion (I/R) injury. However, the underlying mechanism related to platelet activation remains unknown. We proposed that HNG has an effect on platelet function and thrombus formation. In this study, platelet aggregation, granule secretion, clot retraction, integrin activation and adhesion under flow conditions were evaluated. In mice receiving HNG or saline, cremaster arterial thrombus formation induced by laser injury, tail bleeding time and blood loss were recorded. Platelet microtubule depolymerization was evaluated using immunofluorescence staining. Results showed that HNG inhibited platelet aggregation, P‐selectin expression, ATP release, and αIIbβ3 activation and adhesion under flow conditions. Mice receiving HNG had attenuated cremaster arterial thrombus formation, although the bleeding time was not prolonged. Moreover, HNG significantly inhibited microtubule depolymerization, enhanced tubulin acetylation in platelets stimulated by fibrinogen or microtubule depolymerization reagent, nocodazole, and inhibited AKT and ERK phosphorylation downstream of HDAC6 by collagen stimulation. Therefore, our results identified a novel role of HNG in platelet function and thrombus formation potentially through stabilizing platelet microtubules via tubulin acetylation. These findings suggest a potential benefit of HNG in the management of cardiovascular diseases.