bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIntroductionEmicizumab 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.AimTo examine the estimated costs of starting emicizumab in a cohort of real‐world haemophilia A patients with and without inhibitors.MethodsThe 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.ResultsNinety‐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.ConclusionsStarting 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

AbstractTribological 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

AbstractSintering 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

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

AbstractMEK/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

AbstractRegulatory 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

AbstractThe 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

AbstractExtending 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

AbstractInfluenza 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

AbstractA 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.
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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

AbstractBackgroundPulmonary 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.MethodsA 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.ResultsWithin 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).ConclusionOur 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

AbstractThe 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 ApplicationsEmoji 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

AbstractFamily 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

AbstractTo 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

AbstractBackgroundInvasive candidiasis is a growing concern worldwide, especially in immunocompromised patients, including ICU patients.ObjectivesAs Candida albicans is the leading cause of candidaemia, it is important to investigate the evolution of C. albicans in patients with candidaemia.MethodsWe 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.ResultsMultilocus 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.ConclusionsThis 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.