bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal Stem Cell‐Derived Exosomes for Effective Cartilage Tissue Repair and Treatment of Osteoarthritis
Authors: Kim Young Guk , Choi Jonghoon , Kim Kyobum 
Published: June 2020

AbstractOsteoarthritis (OA) is one of the most common musculoskeletal diseases, caused by cellular inflammatory responses and subsequent structural disruption in osteochondral extracellular matrix (ECM) in cartilage tissues. Various cell‐therapies have been recently developed via the exogenous administration of mesenchymal stem cells (MSCs) due to their intrinsic regenerative capacity of self‐renewal and chondrogenic differentiation. However, MSC‐based cellular approaches have exhibited some technical limitations including dedifferentiation during MSC expansion, reduction of regenerative efficacy upon administration, and inconsistent quality control in large‐scale cell production. To overcome these disadvantages, exosome mediated cartilage tissue regeneration has been investigated. Since exosome derived from MSC (MSC‐exosome) transport and deliver multiple cellular components from their original MSC sources, they could be utilized as alternative therapeutic agents for OA treatment. Recent studies have shown that the administration of MSC‐exosome effectively reduced a production of inflammatory cytokines in chondrocytes, increased the expression of cartilage ECM component, and eventually augment cartilage tissue regeneration in a series of in vivo studies. Therefore, this review emphasizes current engineering approaches via MSC‐exosome for cartilage tissue repair, as a functional OA treatment technique.
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

AbstractWe 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

AbstractSustainability 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

AbstractBackgroundIt is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care.ObjectivesTo describe the current role of cardiovascular screening in the clinical care of asymptomatic CCS.MethodsAt 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.ResultsOf 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.ConclusionsWhile 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

AbstractMost 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

AbstractGSK2838232 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

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

AbstractAimsBoth 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 resultsWe 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.ConclusionsDanicamtiv 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

AbstractPulmonary 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

AbstractThe 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

AbstractNo 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.
A nationwide Swedish study of age at retirement and dementia risk
Authors: Sundström Anna , Rönnlund Michael , Josefsson Maria 
Published: June 2020

ObjectivesThe 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/designThis 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.ResultsDuring 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.ConclusionsThe 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.