bluuebunny/crossref_metadata_2025 huggingface dataset:
TROAP regulates cell cycle and promotes tumor progression through Wnt/β‐Catenin signaling pathway in glioma cells
Authors: Zhao Zong‐qing , Wu Xiu‐jie , Cheng Yan‐hao , Zhou Yun‐fei , Ma Xi‐meng , Zhang Jian , Heng Xue‐yuan , Feng Fan
Published: June 2021

Aims

Experimental evidence demonstrated a crucial role of TROAP (Trophinin‐associated protein) in regulating the cell proliferation of multiple tumors, while TROAP expression and function were largely unknown in glioma. We aimed to investigate the oncogenic role of TROAP and its potential mechanisms in gliomagenesis.

Methods

Four gene expression databases (GEO, TCGA, GTEx and CCLE) were enrolled in our study and used for TROAP expression and survival analysis. TROAP expression was quantified by qRT‐PCR, western blot and immunohistochemistry assays in glioma tissues and cell lines. TROAP knockdown and overexpression vector were constructed and transfected into glioma cells. CCK‐8, colony formation, transwell, and wound healing assays were used to evaluate cell viability, migration and invasion, flow cytometry to determine cell cycle arrest. Gene set enrichment analysis (GSEA) was conducted to screen the pathway involved in TROAP‐high phenotype. The expression of cell cycle and Wnt/β‐Catenin signaling proteins were analyzed by immunofluorescence and western blot.

Results

Based on the bioinformatic analysis and a series of functional assays, we found the TROAP was enriched in glioma tissues and cell lines, its overexpression was correlated with the clinicopathologic characteristics and poor prognosis. TROAP knockdown inhibited cell proliferation, migration, invasion, and G1/S cell cycle arrest compared with control group in glioma. Mechanism analysis revealed that TROAP activated Wnt/β‐Catenin pathway and upregulated its downstream targets expression, while silencing β‐Catenin or Axin2 could reverse the tumor‐promoting effects caused by TROAP, confirming that TROAP‐induced malignant phenotype and tumorigenesis via Wnt/β‐Catenin signaling pathway.

Conclusion

The present study found that TROAP accelerated the progression of gliomagenesis through Wnt/β‐Catenin pathway, and TROAP might be considered as a novel target for glioma therapy.
Perioperative instrumental swallowing evaluation in adult airway reconstruction: A retrospective observational cohort study
Authors: Haywood Matthew , Lovell Lindsay , Roe Justin , Clunie Gemma , Sandhu Guri , Al Yaghchi Chadwan
Published: June 2021

Objectives

Airway reconstruction for laryngotracheal stenosis (LTS) encompasses several procedures. Dysphagia is a well‐recognised sequela of LTS and airway surgery, however studies have employed mostly non‐validated assessments post‐operatively in small, heterogenous samples, perpetuating uncertainty around the contributions of LTS and its management to impaired deglutition. Consequently, considerable variation in LTS perioperative nutritional management exists. Our objective was to characterise baseline and post‐operative dysphagia with instrumental assessment in an LTS cohort undergoing airway reconstruction and provide a gold‐standard management framework for its management.

Design, setting, participants and main outcome measures

We performed a retrospective cohort study of adult airway reconstruction procedures from 2016‐2020 at our quaternary centre. Patient background, LTS aetiology, procedure type, tube feeding duration, length of stay and serial Functional Oral Intake Scale (FOIS) and International Dysphagia Diet Standardisation Initiative (IDDSI) scores were noted. Baseline, post‐operative day one and post‐stent removal Fibreoptic Endoscopic Evaluation of Swallow (FEES) generated Penetration Aspiration Scale (PAS) scores.

Results

Forty‐four patients underwent forty‐six reconstructions. Baseline incidence of penetration‐aspiration was considerably higher than the general population and worsened in the immediate post‐operative period, however FOIS and PAS scores generally returned to baseline by discharge. Post‐operative FOIS correlated negatively with tracheostomy or airway stent placement. At discharge, 80% tolerated soft or normal diet and 93% were feeding tube independent.

Conclusions

We present the largest adult airway reconstruction cohort with instrumental swallow assessment perioperatively. LTS patients have a higher incidence of underlying dysphagia but swallowing tends to return to baseline with appropriate postoperative rehabilitation. Such practice may avoid the complications, costs and morbidity of prolonged nutritional support.
Prediction of human pharmacokinetics for low‐clearance compounds using pharmacokinetic data from chimeric mice with humanized livers
Authors: Yoshida Kosuke , Doi Yuki , Iwazaki Norihiko , Yasuhara Hidenori , Ikenaga Yuka , Shimizu Hidetoshi , Nakada Tomohisa , Watanabe Tomoko , Tateno Chise , Sanoh Seigo , Kotake Yaichiro
Published: June 2021

Development of low‐clearance (CL) compounds that are slowly metabolized is a major goal in the pharmaceutical industry. However, the pursuit of low intrinsic CL (CLint) often leads to significant challenges in evaluating the pharmacokinetics of such compounds. Although in vitro–in vivo extrapolation is widely used to predict human CL, its application has been limited for low‐CLint compounds because of the low turnover of parent compounds in metabolic stability assays. To address this issue, we focused on chimeric mice with humanized livers (PXB‐mice), which have been increasingly reported to accurately predict human CL in recent years. The predictive accuracy for nine low‐CLint compounds with no significant turnover in a human hepatocyte assay was investigated using PXB‐mouse methods, such as single‐species allometric scaling (PXB‐SSS) approach and a novel physiologically based scaling (PXB‐PBS) approach that assumes that the CLint per hepatocyte is equal between humans and PXB‐mice. The percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CLint compounds were 89% and 100%, respectively, for both PXB‐SSS and PXB‐PBS approaches. Moreover, the predicted CL was mostly consistent among the methods. Conversely, the percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CLint compounds were 50% and 63%, respectively, for multispecies allometric (MA) scaling. Overall, these PXB‐mouse methods were much more accurate than conventional MA scaling approaches, suggesting that PXB‐mice are useful tools for predicting the human CL of low‐CLint compounds that are slowly metabolized.
The effect of age on blood pressure response by 4‐week treatment perindopril: A pooled sex‐specific analysis of the EUROPA, PROGRESS, and ADVANCE trials
Authors: Schreuder Michelle M. , Mirabito Colafella Katrina M. , Boersma Eric , Brugts Jasper J. , Roeters van Lennep Jeanine E. , Versmissen Jorie
Published: June 2021

Previous studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate treatment or poor response to antihypertensive agents remains unknown. The aim of this study is to analyze treatment response to the most potent renin angiotensin aldosterone system (RAAS) inhibitor perindopril in different age categories in women and men. Individual patient data were used from the combined European Trial on Reduction of Cardiac Events With Perindopril (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), and Action in Diabetes and Vascular disease: Preterax and Diamicron‐MR Controlled Evaluation (ADVANCE) trials, which include patients with vascular disease (n = 29,463). We studied the relative and absolute changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) during a 4‐week run‐in phase in which all patients were treated with the perindopril‐based treatment in different age categories. In total, 8366 women and 21,097 men were included in the analysis. Women greater than 65 years of age showed a significantly smaller blood pressure reduction after perindopril treatment (2.8 mmHg [95% confidence interval {CI} = 0.1–5.5] less reduction compared to women ≤45 years, p = 0.039). In men, the SBP reduction after perindopril in patients greater than 55–65 and greater than 65 years was lower compared to the age category less than or equal to 45 years (adjusted mean difference >55–65: 2.8 mmHg [95% CI = 1.8–3.7], p < 0.001, >65: 3.7 mmHg [95% CI = 2.7–4.7], p < 0.001). A trend of less blood pressure reduction was seen with ageing in both men and women (p < 0.001). To conclude, we observed that in both women and men the perindopril leads to less SBP reduction with increasing age, whereas the DBP reduction increases with age. More research is needed to determine whether it would be beneficial to use age‐adjusted perindopril dosages.
Rewiring of chromatin state and gene expression by transposable elements
Authors: Ohtani Hitoshi , Iwasaki Yuka W.
Published: June 2021

Transposable elements form a major fraction of the genome in various eukaryotic species. Although deleterious effects of transpositions within the genome have been reported, recent findings suggest that transposable elements can function as novel regulatory elements to fine‐tune gene expression. Transposable elements can impact the chromatin state through processes such as heterochromatin formation, enhancer–promoter interactions, and chromatin boundary formation, mainly because of the functions of chromatin‐based pathways that regulate the expression of transposable elements via DNA methylation and repressive histone modification. Therefore, transposable elements can rewire the chromatin state and gene expression depending on their insertions. Here, we review the findings that reveal the role of transposable elements as modifiers of the chromatin state and gene expression as well as the molecular mechanisms capable of inducing these changes.
Does autoimmune vitiligo protect against COVID‐19 disease?
Authors: Post Nicoline F. , Luiten Rosalie M. , Wolkerstorfer Albert , Bekkenk Marcel W. , Böhm Markus
Published: June 2021

The SARS‐CoV‐2 pandemic has evolved to a global health problem with a dramatic morbidity and mortality rate impacting our daily life and those of many patients. While there is evidence that some diseases are associated with an increased risk for development of a more severe course of COVID‐19, little is known on protective conditions. Importantly, clearance of viral infection and protection against disease manifestation crucially depends on functional innate and adaptive immunity and the interferon signalling axis. Here, we hypothesize that patients with non‐segmental vitiligo (NSV), an autoimmune skin (and mucosal) disorder, may clear SARS‐CoV‐2 infection more efficiently and have a lower risk of COVID‐19 development. Conversely, in case of COVID‐19 development, vitiligo autoimmunity may influence the cytokine storm‐related disease burden. In addition, immune activation during SARS‐CoV‐2 infection or COVID‐19 disease might increase vitiligo disease activity. Our hypothesis is based on the shift of the immune system in NSV towards adaptive type 1 (IFNγ and CD8 T cells) and innate immune responses. Identified susceptibility genes of NSV patients may further confer increased antiviral activity. To validate our hypothesis, we suggest an international consortium to perform a retrospective data registry and patient‐reported study on a large number of NSV patients worldwide during the COVID‐19 pandemic.
HUMBOLDT IN VENEZUELA AND CUBA: THE ‘SECOND SLAVERY’
Authors: Zeuske Michael
Published: June 2021

The reception of Humboldt's work now spans more than 200 years. It began with the publication of the texts that form his Opus Americanum (1808–31). Among these works, it was in the Political Essay on Cuba, where a chapter was devoted to the demography of the slave trade from Africa to Cuba, that became a cornerstone of the global historical significance of Humboldt's oeuvre. It can be argued that during the past 200 years the same clichés and slogans of liberal abolitionism (or its opponents, such as J. S. Thrasher) have been heard over and over again, without researchers having taken the trouble to investigate the biographical‐historical and micro‐historical origins of Humboldt's attitude to slavery, the slave trade and its sources. This article aims to show what Humboldt really could (and wanted to) know about slavery and the slave trade, by means of a micro‐distance and a micro‐point, the 25‐day crossing from Nueva Barcelona, in present‐day Venezuela, to Havana in Cuba in November/December 1800, as well as Humboldt's stay at the home of slave trader, Don Juan Luis de la Cuesta, in Havana (1800/1 and 1804).

   

Die Humboldt‐Rezeption umfasst ca. 200 Jahre. Sie begann mit den Publikationen der Werke des Opus Americanum (1808–31). In Bezug auf eines dieser Werke, den Politischen Essay über die Insel Kuba, steht fest, dass die Demografie des Sklavenhandels von Afrika nach Kuba (und in der Karibik) sowie das Kapitel ʻÜber das Sklavenwesenʼ Eckpunkte oder auch Säulen der globalhistorischen Bedeutung des humboldtschen Werkes darstellen. In der Rezeption von Humboldts Werk, und vor allem dieser Eckpunkte/Säulen sind über 200 Jahre eigentlich immer wieder die gleichen Klischees und Fahnenworte des liberalen Abolitionismus benutzt worden (oder seiner Gegner, wie J. S. Thrasher), ohne dass sich Rezipienten die Mühe gemacht hätten, die lebensgeschichtliche und mikrohistorische Entstehung der Haltung Humboldts zu Sklaverei und Sklavenhandel und seine Quellen zu erforschen. Der Beitrag will an einer Mikrostrecke und einem Mikropunkt, der 25‐tägigen Überfahrt von Nueva Barcelona im heutigen Venezuela nach Havanna auf Kuba im November/Dezember 1800 und Humboldts Beherbergung durch den Sklavenhändler Don Juan Luis de la Cuesta in Havanna (1800/1 und 1804), zeigen, was Humboldt realhistorisch zu Sklaverei und Sklavenhandel wissen konnte (und wollte).
Real‐world cost estimates of initiating emicizumab in US patients with haemophilia A
Authors: Samelson‐Jones Benjamin J. , Guelcher Christine , Kuhn Jan , Butler Regina , Massey Gita , Guerrera Michael F. , Raffini Leslie
Published: June 2021

Introduction

Emicizumab is the first approved non‐factor therapy for haemophilia A. It provides superior prophylactic bleeding control compared to other products in both patients with and patients without inhibitors. However, there is no real‐world data about the monetary consequences of starting emicizumab.

Aim

To examine the estimated costs of starting emicizumab in a cohort of real‐world haemophilia A patients with and without inhibitors.

Methods

The cost of haemostatic therapy for 6 months before and after initiating emicizumab for participants in a multicentre observational study was calculated based on the type of product and dosing that was used for prophylaxis and treating breakthrough bleeds, the number of treated bleeds and the participant weight.

Results

Ninety‐two patients were included, 18 with an active inhibitor. The median age was 8.7 years. The median total cost for all patients decreased from $176,720 to $128,099 (p = .04) after initiating emicizumab, largely because of decrease in the total cost of high‐cost outliers. The cost of prophylaxis and the total cost of bleeds also significantly decreased after starting emicizumab, both for patient with and patients without inhibitors.

Conclusions

Starting or switching to prophylaxis with emicizumab results in decreased costs for the treatment of patients with haemophilia A. This real‐world data could inform on payer decisions as well as future cost‐effective analysis.
Perpetual effect of laser surface texturing on tribological properties of Ti3SiC2/GNP composite—A fretting wear study
Authors: Singh Jagtar , Wani Mohammad Farooq
Published: June 2021

Tribological properties of Ti3SiC2 ceramic and Ti3SiC2/GNP composite were investigated using fretting sliding against Si3N4 ball counter body at a load of 50 N for a sliding distance of 900 m, under non‐textured lubricated (NTL), textured lubricated (TL) condition, and textured lubricated high temperature (TLHT). This paper presents the influence of laser surface texturing (LST) on Ti3SiC2 and its graphene nanoplatelets (GNP) reinforced composite established through spark plasma sintering (SPS), tested under fretting wear conditions. The coefficient of friction and wear rate of Ti3SiC2 and its graphene nanoplatelets reinforced composites were incontrovertibly enhanced with laser surface texturing as compared to non‐textured Ti3SiC2 and its GNP composite. The TL surface of Ti3SiC2 composite reinforced with 15% GNP showed the lowest COF and wear rate. Almost negligible changes were observed for TLHT tests. The LST proved to an efficient technique for enhancing the friction and wear properties of Ti3SiC2 and Ti3SiC2/GNP composite.
Glass‐ceramic Ce3+‐doped YAG‐Al2O3 composites prepared by sintering of glass microspheres
Authors: Akusevich Alena , Parchovianská Ivana , Parchovianský Milan , Prnová Anna , Lofaj František , Vojtko Marek , Klement Róbert
Published: June 2021

Sintering by viscous flow in a “kinetic window” between Tg and Tx temperatures was used to prepare bulk glass/glass‐ceramic luminescent materials from rapidly quenched glass microspheres in the system Y2O3–Al2O3 doped with Ce3+ ions. The glass microspheres were prepared from sol–gel synthesized precursor powders in a high‐temperature methane‐oxygen flame. The crystallization of the glasses was analyzed using differential scanning calorimetry and high‐temperature X‐ray diffraction. The crystallization behavior of quenched glass microspheres was found to be strongly dependent on glass composition. The glass microspheres were consolidated into bulk material by hot‐pressing technique at a temperature of up to 1100℃ with the applied pressure 40MPa. The optimized time‐temperature‐pressure regime enables the preparation of bulk glass, and glass‐ceramic with a high fraction of crystalline Ce3+‐doped YAG phase embedded in the Al2O3‐enriched glass matrix. The glass/glass‐ceramics emit blue/yellow light with high intensity under excitation in UV and/or blue spectral region.
Temperament and eating self‐regulation in young children with or at risk for obesity: An exploratory report
Authors: Button Alyssa , Faith Myles S. , Berkowitz Robert I.
Published: June 2021

Background

Few studies have examined the relationship between temperament and eating self‐regulation in early childhood, despite emerging evidence for associations with pediatric obesity.

Method

The aim of this exploratory report was to examine the associations between three eating behaviors and three facets of temperament among 4‐ to 8‐year‐olds with or at risk for obesity.

Results

Among 28 participants in a family intervention to reduce eating speed, we found at baseline that slower child eating speed was associated with less surgency (r = −.39, p = .04) and higher food responsiveness was associated with higher negative affect (r = .40, p = .03).

Conclusions

These findings support the potential yield of integrating temperament with eating self‐regulation assessments in studies of early obesity risk. A better understanding is needed regarding ways in which parents differentially feed in response to child temperament.
High MEK/ERK signalling is a key regulator of diapause maintenance in the cotton bollworm, Helicoverpa armigera
Authors: Lin X. W. , Fan Z. Z. , Liu Y. H. , Li J. , Ma Q. , Yan R. H.
Published: June 2021

MEK/ERK signalling has been identified as a key factor that terminates diapause in Sarcophaga crassipalpis and Bombyx mori. Paradoxically, high p‐MEK/p‐ERK signalling induces diapause in pupae of the moth Helicoverpa armigera; however, the regulatory mechanism is unknown. In the present study, we show that p‐MEK and p‐ERK are elevated in the brain of diapause‐destined pupae and suppression of MEK/ERK activity terminates diapause progress. Reactive oxygen species (ROS) activate MEK/ERK signalling, causing large‐scale phosphorylation of downstream proteins. The levels of ubiquitin‐conjugated proteins are also significantly reduced when ROS or p‐ERK level decreased. Moreover, terminated diapause progress by 20‐hydroxyecdysone injection significantly decreases p‐MEK, p‐ERK and phospho‐ribosomal S6 kinase levels, while phospho‐MAPK substrates and ubiquitin‐conjugated protein levels increase. Our data demonstrate that high MEK/ERK signalling mediated by ROS promotes diapause maintenance via increasing phosphorylation and degradation of downstream substrates. The results of this study may provide important information for understanding the regulatory mechanisms during insect diapause.
Tissue‐resident regulatory T cells accumulate at human barrier lymphoid organs
Authors: Hewavisenti Rehana V , Ferguson Angela L , Gasparini Georgia , Ohashi Tomoki , Braun Asolina , Watkins Thomas S , Miles John J , Elliott Michael , Sierro Frederic , Feng Carl G , Britton Warwick J , Gebhardt Thomas , Tangye Stuart , Palendira Umaimainthan
Published: June 2021

Regulatory T cells (Tregs) play a critical role in immune regulation and peripheral tolerance. While different types of Tregs have been identified in both mice and humans, much of our understanding about how these cells maintain immune homeostasis is derived from animal models. In this study, we examined two distinct human lymphoid organs to understand how repeated exposure to infections at the mucosal surface influences the phenotype and tissue localization of Tregs. We show that while Tregs in both tonsils and spleen express a tissue‐resident phenotype, they accumulate in greater numbers in tonsils. Tonsillar‐resident Tregs exhibit a highly suppressive phenotype with significantly increased expression of CD39, ICOS and CTLA‐4 compared with their counterparts in circulation or in the spleen. Functionally, resident Tregs are able effectively to suppress T cell proliferation. We further demonstrate that tonsillar‐resident Tregs share key features of T follicular helper cells. Spatial analysis reveals that the vast majority of resident Tregs are localized at the border of the T‐zone and B cell follicle, as well as within the lymphocyte pockets enriched with resident memory T cells. Together our findings suggest that resident Tregs are strategically co‐localized to maintain immune homeostasis at sites of recurrent inflammation.
Room‐temperature mechanochemical synthesis of RE molybdates: Impact of structural similarity and basicity of oxides
Authors: Kolbanev Igor V. , Shlyakhtina Anna V. , Degtyarev Evgeniy N. , Konysheva Elena Yu. , Lyskov Nikolay V. , Stolbov Dmitriy N. , Streletskii Andrey N.
Published: June 2021

The feasibility of room‐temperature synthesis of R10Mo2O21 (R = La, Y, Er) molybdates via mechanochemical processing of the 5R2O3+2MoO3 oxide mixtures has been studied using X‐ray powder diffraction (XRD) with Rietveld refinement and electron spin resonance spectroscopy (ESR). In all systems, the initial stage of mechanochemical synthesis is associated with MoO3 dissolution in R2O3 despite the difference in the crystal structure of initial oxides: La2O3 (, no. 164), Er2O3 and Y2O3 (, no. 206). Only for the 5Er2O3 + 2MoO3 system containing magnetic cations, ESR detects A‐type Mo5+ centers, thus enabling to follow the decrease in MoO3 content during room‐temperature mechanochemical synthesis. In the Er‐ and Y‐based systems, the starting oxides and synthesized R10Mo2O21 (R = Y, Er) molybdates have the same bixbyite structure and mechanochemical MoO3 dissolution in these oxides leads to R10Mo2O21 synthesis at room temperature within 80 min. In the La‐based system, MoO3 dissolution leads mainly to mechanochemical synthesis of La10Mo2O21 with the same structure as the starting La2O3 (, no. 164), but the amorphization of La2O3 and formation of basic lanthanum hydroxide during milling also took place. The use of nanosized MoO3 facilitates the slightly formation of La10Mo2O21 (, no. 164), but makes no impact on the synthesis of La10Mo2O21 ( (RI), no. 166).
Co‐doping of P(V) and Ti(III) in leaf‐architectured TiO2 for enhanced visible light harvesting and solar photocatalysis
Authors: Wu Lingling , Guo Cuiping , Feng Ruohan , Zhang Haoyue , Shi Nan , Li Yao , Su Huilan , Cui Xinjiang , Song Fang
Published: June 2021

Extending the absorption spectrum of TiO2 to include more visible light is of great importance to boost the photocatalytic efficiency for hydrogen generation and environmental pollution removal. Chemical doping and microstructure optimization are both effective. However, integrating them into one system at a low cost is a big challenge. Herein, we reported that phosphorus(V) and Titanium(III) were codoped into leaf‐architectured TiO2 via a facile sol‐gel biotemplating approach, which leads to significantly enhanced visible light harvesting and solar photocatalysis. P(V) doping at a moderate level (1.76 atm%) stabilized Ti(III) to achieve heavy self‐doping (Ti(III):Ti(IV) = 1:44) and concurrent oxygen vacancies of high concentration. The bandgap was narrowed to be only 1.9~2.3 eV. The synergistic co‐doping, coupling with the leaf‐architecture, allows efficient light absorption of less than 539~653 nm, as well as improved charge separation/transfer. The solar photocatalytic degradation rate is 2.6 times higher than that for a commercial TiO2 of P25 towards crystal violet. This work would push forward leaf‐architectured TiO2 toward practical application in photocatalysis, given the abundance, low cost, and renewability of green leaves. The codoping strategy combining sol‐gel and biotemplating approaches is potential for the synthesis of photo‐response materials or systems beyond photocatalysis.
Plant‐based, adjuvant‐free, potent multivalent vaccines for avian influenza virus via Lactococcus surface display
Authors: Song Shi‐Jian , Shin Gyeong‐Im , Noh Jinyong , Lee Jiho , Kim Deok‐Hwan , Ryu Gyeongryul , Ahn Gyeongik , Jeon Hyungmin , Diao Hai‐Ping , Park Youngmin , Kim Min Gab , Kim Woe‐Yeon , Kim Young‐Jin , Sohn Eun‐Ju , Song Chang Seon , Hwang Inhwan
Published: June 2021

Influenza epidemics frequently and unpredictably break out all over the world, and seriously affect the breeding industry and human activity. Inactivated and live attenuated viruses have been used as protective vaccines but exhibit high risks for biosafety. Subunit vaccines enjoy high biosafety and specificity but have a few weak points compared to inactivated virus or live attenuated virus vaccines, especially in low immunogenicity. In this study, we developed a new subunit vaccine platform for a potent, adjuvant‐free, and multivalent vaccination. The ectodomains of hemagglutinins (HAs) of influenza viruses were expressed in plants as trimers (tHAs) to mimic their native forms. tHAs in plant extracts were directly used without purification for binding to inactivated Lactococcus (iLact) to produce iLact‐tHAs, an antigen‐carrying bacteria‐like particle (BLP). tHAs BLP showed strong immune responses in mice and chickens without adjuvants. Moreover, simultaneous injection of two different antigens by two different formulas, tHAH5N6 + H9N2 BLP or a combination of tHAH5N6 BLP and tHAH9N2 BLP, led to strong immune responses to both antigens. Based on these results, we propose combinations of plant‐based antigen production and BLP‐based delivery as a highly potent and cost‐effective platform for multivalent vaccination for subunit vaccines.
Proline‐arginine poly‐dipeptide encoded by the C9orf72 repeat expansion inhibits adenosine deaminase acting on RNA
Authors: Suzuki Hiroaki , Matsuoka Masaaki
Published: June 2021

A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9‐ALS/FTD). Unconventional translation of the hexanucleotide repeat expansion generates five dipeptide repeat proteins (DPRs). The molecular mechanism underlying the DPR‐linked neurotoxicity is under investigation. In this study, using cell‐based models, we show that poly‐proline‐arginine DPR (poly‐PR), the most neurotoxic DPR in vitro, binds to adenosine deaminase acting on RNA (ADAR)1p110 and ADAR2 and inhibits their RNA editing activity. We further show that poly‐PR impairs cellular stress response that is mediated by ADAR1p110. These results together suggest that the poly‐PR‐mediated inhibition of the ADAR activity contributes to C9‐ALS/FTD‐linked neurotoxicity.

image
Pulmonary hypertension is associated with an increased incidence of NAFLD: A retrospective cohort study of 18,910 patients
Authors: Jördens Markus S. , Luedde Mark , Roderburg Christoph , Demir Muenevver , Luedde Tom , Kostev Karel , Loosen Sven H.
Published: June 2021

Background

Pulmonary hypertension (PH) represents a multicausal disease with increasing global incidence that eventually leads to right ventricular failure. In addition to cardiac sequelae, noncardiac comorbidities appear to be of increasing relevance, especially in times of improved therapeutic options that often result in long‐term survival. Here, we examined a potential association between PH and nonalcoholic fatty liver disease (NAFLD) as well as liver cirrhosis in an outpatient cohort in Germany.

Methods

A total of 9455 PH patients followed in general and internist practices between 2005 and 2019 were matched by propensity scoring based on age, sex, yearly consultation frequency and relevant comorbidities (obesity, diabetes, heart failure, lipid metabolism disorders) to a cohort of equal size without PH. The association between PH and NAFLD/liver cirrhosis was evaluated using Cox regression models.

Results

Within 10 years from the index date, cumulative incidence rates of NAFLD were significantly higher amongst patients with PH (7.3%) compared to non‐PH patients (3.5%, log‐rank p < 0.001). In regression analysis, this association was significant for both female (HR: 1.93, p < 0.001) and male (HR: 1.51, p = 0.005) patients and was most prominent amongst patients > 80 years (HR: 3.30, p = 0.001). Moreover, PH patients showed a strong trend towards higher incidence rates of liver cirrhosis compared to non‐PH patients (1.4 vs. 1.1%, p = 0.066).

Conclusion

Our data suggest that incidence rates of NAFLD are strongly elevated in patients with PH. This finding should trigger awareness of noncardiac comorbidities in these patients and argues for potential liver‐directed screening programs in patients with PH.
How do consumers use emoji in a food‐related context? Insights for the design and interpretation of emoji questionnaires
Authors: Ares Gastón , Vidal Leticia , Jaeger Sara R.
Published: June 2021

The present research contributed to the growing body of research regarding the use of emoji in sensory and consumer research by filling an acknowledged knowledge gap. Its specific aim was to explore the meaning of emoji in a food‐related context. The empirical approach involved 357 consumers who were tasked with writing a social media post or text message relating to a situation involving eating/drinking which was to be centered around a specific emoji. A total of 21 facial emoji were included in the research. As expected, emoji were used to convey different meanings, including degree of liking/disliking, emotional associations, gestures and expressions. The emoji were also used as part of messages describing negative and positive disconfirmation of expectations, which points to the importance of measuring expectations in a food‐related context. Two emoji were identified as unsuitable for future research due to their nonconsensual meaning ( and ).

Practical Applications

Emoji have significant potential as a research tool, stretching beyond cross‐cultural research or studies involving children, to general applications in food‐related consumer research. This is further enhanced by their versatility which includes use in emotion questionnaires, open‐ended questions and web‐scraped content. The present research provides recommendations for the design of emoji questionnaires, as well as insights on emoji meanings in a food‐related context. Results also highlight the relevance of negative and positive disconfirmation of expectations in shaping emotional associations with eating/drinking experiences, and, as such, serve as a reminder to include these important determinants of consumer behavior in future emotion‐focused research.
Born to rebel? The owner birth order and R&D investments in Chinese family firms
Authors: Li Wen Helena , Luo Jin‐hui , De Sisto Marco , Bartram Timothy
Published: June 2021

Family background has a significant impact on family firms’ strategies such as innovation investments. Going beyond prior studies that exclusively focus on how family governance and management factors determine research and development (R&D) investment decisions, this study investigates a family science factor: family firm owner's birth order, defined as the relative rank of the owner in terms of the age hierarchy among siblings in the family. Joining the family niche model of birth order and socioemotional wealth perspective, we propose that later‐born family firm owners tend to be risk‐takers and invest more in R&D projects compared with their earlier‐born counterparts. We further examine how the two other powerful decision‐makers within family firms (i.e., chairperson of the board and CEO) enable or constrain the owner's birth order–R&D investment relationship. We contend that the positive birth order impact on R&D investment is weaker when a family member is the chairperson of the board, while such a relationship is stronger in the presence of owner–CEO duality. We confirm our hypotheses using a sample of 605 firm‐year observations from Chinese‐listed family firms between 2006 and 2014. This study demonstrates the important impact of family science factors on innovation heterogeneities, which is understudied in the family firm innovation literature.
Rapid validity testing at the front end of innovation
Authors: Peña Häufler Birgit , Globocnik Dietfried , Landaeta Saldías Paola , Salomo Søren
Published: June 2021

To efficiently and effectively reduce the uncertainty inherent in the front‐end of innovation processes, recent literature emphasizes new approaches that facilitate rapid knowledge generation and learning such as design thinking, lean innovation, and pretotyping. However, these approaches differ in their conceptualizations and, despite their popularity, the empirical evidence on the performance relevance of such approaches for established organizations is limited. In this research, we propose rapid validity testing (RVT), in which we conceptualize and harmonize existing approaches toward a unique and comprehensive set of front‐end activities necessary to reduce uncertainty and equivocality inherent to this phase and enable planned flexibility. Drawing on information processing theory, we argue that organizations implementing RVT also increase the probability of achieving innovation outcomes of superior quality on time and within budget. We further argue that the effectiveness of RVT depends upon internal and external environmental factors. Drawing on multirespondent data collected from 1022 informants in 129 firms, we find empirical evidence that organizations implementing the RVT approach in their innovation activities achieve higher performance of their innovation programs, and that the performance relevance of RVT depends upon technological turbulence and the organization's long‐term orientation and risk propensity. We contribute to the literature by conceptualizing RVT as a set of activities that enable planned flexibility. Furthermore, we overcome empirical shortcomings of studies on popular approaches that relied primarily on anecdotal or case study evidence and imply the generalizability of their effectiveness. Our findings highlight that organizations indeed not only benefit from RVT but also challenge the notion of a one‐size‐fits‐all approach to the front end of innovation.
Molecular genotyping of Candidaalbicans isolated from different sites may trace the etiological infection routes: Observation in China
Authors: Tan Jingwen , Song Yinggai , Liu Weixia , Wang Xuejie , Zhang Jinqing , Chen Wei , Li Ruoyu , Liu Wei
Published: June 2021

Background

Invasive candidiasis is a growing concern worldwide, especially in immunocompromised patients, including ICU patients.

Objectives

As Candida albicans is the leading cause of candidaemia, it is important to investigate the evolution of C. albicans in patients with candidaemia.

Methods

We analysed 238 strains of C. albicans isolated from different body sites. Antifungal susceptibility testing, CAI loci genotyping and multilocus sequence typing (MLST) of all isolates were performed. The relationships among the total isolates that differed in sequence at only one of the seven housekeeping gene loci were analysed using eBURST.

Results

Multilocus sequence typing analysis in 238 isolates by combining seven housekeeping alleles revealed 175 diploid sequence types, in which 84 were newly identified. eBURST analysis for these data recognised 19 clonal complexes (CCs) and 79 singletons. Besides, seventy‐three CAI genotypes were identified. Blood isolates showed maximum genotypes (49), and the dominant genotypes were CAI 17‐21 and CAI 21‐21. Oral isolates possessed 25 CAI genotypes, and the dominant genotypes were CAI 17‐21 and CAI 21‐21 as well. Since isolates with CAI allele numbers <30 showed easier transmission, CAI 17‐21 and CAI 21‐21 were the most frequently transmitted. Finally, the CAI genotypes were classified into six groups.

Conclusions

This work revealed the oral and blood strains isolated from the patients with candidaemia in ICU shared the identical dominant CAI genotypes. Our data expanded the C. albicans MLST database and helped with understanding the evolution and spread of invasive candidiasis.
AtDTX25, a member of the multidrug and toxic compound extrusion family, is a vacuolar ascorbate transporter that controls intracellular iron cycling in Arabidopsis
Authors: Hoang Minh Thi Thanh , Almeida Diego , Chay Sandrine , Alcon Carine , Corratge‐Faillie Claire , Curie Catherine , Mari Stephane
Published: June 2021

Iron (Fe) is an essential element, its transport is regulated by the cell redox balance. In seeds, Fe enters the embryo as Fe2+ and is stored in vacuoles as Fe3+. Through its ferric reduction activity, ascorbate plays a major role in Fe redox state and therefore Fe transport within the seed.

We searched for ascorbate membrane transporters responsible for controlling Fe reduction by screening the yeast ferric reductase‐deficient fre1 strain and isolated AtDTX25, a member of the Multidrug And Toxic compound Extrusion (MATE) family.

AtDTX25 was shown to mediate ascorbate efflux when expressed in yeast and Xenopus oocytes, in a pH‐dependent manner. In planta, AtDTX25 is highly expressed during germination and encodes a vacuolar membrane protein. Isolated vacuoles from AtDTX25‐1 knockout mutant contained less ascorbate and more Fe than wild‐type (WT), and mutant seedlings were highly sensitive to Fe deficiency. Iron imaging further showed that the remobilisation of Fe from vacuoles was highly impaired in mutant seedlings.

Taken together, our results established AtDTX25 as a vacuolar ascorbate transporter, required during germination to promote the reduction of the pool of stored Fe3+ and its remobilisation to feed the developing seedling.
Facial aesthetic concern is a powerful predictor of patients' decision to accept orthognathic surgery
Authors: Perkovic Vjera , Pavlic Andrej , Trinajstic Zrinski Magda , Katic Visnja , Zigante Martina , Spalj Stjepan
Published: June 2021

Objective

To investigate differences in quality of life in subjects with and without skeletal malocclusions and factors influencing patients' decision to accept orthognathic surgery.

Materials and methods

Design

Cross‐sectional with stratified sampling.

Settings and sample population

190 Caucasian subjects (65% females), aged 17‐46 years. 95 subjects were consecutive patients referred to University Dental Clinic for skeletal malocclusion treatment of which 58 subjects accepted suggested surgery, 37 refused. The other 95 were age‐and sex‐matched controls, without malocclusions, recruited from the pool of students and employees of local high schools and university.

Main outcome measures

Psychosocial and functional issues were evaluated by Orthognathic Quality of Life Questionnaire. Complexity of malocclusion and treatment need was assessed by the Index of Orthognathic Functional Treatment Need.

Results

Discriminant analysis demonstrated that in quality of life, three groups differed mostly in facial aesthetic concern, followed by altered oral function, then by social interactions which were the highest in the group that accepted surgery. When controlling for age, sex, oral function impairment, awareness of facial deformity and inhibitions in social contacts in a multiple logistic regression analysis, only IOFTN and facial aesthetic concern were significant predictors of orthognathic surgery acceptance, increasing the odds for acceptance by 2.9x and 4.7x, respectively (P ≤ .045).

Conclusion

Facial aesthetic concern is very important factor in patients’ decision‐making process for accepting orthognathic treatment for skeletal malocclusions, with greater importance than high normative need for functional orthognathic treatment.
One‐Stage Percutaneous Endoscopic Lumbar Discectomy for Symptomatic Double‐Level Contiguous Adolescent Lumbar Disc Herniation
Authors: Mao Lu , Zhu Bin , Wu Xiao‐tao
Published: June 2021

Objective

To assess the clinical efficacy of one‐stage percutaneous endoscopic lumbar discectomy (PELD) for symptomatic double‐level contiguous adolescent lumbar disc herniation (ALDH).

Methods

This retrospective study included 16 patients who presented with back and/or leg pain due to double‐level disc herniation underwent PELD for symptomatic lumbar disc herniation (0.27%,16/5877) from January 2014 to September 2019. After follow‐up period of 17.3 months in average, numeric rating scale (NRS) scores and modified Macnab criteria were used to assess the preoperative and postoperative clinical results. Quantitative data were expressed as mean standard deviation (SD) and the data for the variation in the NRS scores before and after the operation were compared using the Wilcoxon two‐sample test. Analyses were performed with IBM SPSS Statistics for Windows, version 19.0 (IBM, Armonk, NY, USA). Values of P < 0.05 were considered significantly different.

Results

There were 11 male and 5 female patients, with an average age of 19.3 years (range, 15–22 years). One case affected the L2‐ L3 /L3‐L4 level, seven cases affected the L3‐ L4 /L4‐ L5 level, and eight cases affected the L4‐ L5 /L5‐S1 level. The NRS scores decreased significantly in both early and late follow‐up evaluations and these scores demonstrated significant improvement in late follow‐up (P < 0.05). For the modified Macnab criteria, the final outcome results were excellent in 14 patients (87.5%), good in 1 patient (6.25%), fair in 1 patient (6.25%), and the overall success rate was 93.75%.

Conclusion

This study's data suggest that one‐stage PELD is promising treatment strategy for selected symptomatic double‐level contiguous adolescent lumbar disc herniation.
Reduced esophageal heating in high‐power short‐duration atrial fibrillation ablation in the contact force catheter era
Authors: Vassallo Fabricio , Meigre Lucas Luis , Serpa Eduardo , Cunha Christiano Lemos , Carloni Hermes , Simoes Aloyr , Amaral Dalton , Lovatto Carlos
Published: June 2021

Background

 Atrial fibrillation (AF) ablation is alternative treatment to medical therapy. Most feared complication is atrioesophageal fistula

Methods

Observational, retrospective analysis of consecutive 355 patients undergoing first AF ablation. Low‐power long‐duration (LPLD) group contained 158 patients, with 121 (76.58%) having paroxysmal AF who underwent ablation with power 20/30W (anterior and posterior left atrial wall), 17 mL/min flow, and a contact force of 10–30 g for 30 s. High‐power short‐duration group (HPSD) contained 197 patients, with 113 (57.36%) having paroxysmal AF who underwent ablation at 45/50W of power with a contact force of 8–15 g/10–20 g and a 35 mL/min flow rate for 6–8 s on the anterior and the posterior left atrial wall, respectively. Both groups had pulmonary veins isolated and atrial flutter was ablated when needed. For patients not in sinus rhythm, cardioversion was performed before ablation

Results

There were no complications. LPLD group: Left atrial time 118.74 min, total 145.32 min, radiofrequency time 4317.99s, X‐ray 13.42 min, and elevation of luminal esophageal temperature (LET) in 132 (84.53%) patients. HPSD group: Left atrial time 72.16 min, total 93.76 min, radiofrequency time 1511.29s, X‐ray 7.6 min, and LET elevation in only 75 (38.07%) patients. A markedly higher rate of first‐pass isolation was observed in HPSD compared to LPLD, 77.16% versus 13.29%, respectively. Recurrence occurred in 64 (40.50%) and 32 (16.24%) in 28.45 and 22.35 months in LPLD and HPSD patients, respectively. In LPLD, 10 patients were submitted to endoscopy, and one (10%) had mild erythema and in HPSD, 13 performed the endoscopy, with two (15.38%) patients showing mild erythema

Conclusion

HPSD technique compared to the LPLD technique showed significant reduced radiofrequency and fluoroscopy times, higher rate of first‐pass isolation, lower recurrence rate, and esophageal temperature elevation and may also have a protective effect avoiding incidental esophageal injury due to these findings.
Faculty perspectives on transitioning public health nursing clinical to virtual in response to COVID‐19
Authors: Bejster Mallory , Cygan Heide , Morris Burnett Glenda , Smith Diane Y. , Brown Walker Mary , Friese Tanya
Published: June 2021

The COVID‐19 pandemic has highlighted the need for public health nursing as an integral part of a strong public health workforce. However, it has also created challenges in preparing future nurses as much of nursing instruction, including clinical experiences, needed to urgently transition learning to a virtual environment. This paper describes the process faculty experienced during spring 2020 to quickly transition public health nursing clinicals from in‐person to virtual learning in response to COVID‐19. Further, faculty lessons learned are shared and include the importance of creating a supportive team dynamic, embracing innovation, continuing to engage with community partners, and adapting to meet emerging student needs during the evolving pandemic. The process and lessons learned may act as a guide for other nursing programs as we continue to navigate nursing education during this and future pandemics.
Varieties of Artifacts: Embodied, Perceptual, Cognitive, and Affective
Authors: Heersmink Richard
Published: June 2021

The primary goal of this essay is to provide a comprehensive overview and analysis of the various relations between material artifacts and the embodied mind. A secondary goal of this essay is to identify some of the trends in the design and use of artifacts. First, based on their functional properties, I identify four categories of artifacts co‐opted by the embodied mind, namely (a) embodied artifacts, (b) perceptual artifacts, (c) cognitive artifacts, and (d) affective artifacts. These categories can overlap and so some artifacts are members of more than one category. I also identify some of the techniques (or skills) we use when interacting with artifacts. Identifying these categories of artifacts and techniques allows us to map the landscape of relations between embodied minds and the artifactual world. Second, having identified categories of artifacts and techniques, this essay then outlines some of the trends in the design and use of artifacts, focusing on neuroprosthetics, brain‐computer interfaces, and personalization algorithms nudging their users toward particular epistemic paths of information consumption.