bluuebunny/crossref_metadata_2025 huggingface dataset:
Democratic Public or Populist Rabble: Repositioning the City amidst Social Fracture
Authors: Rivero Juan J. , Sotomayor Luisa , Zanotto Juliana M. , Zitcer Andrew
Published: March 2020

The current degree of social fracture that has attended the growing prevalence of populist movements calls into question the viability of democratic practices grounded in collective deliberation. Urban practitioners committed to democratic inclusion must confront the practical question of how to deal with a divided public. Any such effort must address longstanding and mutually reinforcing trends that have both aggravated social fragmentation and enabled the rise of populist regimes whose policies exacerbate divisiveness and inequity. These trends include economic restructuring and rising inequality, cultural division, and a post‐truth trap resulting from disagreement over epistemological and ontological assumptions. We argue that, while local governments can play a role in addressing these dynamics, a more fundamental renewal of a meaningfully democratic polity depends on a capacity to help cultivate solidarity across difference. We then recast the city as a site of political encounter and experimentation that might enable both a re‐examination of prevailing modes of public engagement and the emergence of solidarities and infrastructures through which populism might be challenged. Finally, we consider how a progressive urban politics of place might use populism as a point of departure for transforming urban futures.
Overweight and obesity status from the prenatal period to adolescence and its association with non‐alcoholic fatty liver disease in young adults: cohort study
Authors: Cantoral A , Montoya A , Luna‐Villa L , Roldán‐Valadez EA , Hernández‐Ávila M , Kershenobich D , Perng W , Peterson KE , Hu H , Rivera JA , Téllez‐Rojo MM
Published: March 2020

Objective

To examine the associations of maternal and child overweight status across multiple time‐points with liver fat content in the offspring during young adulthood.

Design

Cohort study.

Setting

ELEMENT Cohort in Mexico City.

Population

Pregnant women with singleton births (n = 97).

Methods

We quantified hepatic triglyceride content (liver fat content) by proton magnetic resonance spectroscopy (1H MRS) and conventional T2‐weighted MRIs (3T scanner) in 97 young adults from the ELEMENT birth cohort in Mexico City. Historical records of the cohort were used as a source of pregnancy, and childhood and adolescence anthropometric information, overweight and obesity (OWOB) were defined. Adjusted structural equation models were run to identify the association between OWOB in different life stages with liver fat content (log‐transformed) in young adulthood.

Main outcome

Maternal OWOB at the time of delivery was directly and indirectly associated with the liver fat content in the offspring at young adulthood.

Results

Seventeen percent of the participants were classified as having NAFLD. We found a strong association of OWOB between all periods assessed. Maternal OWOB at time of delivery (β = 1.97, 95% CI 1.28–3.05), and OWOB status in the offspring at young adulthood (β = 3.17, 95% CI 2.10–4.77) were directly associated with the liver fat content in the offspring. Also, maternal OWOB was indirectly associated with liver fat content through offspring OWOB status.

Conclusion

We found that maternal OWOB status is related to fatty liver content in the offspring as young adults, even after taking into account OWOB status and lifestyle factors in the offspring.

Tweetable abstract

There was an association between pre‐pregnancy overweight and the development of NAFLD in adult offspring.
Complications after benign hysterectomy, according to procedure: a population‐based prospective cohort study from the Danish hysterectomy database, 2004–2015
Authors: Settnes A , Moeller C , Topsoee MF , Norrbom C , Kopp TI , Dreisler E , Joergensen A , Dueholm M , Rasmussen SC , Froeslev PA , Ottesen B , Gimbel H
Published: March 2020

Objective

To compare the risk of complications associated with benign hysterectomy according to surgical procedure.

Design

Register‐based prospective cohort study.

Setting

Danish Hysterectomy Database, 2004–2015.

Population

All Danish women with benign elective hysterectomy (n = 51 141).

Methods

Multivariate log‐binomial regression to compute relative risks (RRs) stratified by calendar period, and adjusted for age, height, weight, smoking habits, use of alcohol, comorbidity, indications, uterine weight and adhesions. Multiple imputation and ‘intention to treat’ analyses were performed.

Main outcome measures

Major (grades III–V) and minor (grades I–II) Clavien–Dindo modified complications within 30 days.

Results

Overall, major complications occurred in 3577 (7.0%) hysterectomies and minor complications occurred in 4788 (9.4%). The proportions of major and minor complications according to type of hysterectomy were: 10.3 and 9.6% for abdominal hysterectomy (AH); 4.1 and 12.1% for laparoscopic hysterectomy (LH); and 4.9 and 8.0% for vaginal hysterectomy (VH) for non‐prolapse, and 2.3 and 6.4% for prolapse. In multivariate analyses, compared with VH for non‐prolapse, the risk of major complications was higher for AH (RR 1.82, 95% CI 1.63–2.03) but lower for both LH (RR 0.78, 95% CI 0.68–0.90) and VH for prolapse (RR 0.55; 95% CI 0.41–0.75). For LH, the risk of major complications reduced from a RR of 0.96 (95% CI 0.75–1.22) in the time period 2004–2009 to an RR of 0.72 (95% CI 0.60–0.87) between 2010 and 2015.

Conclusion

Laparoscopic hysterectomy and VH for uterine prolapse are associated with fewer major complications, and AH is associated with more major complications, compared with VH performed in the absence of uterine prolapse.

Tweetable abstract

Laparoscopic hysterectomy has fewer major complications compared with vaginal hysterectomy, in the absence of uterine prolapse.
Botanical origin authentication of dietary supplements by DNA‐based approaches
Authors: Grazina Liliana , Amaral Joana S. , Mafra Isabel
Published: March 2020

Herbal products, such as dietary supplements, have become a subject of increasing global importance for their health benefits and economic considerations. However, they have also been targets of adulteration practices, being the accurate identification of botanicals in herbal products of utmost importance to protect the health and expectations of consumers. Particularly, in the case of dietary supplements, which can have different types of formulations, the identification of plant material used in their production is often a research challenge. DNA‐based techniques have played a crucial role on the development of a wide range of tools for the authentication of herbal products. Therefore, this review intends to describe their main progresses, critically discussing their advantages and drawbacks when applied to authenticate herbal products, focusing on dietary supplements. DNA barcoding is particularly emphasized because it has provided the highest number of applications, followed by the advances on high‐resolution melting analysis combined with DNA barcodes. A special emphasis is also given to the promising approaches relying on DNA metabarcoding and isothermal amplification.
Effects of soybean isoflavone on metabolism of rat osteoblasts and cytokines in vitro
Authors: Lu Minan , Xie Kegong , Huang Ke , Lu Xianzhe , Lu Lu , Shi Yu , Tang Yujin
Published: March 2020

The effects and mechanisms of soybean isoflavone on osteoblast (OB) proliferation in vitro were investigated. Fifty female Wistar rats were randomly divided into five groups with 10 rats in each group. Rat OBs were separated and cultured. The first generation of OBs cultured for 48 hr at various concentrations of isoflavone were set as the experimental groups, the OBs exposed to estradiol (E2) culture were considered as positive control group. The biological characterization of OBs was investigated by phase contrast microscopy and alkaline phosphatase (ALP) histochemistry. The concentrations of interleukin (IL‐1), osteoprotegerin (OPG), transforming growth factor (TGF), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and vascular endothelial growth factor (VEGF) in isoflavone culture solutions were determined. Proliferation rate of OBs was increased in experimental group comparing that in the blank group. ALP activity in experimental group was higher than that in blank group. No significant differences of ALP activity were observed between E2 culture group and isoflavone group at concentrations of 10−5 and 10−7 mM (P > 0.05). Furthermore, in the experimental groups at low isoflavone concentrations, the concentrations of OPG, TGF, and VEGF were increased and positively correlated with OB proliferation. However, the concentrations of IL‐1, GM‐CSF were decreased at higher concentration of isoflavone and were negatively correlated with OB proliferation. Soybean isoflavone could promote the growth and proliferation of rat OB, it might act as the stimulator of OPG, TGF, and VEGF pathway, and the inhibitor of IL‐1, GM‐CSF pathway as well.
Microgreens: Consumer sensory perception and acceptance of an emerging functional food crop
Authors: Michell Kiri A. , Isweiri Hanan , Newman Steven E. , Bunning Marisa , Bellows Laura L. , Dinges Michelle M. , Grabos Lauren E. , Rao Sangeeta , Foster Michelle T. , Heuberger Adam L. , Prenni Jessica E. , Thompson Henry J. , Uchanski Mark E. , Weir Tiffany L. , Johnson Sarah A.
Published: March 2020

Microgreens are an emerging functional food crop with promise for sustainably diversifying global food systems, facilitating adaptations to urbanization and global climate change, and promoting human health. Previous work suggests microgreens have high nutritional quality, low environmental impacts, and broad consumer acceptance. For better reception into the global food system and increased per capita consumption, research is needed to elucidate consumer acceptance of various microgreens species, including factors contributing to their acceptance or lack thereof. Using a consumer panel (n = 99), this study evaluated consumer sensory perception and acceptability of six microgreens species (arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth, and tendril pea), and potential drivers and barriers to consumer acceptance. All microgreens species received high mean liking scores for acceptability by consumers (means ranged from highly acceptable to slightly acceptable), with more distinct differences across microgreens species for flavor and overall acceptability, which appeared to be driven by specific sensory properties. Data from principal component analysis demonstrated that high acceptability scores were associated with higher intent to purchase microgreens and negatively associated with food neophobia. Participants indicated that factors such as knowledge and familiarity of microgreens, cost, access/availability, freshness/shelf life, among other factors, influence their intention to purchase microgreens. These findings suggest that further integration of microgreens into the global food system will be met with high consumer acceptability, but needs to be aligned with enhanced consumer education regarding microgreens, as well as considerations of cost, availability/access, and freshness/shelf life.

Practical Application

Researchers investigated consumer sensory perception and acceptability of six microgreens species (arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth, and tendril pea), and potential drivers and barriers to consumer acceptance. All microgreens tested had high consumer acceptability, but certain factors such as sensory perception and food neophobia impacted their acceptability. Additionally, participants indicated that factors such as knowledge, access and availability, cost, freshness, and shelf life may impact the purchasing of microgreens and thus are important factors to consider for further integration of this emerging functional food crop into the global food system.
Spontaneously fermented curly kale juice: Microbiological quality, nutritional composition, antioxidant, and antimicrobial properties
Authors: Szutowska Julia , Rybicka Iga , Pawlak‐Lemańska Katarzyna , Gwiazdowska Daniela
Published: March 2020

Nondairy fermented products, such as fruit and vegetable juices, are gaining popularity among consumers worldwide for health‐related and economic reasons. The purpose of this study was to determine the changes in microbiological quality; antimicrobial and antioxidant activity; and phenolic, vitamin C, minerals, and cadmium content occurring during spontaneous fermentation of curly kale juice. The fermentation process contributed to a significant growth of lactic acid bacteria, enterococci, and yeasts, while no pathogens of Escherichia coli and Salmonella spp. were observed. The antimicrobial properties of the obtained juice improved during fermentation for all indicator microorganisms. Total phenolic content and antioxidant activity increased from 48 to 116 mg gallic acid equivalent/100 mL and from 4.5 to 6.8 mM Trolox/100 mL, respectively, while the content of vitamin C decreased. The results indicated that 100 mL of juice provided a significant contribution to the recommended mineral intake. Moreover, the content of heavy metal Cd was within acceptable limit (6 µg/kg). Overall, our findings indicate that fermented curly kale juice may become popular in the functional food sector, especially among vegetarians and consumers with lactose intolerance or allergy to milk proteins.

Practical Application

As the market for fermented fruit and vegetable products grows, new plant materials rich in biologically active compounds are being sought. Considering the high demand for sauerkraut, the fermentation of other cruciferous vegetables seems interesting. One example is curly kale, which has been classified as “superfood” due to its numerous beneficial health properties, such as strong antioxidant activity, high vitamins, and minerals content. In addition, a market niche exists due to a lack of fermented green curly kale products on the market, making our study particularly relevant.
Systematic evaluation of nutritional and safety characteristics of Hengshan goat leg meat affected by multiple thermal processing methods
Authors: Jiao Yang , Liu Yongfeng , Quek Siew Young
Published: March 2020

Hengshan goat meat produced exclusively in Shaanxi province of China is the product of national geographical indication. In current study, nutritional and safety indexes of Hengshan goat leg meat were investigated and the quality changes induced by seven commonly used processing methods were systematically evaluated. Comparing with control, meats treated with thermal processing demonstrated decreased redness, enhanced texture properties, increased protein, fat and mineral contents, as well as sharply raised fatty acids. Amino acid contents in pan‐fried, deep‐fried, and roasted samples were reduced with the most obvious valine scores declined 15%, 13%, and 21%, respectively. Also, thermal treatments conducted in smoke exposure circumstances caused mass formation of nitrite and polycyclic aromatic hydrocarbons (PAHs), evidenced by the 5.8‐fold, 3.3‐fold, and 3.8‐fold increments of nitrite contents in pan‐fried, deep‐fried, and roasted meats, respectively, and the appearance of six extra PAHs. Steaming, boiling, and braising were proved to be suitable processing methods for preserving better nutritional values while delivering less carcinogenic hazard. Our results established nutritional database for Hengshan goat leg meat and provide reference for choosing its reasonable thermal processing pattern.

Practical Application

Processed meats showed decreased redness, enhanced texture properties, increased protein, fat and mineral contents, as well as sharply raised fatty acids compared with those of raw meat. Steaming, boiling, and braising delivered more balanced nutrition and less carcinogens in contrast to meats processed with other methods. Frying and roasting caused low amino acid levels and formed mass nitrite and polycyclic aromatic hydrocarbons in meats. Our results established nutritional database for Hengshan goat leg meat and provide reference for its reasonable thermal processing.
Polylactic acid–based materials encapsulating carvacrol obtained by solvent casting and electrospinning
Authors: Tampau Alina , González‐Martínez Chelo , Chiralt Amparo
Published: March 2020

Polylactic acid (PLA) dissolved (15 wt.%) in ethyl acetate (EtAc): dimethyl sulfoxide (DMSO) binary systems (0:1; 1:3, and 2:3 v/v) was used as carrier to obtain carvacrol (CA)‐loaded (20 wt.% with respect to PLA) matrices by electrospinning, in comparison with solvent casting. Field emission scanning electron microscopy (FESEM) observations showed that CA‐loaded electrospun fibers were thinner than the CA‐free ones, and their encapsulating efficiency (EE) increased when EtAc was present in the solvent. The cast films had higher EE (up to 89%) than the electrospun mats (maximum 68%). Thermogravimetric analysis and differential scanning calorimetry revealed that CA‐free matrices retain more solvent than the samples with CA; this effect is being more noticeable in fibers rather than in cast films. The thermal analysis revealed stronger retention forces of CA in the fibers than in the cast material and the CA plasticizing effect in the PLA matrices, in accordance with its retained amount.

Practical Application

The carvacrol‐loaded polylactic acid materials obtained in this study are intended to serve as possible active layer in obtaining active (antimicrobial and/or antioxidant) multilayer materials for the packaging of foodstuffs, when applied onto a supporting polymer layer. Active properties of the material, as well as the potential carvacrol sensory impact, in packaged products should be assessed in further studies.
Single nucleotide polymorphisms of the HIF1A gene are associated with susceptibility to pulmonary arterial hypertension in systemic sclerosis and contribute to SSc‐PAH disease severity
Authors: Takagi Kae , Kawamoto Manabu , Higuchi Tomoaki , Tochimoto Akiko , Harigai Masayoshi , Kawaguchi Yasushi
Published: March 2020

Aim

Hypoxia‐inducible factor (HIF)1α is induced by endothelial cells under hypoxic conditions, suggesting that HIF1α may be involved in vascular impairment in patients with systemic sclerosis (SSc). The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) of the HIF1A gene are associated with susceptibility to SSc and its complications, including pulmonary arterial hypertension (PAH).

Method

This study involved 182 Japanese SSc patients (discovery cohort) and 178 healthy controls. Four SNPs (rs11549465, rs11549467, rs1957757, and rs12434438) of the HIF1A gene were genotyped using specific TaqMan probes. We also employed another SSc cohort (N = 135) to validate the significant results of SNPs found in the discovery SSc cohort.

Results

The frequencies of the four SNPs did not show any significant differences between the SSc and healthy control groups. The AA genotype at rs12434438 was significantly higher in SSc patients with PAH than in those without PAH (P = .012). These results were validated using another SSc cohort (N = 135, P = .006). Moreover, the AA genotype was significantly associated with the severity of PAH.

Conclusion

Although HIF1A gene polymorphisms were not associated with susceptibility to SSc, the AA genotype at rs12434438 was associated with a subset of SSc patients with severe PAH, suggesting that the rs12434438 SNP may contribute to the development of PAH with SSc.
The effects of lipid extraction on δ13C and δ15N values and use of lipid‐correction models across tissues, taxa and trophic groups
Authors: Cloyed Carl S. , DaCosta Kayla P. , Hodanbosi Matthew R. , Carmichael Ruth H.
Published: March 2020

Lipid‐rich animal tissues have low δ13C values, which can lead to inaccurate ecological inferences. Chemical lipid extraction (LE) or correction models account for this depletion, but the need for LE or correction is tissue‐ and species‐specific. Also, LE can alter δ15N values, increasing labour and costs because bulk samples must be analysed for δ15N values separately.

We studied the effects of LE on δ13C and δ15N values in liver, muscle and skin of common bottlenose dolphins Tursiops truncatus and West Indian manatees Trichechus manatus, two ecologically important species that occupy different trophic levels. We fit lipid‐correction models to each species. We also performed a meta‐analysis to more broadly determine the effects of LE across taxa, tissues and trophic groups (carnivores, omnivores and herbivores) and to fit lipid‐correction models to different taxonomic and trophic groups.

Lipid extraction increased the δ13C values in dolphin tissues but had little effect on manatee tissues and no effect on the δ15N values in either species. A mass balance lipid‐correction model best fit the data from all dolphin tissues, and a linear model best fit data for manatee liver while null models best fit data from manatee muscle and skin. Across 128 terrestrial and aquatic species, the effects of LE varied among tissues and were lower for herbivores compared to carnivores. The best‐fitting lipid‐correction models varied among tissue, taxa and trophic groups. Finally, the δ15N values from muscle and liver were affected by LE.

Our results strengthen the growing body of evidence that the need for LE is tissue‐ and species‐specific, without a reliable C:N ratio predictive threshold. The prediction errors of lipid‐correction models generally decreased with taxonomic and trophic specificity. The smaller effects of LE in herbivores may be due to differences in diet composition or the physiology of lipid synthesis in members of this trophic group. These results suggest that researchers should use the most species‐, tissue‐ and trophic group‐specific information on LE available and, if not available, perform LE on a subset of samples prior to analysis to determine effects.
Network structure and the optimization of proximity‐based association criteria
Authors: Gomes Ana Cristina R. , Boogert Neeltje J. , Cardoso Gonçalo C.
Published: March 2020

Animal social network analysis (SNA) often uses proximity data obtained from automated tracking of individuals. Identifying associations based on proximity requires deciding on quantitative criteria such as the maximum distance or the longest time interval between visits of different individuals to still consider them associated. These quantitative criteria are not easily chosen based on a priori biological arguments alone.

Here we propose a procedure for optimizing proximity‐based association criteria in SNA, whereby different spatial and temporal criteria are screened to determine which combination detects more network structure. If we assume that biologically relevant associations among individuals are non‐random, and that proximity data are mostly influenced by those associations, then it is logical to select criteria that minimise random associations and show the underlying network structure more clearly.

We first used simulations to evaluate which of four simple descriptors of network structure remain unbiased (i.e. do not change directionally) when reducing the number of observations, since unbiased descriptors are necessary for comparing the structure of networks using different association criteria. Then, using two of those descriptors (coefficient of variation of the strength of associations and network entropy) and empirical proximity data from automated tracking of common waxbills Estrilda astrild in a mesocosm environment, we found that the structure‐based optimization procedure selected the most biologically relevant combination of spatial and temporal proximity criteria, in the sense that those criteria were also the best at distinguishing between previously known social subgroups of individuals.

These results indicate that, provided that the assumptions for structure‐based optimization are met, this procedure can find the most biologically relevant association criteria. Thus, under the condition that proximity data are shaped by non‐random social associations, and if using adequate descriptors of network structure, structure‐based optimization may be a useful tool for SNA, particularly when a priori biological arguments are insufficient to inform the choice of proximity‐based association criteria.
Identifying the cognitive underpinnings of voice‐hearing by comparing never, past and current voice‐hearers
Authors: Toh W. L. , Tan E. J. , Neill E. , Van Rheenen T. E. , Gurvich C. , Sumner P. J. , Carruthers S. P. , Thomas E. H. X. , Rossell S. L.
Published: March 2020

Objective

The current study aimed to compare specific cognitive profiles corresponding to auditory verbal hallucinations (AVH) status and elucidate which pattern of cognitive deficits may predict voice‐hearing status.

Method

Clinical participants with schizophrenia spectrum disorders were partitioned into: (i) current voice‐hearers (n = 46), (ii) past voice‐hearers (n = 37) and (iii) never voice‐hearers (n = 40), and compared with 319 non‐clinical controls. Cognitive assessment employed the MATRICS Consensus Cognitive Battery (MCCB), supplemented by the Delis–Kaplan Executive Function System (D‐KEFS) Colour–Word Interference Test (Stroop) as a robust measure of executive function.

Results

On the Visual Learning domain, current and past voice‐hearers had significantly poorer performance relative to never voice‐hearers, who in turn had significantly poorer performance than non‐clinical controls. Current and never voice‐hearers had significantly poorer performance on the Social Cognition domain relative to non‐clinical controls. Current voice‐hearers also had significantly poorer performance on the Inhibition domain relative to non‐clinical controls. Binary logistic regression revealed that Visual Learning was the only significant cognitive predictor of AVH presence.

Conclusion

Visual learning, and potentially inhibition, may be viable therapeutic targets when addressing cognitive mechanisms associated with AVHs. Future research should focus on investigating additional cognitive mechanisms, employing diverse voice‐hearing populations and embarking on related longitudinal studies.
Platelet‐rich plasma and regenerative dentistry
Authors: Xu J , Gou L , Zhang P , Li H , Qiu S
Published: March 2020

Regenerative dentistry is an emerging field of medicine involving stem cell technology, tissue engineering and dental science. It exploits biological mechanisms to regenerate damaged oral tissues and restore their functions. Platelet‐rich plasma (PRP) is a biological product that is defined as the portion of plasma fraction of autologous blood with a platelet concentration above that of the original whole blood. A super‐mixture of key cytokines and growth factors is present in platelet granules. Thus, the application of PRP has gained unprecedented attention in regenerative medicine. The rationale underlies the utilization of PRP is that it acts as a biomaterial to deliver critical growth factors and cytokines from platelet granules to the targeted area, thus promoting regeneration in a variety of tissues. Based on enhanced understanding of cell signalling and growth factor biology, researchers have begun to use PRP treatment as a novel method to regenerate damaged tissues, including liver, bone, cartilage, tendon and dental pulp. To enable better understanding of the regenerative effects of PRP in dentistry, this review describes different methods of preparation and application of this biological product, and provides detailed explanations of the controversies and future prospects related to the use of PRP in dental regenerative medicine.
Protein S protects against allergic bronchial asthma by modulating Th1/Th2 balance
Authors: Asayama Kentaro , Kobayashi Tetsu , D'Alessandro‐Gabazza Corina N. , Toda Masaaki , Yasuma Taro , Fujimoto Hajime , Okano Tomohito , Saiki Haruko , Takeshita Atsuro , Fujiwara Kentaro , Fridman D’Alessandro Valeria , Nishihama Kota , Totoki Toshiaki , Inoue Ryo , Takei Yoshiyuki , Gabazza Esteban C.
Published: March 2020

Background

Bronchial asthma is a chronic disease characterized by inflammation, obstruction, and hyperresponsiveness of the airways. There is currently no curative therapy for asthma. Type 2 helper T cell response plays a critical role in the pathogenesis of the disease. Protein S is a glycoprotein endowed with anticoagulant, anti‐inflammatory, and anti‐apoptotic properties. Whether protein S can suppress bronchial asthma and be useful for its therapy is unknown.

Methods

To address this question here we compared the development of allergen‐associated bronchial asthma between wild type and protein S‐overexpressing transgenic mice. Mice were sensitized and challenged with ovalbumin. We also evaluated the circulating levels of total and active protein S in patients with bronchial asthma and healthy controls.

Results

The circulating level of total protein S and of its active form was significantly decreased in patients with bronchial asthma compared to controls. Allergic protein S transgenic mice showed a significant reduction of airway hyperresponsiveness, lung tissue inflammatory cell infiltration, lung levels of Th2 cytokines and IgE compared to their wild‐type counterparts. Administration of exogenous human protein S also decreased airway hyperresponsiveness and Th2‐mediated lung inflammation in allergic wild‐type mice compared with their untreated mouse counterparts. Human protein S significantly shifted the Th1/Th2 balance to Th1 and promoted the secretion of Th1 cytokines (IL‐12, tumor necrosis factor‐α) from dendritic cells.

Conclusions

These observations suggest the strong protective activity of protein S against the development of allergic bronchial asthma implicating its potential usefulness for the disease treatment.
Basophil sensitivity reflects long‐term clinical outcome of subcutaneous immunotherapy in grass pollen‐allergic patients
Authors: Schmid Johannes M. , Würtzen Peter A. , Siddhuraj Premkumar , Jogdand Prajakta , Petersen Claus G. , Dahl Ronald , Erjefält Jonas S. , Hoffmann Hans Jürgen
Published: March 2020

Background

Allergic rhinoconjunctivitis is a public health problem. Allergen Immunotherapy is an effective and safe treatment, that modifies the natural course of allergic disease and induces long‐term tolerance.

Objective

To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue.

Methods

Adults suffering from allergic rhinoconjunctivitis due to grass pollen allergy were randomized to receive subcutaneous immunotherapy (n = 18) or to an open control group (n = 6). Patients reported daily symptom and medication scores and weekly rhinitis related quality of life scores during four pollen seasons. Biomarkers were measured every 3 months for three years treatment and every 6 months in the follow‐up year. Nasal and cutaneous allergen challenge tests were performed annually. Leukocyte subsets were assessed in nasal mucosa biopsies at baseline and after treatment.

Results

Subcutaneous immunotherapy led to a 447‐fold decrease in basophil sensitivity during the first treatment year. This remained 100‐fold lower than baseline during the 3 year‐treatment period and 10‐fold lower during the follow‐up year (n = 18, P = .03). Decrease in basophil sensitivity after three weeks of treatment predicted long‐term improvement in seasonal combined symptom and medication scores (ῥ=−0.69, P = .0027) during three years of treatment. AUC of IgE‐blocking factor correlated to nasal allergen challenge (ῥ = 0.63, P = .0012) and SPT (ῥ = 0.45, P = .03). Plasma cell numbers in the nasal mucosa increased during treatment (P = .02).

Conclusion

Decrease in basophil sensitivity after three weeks of subcutaneous allergen immunotherapy predicted the clinical outcome of this treatment.
Anticipated difficult airway during obstetric general anaesthesia: narrative literature review and management recommendations.
Authors: Mushambi M. C. , Athanassoglou V. , Kinsella S. M.
Published: March 2020

We reviewed the literature on management of general and regional anaesthesia in pregnant women with anticipated airway difficulty. We identified 138 publications comprising 158 cases; these either described equipment or techniques for the provision of general anaesthesia, or the management of women with regional analgesia or anaesthesia, with the aim of avoiding general anaesthesia. Most of the former group described women requiring caesarean section alone, or in combination with other surgery, which was sometimes airway‐related. Management techniques were largely similar to those in non‐obstetric patients requiring surgery who have airway difficulties, although suggested differences related to physiological changes of pregnancy and avoidance of nasal intubation. In the reports discussing regional anaesthesia, consideration was often given to the possible requirement for urgent out‐of‐hours anaesthetic intervention, and the predicted difficulty of management of general anaesthesia should it be required. In a number of reported cases, multidisciplinary planning led to the conclusion that elective caesarean section should be performed in order to avoid emergency airway management. Based on this literature review, we advise antenatal planning that includes: assessment of the patient's clinical characteristics; consideration of the equipment and personnel available to provide safe airway management out‐of‐hours; and elective caesarean section should these be lacking. If general anaesthesia is required, a risk assessment must be made as to the probability of safe airway management after the induction of anaesthesia, and awake tracheal intubation should be used if this cannot be assured. Decision aids are provided to illustrate these points. Online appendices include a comprehensive compendium of case reports on the management of a number of rare syndromes and airway conditions.
The effect of corporate real estate ownership on R&D innovation: credit relief vs. resource replacement in China
Authors: Deng Jie , Yang Jingjing
Published: March 2020

Against the background of supply‐side structural reform and the real estate financialisation in China, this study investigates the impact of real estate holdings on R&D investment using data of enterprises listed on the Shanghai and Shenzhen stock exchanges. Our empirical results yield five main findings. First, enterprises holding more real estate assets face more serious financial constraints, thus restraining corporate innovation efficiency. Second, when the profit margin gap between entity enterprises and the real estate industry is larger, enterprises are more inclined to transfer industrial capital into the real estate industry, thus reducing R&D investment. Third, when the degree of marketisation is high, intensified market competition, the optimal allocation of factor and product markets, and stronger patent protection will weaken the restraining effect of corporate real estate holdings on R&D investment. Fourth, monopoly enterprises obtain potential profits more than undertaking risks from the real estate industry, they are more willing to hold real estate, thus strengthening the restraining effect of real estate holdings on innovation. Finally, investors' regional preference intensifies the restraining effect of corporate real estate holdings on R&D investment. Our empirical evidence can guide entity enterprises on how to effectively balance short‐term (non‐productive) and long‐term (productive) capital investment.
Model‐based meta‐analysis of individual International Prostate Symptom Score trajectories in patients with benign prostatic hyperplasia with moderate or severe symptoms
Authors: D'Agate Salvatore , Wilson Timothy , Adalig Burkay , Manyak Michael , Palacios‐Moreno Juan Manuel , Chavan Chandrashekhar , Oelke Matthias , Roehrborn Claus , Della Pasqua Oscar
Published: March 2020

Aims

International Prostate Symptom Score (IPSS) is a marker of lower urinary tract symptoms (LUTS) deterioration or improvement in benign prostate hyperplasia (BPH). Whereas changes in IPSS relative to baseline have been used as endpoints in clinical trials, little attention has been given to the time course of symptoms. The current investigation aimed to develop a drug‐disease model to describe individual IPSS trajectories in moderate and severe BPH patients.

Methods

A model‐based meta‐analytical approach was used including data from 10 238 patients enrolled into Phase III and IV studies receiving placebo, tamsulosin, dutasteride or combination therapy over a period of up to 4 years. Model predictive performance was assessed using statistical and graphical criteria. Subsequently, simulations were performed to illustrate the implications of treatment with drugs showing symptomatic and disease‐modifying properties in patients with varying disease progression rates.

Results

Improvement and worsening of IPSS could be characterized by a model including a sigmoid function which disentangles drug effects from placebo and varying disease progression rates on IPSS. Mean estimate (95% confidence intervals) for the disease progression rate was 0.319 (0.271–0.411) month−1. Treatment effect on IPSS (DELTA) was found to be 0.0605, 0.0139 and 0.0310 month−1 for placebo, tamsulosin and combination therapy, respectively. In addition, it appears that individual trajectories can be clustered together into different phenotypes describing the underlying disease progression rate (i.e. slow, moderate and fast progressors).

Conclusions

The availability of a drug‐disease model enables the evaluation of interindividual differences in disease progression rate, deterioration of symptoms and treatment effects on LUTS/BPH.
Dose‐dependent naloxone‐induced morphine withdrawal symptoms in opioid‐dependent males—a double‐blinded, randomized study
Authors: Weisshaar Stefan , Brandt Laura , Litschauer Brigitte , Sheik‐Rezaei Safoura , Moser Laura , Nirnberger Günther , Kühberger Elisabeth , Bauer Ulrike , Firbas Christa , Gouya Ghazaleh , Wolzt Michael , Fischer Gabriele
Published: March 2020

Aims

Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine–naloxone dose ratio for an abuse‐deterrent oral opioid formulation.

Methods

In a randomized, double‐blinded, 2 × 2 cross‐over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine–naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine–naloxone 200:1]). Acute naloxone‐induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale–German [SOWS‐G]) and observer‐rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated.

Results

Intravenous morphine–naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose‐dependently (morphine–naloxone 100:1 > morphine–naloxone 200:1) increased SOWS‐G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone.

Conclusion

Morphine–naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine–naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.
Bridging learning sciences, machine learning and affective computing for understanding cognition and affect in collaborative learning
Authors: Järvelä Sanna , Gašević Dragan , Seppänen Tapio , Pechenizkiy Mykola , Kirschner Paul A.
Published: March 2020

Collaborative learning (CL) can be a powerful method for sharing understanding between learners. To this end, strategic regulation of processes, such as cognition and affect (including metacognition, emotion and motivation) is key. Decades of research on self‐regulated learning has advanced our understanding about the need for and complexity of those mediating processes in learning. Recent research has shown that it is not only the individual's but also the group's shared processes that matter and, thus, that regulation at the group level is critical for learning success. A problem here is that the “shared” processes in CL are invisible, which makes it almost impossible for researchers to study and understand them, for learners to recognize them and for teachers to support them. Traditionally, research has not been able to make these processes visible nor has it been able to collect data about them. With the aid of advanced technologies, signal processing and machine learning, we are on the verge of “seeing” these complex phenomena and understanding how they interact. We posit that technological solutions and digital tools available today and in the future will help advance the theory underlying the cognitive, metacognitive, emotional and social components of individual, peer and group learning when seen through a multidisciplinary lens. The aim of this paper is to discuss and demonstrate how multidisciplinary collaboration among the learning sciences, affective computing and machine learning is applied for understanding and facilitating CL.

Practitioner Notes

What is already known about this topic

Collaborative learning occurs when team members systematically activate, sustain and regulate their cognition, motivation, emotions and behaviors towards the attainment of their goals.

Socially shared regulation in learning contributes to success in collaborative learning.

What this paper adds

“Shared” processes in collaborative learning are hard for researchers to study and understand them, for learners to recognize them and for teachers to support them.

Multimodal data collection provides opportunities to study multiple aspects of student behaviors and regulation processes.

With the aid of advanced technologies multidisciplinary collaboration between the learning sciences, affective computing and machine learning can help to study these complex phenomena.

Implications for practice and/or policy

The case examples demonstrate how multidisciplinary collaboration can meet the challenges in understanding and facilitating collaborative learning.

Multidisciplinary efforts with multimodal data will contribute to collaborative learning practice by providing theoretically informed feedback and personalized support.
Inhibition of erythropoietin‐producing hepatoma receptor B4 (EphB4) signalling suppresses the vascularisation and growth of endometriotic lesions
Authors: Rudzitis‐Auth Jeannette , Fuß Sophia A. , Becker Vivien , Menger Michael D. , Laschke Matthias W.
Published: March 2020

Background and Purpose

The development of endometriotic lesions is crucially dependent on the formation of new blood vessels. In the present study, we analysed whether this process is regulated by erythropoietin‐producing hepatoma receptor B4 (EphB4) signalling.

Experimental Approach

We first assessed the anti‐angiogenic action of the EphB4 inhibitor NVP‐BHG712 in different in vitro angiogenesis assays. Then, endometriotic lesions were surgically induced in the dorsal skinfold chamber and peritoneal cavity of NVP‐BHG712‐ or vehicle‐treated BALB/c mice. This allowed to study the effect of EphB4 inhibition on their vascularisation and growth by means of intravital fluorescence microscopy, high‐resolution ultrasound imaging, histology and immunohistochemistry.

Key Results

Non‐cytotoxic doses of NVP‐BHG712 suppressed the migration, tube formation and sprouting activity of both human dermal microvascular endothelial cells (HDMEC) and mouse aortic rings. Accordingly, we also detected a lower blood vessel density in NVP‐BHG712‐treated endometriotic lesions. This was associated with a reduced lesion growth due to a significantly lower number of proliferating stromal cells when compared to vehicle‐treated controls.

Conclusions and Implications

Inhibition of EphB4 signalling suppresses the vascularisation and growth of endometriotic lesions. Hence, EphB4 represents a promising pharmacological target for the treatment of endometriosis.
Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF‐1α‐independent VEGF expression and angiogenesis in hepatocellular carcinoma
Authors: Zhang Cheng , Wang Ning , Tan Hor‐Yue , Guo Wei , Chen Feiyu , Zhong Zhangfeng , Man Kwan , Tsao Sai Wah , Lao Lixing , Feng Yibin
Published: March 2020

Background and Purpose

As a typical hypervascular tumour, hepatocellular carcinoma (HCC) is predominantly grown through angiogenesis. Geniposide is a promising anti‐inflammatory compound found in Gardenia jasminoides, but its effects on the progression of HCC remain untested.

Experimental Approach

The anti‐HCC effects of geniposide was investigated in cellular models and orthotopic HCC mice. Transcriptional regulation of the VEGF promoter was measured by dual‐luciferase reporter assay. The anti‐angiogenic action of geniposide was measured by tube formation assay. Both surface plasmon resonance techniques and human phospho‐kinase array analysis were utilized to validate the relationship between targets of geniposide and hepatocarcinogenesis.

Key Results

Geniposide exhibited significant disruption of HCC proliferation, invasion, angiogenesis and lung metastasis in orthotopic HCC mice. Geniposide inhibited secretion of VEGF by HCC and suppressed the migration of endothelial cells and the formation of intra‐tumour blood vessels, without cytotoxicity and independently of the transcription factor HIF‐1α. Direct inhibition of TLR4 by geniposide led to the shutdown of the TLR4/MyD88 pathway and STAT3/Sp1‐dependent VEGF production. However, LPS, an agonist of TLR4, restored STAT3/Sp1‐related VEGF production in geniposide‐inhibited HCC angiogenesis.

Conclusion and Implications

The direct inhibitory effect of geniposide on TLR4/MyD88 activation contributes to the suppression of STAT3/Sp1‐dependent VEGF overexpression in HCC angiogenesis and pulmonary metastasis. This action of geniposide was not affected by stabilization of HIF‐1α. Our study offers a novel anti‐VEGF mechanism for the inhibition of HCC.
Updates in antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis for the ENT surgeon
Authors: Coates Matthew L. , Martinez Del Pero Marcos
Published: March 2020

ENT involvement is common in ANCA‐associated vasculitis (AAV), particularly in GPA and EGPA. Early recognition and treatment is important for good outcomes, yet evidence suggests that UK ENT surgeons may not consistently recognise the early features of AAV, despite a similar incidence to vestibular schwannoma. AAV is a rapidly advancing field, with significant developments in the understanding of its pathogenesis, classification and treatment over the past decade. Relevant vasculitis mimics are also discussed with a particular focus on the increasing prevalence of vasculitis mimics driven by an increase in recreational cocaine use, as well as the emergence and reclassification of several other vasculitis mimics in the head and neck. This article reviews key recent updates in the vasculitis literature, with a particular focus on those relevant to recognition and diagnosis of AAV for the ENT surgeon. Strengths and limitations of relevant diagnostic testing are discussed, and a method of evaluation of patients with features of AAV presenting to ENT services is outlined.