bluuebunny/crossref_metadata_2025 huggingface dataset:
The determination of β‐agonist residues in bovine tissues using liquid chromatography–tandem mass spectrometry
Authors: Yikilmaz Yeliz , Kuzukiran Ozgur , Erdogan Ekrem , Sen Filiz , Kirmizibayrak Ozlem , Filazi Ayhan
Published: June 2020

We aimed to develop a rapid, simple and reproducible method based on LC–tandem mass spectrometry (LC–MS/MS) to analyze β‐agonist residues (clenbuterol, zilpaterol, ractopamine and isoxsuprine) in bovine tissues. The method was validated in accordance with the European Council Decision 2002/657/EC. The samples were homogenized, and then 10 mL of an acetate buffer was added to a 5‐g sample. The sample was then centrifuged at 12,000 rpm and filtered. Sodium hydroxide (2 m) was added to adjust pH of the sample that was centrifuged again. The extract was filtered through a solid‐phase extraction column. The residue was re‐dissolved in 250 μL acetonitrile and then subjected to LC–MS/MS. The separation was done on a C18 column. The mobile phase consisted of 0.1% formic acid in deionized water and 0.1% formic acid in methanol. The mean recoveries of β‐agonists were in the range of 84.3%–119.1% with relative standard deviations (%RSDs) of 0.683%–4.05%. Decision limits and detection capabilities of the analytes ranged from 0.0960 to 4.9349 μg/kg and from 0.0983 to 5.0715, respectively. This method was used to detect four β‐agonists in 100 bovine muscle, 100 liver and 100 kidney tissues from a slaughterhouse. No residue was found above the maximum residue limit level.
Sustainability concerns in luxury supply chains: European brand strategies and French consumer expectations
Authors: Jaegler Anicia , Goessling Tobias
Published: June 2020

Sustainability in supply chain management has become a concern in both research and practice. Although consumption and purchasing have been significantly explored in the luxury sector, a gap in supply chain studies is still evident. Therefore, the aim of this article is to examine how industry bodies and supply chain partners address sustainability concerns in the European luxury sector and how they respond to consumer expectations. In an explanatory study, we have collected data about sustainable supply chain practices in 11 European luxury good companies, by interviewing and surveying 13 managers. In a first consumer study, we held interviews with French luxury consumers in Bordeaux about their sustainability expectations (N= 170). The results show that while the distribution of attention is dependent on the respective supply chain activities, luxury goods companies address sustainability concerns and aim to take responsibility for their activities. However, the emphasis is on the dimension of economic sustainability. A comparison with sustainability expectations of French luxury goods consumers suggests that business practices are not perfectly well aligned with these expectations. Consumers put more emphasis on social and environmental sustainability dimensions. On the other hand, business activities concerning waste reduction and raw material management rather well match consumer expectations.
Cardiovascular disease and asymptomatic childhood cancer survivors: Current clinical practice
Authors: Bottinor Wendy J. , Friedman Debra L. , Ryan Thomas D. , Wang Li , Yu Chang , Borinstein Scott C. , Godown Justin
Published: June 2020

Background

It is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care.

Objectives

To describe the current role of cardiovascular screening in the clinical care of asymptomatic CCS.

Methods

At 50 pediatric academic medical centers, a childhood cancer survivorship clinic director, pediatric cardiologist, and adult cardiologist with a focus on CCS were identified and invited to participate in a survey. Surveys were managed electronically. Categorical data were analyzed using nonparametric methods.

Results

Of the 95 (63%) respondents, 39% were survivorship practitioners, and 61% were cardiologists. Eighty‐eight percent of survivorship practitioners reported that greater than half of CCS received cardiovascular screening. CCS followed by adult cardiology were more likely to be seen by a cardio‐oncologist. Those followed by pediatric cardiology were more likely to be seen by a heart failure/transplant specialist. Common reasons for referral to cardiology were abnormal cardiovascular imaging or concerns a CCS was at high risk for cardiovascular disease. Ninety‐two percent of cardiologists initiated angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy for mild systolic dysfunction. Adult cardiologists initiated beta‐blocker therapy for less severe systolic dysfunction compared to pediatric cardiologists (P < .001). Pediatric cardiologists initiated mineralocorticoid therapy for less severe systolic dysfunction compared to adult cardiologists (P = .025). Practitioners (93%) support a multi‐institutional collaboration to standardize cardiovascular care for CCS.

Conclusions

While there is much common ground in the clinical approach to CCS, heterogeneity is evident. This highlights the need for cohesive, multi‐institutional, standardized approaches to cardiovascular management in CCS.
Two‐Dimensional NiO@C‐N Nanosheets Composite as a Superior Low‐Temperature Anode Material for Advanced Lithium‐/Sodium‐Ion Batteries
Authors: Bai Zhengyu , Lv Xiao , Liu Dai‐Huo , Dai Dongmei , Gu Jiali , Yang Lin , Chen Zhongwei
Published: June 2020

Most of the anodes used in lithium‐/sodium‐ion batteries (LIBs/SIBs) have poor low‐temperature (LT) performances, which severely limit their applications under LT environment. Herein, two‐dimensional nickel oxide nanosheet encapsulated in N‐doped carbon coated layer (abbreviated as NiO@C−N NSs) is successfully prepared and investigated for the first time as a LT anode for LIBs/SIBs. As a result, the prepared NiO@C−N NSs electrode delivers a high room temperature (RT) Li‐storage capacity (1036 mA h g−1 at 0.05 A g−1) and excellent LT Li‐storage performance (428 mA h g−1 at 0.05 A g−1 at −40 °C). Furthermore, the prepared NiO@C−N NSs also exhibits a superior RT Na‐storage capacity of 529 mA h g−1 at 0.05 A g−1 and superior LT Na‐storage performance. Through electrochemical impedance spectroscopy analysis, we find that the LT Li‐/Na‐storage performances of NiO@C−N NSs electrodes are mainly dominated by the RSEI of SEI membrane formation at the electrode/electrolyte interface. Moreover, the LT Li‐/Na‐storage properties of NiO@C−N NSs can be effectively improved by using commercial LT electrolyte with low viscosity and low melting point.
A Phase 1 Study to Assess the Relative Bioavailability, Food Effect, and Safety of a Tablet Formulation of GSK2838232, a Novel HIV Maturation Inhibitor in Healthy Participants After Single and Repeated Doses
Authors: Johnson Mark , Jewell Roxanne C. , Gan Jianjun , Dumont Etienne , Burns Olivia , Johns Brian A.
Published: June 2020

GSK2838232 is a novel, potent HIV‐1 maturation inhibitor for use in regimen‐based combination antiretroviral therapy from a once‐daily oral dose boosted with a pharmacoenhancer (ritonavir or cobicistat). This phase 1 study in healthy participants was conducted in 2 parts. Part 1 (n = 14) assessed the relative bioavailability of single doses of a 200‐mg GSK2838232 tablet and capsule formulation boosted with 100 mg ritonavir in fed and fasted (tablet‐only) subjects. Part 2 (n = 10) assessed the pharmacokinetics of repeated 500‐mg once‐daily doses of GSK2838232 without a pharmacoenhancing boosting agent. In part 1, GSK2838232 demonstrated comparable bioavailability following a single dose of 200 mg GSK2838232 as capsule and tablet formulations in combination with ritonavir (RTV) under fed conditions, with lower intrasubject variability observed for the tablet formulation. In part 2, following administration of 500 mg GSK2838232 once daily for 11 days under fed conditions, Cmax, AUC0‐τ, and Cτ showed a small degree of accumulation (1.2‐ to 1.3‐fold) of GSK2838232. The median tmax was approximately 4 hours on both day 1 and day 11 when given with food. The mean t½ was approximately 23 hours on day 11. Steady‐state concentrations were achieved by day 3 with a geometric mean steady‐state Cτ on day 11 of 28 ng/mL. The tablet formulation was generally well tolerated as a single 200‐mg dose with RTV under fed and fasted conditions and following administration of multiple daily doses (11 days) of 500 mg unboosted.
Effect of High‐Dose Esomeprazole on CYP1A2, CYP2C19, and CYP3A4 Activities in Humans: Evidence for Substantial and Long‐lasting Inhibition of CYP2C19
Authors: Kaartinen Taavi J. K. , Tornio Aleksi , Tapaninen Tuija , Launiainen Terhi , Isoherranen Nina , Niemi Mikko , Backman Janne T.
Published: June 2020

In vitro, esomeprazole is a time‐dependent inhibitor of CYP2C19. Additionally, racemic omeprazole induces CYP1A2 and omeprazole and its metabolites inhibit CYP3A4 in vitro. In this 5‐phase study, 10 healthy volunteers ingested 20 mg pantoprazole, 0.5 mg midazolam, and 50 mg caffeine as respective index substrates for CYP2C19, 3A4, and 1A2 before and 1, 25, 49 (pantoprazole only), and 73 hours after an 8‐day pretreatment with 80 mg esomeprazole twice daily. The area under the plasma concentration‐time curve (AUC) of R‐pantoprazole increased 4.92‐fold (90% confidence interval (CI) 3.55–6.82), 2.31‐fold (90% CI 1.85–2.88), and 1.33‐fold (90% CI 1.06–1.68) at the 1‐hour, 25‐hour, and 73‐hour phases, respectively, consistent with a substantial and persistent inhibition of CYP2C19. The AUC of midazolam increased up to 1.44‐fold (90% CI 1.22–1.72) and the paraxanthine/caffeine metabolic ratio up to 1.19‐fold (90% CI 1.04–1.36), when the index substrates were taken 1 hour after esomeprazole. Based on the recovery of R‐pantoprazole oral clearance, the turnover half‐life of CYP2C19 was estimated to average 53 hours. Pharmacokinetic simulation based on the observed concentrations of esomeprazole and its metabolites as well as their published CYP2C19 inhibitory constants was well in line with the observed changes in R‐pantoprazole pharmacokinetics during the course of the study. Extrapolations assuming linear pharmacokinetics of esomeprazole suggested weak to moderate inhibition at 20 and 40 mg twice daily dosing. In conclusion, high‐dose esomeprazole can cause strong inhibition of CYP2C19, but only weakly inhibits CYP3A4 and leads to minor induction of CYP1A2. The enzymatic activity of CYP2C19 recovers gradually in ~ 3–4 days after discontinuation of esomeprazole treatment.
Positive facilitators of diabetes management in emerging adults with type 1 diabetes—A qualitative analysis of blogs
Authors: Johansen Clea Bruun , Pouwer Frans , Beck‐Nielsen Henning , Rothmann Mette Juel
Published: June 2020

Introduction

Emerging adults (18‐30 years) with type 1 diabetes must manage a demanding chronic illness as well as navigate a life phase full of instability and transitions. Clinical care for this age group remains a challenge. An improved understanding of psychological facilitators of diabetes management may contribute to optimized clinical care to this age group.

Aim

To explore which individual strategies facilitated emerging adults’ diabetes management and what kind of support they regard helpful from peers, family and healthcare providers.

Methods

Qualitative analysis of web blogs. We identified personal blogs by emerging adults with type 1 diabetes through a search at the websites for diabetes associations in Denmark, UK and the USA, a snowball search at identified blogs and an internet search (Google). Blog posts from approximately the last year were analysed with thematic analysis as described by Braun and Clarke.

Results

We included 16 blogs from UK, the USA, Australia and Denmark, focusing on blog entries from 2017 to 2018. Several psychological facilitators of management of type 1 diabetes were identified. Positive individual strategies involved: developing a balanced approach to blood glucoses, sharing diabetes with peers and making space for emotional reactions. Supportive involvement from peers, family and health care providers included: normalization, emotional backup and a nonjudgmental attitude.

Conclusion

Diabetes management in emerging adulthood can be facilitated by several individual strategies as well as by supportive involvement from peers, family and health care providers. It is worthwhile to further investigate how individual strategies as well as supportive involvement can be promoted in diabetes care.
Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial
Authors: Voors Adriaan A. , Tamby Jean‐François , Cleland John G. , Koren Michael , Forgosh Leslie B. , Gupta Dinesh , Lund Lars H. , Camacho Albert , Karra Ravi , Swart Henk P. , Pellicori Pierpaolo , Wagner Frank , Hershberger Ray E. , Prasad Narayana , Anderson Robert , Anto Anu , Bell Kaylyn , Edelberg Jay M. , Fang Liang , Henze Marcus , Kelly Cynthia , Kurio Gregory , Li Wanying , Wells Kate , Yang Chun , Teichman Sam L. , del Rio Carlos L. , Solomon Scott D.
Published: June 2020

Aims

Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction.

Methods and results

We studied the effects of danicamtiv on LV and LA function in non‐clinical studies (ex vivo: skinned muscle fibres and myofibrils; in vivo: dogs with heart failure) and in a randomized, double‐blind, single‐ and multiple‐dose phase 2a trial in patients with stable HFrEF (placebo, n = 10; danicamtiv, n = 30; 50–100 mg twice daily for 7 days). Danicamtiv increased ATPase activity and calcium sensitivity in LV and LA myofibrils/muscle fibres. In dogs with heart failure, danicamtiv improved LV stroke volume (+10.6 mL, P < 0.05) and LA emptying fraction (+10.7%, P < 0.05). In patients with HFrEF (mean age 60 years, 25% women, ischaemic heart disease 48%, mean LV ejection fraction 32%), treatment‐emergent adverse events, mostly mild, were reported in 17 patients (57%) receiving danicamtiv and 4 patients (40%) receiving placebo. Danicamtiv (at plasma concentrations ≥2000 ng/mL) increased stroke volume (up to +7.8 mL, P < 0.01), improved global longitudinal (up to −1.0%, P < 0.05) and circumferential strain (up to −3.3%, P < 0.01), decreased LA minimal volume index (up to −2.4 mL/m2, P < 0.01) and increased LA function index (up to 6.1, P < 0.01), when compared with placebo.

Conclusions

Danicamtiv was well tolerated and improved LV systolic function in patients with HFrEF. A marked improvement in LA volume and function was also observed in patients with HFrEF, consistent with pre‐clinical findings of direct activation of LA contractility.
The domestic pig as human‐relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus
Authors: Schmidt Stefanie , Ebner Friederike , Rosen Kerstin , Kniemeyer Olaf , Brakhage Axel A. , Löffler Jürgen , Seif Michelle , Springer Jan , Schlosser Josephine , Scharek‐Tedin Lydia , Scheffold Alexander , Bacher Petra , Kühl Anja A. , Rösler Uwe , Hartmann Susanne
Published: June 2020

Pulmonary mucosal immune response is critical for preventing opportunistic Aspergillus fumigatus infections. Although fungus‐specific CD4+ T cells in blood are described to reflect the actual host–pathogen interaction status, little is known about Aspergillus‐specific pulmonary T‐cell responses. Here, we exploit the domestic pig as human‐relevant large animal model and introduce antigen‐specific T‐cell enrichment in pigs to address Aspergillus‐specific T cells in the lung compared to peripheral blood. In healthy, environmentally Aspergillus‐exposed pigs, the fungus‐specific T cells are detectable in blood in similar frequencies as observed in healthy humans and exhibit a Th1 phenotype. Exposing pigs to 106 cfu/m3 conidia induces a long‐lasting accumulation of Aspergillus‐specific Th1 cells locally in the lung and also systemically. Temporary immunosuppression during Aspergillus‐exposure showed a drastic reduction in the lung‐infiltrating antifungal T‐cell responses more than 2 weeks after abrogation of the suppressive treatment. This was reflected in blood, but to a much lesser extent. In conclusion, by using the human‐relevant large animal model the pig, this study highlights that the blood clearly reflects the mucosal fungal‐specific T‐cell reactivity in environmentally exposed as well as experimentally exposed healthy pigs. But, immunosuppression significantly impacts the mucosal site in contrast to the initial systemic immune response.
Restoring a glacier‐fed river: Past and present morphodynamics of a degraded channel in the Italian Alps
Authors: Scorpio Vittoria , Andreoli Andrea , Zaramella Mattia , Moritsch Sara , Theule Joshua , Dell'Agnese Andrea , Muhar Susanne , Borga Marco , Bertoldi Walter , Comiti Francesco
Published: June 2020

The present study explores the evolutionary trajectory of the glacier‐fed Mareit River (South Tyrol, Italian Alps), where a large restoration programme was implemented in 2008–2009. River corridor changes before and after the restoration works were assessed using historical maps, recent field observations, topographic surveys and topographic differencing. Trends of anthropic (forest cover, channel works, gravel mining) and natural (glacial cover, precipitation, flow regime) factors controlling channel morphology – at both catchment and reach scales – were reconstructed. From the mid‐19th century, the evolutionary trajectory of the Mareit River followed a degradational trend, characterized by channel narrowing, bed incision and planform simplification. Direct, in‐channel human alterations – mainly in the form of bank protections (in the late 19th century), gravel mining (mostly in the 1970s) and grade‐control works (since the 1980s) – dominated the historical adjustments before the restoration. In 2008–2009, a segment of the Mareit was restored by widening the channel, partly removing the check‐dams and shaping a braided pattern within a laterally constrained corridor. Post‐work monitoring shows that the restoration improved both the morphological quality and the geomorphic diversity. At present, the channel is subject to narrowing and slight bed level incision, with islands and floodplains progressively expanding at the expenses of the active channel. This trend is likely to continue in the next decades based on the expected future flow regime, and indeed the Mareit River seems to be attaining a ‘miniaturized’ version of the anabranching pattern of the mid‐19th century. Overall, this restoration approach and the associated evolutionary trajectory is considered positive, because it leads to a complex mosaic of geomorphic units, dynamically self‐adjusting to the time‐varying driving variables. The formation of a morphodynamically active corridor, while keeping artificially non‐erodible boundaries, represents an optimal strategy to integrate ecological improvements with flood risk mitigation in the densely populated Alpine valleys. © 2020 John Wiley & Sons, Ltd.
A novel translocation t(10;17)(p13;q11.2) harboring two cryptic deletions identified by array‐CGH and characterized by SUZ12 overexpression in a patient with chronic thrombocytosis
Authors: Batanian Jacqueline R. , Malherbe Jacques A. J. , Erber Wendy N.
Published: June 2020

No specific translocation is associated with myeloproliferative neoplasms (MPNs). However, an interstitial deletion involving subband 17q11.2 which includes the NF1 gene, although rare, is a recurrent aberration in several myeloid disorders including MPNs. For the first time, we report an acquired novel translocation involving 10p13 and 17q11.2 in a 62‐year‐old Caucasian female which was referred for investigation of chronic and persistent unexplained thrombocytosis. The patient had no history of hematological sequelae and genomic testing for JAK2, CALR, and MPL mutations were negative. She was subsequently diagnosed with a triple negative essential thrombocythemia. Array‐CGH analysis noted that the translocation harbored two cryptic deletions, one of which involved 17q11.2 encompassing the NF1 gene. One of the junction breakpoints involved the SUZ12 gene. Immunohistochemical assessment of the marrow trephine showed increased megakaryocytic expression of the SUZ12 protein, as well as EZH2 and Ki67; biochemical abnormalities suggestive of excess megakaryocytic hyperplasia. This novel translocation may affect the expression of SUZ12 and its downstream targets, and may represent a unique pathogenomic etiology which drives chronic thrombocytosis in essential thrombocythemia.
Microstructure and geochemistry of pseudotachylyte veins from Sarwar‐Junia Fault Zone, India: Implications for frictional melting process in a seismic fault zone
Authors: Sarkar Arindam , Chattopadhyay Anupam
Published: June 2020

Pseudotachylyte (Pt) veins associated with ancient fault zones are considered as reliable palaeoseismic indicators as they are produced by a combination of cataclasis and frictional melting of the host rock during rapid (seismic rate) fault slip. In spite of a large amount of work done on pseudotachylytes, several issues related to the frictional melting process are not completely resolved for example, the nature and origin of domain‐scale chemical heterogeneity of the Pt matrix, the contribution of different minerals of the host rocks in forming the melt product, temperature variation in different domains of the Pt veins, among others. To revisit these issues, pseudotachylyte veins hosted entirely within pelitic gneisses (Pt‐I) and those formed along the contact of gneisses with intrusive meta‐dolerite dykes (Pt‐II) within the Sarwar‐Junia Fault Zone in Rajasthan, India, are studied in detail using optical and scanning electron microscope, X‐ray diffraction (XRD), X‐ray fluorescence, and electron probe micro‐analyser, with an intention to better understand the evolution of the microstructures and the heterogeneous chemical character of the pseudotachylyte veins and their host rocks. Unequivocal melt‐origin microstructures (e.g., microlites, spherulites, melt flow structure) are observed in the pseudotachylyte matrix, and an indirect evidence of amorphous (glass?) phase is found through XRD. The Pt‐matrix is more mafic than the host rock or the bulk Pt‐vein, irrespective of the rock types involved, indicating preferential melting of mafic minerals of the host rock(s). Microdomain‐scale variation in mineralogical and chemical character of Pt‐matrix suggests co‐existence of melts of different composition which remained unmixed due to rapid quenching of the melt. Mineral chemistry of fine microlites and spherulites within the Pt‐matrix differs significantly from the corresponding parent mineral grains in the respective host rocks suggesting their formation by direct crystallization from a melt phase. Formation of microlites by devitrification of solidified glass is discounted due to the absence of fluid activity, and due to the spatial distribution of finer microlites (near the Pt‐vein boundary), and coarser spherulites (near the centre). It is surmised that frictional heating attains different temperatures within a single Pt‐vein, and in adjacent Pt‐veins, and the constituent minerals melt selectively as the temperature rises beyond the melting points of different constituent minerals of the host rock. Neither preferential crushing of mafic minerals followed by bulk melting, nor eutectic (equilibrium) melting of the host rock can explain the strongly heterogeneous character of pseudotachylyte melt observed in this study.
A nationwide Swedish study of age at retirement and dementia risk
Authors: Sundström Anna , Rönnlund Michael , Josefsson Maria
Published: June 2020

Objectives

The aim of this nationwide study was to examine the association between age at retirement and dementia risk, with a follow‐up period of up to 24 years.

Methods/design

This cohort study comprised Swedish citizens born in 1930 who were alive in the year 1990 (n = 63 505). The cohort was followed for incidents of dementia through data provided by the Swedish National Patient Register and the Cause of Death Register. Age at retirement and socioeconomic variables were retrieved from Statistics Sweden.

Results

During the follow‐up, 5181 individuals received a dementia diagnosis. Competing risk regression models, adjusted for sex, education, marital status, occupation, and previous history of cardiovascular diseases, showed that later‐than‐average retirement age was associated with decreased dementia risk.

Conclusions

The present results support the idea that individuals who retired at an older age have a decrease risk of dementia. However, as this was an observation study, unmeasured factors, such as premorbid cognitive level and genetic predisposition, may have influenced our findings and remains to be elucidated in future studies.
Coronavirus Disease 2019 (COVID‐19): Potential implications for weak health systems and conflict zones in the Middle East and North Africa region
Authors: Da'ar Omar B. , Haji Mohamed , Jradi Hoda
Published: June 2020

This short communication recognizes the underbelly of weak and conflict‐prone health systems in the Middle East and North Africa region in the wake of COVID‐19 pandemic. The communication highlights how the lack of basic resources, absence of a well‐functioning health system and the dearth of well‐coordinated communication channels, can bode ill for the successful fight against COVID‐19. The article elucidates COVID‐19 potential health, social, and economic implications for such countries. The communication cautions that if COVID‐19 is left to incubate and makes a home in weak systems, it will have a much better chance of mutating and coming back to infect many people globally. The communication calls on the international institutions in collaboration with developed nations to be prepared to probe up health systems in weak and conflict‐prone health systems with much‐needed resources in order to nip COVID‐19 in the bud.
The challenge of increasing employees' well‐being and performance: How human resource management practices and engaging leadership work together toward reaching this goal
Authors: Salas‐Vallina Andrés , Alegre Joaquín , López‐Cabrales Álvaro
Published: June 2020

Despite continuing interest in employees' well‐being, there are still large gaps in our understanding of the mediating role this concept plays in the human resource management (HRM)–performance relationship. In addition, more insights as to how HRM is implemented by leaders are required, as studies largely center either on leadership or on HRM, with little research addressing how HRM and leadership jointly determine employees' well‐being and performance. This study examines the link between well‐being‐oriented human resource management (WBHRM) and performance in a sample of very large organizations, based on the job demands–resource model and social exchange theory. In addition, we explore the moderating role of middle managers' leadership in the relationship between WBHRM and employees' well‐being. The results reveal that engaging leadership behavior fosters genuine implementation of WBHRM and has a direct impact on employees' performance.
KSHV dysregulates bulk macroautophagy, mitophagy and UPR to promote endothelial to mesenchymal transition and CCL2 release, key events in viral‐driven sarcomagenesis
Authors: Santarelli Roberta , Arteni Ana Maria Brindusa , Gilardini Montani Maria Saveria , Romeo Maria Anele , Gaeta Aurelia , Gonnella Roberta , Faggioni Alberto , Cirone Mara
Published: June 2020

Kaposi's sarcoma‐associated herpesvirus (KSHV) is the causative agent of KS, an aggressive neoplasm that mainly occurs in immune‐compromised patients. Spindle cells represent the main feature of this aggressive malignancy and arise from KSHV‐infected endothelial cells undergoing endothelial to mesenchymal transition (EndMT), which changes their cytoskeletal composition and organization. As in epithelial to mesenchymal transition (EMT), EndMT is driven by transcription factors such as SNAI1 and ZEB1 and implies a cellular reprogramming mechanism regulated by several molecular pathways, particularly PI3K/AKT/MTOR. Here we found that KSHV activated MTOR and its targets 4EBP1 and ULK1 and reduced bulk macroautophagy and mitophagy to promote EndMT, activate ER stress/unfolded protein response (UPR), and increase the release of the pro‐angiogenic and pro‐inflammatory chemokine CCL2 by HUVEC cells. Our study suggests that the manipulation of macroautophagy, mitophagy and UPR and the interplay between the three could be a promising strategy to counteract EndMT, angiogenesis and inflammation, the key events of KSHV‐driven sarcomagenesis.
Identifying brain regions contributing to Alzheimer's disease using self regulating particle swarm optimization
Authors: Ganotra Reema , Dora Shirin , Gupta Shailender
Published: June 2020

In this article, we developed an approach for detecting brain regions that contribute to Alzheimer's disease (AD) using support vector machine (SVM) classifiers and the recently developed self regulating particle swarm optimization (SRPSO) algorithm. SRPSO employs strategies inspired by the principles of learning in humans to achieve faster and better optimization results. The classifiers for distinguishing subjects into AD patients and cognitively normal (CN) individuals were built using grey matter (GM) and white matter (WM) volumetric features extracted from structural magnetic resonance (MR) images. It could be observed from results that the classifier built using both GM and WM features provided accuracy of 89.26% which is better than the performance of classifiers built using either GM or WM features only. Moreover, consideration of clinical features in addition to volumetric features improves the accuracy further to 94.63% which is better than the performance reported by recent works in literature. In order to identify the brain regions that are important for AD vs CN classification problem, we used SRPSO to extract GM and WM features that yield better classification performance. Using 50 features identified by SRPSO, an accuracy of 89.39% was obtained which is close to the accuracy based on all features. The features identified by SRPSO were mapped back to the brain to identify brain regions that exhibit degeneration in AD. In addition to identifying areas known to be involved in AD like cerebellum, hippocampus, this helped in finding newer areas that might contribute towards AD.
RegTech—the application of modern information technology in regulatory affairs: areas of interest in research and practice
Authors: Becker Michael , Merz Kevin , Buchkremer Rüdiger
Published: June 2020

We provide a high‐level view on topics addressed in scientific articles about regulatory technology (RegTech), with a particular focus on technologies used. For this purpose, we first explore different denominations for RegTech and derive search queries to search relevant literature portals. From the hits of that information retrieval process, we select 55 articles outlining the application of information technology in regulatory affairs with an emphasis on the financial sector. In comparison, we examine the technological scope of 347 RegTech companies and compare our findings with the scientific literature. Our research reveals that ‘compliance management’ is the most relevant topic in practice, and ‘risk management’ is the primary subject in research. The most significant technologies as of today are ‘artificial intelligence’ and distributed ledger technologies such as ‘blockchain’.
Long non‐coding RNA SCARNA2 induces cutaneous squamous cell carcinoma progression via modulating miR‐342‐3p expression
Authors: Zhang Zhongzhao , Jia Min , Wen Changhui , He Aijuan , Ma Zunfeng
Published: June 2020

Background

Long non‐coding RNAs (lncRNAs) play important roles in the progression of tumors. However, the function and expression of SCARNA2 in cutaneous squamous cell carcinoma (cSCC) is still unreported.

Methods

A quantitative polymerase chain reaction was applied to study the expression of SCARNA2 and miR‐342‐3p. Cell counting kit‐8, flow cytometry and transwell assays were performed to study cell growth, cycle and cell invasion.

Results

We found that SCARNA2 expression is up‐regulated in cSCC cell lines and SCARNA2 expression is higher in cSCC tissues than in adjacent non‐tumor specimens. Ectopic expression of SCARNA2 promoted cell growth, cell cycle and invasion in SCC13 cells. In addition, the data indicate that miR‐342‐3p expression is down‐regulated in cSCC cell lines and miR‐342‐3p is down‐regulated in cSCC tissues compared to adjacent non‐tumor specimens. We showed that the SCARNA2 expression is negatively associated with miR‐342‐3p in cSCC. Moreover, we noted that SCARNA2 sponges miR‐342‐3p expression in cSCC cells. Overexpression of SCARNA2 suppressed the miR‐342‐3p expressed in SCC13 cells. We found that elevated expression of SCARNA2 promotes cell growth, cell cycle and invasion via regulating miR‐342‐3p expression in SCC13 cells.

Conclusions

These data suggest that SCARNA2 acts in an oncogenic role and may be a potential target for cSCC.
Runx2 silencing promotes adipogenesis via down‐regulation of DLK1 in chondrogenic differentiating MSCs
Authors: Rahim Fakher , Abbasi Pashaki Pejman , Jafarisani Moslem , Ghorbani Fatemeh , Ebrahimi Ammar
Published: June 2020

Background

For cartilage regeneration, stem cells are a promising cell source; however, even the advances made in the differentiation of stem cells into precursor‐differentiated cartilage cells have not been successful with respect to reprograming these cells to achieve complete differentiation and fully functioning cells until now. Previous findings suggest that Runx2 plays a major role in chondrocyte differentiation and maturation. Although targeting Runx2 has enhanced some chondrocyte properties, the adipogenic lineage shift has eventually occurred in these cells. The present study mainly aimed to reveal the mechanism of this adipogenesis.

Methods

To create inducible artificial shRNA‐miR expressing vectors, the designed short hairpin RNAs (shRNAs) were inserted into the pri‐mir‐30 backbone, cloned into lentiviral pLVET‐Tet‐on, and transducted into mesenchymal stem cells (MSCs). Runx2 gene was silenced in MSCs either for 1 week or 4 weeks and cultured in the chondrogenic medium. At days 7, 14 and 28, cells were harvested, and chondrogenesis, adipogenesis and hypertrophic states were examined using histochemical staining and a real‐time polymerase chain reaction assay.

Results

The results showed that the designed shRNA‐miR effectively targeted Runx2 in mRNA and protein levels. Chondrogenic markers were up‐regulated in constantly silenced Runx2 group; however, adipogenic markers and fat droplets appeared gradually. DLK1 gene was also significantly down‐regulated in this group, and overexpression of DLK1 abrogated adipogenesis in the Runx2 targeted group.

Conclusions

Based on these results, it can be concluded that DLK1 is responsible for the lineage shift in Runx2 targeted chondrogenic differentiating MSCs.
Novel Associations Between Genome‐Wide Single Nucleotide Polymorphisms and MR Enterography Features in Crohn's Disease Patients
Authors: Cruz‐Romero Cinthia , Guo Abra , Bradley William F. , Vicentini Joao R.T. , Yajnik Vijay , Gee Michael S.
Published: June 2020

Background

Patient genetic polymorphism is associated with Crohn's clinical behavior; however, its association with magnetic resonance enterography (MRE) imaging appearance is not known.

Purpose

To analyze a set of known Crohn's disease (CD)‐related single nucleotide polymorphisms for associations with MRE imaging phenotype and frequency of imaging.

Study Type

Retrospective.

Population

54 patients (mean age 40 years; 32 females and 22 males) with established CD from 2009 to 2016 who underwent baseline MRE and genetic testing for the presence of 168 single nucleotide polymorphisms (SNPs) potentially associated with inflammatory bowel disease.

Field Strength/Sequence

1.5T or 3T clinical scanners, standard MRE clinical pulse sequences, including T2‐weighted single‐shot fast spin echo, balanced steady‐state free precession, T2‐weighted fast spin echo fat‐suppressed, and T1‐weighted fat‐suppressed pre‐ and postcontrast imaging.

Assessment

Three readers (all body imaging fellowship‐trained radiologists) independently evaluated all imaging for the presence or absence of active disease and penetrating complications. Date of onset and frequency of endoscopies and cross‐sectional imaging (CSI) were recorded. Disease behavior and distribution were categorized according to the Vienna and Montreal classifications, respectively.

Statistical Tests

Student's t‐test and Fisher's exact test were used to assess significance of continuous and categorical variables, respectively. A hidden Markov model statistical knockoff approach was also applied for the analysis of genetic‐imaging associations, with corrected P < 0.05 considered significant.

Results

MRE demonstrated active bowel inflammation in 42 (78%) patients, strictures in 13 (28%), and fistulae in 13 (28%). The SNP rs1292053 (RBS6KB1) was highly associated with small bowel inflammation and luminal narrowing, with observed frequencies of association 0.66 and 0.39, respectively (P = 0.001). rs6062504 (Decoy receptor 3) was associated with lower age of onset (P = 0.012), higher proportion of early disease onset patients (P = 0.012), and higher average number of CSI/year (P = 0.014).

Data Conclusion

This study demonstrated significant associations between CD genotype and MRE phenotype and frequency of cross‐sectional imaging.

Level of Evidence

3

Technical Efficacy Stage

2
Dynamical role of the Changbai Mountains and the Korean Peninsula in the wintertime quasi‐stationary convergence zone over the Sea of Japan
Authors: Shinoda Yuta , Kawamura Ryuichi , Kawano Tetsuya , Shimizu Hiroyuki
Published: June 2020

This study focused on a quasi‐stationary convergence zone over the Sea of Japan (Japan Sea polar airmass convergence zone, JPCZ) in early winter and examined how the Changbai Mountains and the Korean Peninsula play an influential role in the formation and maintenance of the JPCZ and associated precipitation amounts in the coastal regions of central and western Japan. We performed numerical simulations with and without modified topography of the Changbai Mountains and the Korean Peninsula using a regional atmospheric model. The results show that the presence of the mountains is largely responsible for the JPCZ formation and usually contributes to the reduction of precipitation in the coastal regions. If specific conditions are satisfied, however, it can trigger heavy precipitation. One condition is the rapid growth of mesoscale eddies off the Sea of Japan coast under strong low‐level wind convergence. The precipitation band involved in the enhanced eddies slowly migrates southward and reaches the coastal regions, causing heavy snowfall. Another condition is the change in background monsoonal flows associated with synoptic‐scale cyclone development due to the orographic effect. The resultant background flows may help sustain a significant amount of precipitation in the coastal regions. Under the prevailing JPCZ, the mountains play two contradictory roles in modulating precipitation amounts in the coastal regions.
Study on the Adaptability of Alkanolamide (LDEA) Lowering Oil/Water Interfacial Tension to Different Crude Oils
Authors: Pu Di , Xiong Ya‐chun , Feng Ru‐sen , Guo Yong‐jun , Lin Ling , Xu Cheng‐jun , Yu Wen‐ke
Published: June 2020

In order to investigate the high interfacial activity and fair oil phase adaptability of alkanolamide, “1:1” type lauric acid diethanolamide impurities (LDEA) were synthesized and purified by the column chromatography method to obtain dodecanoic acid diethanolamide (C12DEA), ester mixture, etc. The exact structures of these compounds were further confirmed by IR, gas chromatogrph with mass spectroscopy (GC–MS), and NMR. The influence of each component on the interfacial tension of oil/water (IFT) was studied by systematic quantitative analysis. The results showed that (i) the strength of each system to reduce oil/water IFT is C12DEA /DEA ≈ LDEA > C12DEA/DEA/ESTER > C12DEA/NaOH > C12DEA > C12DEA/ESTER > DEA. This indicates that LDEA contributes to the reduction of the oil/water IFT and the enhanced adaptability of crude oil in this order: DEA > > ESTER; (ii) when the IFT of the LDEA/DEA system reached an ultralow value, the minimum content of DEA in the system was 1%, and the maximum ester content was less than 5% when the LDEA/DEA/ESTER system reached the ultralow IFT; (iii) the possible mechanism of effect of LDEA components on the IFT and oil phase adaptability was proposed as the synergistic process among the hydrogen bonding, alkali effect, and interface self‐assembly of molecules in the interfacial layer. The contribution of these three factors were hydrogen bonding > alkali effect > interface self‐assembly.
Proinflammatory intervertebral disc cell and organ culture models induced by tumor necrosis factor alpha
Authors: Du Jie , Pfannkuche Judith‐J. , Lang Gernot , Häckel Sonja , Creemers Laura B. , Alini Mauro , Grad Sibylle , Li Zhen
Published: June 2020

Inflammation plays an important role in the pathogenesis of intervertebral disc (IVD) degeneration. The proinflammatory cytokine tumor necrosis factor alpha (TNF‐α) has shown markedly higher expression in degenerated human disc tissue compared with healthy controls. Anti‐inflammatory treatment targeting TNF‐α has shown to alleviate discogenic pain in patients with low back pain. Therefore, in vitro and ex vivo inflammatory models utilizing TNF‐α provide relevant experimental conditions for drug development in disc degeneration research.

The current method article addressed several specific questions related to the model establishment.

(a) The effects of bovine and human recombinant TNF‐α on bovine nucleus pulposus (NP) cells were compared. (b) The required dose for an inflammatory IVD organ culture model with intradiscal TNF‐α injection was studied. (c) The effect of TNF‐α blocking at different stages of inflammation was evaluated.

Outcomes revealed that bovine and human recombinant TNF‐α induced equivalent inflammatory effects in bovine NP cells. A bovine whole IVD inflammatory model was established by intradiscal injection of 100 ng TNF‐α/ cm3 disc volume, as indicated by increased nitric oxide, glycosaminoglycan, interleukin 6 (IL‐6), and interleukin 8 (IL‐8) release in culture media, and upregulation of MMP3, ADAMTS4, IL‐8, IL‐6, and cyclooxygenase (COX)‐2 expression in NP tissue. However, results in human NP cells showed that the time point of anti‐inflammatory treatment was crucial to achieve significant effects. Furthermore, anticatabolic therapy in conjunction with TNF‐α inhibition would be required to slow down the pathologic cascade of disc degeneration.
Tissue engineering applications in otolaryngology—The state of translation
Authors: Niermeyer Weston L. , Rodman Cole , Li Michael M. , Chiang Tendy
Published: June 2020

While tissue engineering holds significant potential to address current limitations in reconstructive surgery of the head and neck, few constructs have made their way into routine clinical use. In this review, we aim to appraise the state of head and neck tissue engineering over the past five years, with a specific focus on otologic, nasal, craniofacial bone, and laryngotracheal applications. A comprehensive scoping search of the PubMed database was performed and over 2000 article hits were returned with 290 articles included in the final review. These publications have addressed the hallmark characteristics of tissue engineering (cellular source, scaffold, and growth signaling) for head and neck anatomical sites. While there have been promising reports of effective tissue engineered interventions in small groups of human patients, the majority of research remains constrained to in vitro and in vivo studies aimed at furthering the understanding of the biological processes involved in tissue engineering. Further, differences in functional and cosmetic properties of the ear, nose, airway, and craniofacial bone affect the emphasis of investigation at each site. While otolaryngologists currently play a role in tissue engineering translational research, continued multidisciplinary efforts will likely be required to push the state of translation towards tissue‐engineered constructs available for routine clinical use.

Level of Evidence

NA.
Functional polymorphisms of the mineralocorticoid receptor gene NR3C2 are associated with diminished memory decline: Results from a longitudinal general‐population study
Authors: Terock Jan , Van der Auwera Sandra , Janowitz Deborah , Wittfeld Katharina , Teumer Alexander , Grabe Hans J.
Published: June 2020

Background

The mineralocorticoid receptor (MR) in the brain has a key role in the regulation of the central stress response and is associated with memory performance. We investigated whether the genetic polymorphisms rs5522 and rs2070951 of NR3C2 showed main and interactive effects with childhood trauma on memory decline.

Methods

Declarative memory was longitudinally assessed in 1,318 participants from the community‐dwelling Study of Health in Pomerania using the Verbal Learning and Memory Test (VLMT). In a subsample of 377 participants aged 60 and older, the Mini‐Mental Status Examination (MMSE) was additionally applied. Mean follow‐up time for the VLMT and MMSE were 6.4 and 10.7 years, respectively.

Results

Homozygous carriers of the G allele of rs2070951 (p < .01) and of the A allele of rs5522 (p < .001) showed higher immediate recall of words as compared to carriers of C allele (rs2070951) or the G allele (rs5522). The CG haplotype was associated with decreased recall (p < .001). Likewise, in the subsample of older patients, the AA genotype of rs5522 was associated with higher MMSE scores (p < .05). CG haplotypes showed significantly reduced MMSE scores in comparison to the reference haplotype (β = −0.60; p < .01).

Conclusions

Our results indicate that the GG genotype of rs2070951 as well as the AA genotype of rs5522 are associated with diminished memory decline.
Pediatric access to MH care service models still thriving
Authors: Canady Valerie A.
Published: June 2020

In the 15 years since an innovative program in Massachusetts helped families access children's mental health services by allowing primary care doctors to receive consultations from mental health experts, the program continues to reap benefits. Many states have since initiated similar programs using a wide variety of models. A recent symposium addressed the history and evidence to support the model.
A 24 GHz hydrology radar system capable of wide‐range surface velocity detection for water resource management applications
Authors: Lin Yo‐Sheng , Chiu Shang‐Feng , Chang Chi‐Ho
Published: June 2020

We demonstrate a 24 GHz hydrology radar system. The continuous‐wave Doppler radar is capable of noncontact and wide‐range surface‐flow velocity detection in various scenarios. The radar receives the reflected echo signal through a directional narrow‐beam antenna. After amplification and demodulation by the proposed low‐noise amplifier and the subharmonic down‐conversion mixer, respectively, the Doppler frequency‐shift is analyzed by the digital signal processing (DSP) module for estimation of the water flow velocity. Moreover, for water level detection, a phase‐locked loop with micro control unit (MCU)‐controlled division ratio is included in the RF module for generating a stable and tunable (or frequency modulation) 24‐GHz‐band transmitting signal with low phase noise. To verify the radar system, outdoor field tests have been conducted. The measured results are consistent with the theoretical values, and the results of both the float method and the commercial handheld (Stalker Pro II) surface velocity radar. In the condition of water ripple lower than 3 cm, the radar functions well for flow speed range of 0.3 ~ 34.6 m/s. Overall, the hydrology radar is suitable for surface‐flow velocity detection (especially in bad weather) and water resource management (such as water‐level detection).