bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of preparation and combustion rig tests of an effusive cooled SiC/SiCN panel
Authors: Hönig Sandrine , Süß Fabia , Jain Neraj , Jemmali Raouf , Behrendt Thomas , Mainzer Bernd , Koch Dietmar
Published: March 2020

SiC/SiCN ceramic matrix composites (CMCs) are promising candidates for components of aero‐engines. To evaluate the properties of these CMCs under realistic conditions, a quasi‐flat panel with effusion cooling holes was investigated in a high pressure combustor rig. A Tyranno SA3 fabric‐based SiC/SiCN composite with high strength and strain to failure was manufactured via polymer infiltration and pyrolysis process. Due to its weak matrix no fiber coating was necessary for damage tolerant behavior. The cooling holes in the panel were introduced via laser drilling. An outer coating of CVD‐based SiC was finally applied for enhanced oxidation resistance. The specimen was tested in the combustor rig and the cooling effectiveness was evaluated. The microstructure of laser machined holes was studied via microscopy and energy‐dispersive X‐ray spectroscopy. The macrostructure was investigated via computing tomography scans before and after the combustor test. Material performances at higher temperatures were estimated via a material performance index. Local microstructure modifications were observed after laser drilling. No crack formation was observed in the CMC panels after rig tests. The measured global cooling effectiveness of 0.76 and the analytical performance evaluation demonstrate the potential benefit of SiC/SiCN materials in combustor applications.
Addressing privacy predicaments in the digital marketplace: A power‐relations perspective
Authors: Bandara Ruwan , Fernando Mario , Akter Shahriar
Published: March 2020

The utilization and governance of the internet and adjacent disruptive technologies have created numerous challenges to ensuring consumer online privacy. This study employs the power–responsibility equilibrium theory to explore emerging online privacy issues in the data‐driven marketplace. This exploratory study, based on semi‐structured interviews, explains why online shopping consumers are increasingly worried about their privacy and why they behave in a manner that could be detrimental to the consumer–vendor relationship. The findings suggest that deficiencies of corporate privacy responsibility and regulatory protection have deprived consumers of privacy empowerment. These deficiencies have also accentuated perceived privacy contract violations to trigger privacy concerns and subsequent defensive responses. We identify enhancement of consumer privacy empowerment and assuagement of privacy contract violations as two separate mechanisms of addressing online privacy issues. We also highlight the importance of addressing power and responsibility dynamics for maintaining a healthy information‐exchange environment.
Thou shalt not covet: Role of family religiosity in anti‐consumption
Authors: Casabayó Mònica , Dávila Juan Francisco , Rayburn Steven W.
Published: March 2020

Anti‐consumption movements, as resistance or rejection of consumption, are opposed in nature to the values of materialism or the idea that possessions are essential to happiness. This article links one anti‐consumption practice, voluntary simplicity, to family religiosity by exploring whether parents' religiosity induces reduced levels of materialism in their children. Children aged 6–14 years and their parents in three secular and one religious school were surveyed, and data were analysed using structural equation modelling. Materialism was divided in four factors: money desire, shopping pleasure, possession pleasure and non‐generosity. Results show that parents with strong religious behaviours have children who exhibit less desire for money and less non‐generosity, but experience a higher shopping pleasure. The effects of parents' religious behaviours on children's materialism are both direct and partially mediated by school type (religious or secular). Religious values in the family environment may contribute to increased anti‐consumption lifestyles in following generations.
Steam‐assisted roasting inhibits formation of heterocyclic aromatic amines and alters volatile flavour profile of beef steak
Authors: Feng Ruihong , Bao Yulong , Liu Dongmei , Zhang Shuang , Wang Yong , Chen Dongpo , Zhou Peng
Published: March 2020

In order to evaluate the effect of steam addition during meat roasting, beef sirloin steaks were cooked at five humidities (0%, 25%, 50%, 75% and 100%) under 230 °C to a centre temperature of 71 °C. With increased humidity, heating rate generally increased and the cooked steak gradually lost the typical roasted appearance. Thiobarbituric acid‐reactive substances (TBARS) values generally increased, while carbonyl groups were not affected. Increased humidity promoted the formation of volatile aldehydes and alcohols, while pyrazines decreased significantly from 0% to 25% humidity. Steam‐assisted roasting inhibited the formation of heterocyclic aromatic amines (HAAs; except for IQ and Norharman). However, further increase in humidity (larger than 25%) did not have additional inhibition effect. Based on the results, it is recommended to roast beef with steam addition to reduce toxic HAAs, but the humidity should be kept at a relatively low level to maintain a typical roasted appearance and flavour profile.
Insights into the structural characterisations, bioactivities and their correlations with water‐soluble polysaccharides extracted from different pomelo (Citrus maxima Merr.) tissues
Authors: Wu Zhen , Li Hong , Luo Yang , Chen Gang , Li Juan , Wang Yongde , Yang Yong , Tan Hongjun
Published: March 2020

Pomelo (Citrus maxima Merr.), known as a famous fruit and folk medicine, is widely cultivated in China. Nonedible pomelo tissues contain peels, seeds, and segment membranes, which generally being discarded. Polysaccharides relationships among different pomelo tissues remain uncertain. Four water‐soluble polysaccharides, PPPs, PSPs, FPPs and SMPs, were extracted from pomelo peels, seeds, pulps and segment membranes, respectively. Molecular structure and conformation were investigated by a combination of chemical and instrumental analyses. PPPs and FPPs were consisted of Ara, GalA, GlcA, Rha, Glc, Xyl and Gal, while PSPs and SMPs did not contain GalA and Gal. The average molecular weight (Mw) of PPPs, PSPs, FPPs and SMPs was 4.604 × 105, 10.85 × 105, 5.795 × 105 and 16.06 × 105 Da, respectively. PPPs, PSPs and SMPs all showed totally spherical structures, while FPPs primarily comprised linear chains. The structures–bioactivities correlations analysis revealed that low‐Mw polysaccharides had strong DPPH•, OH• scavenging and HeLa cells inhibiting activities. These data revealed that the bioactivities of pomelo tissues polysaccharides were not a function of a single factor but a combination of various characteristics.
NF‐κB‐inducing kinase contributes to normal development of cortical thymic epithelial cells: its possible role in shaping a proper T‐cell repertoire
Authors: Eshima Koji , Misawa Kana , Ohashi Chihiro , Noma Haruka , Iwabuchi Kazuya
Published: March 2020

Nuclear factor (NF)‐κB‐inducing kinase (NIK) is known to be a critical regulator of multiple aspects of the immune response. Although the role of NIK in the development of medullary thymic epithelial cells (mTECs) has been well documented, the impact of NIK on the differentiation and function of cortical thymic epithelial cells (cTECs) remains ambiguous. To investigate the possible involvement of NIK in cTEC differentiation, we have compared the gene expression and function of cTECs from a NIK‐mutant mouse, alymphoplasia (aly/aly) with those of cTECs from wild‐type (WT) mice. Flow cytometric analyses revealed that expression levels of MHC class II, but not MHC class I or other TEC markers, were higher in aly/aly cells than in WT cells. Notably, the proportion of MHC class IIhi+ cTECs was elevated in aly/aly mice. We also demonstrated that expression of Ccl5 mRNA in the MHC class IIhi+ subset of aly/aly cTECs was decreased compared with that in WT cells, implying an abnormal pattern of gene expression in aly/aly cTECs. Analyses of bone marrow chimera using aly/aly or aly/+ mice as hosts suggested that Vβ usage and CD5 expression on WT T‐cells were altered when they matured in aly/aly thymi. These results collectively indicate that NIK may be involved in controlling the function of cTEC in selecting a proper T‐cell repertoire.
Immediate versus early non‐occlusal loading of dental implants placed flapless in partially edentulous patients: A 10‐year randomized clinical trial
Authors: Merli Mauro , Merli Marco , Mariotti Giorgia , Pagliaro Umberto , Moscatelli Marco , Nieri Michele
Published: March 2020

Aim

To compare immediate versus early non‐occlusal loading of dental implants placed flapless in a 10‐year, parallel group, randomized clinical trial.

Materials and Methods

Patients were randomized to receive implants for fixed partial dentures. The immediate group was represented by immediate non‐occlusal implant loading, whereas the early group was represented by early non‐occlusal implant loading. The outcome variables were implant failure, complications, subjective satisfaction and radiographic bone level at implant sites 10 years after loading.

Results

Sixty patients were randomized: 30 to the immediately loaded group and 30 to the early loaded group. Three patients dropped out in the immediate group, and three patients dropped out in the early group. One implant failure occurred in the early group (p = 1.0). Three complications occurred in the immediate group and four in the early group (RR = 0.75, 95% CI 0.19 to 3.04, p = 1.0). The difference in bone level was 0.1 mm (95% CI −0.2 to 0.5, p = .3752) favouring the early group. Difference in subjective functional satisfaction was 0.2 (95% CI −0.2 to 0.7; p = .3271). Difference in subjective aesthetic satisfaction was 0.0 (95% CI −0.4 to 0.4; p = .9656).

Conclusion

At 10‐year follow‐up, no differences between implants loaded immediately and early were detected in this randomized clinical trial.
Three‐dimensional characterization of osteocyte volumes at multiple scales, and its relationship with bone biology and genome evolution in ray‐finned fishes
Authors: Davesne Donald , Schmitt Armin D. , Fernandez Vincent , Benson Roger B. J. , Sanchez Sophie
Published: March 2020

Osteocytes, cells embedded within the bone mineral matrix, inform on key aspects of vertebrate biology. In particular, a relationship between volumes of the osteocytes and bone growth and/or genome size has been proposed for several tetrapod lineages. However, the variation in osteocyte volume across different scales is poorly characterized and mostly relies on incomplete, two‐dimensional information. In this study, we characterize the variation of osteocyte volumes in ray‐finned fishes (Actinopterygii), a clade including more than half of modern vertebrate species in which osteocyte biology is poorly known. We use X‐ray synchrotron micro‐computed tomography (SRµCT) to achieve a three‐dimensional visualization of osteocyte lacunae and direct measurement of their size (volumes). Our specimen sample is designed to characterize variation in osteocyte lacuna morphology at three scales: within a bone, among the bones of one individual and among species. At the intra‐bone scale, we find that osteocyte lacunae vary noticeably in size between zones of organized and woven bone (being up to six times larger in woven bone), and across cyclical bone deposition. This is probably explained by differences in bone deposition rate, with larger osteocyte lacunae contained in bone that deposits faster. Osteocyte lacuna volumes vary 3.5‐fold among the bones of an individual, and this cannot readily be explained by variation in bone growth rate or other currently observable factors. Finally, we find that genome size provides the best explanation of variation in osteocyte lacuna volume among species: actinopterygian taxa with larger genomes (polyploid taxa in particular) have larger osteocyte lacunae (with a ninefold variation in median osteocyte volume being measured). Our findings corroborate previous two‐dimensional studies in tetrapods that also observed similar patterns of intra‐individual variation and found a correlation with genome size. This opens new perspectives for further studies on bone evolution, physiology and palaeogenomics in actinopterygians, and vertebrates as a whole.
Impact of neural stem cell‐derived extracellular vesicles on mitochondrial dysfunction, sirtuin 1 level, and synaptic deficits in Alzheimer’s disease
Authors: Li Bo , Liu Jianhui , Gu Guojun , Han Xu , Zhang Qi , Zhang Wei
Published: March 2020

Small extracellular vesicles (EVs), including exosomes, play multiple physiological roles. In neurodegenerative diseases, EVs can be pivotal in dispersing neuropathogenic proteins. This study investigates the role of neural stem cell (NSC)‐derived EVs in a transgenic (Tg) mouse model of Alzheimer's disease (AD). Five weeks following treatment on 9‐month‐old APP/PS1 mice, the effects of NSC‐derived EVs on cognitive behavior, mitochondrial function, sirtuin1 (SIRT1), synaptic function and morphology, quantification of amyloid‐β (Aβ) level, and inflammatory response were investigated. The results showed that mice in the Tg‐NSCs‐ev group exhibited significant improvement in cognitive performance compared with Tg‐Veh group. Furthermore, the expression of mitochondrial function‐related factors (peroxisome proliferator‐activated receptor‐γ coactivator‐1α [PGC1α], nuclear respiratory factor 1 and 2 [NRF1 and 2], and fission 1 [Fis1]), SIRT1 as well as synaptic proteins (growth‐associated protein 43 [GAP43], synaptophysin [SYP], post‐synaptic density 95 [PSD95] and microtubule‐associated protein 2 [MAP2]) were significantly higher in the Tg‐NSCs‐ev group, when compared with the Tg‐Veh group. In addition, oxidative damage markers (anti‐4‐Hydroxynonenal [4‐HNE] and anti‐3 nitrotyrosine [3‐NT]), inflammatory cytokines and the microglial marker (Iba1) were significantly lower in the Tg‐NSCs‐ev group, compared to the Tg‐Veh group. Moreover, synaptic morphology was distinctly improved in the Tg‐NSCs‐ev group, whereas the Aβ level was not altered. Our study provides novel evidences that NSC‐derived EVs enhanced mitochondrial function, SIRT1 activation, synaptic activity, decreased inflammatory response, and rescued cognitive deficits in AD like mice.

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Efficacy of hyaluronidase combined with corticosteroids in treatment of oral submucous fibrosis: A meta‐analysis of randomized controlled clinical trials
Authors: Guo Jincai , Xie Hui , Mao Shun , Liang Mining , Wu Hao
Published: March 2020

Objective

This meta‐analysis was performed to systematically evaluate the efficacy of hyaluronidase combined with corticosteroids compared with other drugs in improving maximum mouth opening and alleviating the burning sensation in patients with oral submucous fibrosis (OSF).

Methods

PubMed, Embase, Web of Science and the Cochrane Library were searched. RevMan 5.3 software was used for the meta‐analysis.

Results

Six studies involving 244 patients with OSF were analysed. No significant difference in improvement of maximum mouth opening was found between the hyaluronidase and control groups (lycopene, pentoxifylline, aloe vera, dexamethasone, Turmix [curcumin + piperine] and isoxsuprine) at 1 month (mean difference [MD]: 0.32, 95% confidence interval [CI]: −0.92‐1.56, P = .61, I2 = 57%), 2 months (MD: 0.49, 95% CI: −0.14‐1.12, P = .12, I2 = 41%) or 3 months (MD: 0.40, 95% CI: −1.08‐1.87, P = .60, I2 = 92%). Additionally, no statistically significant difference was found in alleviation of the burning sensation between the two groups at 1 month (MD: 0.54, 95% CI: −0.62‐1.71, P = .36, I2 = 0%), 2 months (MD: 0.53, 95% CI: −0.85‐1.91, P = .45, I2 = 0%) or 3 months (MD: 0.64, 95% CI: −1.07 to 2.35, P = .46, I2 = 0%).

Conclusions

According to this meta‐analysis, weak evidence indicates that hyaluronidase combined with corticosteroids has no additional clinical benefit over control drugs (lycopene, pentoxifylline, aloe vera, dexamethasone, Turmix and isoxsuprine) in improving maximum mouth opening and alleviating the burning sensation in patients with OSF. Therefore, more high‐quality, multi‐centre randomized controlled trials with larger samples are needed to further assess the efficacy of hyaluronidase combined with corticosteroids in the treatment of OSF.
Is the negative always that bad? Or how emotion regulation and integration of negative memories can positively affect well‐being
Authors: Houle Iliane , Philippe Frederick L.
Published: March 2020

Objective

The purpose of this study was to determine whether coherent integration of negative memories into the self could positively predict well‐being over time, and whether certain emotion regulation strategies could facilitate this coherent integration. In turn, coherent integration of negative memories was expected to further facilitate adaptive emotion regulation strategies over time.

Method

A total of 303 participants took part in this longitudinal study. At Phase 1, they completed measures of emotion regulation and well‐being. Three months later, they described the memory of the most negative event they experienced since Phase 1, and completed measures assessing its integration. One month later, participants completed the well‐being measures again, and another month later, their emotion regulation was reassessed.

Results

Adaptive emotion regulation predicted adaptive memory integration, which in turn led to increases in well‐being and adaptive emotion regulation. Contrariwise, the incapacity to adaptively regulate emotions predicted poor memory integration, which in turn led to decreases in well‐being.

Conclusion

The way people regulate their negative emotions acts as an individual difference influencing how negative memories are integrated into the self, which can in return alter well‐being and emotion regulation capacity over time.
Age differences in Machiavellianism across the life span: Evidence from a large‐scale cross‐sectional study
Authors: Götz Friedrich M. , Bleidorn Wiebke , Rentfrow Peter J.
Published: March 2020

Objective

Lifespan perspectives on personality development have gained much momentum in recent years, mostly focusing on benevolent and neutral traits such as the Big Five. Despite their strong associations with critical personal outcomes, surprisingly little research has investigated the development of malevolent traits. Addressing this gap, we examined age trends in Machiavellianism across the lifespan.

Methods

Using data from a large‐scale cross‐sectional sample (n = 1,118,643), we analyzed mean‐level changes from age 10 to 67.

Results

Age differences in Machiavellianism were most pronounced as a strong upward trend during the transition from late childhood to adolescence, when it peaked. Throughout adulthood it exhibited a steady downward trend, reaching an overall minimum at age 65. Across the lifespan, Machiavellianism tended to be higher in men and high‐income participants. Compared to Machiavellianism, the age trends in Agreeableness and—to a lesser extent—Conscientiousness showed almost perfectly polar opposite patterns.

Conclusions

Age trends in malevolent personality conform to established patterns of normative change, indicating temporary disruption in adolescence and social maturation across adulthood. The results advance theory and research on personality trait development across the lifespan and highlight crucial developmental windows that can inform targeted interventions to keep socially aversive traits in check.
Glucuronidation and its effect on the bioactivity of amentoflavone, a biflavonoid from Ginkgo biloba leaves
Authors: Gan Lili , Ma Jiating , You Guoquan , Mai Jinxia , Wang Zhaoyu , Yang Ruopeng , Xie Cong , Fei Jingrao , Tang Lan , Zhao Jie , Cai Zheng , Ye Ling
Published: March 2020

Objectives

Ginkgo biloba leaves contain amentoflavone (AMF), a dietary flavonoid that possesses antioxidant and anticancer activity. Flavonoids are extensively subjected to glucuronidation. This study aimed to determine the metabolic profile of AMF and the effect of glucuronidation on AMF bioactivity.

Methods

A pharmacokinetic study was conducted to determine the plasma concentrations of AMF and its metabolites. The metabolic profile of AMF was elucidated using different species of microsomes. The antioxidant activity of AMF metabolites was determined using DPPH/ABTS radical and nitric oxide assays. The anticancer activity of AMF metabolites was evaluated in U87MG/U251 cells.

Key findings

Pharmacokinetic studies indicated that the oral bioavailability of AMF was 0.06 ± 0.04%, and the area under the curve of the glucuronidated AMF metabolites (410.938 ± 62.219 ng/ml h) was significantly higher than that of AMF (194.509 ± 16.915 ng/ml h). UGT1A1 and UGT1A3 greatly metabolized AMF. No significant difference was observed in the antioxidant activity between AMF and its metabolites. The anticancer activity of AMF metabolites significantly decreased.

Conclusions

A low AMF bioavailability was due to extensive glucuronidation, which was mediated by UGT1A1 and UGT1A3. Glucuronidated AMF metabolites had the same antioxidant but had a lower anticancer activity than that of AMF.
Melatonin and its analogues for the prevention of postoperative delirium: A systematic review and meta‐analysis
Authors: Han Yunyang , Wu Jie , Qin Zaisheng , Fu Weijun , Zhao Bingcheng , Li Xue , Wang Wenyan , Sha Tong , Sun Maomao , Li Jiaxin , Zeng Zhenhua , Chen Zhongqing
Published: March 2020

It remains unclear whether melatonin and its analogues prevent postoperative delirium (POD). Therefore, we conducted a systematic review and meta‐analysis to evaluate the effect of melatonin and its analogues on POD prevention. PubMed, Cochrane Library, Web of Science, Embase and CINAHL databases were searched. Primary outcome was the incidence of POD. Six randomized controlled trials, 2 cohort studies and 1 case‐control study were included in this meta‐analysis. Results showed that melatonin and its analogue ramelteon decreased the incidence of POD in the entire adult surgical population (odds ratio [OR] = 0.45, 95% confidence interval [CI] 0.24‐0.84, P = .01). When administered at a higher dose (5 mg), melatonin was effective in reducing the POD incidence (OR = 0.32, 95% CI 0.20‐0.52, P < .00001). Melatonin administered less than 5 elimination half‐lives before the surgery significantly reduced the POD incidence (OR = 0.31, 95% CI 0.19‐0.49, P < .00001). Current literature supports the effectiveness of melatonin and its analogue ramelteon in POD prevention. However, the present study was limited by the significant heterogeneity of the included studies. More studies are needed to ascertain the preventive effect of melatonin and its analogues on the incidence of delirium after cardiac and noncardiac surgeries.
Analysis of macrofungal communities reveals a complex reciprocal influence between Mediterranean montane calcareous grassland and surrounding forest habitats
Authors: Pecoraro Lorenzo , Caruso Tancredi , Kumar Gupta Vijai , Borris Robert P. , Zhang Yun‐Chun , Cai Lei
Published: March 2020

Fungi are essential components of all terrestrial ecosystems. Despite the crucial ecological role of soil fungi in grasslands, knowledge about fungal community diversity and structure in Mediterranean meadow habitats is still fragmentary. We analyzed macrofungal communities in three geographically distinct Mediterranean montane calcareous grasslands and surrounding forests, by means of fruit body surveys. We investigated a number of biotic and abiotic factors influencing the studied fungal communities, including plant species composition. Out of 6365 fruit bodies, a total of 268 species belonging to 84 genera were found. In general, there was a significant correlation between plant species richness and fungal richness. Variation in vegetation and plant community structure accounted for approximately 20% of variance in fungal community structure. Tree and shrub vegetation played a dominant role in shaping the analyzed fungal communities, both in meadows and surrounding forests, with particular influence on ectomycorrhizal, litter, and lignicolous saprotrophic fungi. Fungal biodiversity in the studied meadows was increased by the presence of tree and shrub species from the adjacent forests, but was reduced by the increasing vegetation cover.
Targeting ferroptosis alleviates methionine‐choline deficient (MCD)‐diet induced NASH by suppressing liver lipotoxicity
Authors: Li Xiaoya , Wang Tian‐Xiang , Huang Xinmei , Li Yue , Sun Tiange , Zang Shufei , Guan Kun‐Liang , Xiong Yue , Liu Jun , Yuan Hai‐Xin
Published: March 2020

Background

NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non‐apoptotic form of cell death induced by iron‐dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression.

Method

Mice were fed on MCD‐diet to mimic NASH progression and gene expression in liver was analysed by RNA‐seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets accumulation was investigated by in vitro cell culture.

Results

RNA‐seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD‐diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the serum of MCD‐fed mice. Scavenging of ferroptosis‐linked lipid peroxides reduced lipid accumulation both in vivo and in vitro. Importantly, ferroptosis inhibitors alleviated MCD‐diet induced inflammation, fibrogenesis and liver injury. Finally, lipid ROS promotes liver steatosis by boosting lipid droplets formation.

Conclusion

Our results demonstrate an important role of ferroptosis in the progression of MCD‐diet induced NASH and suggest that ferroptosis may serve as a therapeutic target for NASH treatment.
Reduction and stabilization of bilirubin with obeticholic acid treatment in patients with primary biliary cholangitis
Authors: Parés Albert , Shiffman Mitchell , Vargas Victor , Invernizzi Pietro , Malecha Elizabeth S. , Liberman Alexander , MacConell Leigh , Hirschfield Gideon
Published: March 2020

Background & Aims

Total bilirubin is a predictor of survival in primary biliary cholangitis, with the main elevated component being direct bilirubin. The purpose of this post hoc analysis was to assess the efficacy and safety of obeticholic acid across quartiles of varying baseline levels of direct bilirubin in the phase 3, randomized, placebo‐controlled Primary Biliary Cholangitis Obeticholic Acid International Study of Efficacy.

Methods

This analysis assessed patients on the basis of their baseline direct bilirubin level (divided by quartile). Biochemistry and safety outcomes were evaluated within each quartile over time.

Results

In the quartile with the highest baseline direct bilirubin (>5.47 µmol/L), there was a significant reduction in both direct and total bilirubin at Month 12 compared with placebo. Least squares mean (standard error) change from baseline in direct bilirubin at Month 12 was 4.17 (1.42) µmol/L for placebo, −3.48 (1.63) µmol/L for obeticholic acid 5‐10 mg and −3.66 (1.51) µmol/L for obeticholic acid 10 mg (P < .0001, obeticholic acid vs placebo); the corresponding values for total bilirubin at Month 12 were 4.38 (1.55) µmol/L for placebo, −4.53 (1.83) µmol/L for obeticholic acid 5‐10 mg and −5.06 (1.64) µmol/L for obeticholic acid 10 mg (P < .0001, obeticholic acid vs placebo).

Conclusions

Obeticholic acid treatment was associated with significant reductions in total and direct bilirubin, particularly in patients with high baseline direct bilirubin. Because raised direct bilirubin levels, even within the normal range, are predictive of survival in primary biliary cholangitis, these results suggest substantial benefits of obeticholic acid in at‐risk patients.
Fungaemia due to rare yeasts in a tertiary care university centre within 18 years
Authors: Alp Sehnaz , Gulmez Dolunay , Ayaz Caglayan Merve , Arikan‐Akdagli Sevtap , Akova Murat
Published: March 2020

Background

Fungaemia due to rare yeasts has been recognised as an emerging, clinically relevant, but less investigated condition. Intrinsic resistance or reduced susceptibility of these species to echinocandins or fluconazole remains as a challenge in empirical treatment.

Objectives

To describe the clinical characteristics, administered antifungal agents, outcomes of patients with rare yeasts other than Candida (RY‐OTC) fungaemia and determine the antifungal susceptibility profiles of the isolates.

Patients and methods

RY‐OTC fungaemia between January‐2001 and December‐2018 were retrospectively evaluated. Antifungal susceptibility tests were performed according to CLSI M27‐A3.

Results

We identified 19 patients with fungaemia due to 20 RY‐OTC (8 Trichosporon asahii, 4 Cryptococcus neoformans, 4 Saprochaete capitata, 3 Rhodotorula mucilaginosa, 1 Trichosporon mucoides) with an incidence of 2.2% among 859 fungaemia episodes. Haematological malignancy was the most common (42%) underlying disorder. In 6 patients, RY‐OTC fungaemia developed as breakthrough infection while receiving echinocandins, amphotericin B or fluconazole. Amphotericin B, fluconazole or voriconazole were the drugs of choice for the initial treatment of breakthrough fungaemia. Among patients without previous exposure to antifungals, the most common empirical treatment was an echinocandin (50%), followed by fluconazole (42%) and amphotericin B (8%). Overall mortality was 47%. Worse outcome was most common among patients receiving echinocandins (83% vs 25%, P < .05). Voriconazole and posaconazole showed the highest in vitro activity against all the isolates tested. Amphotericin B MICs were relatively higher and the degree of activity of fluconazole and itraconazole was variable.

Conclusions

Early recognition of RY‐OTC and knowledge about their susceptibility patterns remain crucial in initial treatment pending susceptibility data of isolates.
Root‐specific NF‐Y family transcription factor, PdNF‐YB21, positively regulates root growth and drought resistance by abscisic acid‐mediated indoylacetic acid transport in Populus
Authors: Zhou Yangyan , Zhang Yue , Wang Xuewen , Han Xiao , An Yi , Lin Shiwei , Shen Chao , Wen JiaLong , Liu Chao , Yin Weilun , Xia Xinli
Published: March 2020

Root growth control plays an important role in plant adaptation to drought stress, but the underlying molecular mechanisms of this control remain largely elusive.

Here, a root‐specific nuclear factor Y (NF‐Y) transcription factor PdNF‐YB21 was isolated from Populus. The functional mechanism of PdNF‐YB21 was characterised by various morphological, physiological, molecular, biochemical and spectroscopy techniques.

Overexpression of PdNF‐YB21 in poplar promoted root growth with highly lignified and enlarged xylem vessels, resulting in increased drought resistance. By contrast, CRISPR/Cas9‐mediated poplar mutant nf‐yb21 exhibited reduced root growth and drought resistance. PdNF‐YB21 interacted with PdFUSCA3 (PdFUS3), a B3 domain transcription factor. PdFUS3 directly activated the promoter of the abscisic acid (ABA) synthesis key gene PdNCED3, resulting in a significant increase in root ABA content in poplars subjected to water deficit. Coexpression of poplar NF‐YB21 and FUS3 significantly enhanced the expression of PdNCED3. Furthermore, ABA promoted indoylacetic acid transport in root tips, which ultimately increased root growth and drought resistance.

Taken together, our data indicate that NF‐YB21–FUS3‐NCED3 functions as an important avenue in auxin‐regulated poplar root growth in response to drought.
H‐type blood vessels participate in alveolar bone remodeling during murine tooth extraction healing
Authors: Yan Zi‐Qi , Wang Xiao-Kai , Zhou Yong , Wang Zheng‐Guang , Wang Zhen‐Xing , Jin Ling , Yin Hao , Xia Kun , Tan Yi‐Juan , Feng Shi‐Kai , Xie Ping‐Li , Tang Si‐Yuan , Fang Chang‐Yun , Cao Jia , Xie Hui
Published: March 2020

Objectives

We aimed to investigate whether skeletal‐specific H‐type blood vessels exist in alveolar bone and how they function in alveolar bone remodeling.

Materials and Methods

H‐type vessels with high expression of CD31 and Endomucin (CD31hiEmcnhi) were immunostained in alveolar bone. Abundance and age‐related changes in CD31hiEmcnhi endothelial cells (H‐ECs) were detected by flow cytometry. Osteoprogenitors association with H‐type vessels and bone mass were detected in tooth extraction model of alveolar bone remodeling by immunohistofluorescence and micro‐CT, respectively. Transcription and expression of H‐EC feature genes during in vitro Notch inhibition were measured by RT‐qPCR and immunocytofluorescence.

Results

We verified that H‐type vessels existed in alveolar bone, the abundance of which was highest at infancy age, then decreased but maintained a constant level during aging. In tooth extraction model, H‐ECs significantly increased with concomitant perivascular accumulation of Runx2+ osteoprogenitors and gradually augmentation of bone mass. Notch inhibition of in vitro cultured H‐ECs resulted in decreased expression levels of Emcn and hes1, but not Pecam1 or Kdr genes, with decreased expression levels of H‐EC numbers, accordingly.

Conclusions

The present study suggests that H‐type vessels promote osteogenesis during alveolar bone remodeling. Notch signaling pathway regulates expression of Emcn and possibly determines fate and functions of alveolar H‐ECs.
Human papillomavirus prevalence in oral potentially malignant disorders: Systematic review and meta‐analysis
Authors: de la Cour Cecilie D. , Sperling Cecilie D. , Belmonte Federica , Syrjänen Stina , Kjaer Susanne K.
Published: March 2020

Objectives

We aimed to provide pooled estimates of human papillomavirus (HPV) prevalence in oral potentially malignant disorders (OPMD) and evaluate the impact of presence of epithelial dysplasia.

Methods

We searched PubMed, Embase, and Cochrane Library databases for studies that examined the prevalence of HPV DNA in OPMD tested by polymerase chain reaction (PCR).

Results

Across 52 eligible studies (2,677 cases), we found an overall pooled HPV prevalence of 22.5% (95% confidence interval [CI] 16.6–29.0). Between‐study heterogeneity was 93%. When stratified by subgroup, the pooled HPV prevalence in leukoplakia (1,232 cases) was 20.2% (95% CI 11.2–31.1), lichen planus (767 cases) 23.0% (95% CI 15.0–32.2), oral submucous fibrosis (238 cases) 28.6% (95% CI 23.0–34.5), proliferative verrucous leukoplakia (60 cases) 24.7% (95% CI 1.8–62.0), and OPMD unspecified (377 cases) 25.4% (95% CI 16.2–35.8). Information on presence of epithelial dysplasia was available in 19 studies, and the results did not vary substantially between non‐dysplastic and dysplastic samples. HPV16 was the predominant genotype among HPV‐positive OPMD cases (48.2%, 95% CI 31.4–65.2).

Conclusion

We found a pooled HPV DNA prevalence of 22.5% in OPMD cases with great between‐study heterogeneity. The HPV prevalence appeared to be comparable across subgroups and independent of epithelial dysplasia.
Transvenous lead extraction: Efficacy and safety of the procedure in octogenarian patients
Authors: Giannotti Santoro Mario , Segreti Luca , Zucchelli Giulio , Barletta Valentina , Fiorentini Federico , Di Cori Andrea , De Lucia Raffaele , Bongiorni Maria Grazia
Published: March 2020

Background

Managing elderly patients with infection or malfunction deriving from a cardiac implantable electronic device (CIED) may be challenging. The aim of this study was to evaluate safety and efficacy of mechanical transvenous lead extraction (TLE) in elderly patients.

Methods

Patients who had undergone TLE in single tertiary referral center were divided in two groups (group 1: ≥ 80 years; group 2: < 80 years) and their acute and chronic outcomes were compared. All patients were treated with manual traction or mechanical dilatation.

Results

Our analysis included 1316 patients (group 1: 202; group 2: 1114 patients), with a total of 2513 leads extracted. Group 1 presented more comorbidities, more pacemakers than implantable cardioverter‐defibrillators, whereas the dwelling time of the oldest lead and the number of leads were similar, irrespective of patient's age. In group 1, the radiological success rate for lead was higher (99.0% vs 95.9%; P < .001) and the fluoroscopy time lower (13.0 vs 15.0 min; P = .04) than in group 2. Clinical success was reached in 1273 patients (96.7%), without significant differences between groups (group 1: 98.0% vs group 2: 96.4%; P = .36). Major complications occurred in 10 patients (0.7%) without significative differences between patients with more or less than 80 years (group 1: 1.5% vs group 2: 0.6%; P = .24) and with no procedure‐related deaths in elderly group.

Conclusions

Mechanical TLE in elderly patients is a safe and effective procedure. In the over‐80s, a comparable incidence of major complications with younger patients was observed, with at least a similar efficacy of the procedure.
Subnational Non‐Hispanic White Natural Decrease in the United States
Authors: Johnson Kenneth M.
Published: March 2020

This research is the first to examine the prevalence and dynamics of non‐Hispanic white natural decrease in fine scale subregional units of the United States. In 2015, more non‐Hispanic Whites died than were born in 65 percent of the US counties. This is the highest incidence of non‐Hispanic white natural decrease ever reported. It results from a complex interaction among fertility, mortality, and migration over a protracted period. Spatial regression is used to identify three critical variables (over‐65 population, child–women ratio, and women of childbearing age) that are the immediate demographic causes of this natural decrease. The timely, factual information in this paper provides a demographic context for analysis of the social, political, and policy implications of this emergent demographic phenomenon.
Cooperative behaviour and phenotype plasticity evolve during melanoma progression
Authors: Rowling Emily J. , Miskolczi Zsofia , Nagaraju Raghavendar , Wilcock Daniel J. , Wang Ping , Telfer Brian , Li Yaoyong , Lasheras-Otero Irene , Redondo-Muñoz Marta , Sharrocks Andrew D. , Arozarena Imanol , Wellbrock Claudia
Published: March 2020

A major challenge for managing melanoma is its tumour heterogeneity based on individual co‐existing melanoma cell phenotypes. These phenotypes display variable responses to standard therapies, and they drive individual steps of melanoma progression; hence, understanding their behaviour is imperative. Melanoma phenotypes are defined by distinct transcriptional states, which relate to different melanocyte lineage development phases, ranging from a mesenchymal, neural crest‐like to a proliferative, melanocytic phenotype. It is thought that adaptive phenotype plasticity based on transcriptional reprogramming drives melanoma progression, but at which stage individual phenotypes dominate and moreover, how they interact is poorly understood. We monitored melanocytic and mesenchymal phenotypes throughout melanoma progression and detected transcriptional reprogramming at different stages, with a gain in mesenchymal traits in circulating melanoma cells (CTCs) and proliferative features in metastatic tumours. Intriguingly, we found that distinct phenotype populations interact in a cooperative manner, which generates tumours of greater “fitness,” supports CTCs and expands organotropic cues in metastases. Fibronectin, expressed in mesenchymal cells, acts as key player in cooperativity and promotes survival of melanocytic cells. Our data reveal an important role for inter‐phenotype communications at various stages of disease progression, suggesting these communications could act as therapeutic target.
Phototherapy May be a Useful Adjuvant Therapy for Retractable Chronic Spontaneous Urticaria: A Systematic Review
Authors: Hong Ji Yeon , Kim Myung Hwa , Lee Ji Hyun , Han Hye Sung , Seo Seong Jun , Park Kui Young , Park Young Min
Published: March 2020

The recent guideline on the management of urticaria recommends second‐generation H1 antihistamine as the first‐line therapy, with dose increases of up to fourfold and the addition of omalizumab or cyclosporine if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing. Therefore, a safe and effective treatment option is needed for refractory CSU. To evaluate whether phototherapy can relieve urticarial symptoms and serve as an additional treatment for CSU uncontrolled with antihistamine, we performed a qualitative systematic review. Our result suggests that NBUVB could be an effective complementary treatment modality to manage refractory CSU.
Efficacy of narrow‐band ultraviolet‐B therapy in patch‐stage mycosis fungoides: A clinical study and review of the literature
Authors: Atci Tugba , Baykal Can
Published: March 2020

Background/Purpose

We investigated the efficacy of narrow‐band UVB in patch‐stage MF and reviewed the literature to re‐evaluate the role of this phototherapy method in early MF.

Methods

Early‐stage MF patients treated with narrow‐band UVB were included. Number of narrow‐band UVB treatment sessions, treatment duration, cumulative UV dose, clinical response results, side effects, duration of the remission period and relapse rate were evaluated.

Results

Complete response rate was 86.7% in sixty patients with MF. Mean number of treatment sessions was 62.9 ± 15.1, treatment duration was 32.1 ± 10.7 weeks, and mean cumulative UV dose was 62.1 ± 41.9 J/cm2 in patients with complete response. Mean duration of remission was 10.3 ± 11.0 months, and relapse rate was 70% in a mean follow‐up of 21.9 ± 16.4 months. Mild regional erythema (6.7%) and pruritus (8.3%) were main side effects. There were no significant differences between stage IA and stage IB patients in terms of treatment parameters and duration of remission period.

Conclusions

Our study confirms that narrow‐band UVB is effective for the management of the patch‐stage MF without serious side effects. Extent of the skin lesions did not affect the efficacy of phototherapy. However, due to the short duration of remission, a further option such as an optimal maintenance therapy protocol should be considered.
Cytokine and goblet cell gene expression in equine cyathostomin infection and larvicidal anthelmintic therapy
Authors: Steuer Ashley E. , Stewart John C. , Barker Virginia D. , Adams Amanda A. , Nielsen Martin K.
Published: March 2020

Aims

The role of the immune response to cyathostomin infections in horses remains unknown. Intestinal goblet cell hyperplasia has previously been noted as a component in cyathostomin infection; however, the function is unclear. The goal of this study was to evaluate the local and systemic gene expression to cyathostomin infections following larvicidal treatment and explore their relation to goblet cells.

Methods and Results

Thirty‐six ponies with naturally acquired cyathostomin infections were randomly allocated into three groups: fenbendazole‐treated (10 mg/kg PO 5 days), moxidectin‐treated (0.4 mg/kg PO once) and untreated control. Whole blood from all horses was collected weekly, and tissue samples from the large intestine collected during necropsy at 2 and 5 weeks post‐treatment (WPT). Gene expression of interleukin (IL)‐4, IL‐5, IL‐6, IL‐10, IL‐13, IL‐17A, IL‐22, IFN‐γ, resistin‐like molecule beta (RELM‐β), Mucin 2 (MUC2) and tumour necrosis factor (TNF)‐α was measured using qRT‐PCR. There were statistically significant linear correlations between luminal worm burdens and MUC2 (r = −.2358) and RELM‐β (r = −.2261).

Conclusion

This suggests an active role of immune system post‐treatment in parasite expulsion, specifically in goblet cells, and that the organs respond differently to treatment and the larvae themselves. This may have implications in the disease process and treatment.
The peripheral immune response of mice infected with a neuropathogenic schistosome
Authors: Majer Martin , Macháček Tomáš , Súkeníková Lenka , Hrdý Jiří , Horák Petr
Published: March 2020

Trichobilharzia regenti (Schistosomatidae) percutaneously infects birds and mammals and invades their central nervous system (CNS). Here, we characterized the peripheral immune response of infected mice and showed how it was influenced by the parasite‐induced inflammation in the skin and the CNS. As revealed by flow cytometry, T cells expanded in the spleen and the CNS‐draining lymph nodes 7‐14 days post‐infection. Both T‐bet+ and GATA‐3+ T cells were markedly elevated suggesting a mixed type 1/2 immune response. However, it dropped after 7 dpi most likely being unaffected by the neuroinflammation. Splenocytes from infected mice produced a high amount of IFN‐γ and, to a lesser extent, IL‐10, IL‐4 and IL‐17 after in vitro stimulation by cercarial homogenate. Nevertheless, it had only a limited capacity to alter the maturation status of bone marrow‐derived dendritic cells (BMDCs), contrary to the recombinant T. regenti cathepsin B2, which also strongly augmented expression of Ccl5, Cxcl10, Il12a, Il33 and Il10 by BMDCs. Taken together, mice infected with T. regenti developed the mixed type 1/2 immune response, which was driven by the early skin inflammation rather than the late neuroinflammation. Parasite peptidases might play an active role in triggering the host immune response.
Evaluation of the cold tolerance of Saccharum spontaneum L. clones with different ploidy levels on the basis of morphological and physiological indices
Authors: Yang H.‐L. , Yu X.‐H. , Wang C.‐F. , Yang Y. , Wang X.‐H. , Yang Q.‐H.
Published: March 2020

Saccharum spontaneum L. is one of the most important germplasm resources for modern sugarcane breeding. Exploring the cold tolerance of S. spontaneum clones with different ploidy levels and screening for cold‐tolerant material can be helpful in parent selection for breeding cold‐tolerant sugarcane.

Morphological indices, leaf ultrastructure and physiological indices were used to evaluate the cold tolerance of 36 S. spontaneum clones with different ploidy levels (2n = 40, 48, 54, 60, 64, 78, 80, 88, 92 and 96).

The morphological indices of S. spontaneum clones with different ploidy levels were positively correlated with ploidy. Under low‐temperature stress, the chloroplast and mitochondrial structures of the clones with high ploidy were more severely damaged than were those of clones with low ploidy. A comprehensive evaluation of the physiological indices showed that the 36 S. spontaneum clones could be divided into four categories: strongly cold tolerant, cold tolerant, moderately cold tolerant and cold sensitive. Correlation analysis of the morphological indices and cold tolerance revealed a significant negative correlation between cold tolerance and ploidy. On the basis of the morphological and physiological indices, optimal stepwise regression equations that can be used for the selection of cold‐tolerant S. spontaneum resources were established.

The S. spontaneum clones with low ploidy are more cold tolerant than those with high ploidy. Clones 12‐37, 13‐10 and 12‐23 are strongly cold‐tolerant germplasm resources, which suggests these germplasm sources have high potential for use in breeding cold‐tolerant sugarcane.